CleftGeneDB-Search

Gene: DHFR

Basic information

Tag	Content
Uniprot ID	P00374; B4DDD2; Q14130; Q6IRW8;
Entrez ID	1719
Genbank protein ID	CAA23765.1; AAH00192.1; AAH71996.1; AAA58485.1; AAH03584.2; AAH70280.1; BAG56693.1; AAA58484.1; CAA25409.1;
Genbank nucleotide ID	NM_001290354.1; NM_000791.3;
Ensembl protein ID	ENSP00000426474; ENSP00000396308; ENSP00000421334;
Ensembl nucleotide ID	ENSG00000228716
Gene name	Dihydrofolate reductase
Gene symbol	DHFR
Organism	Homo sapiens
NCBI taxa ID	9606
Cleft type	CPO,CL/P
Developmental stage
Data sources	Manually collected
Reference	24361572; 26221921;
Functional description	Key enzyme in folate metabolism. Contributes to the de novo mitochondrial thymidylate biosynthesis pathway. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis. Binds its own mRNA and that of DHFR2.
Sequence	MVGSLNCIVA VSQNMGIGKN GDLPWPPLRN EFRYFQRMTT TSSVEGKQNL VIMGKKTWFS 60 IPEKNRPLKG RINLVLSREL KEPPQGAHFL SRSLDDALKL TEQPELANKV DMVWIVGGSS 120 VYKEAMNHPG HLKLFVTRIM QDFESDTFFP EIDLEKYKLL PEYPGVLSDV QEEKGIKYKF 180 EVYEKND 187

Abbreviation :
CLO : cleft lip only. CPO : cleft palate only. CLP : cleft lip and palate. CL/P : cleft lip with/without cleft palate.
For humans: CL/P, CLO, CPO, and CLP. For mice: CLO, CLP, and CPO.

Gene expression information

Gene expression in different tissues (GTEx V7)

Gene expression in different tissues (ENCODE)

Protein structural annotations

3D structure in PDB database

PDB ID
1BOZ
1DHF
1DLR
1DLS
1DRF
1HFP
1HFQ
1HFR
1KMS
1KMV
1MVS
1MVT
1OHJ
1OHK
1PD8
1PD9
1PDB
1S3U
1S3V
1S3W
1U71
1U72
1YHO
2C2S
2C2T
2DHF
2W3A
2W3B
2W3M
3EIG
3F8Y
3F8Z
3F91
3FS6
3GHC
3GHV
3GHW
3GI2
3GYF
3L3R
3N0H
3NTZ
3NU0
3NXO
3NXR
3NXT
3NXV
3NXX
3NXY
3NZD
3OAF
3S3V
3S7A
4DDR
4G95
4KAK
4KBN
4KD7
4KEB
4KFJ
4M6J
4M6K
4M6L
4QHV
4QJC
5HPB
5HQY
5HQZ
5HSR
5HSU
5HT4
5HT5
5HUI
5HVB
5HVE
6A7C
6A7E
6DAV
6DE4
1KMS
1KMV
3S7A
4M6K
5HQY

Protein disorder information

Orthologous information

There is no orthologous record for this gene !

Identified variants/mutations related to cleft phenotype

Gene symbol	Significant Variants/SNPS	Methods	PubMed ID
DHFR	19bp deletion	PCR	26221921
DHFR	rs1677693	TaqMan genotyping	24361572

Other genetic variants/mutations

ID	Variant	Type	Disease	Chromosome\Coordinate	Evidence
rs1245883641	p.Val2Phe	missense variant	-	NC_000005.10:g.80654486C>A	gnomAD
rs1381483540	p.Gly3Ala	missense variant	-	NC_000005.10:g.80654482C>G	gnomAD
rs199586723	p.Ser4Leu	missense variant	-	NC_000005.10:g.80654479G>A	ExAC,TOPMed,gnomAD
rs1281942097	p.Ser4Ala	missense variant	-	NC_000005.10:g.80654480A>C	TOPMed,gnomAD
rs199586723	p.Ser4Ter	stop gained	-	NC_000005.10:g.80654479G>T	ExAC,TOPMed,gnomAD
rs780338583	p.Leu5Ile	missense variant	-	NC_000005.10:g.80654477G>T	ExAC,TOPMed,gnomAD
rs756401520	p.Asn6Lys	missense variant	-	NC_000005.10:g.80654472G>C	ExAC,gnomAD
rs746083870	p.Cys7Phe	missense variant	-	NC_000005.10:g.80654470C>A	ExAC,gnomAD
rs781563390	p.Ala10Ser	missense variant	-	NC_000005.10:g.80654462C>A	ExAC,gnomAD
rs1197644951	p.Gln13Leu	missense variant	-	NC_000005.10:g.80654452T>A	gnomAD
NCI-TCGA novel	p.Asn14Ser	missense variant	-	NC_000005.10:g.80654449T>C	NCI-TCGA
rs61736208	p.Gly18Arg	missense variant	-	NC_000005.10:g.80654438C>G	ExAC,gnomAD
rs61736208	p.Gly18Ser	missense variant	-	NC_000005.10:g.80654438C>T	ExAC,gnomAD
rs1490962892	p.Asn20Lys	missense variant	-	NC_000005.10:g.80654430G>T	gnomAD
NCI-TCGA novel	p.Asp22AlaPheSerTerUnkUnk	frameshift	-	NC_000005.10:g.80654425T>-	NCI-TCGA
rs758957010	p.Asp22Val	missense variant	-	NC_000005.10:g.80654425T>A	ExAC,gnomAD
rs1364132118	p.Leu23Pro	missense variant	-	NC_000005.10:g.80654422A>G	TOPMed
rs1339446031	p.Arg29Lys	missense variant	-	NC_000005.10:g.80654404C>T	TOPMed,gnomAD
rs1215835047	p.Arg29Gly	missense variant	-	NC_000005.10:g.80654405T>C	gnomAD
RCV000286239	p.Asn30Lys	missense variant	-	NC_000005.10:g.80654054A>C	ClinVar
rs201745474	p.Asn30Lys	missense variant	-	NC_000005.10:g.80654054A>C	ESP,ExAC,TOPMed,gnomAD
rs765924078	p.Asn30Thr	missense variant	-	NC_000005.10:g.80654055T>G	ExAC
rs1197915916	p.Tyr34Cys	missense variant	-	NC_000005.10:g.80654043T>C	TOPMed
rs767425256	p.Gln36Glu	missense variant	-	NC_000005.10:g.80654038G>C	ExAC,gnomAD
rs1414898962	p.Arg37Lys	missense variant	-	NC_000005.10:g.80654034C>T	TOPMed
rs761785469	p.Thr40Ile	missense variant	-	NC_000005.10:g.80654025G>A	ExAC,gnomAD
rs1473186463	p.Thr41Ile	missense variant	-	NC_000005.10:g.80654022G>A	TOPMed
rs1382860073	p.Val44Ile	missense variant	-	NC_000005.10:g.80654014C>T	TOPMed
rs1032250222	p.Glu45Lys	missense variant	-	NC_000005.10:g.80654011C>T	TOPMed
RCV000480515	p.Glu45Ter	frameshift	-	NC_000005.10:g.80654011del	ClinVar
rs1251977833	p.Asn49Lys	missense variant	-	NC_000005.10:g.80649484A>C	gnomAD
rs1301676659	p.Leu50Gln	missense variant	-	NC_000005.10:g.80649482A>T	gnomAD
rs1213637006	p.Ile52Thr	missense variant	-	NC_000005.10:g.80649476A>G	gnomAD
rs755733770	p.Met53Arg	missense variant	-	NC_000005.10:g.80649473A>C	ExAC,TOPMed,gnomAD
rs755733770	p.Met53Thr	missense variant	-	NC_000005.10:g.80649473A>G	ExAC,TOPMed,gnomAD
NCI-TCGA novel	p.Gly54Ala	missense variant	-	NC_000005.10:g.80649470C>G	NCI-TCGA
rs1474639123	p.Gly54Cys	missense variant	-	NC_000005.10:g.80649471C>A	TOPMed
rs1285372695	p.Gly54Asp	missense variant	-	NC_000005.10:g.80649470C>T	gnomAD
rs750068317	p.Lys55Glu	missense variant	-	NC_000005.10:g.80649468T>C	ExAC,gnomAD
rs1161850054	p.Lys56Thr	missense variant	-	NC_000005.10:g.80649464T>G	TOPMed
rs371161421	p.Ser60Cys	missense variant	-	NC_000005.10:g.80649452G>C	ESP,ExAC,gnomAD
rs371161421	p.Ser60Phe	missense variant	-	NC_000005.10:g.80649452G>A	ESP,ExAC,gnomAD
rs1322225765	p.Ile61Val	missense variant	-	NC_000005.10:g.80649450T>C	gnomAD
rs200232379	p.Glu63Lys	missense variant	-	NC_000005.10:g.80649444C>T	ESP,ExAC,TOPMed,gnomAD
rs200232379	p.Glu63Gln	missense variant	-	NC_000005.10:g.80649444C>G	ESP,ExAC,TOPMed,gnomAD
rs762790419	p.Glu63Gly	missense variant	-	NC_000005.10:g.80649443T>C	ExAC,gnomAD
rs1464614335	p.Asn65Thr	missense variant	-	NC_000005.10:g.80649437T>G	gnomAD
rs752733264	p.Arg66Leu	missense variant	-	NC_000005.10:g.80649434C>A	ExAC,gnomAD
rs1421050089	p.Arg66Ter	stop gained	-	NC_000005.10:g.80649435G>A	TOPMed,gnomAD
rs752733264	p.Arg66Gln	missense variant	-	NC_000005.10:g.80649434C>T	ExAC,gnomAD
rs1480679070	p.Leu68Ter	stop gained	-	NC_000005.10:g.80649428A>C	TOPMed,gnomAD
rs766341761	p.Gly70Val	missense variant	-	NC_000005.10:g.80649422C>A	ExAC,TOPMed,gnomAD
rs766341761	p.Gly70Asp	missense variant	-	NC_000005.10:g.80649422C>T	ExAC,TOPMed,gnomAD
rs1435266382	p.Arg71Thr	missense variant	-	NC_000005.10:g.80649419C>G	gnomAD
NCI-TCGA novel	p.Asn73SerPheSerTerUnkUnk	frameshift	-	NC_000005.10:g.80649409_80649413TAAAT>-	NCI-TCGA
rs773305047	p.Asn73Ile	missense variant	-	NC_000005.10:g.80649413T>A	ExAC,gnomAD
rs760708940	p.Asn73His	missense variant	-	NC_000005.10:g.80649414T>G	ExAC,gnomAD
rs1355100511	p.Leu74Val	missense variant	-	NC_000005.10:g.80649411A>C	TOPMed
rs1456478807	p.Leu76Ile	missense variant	-	NC_000005.10:g.80649405G>T	gnomAD
rs969810454	p.Leu76Pro	missense variant	-	NC_000005.10:g.80649404A>G	TOPMed,gnomAD
NCI-TCGA novel	p.Arg78Lys	missense variant	-	NC_000005.10:g.80649398C>T	NCI-TCGA
NCI-TCGA novel	p.Glu79Gly	missense variant	-	NC_000005.10:g.80649395T>C	NCI-TCGA
rs1023990945	p.Glu79Lys	missense variant	-	NC_000005.10:g.80649396C>T	TOPMed
COSM1438884	p.Glu79Ter	stop gained	Variant assessed as Somatic; HIGH impact.	NC_000005.10:g.80649396C>A	NCI-TCGA Cosmic
RCV000022524	p.Leu80Phe	missense variant	Megaloblastic anemia due to dihydrofolate reductase deficiency	NC_000005.10:g.80649393G>A	ClinVar
rs387906619	p.Leu80Phe	missense variant	Megaloblastic anemia due to dihydrofolate reductase deficiency (DHFRD)	NC_000005.10:g.80649393G>A	UniProt,dbSNP
VAR_065818	p.Leu80Phe	missense variant	Megaloblastic anemia due to dihydrofolate reductase deficiency (DHFRD)	NC_000005.10:g.80649393G>A	UniProt
rs387906619	p.Leu80Phe	missense variant	-	NC_000005.10:g.80649393G>A	ExAC,gnomAD
rs540527930	p.Lys81Arg	missense variant	-	NC_000005.10:g.80649389T>C	TOPMed,gnomAD
rs774576661	p.Lys81Glu	missense variant	-	NC_000005.10:g.80649390T>C	ExAC,gnomAD
rs750437833	p.Gly86Glu	missense variant	-	NC_000005.10:g.80637995C>T	ExAC,gnomAD
rs1000980239	p.Ala87Gly	missense variant	-	NC_000005.10:g.80637992G>C	TOPMed
rs1000980239	p.Ala87Val	missense variant	-	NC_000005.10:g.80637992G>A	TOPMed
rs767651918	p.His88Arg	missense variant	-	NC_000005.10:g.80637989T>C	ExAC,gnomAD
rs1238594552	p.Leu90Ile	missense variant	-	NC_000005.10:g.80637984G>T	TOPMed,gnomAD
rs774682803	p.Ser91Phe	missense variant	-	NC_000005.10:g.80637980G>A	ExAC,gnomAD
rs764333131	p.Arg92Gly	missense variant	-	NC_000005.10:g.80637978T>C	ExAC,TOPMed,gnomAD
rs781727821	p.Asp95His	missense variant	-	NC_000005.10:g.80637969C>G	ExAC,TOPMed,gnomAD
rs942272996	p.Thr101Ile	missense variant	-	NC_000005.10:g.80637950G>A	gnomAD
rs1045276866	p.Pro104Ala	missense variant	-	NC_000005.10:g.80637942G>C	TOPMed
rs201584784	p.Glu105Asp	missense variant	-	NC_000005.10:g.80637937T>A	1000Genomes,ExAC,gnomAD
rs770618811	p.Leu106Ile	missense variant	-	NC_000005.10:g.80637936A>T	ExAC,gnomAD
rs777444850	p.Asp111Gly	missense variant	-	NC_000005.10:g.80637920T>C	ExAC,gnomAD
rs1214007828	p.Val113Phe	missense variant	-	NC_000005.10:g.80637915C>A	TOPMed
NCI-TCGA novel	p.Val116Gly	missense variant	-	NC_000005.10:g.80637905A>C	NCI-TCGA
rs1262938206	p.Ser119Arg	missense variant	-	NC_000005.10:g.80637897T>G	gnomAD
rs1214817753	p.Ser119Arg	missense variant	-	NC_000005.10:g.80637895A>T	gnomAD
NCI-TCGA novel	p.Ser120Pro	missense variant	-	NC_000005.10:g.80637894A>G	NCI-TCGA
COSM1070683	p.Ser120Tyr	missense variant	Variant assessed as Somatic; MODERATE impact.	NC_000005.10:g.80637893G>T	NCI-TCGA Cosmic
rs747921931	p.Val121Ala	missense variant	-	NC_000005.10:g.80637890A>G	ExAC,gnomAD
rs1293072146	p.Tyr122Phe	missense variant	-	NC_000005.10:g.80637887T>A	gnomAD
rs1228153803	p.Ala125Thr	missense variant	-	NC_000005.10:g.80633989C>T	TOPMed
rs1287152741	p.Met126Ile	missense variant	-	NC_000005.10:g.80633984C>T	gnomAD
rs1266838564	p.His128Gln	missense variant	-	NC_000005.10:g.80633978G>C	TOPMed
rs772613889	p.Pro129Gln	missense variant	-	NC_000005.10:g.80633976G>T	ExAC,gnomAD
rs772613889	p.Pro129Leu	missense variant	-	NC_000005.10:g.80633976G>A	ExAC,gnomAD
rs760187947	p.Pro129Ala	missense variant	-	NC_000005.10:g.80633977G>C	ExAC,TOPMed,gnomAD
NCI-TCGA novel	p.His131Tyr	missense variant	-	NC_000005.10:g.80633971G>A	NCI-TCGA
rs1277129985	p.His131Arg	missense variant	-	NC_000005.10:g.80633970T>C	gnomAD
NCI-TCGA novel	p.Leu132Arg	missense variant	-	NC_000005.10:g.80633967A>C	NCI-TCGA
rs972884214	p.Leu132Phe	missense variant	-	NC_000005.10:g.80633968G>A	TOPMed
NCI-TCGA novel	p.Leu134Ile	missense variant	-	NC_000005.10:g.80633962G>T	NCI-TCGA
COSM4405036	p.Leu134Pro	missense variant	Variant assessed as Somatic; MODERATE impact.	NC_000005.10:g.80633961A>G	NCI-TCGA Cosmic
rs747824863	p.Thr137Ala	missense variant	-	NC_000005.10:g.80633953T>C	ExAC,gnomAD
rs141831067	p.Met140Leu	missense variant	-	NC_000005.10:g.80633944T>G	1000Genomes,ESP,ExAC,TOPMed,gnomAD
rs1331010891	p.Asp142Glu	missense variant	-	NC_000005.10:g.80633936G>C	TOPMed,gnomAD
rs1466161664	p.Asp146Gly	missense variant	-	NC_000005.10:g.80633925T>C	gnomAD
rs768490218	p.Thr147Met	missense variant	-	NC_000005.10:g.80633922G>A	ExAC,TOPMed,gnomAD
rs1481660079	p.Phe148Leu	missense variant	-	NC_000005.10:g.80633918A>C	gnomAD
rs954427933	p.Pro150Ala	missense variant	-	NC_000005.10:g.80633914G>C	TOPMed,gnomAD
RCV000022525	p.Asp153Val	missense variant	Megaloblastic anemia due to dihydrofolate reductase deficiency	NC_000005.10:g.80633904T>A	ClinVar
rs1190920458	p.Asp153Tyr	missense variant	-	NC_000005.10:g.80633905C>A	TOPMed,gnomAD
rs1190920458	p.Asp153His	missense variant	-	NC_000005.10:g.80633905C>G	TOPMed,gnomAD
rs121913223	p.Asp153Val	missense variant	Megaloblastic anemia due to dihydrofolate reductase deficiency (DHFRD)	NC_000005.10:g.80633904T>A	UniProt,dbSNP
VAR_065819	p.Asp153Val	missense variant	Megaloblastic anemia due to dihydrofolate reductase deficiency (DHFRD)	NC_000005.10:g.80633904T>A	UniProt
rs121913223	p.Asp153Val	missense variant	-	NC_000005.10:g.80633904T>A	gnomAD
rs1235066479	p.Lys156Glu	missense variant	-	NC_000005.10:g.80633896T>C	gnomAD
rs756026129	p.Tyr157Ter	stop gained	-	NC_000005.10:g.80633891A>C	ExAC,TOPMed,gnomAD
rs371824049	p.Pro161Ser	missense variant	-	NC_000005.10:g.80633881G>A	ESP,ExAC,gnomAD
rs1240762913	p.Tyr163Cys	missense variant	-	NC_000005.10:g.80629163T>C	gnomAD
COSM1070681	p.Leu167Ile	missense variant	Variant assessed as Somatic; MODERATE impact.	NC_000005.10:g.80629152G>T	NCI-TCGA Cosmic
rs1352816111	p.Asp169Asn	missense variant	-	NC_000005.10:g.80629146C>T	gnomAD
rs1445173661	p.Gln171Arg	missense variant	-	NC_000005.10:g.80629139T>C	TOPMed
rs1307188069	p.Glu173Lys	missense variant	-	NC_000005.10:g.80629134C>T	gnomAD
NCI-TCGA novel	p.Gly175Asp	missense variant	-	NC_000005.10:g.80629127C>T	NCI-TCGA
rs1454614314	p.Ile176Val	missense variant	-	NC_000005.10:g.80629125T>C	gnomAD
rs1223136219	p.Lys179Asn	missense variant	-	NC_000005.10:g.80629114T>G	TOPMed
rs768327109	p.Phe180Cys	missense variant	-	NC_000005.10:g.80629112A>C	ExAC
rs1477523853	p.Glu184Ter	stop gained	-	NC_000005.10:g.80629101C>A	TOPMed
rs1191351549	p.Glu184Val	missense variant	-	NC_000005.10:g.80629100T>A	TOPMed
NCI-TCGA novel	p.Asn186Ser	missense variant	-	NC_000005.10:g.80629094T>C	NCI-TCGA
rs200904105	p.Asp187Tyr	missense variant	-	NC_000005.10:g.80629092C>A	gnomAD

Disease or phenotype associated information

Disease ID	Disease Name	Disease Type	Source
C0000786	Spontaneous abortion	phenotype	CTD_human
C0000822	Abortion, Tubal	disease	CTD_human
C0001175	Acquired Immunodeficiency Syndrome	group	BEFREE
C0001486	Adenovirus Infections	group	BEFREE
C0002736	Amyotrophic Lateral Sclerosis	disease	BEFREE
C0002888	Anemia, Megaloblastic	disease	BEFREE;CTD_human;HPO
C0003873	Rheumatoid Arthritis	disease	BEFREE;CTD_human
C0004135	Ataxia Telangiectasia	disease	BEFREE
C0004352	Autistic Disorder	group	BEFREE;CTD_human;LHGDN
C0004623	Bacterial Infections	group	BEFREE
C0006118	Brain Neoplasms	group	BEFREE
C0006142	Malignant neoplasm of breast	disease	BEFREE;CTD_human
C0007102	Malignant tumor of colon	disease	BEFREE
C0007114	Malignant neoplasm of skin	disease	BEFREE
C0007131	Non-Small Cell Lung Carcinoma	disease	BEFREE
C0007758	Cerebellar Ataxia	phenotype	HPO
C0007766	Intracranial Aneurysm	disease	BEFREE
C0008497	Choriocarcinoma	disease	BEFREE
C0009207	Cockayne Syndrome	disease	BEFREE
C0009402	Colorectal Carcinoma	disease	BEFREE;CTD_human
C0009404	Colorectal Neoplasms	group	BEFREE;CTD_human
C0010828	Cytopenia	phenotype	GENOMICS_ENGLAND
C0011991	Diarrhea	phenotype	BEFREE
C0013221	Drug toxicity	group	CTD_human
C0013264	Muscular Dystrophy, Duchenne	disease	BEFREE
C0013371	Shigella Infections	group	BEFREE
C0015625	Fanconi Anemia	disease	BEFREE
C0016412	Folic Acid Deficiency	disease	CTD_human
C0019193	Hepatitis, Toxic	disease	CTD_human
C0019209	Hepatomegaly	phenotype	HPO
C0021361	Female infertility	phenotype	CTD_human
C0021400	Influenza	disease	BEFREE
C0022346	Icterus	phenotype	HPO
C0023418	leukemia	disease	BEFREE
C0023449	Acute lymphocytic leukemia	disease	BEFREE
C0023452	Childhood Acute Lymphoblastic Leukemia	disease	BEFREE
C0023470	Myeloid Leukemia	disease	BEFREE
C0023479	Acute myelomonocytic leukemia	disease	BEFREE
C0023530	Leukopenia	disease	BEFREE
C0023903	Liver neoplasms	group	BEFREE
C0024299	Lymphoma	group	BEFREE
C0024530	Malaria	disease	BEFREE
C0024535	Malaria, Falciparum	disease	BEFREE
C0024537	Malaria, Vivax	disease	BEFREE
C0025149	Medulloblastoma	disease	BEFREE
C0025202	melanoma	disease	BEFREE
C0025521	Inborn Errors of Metabolism	group	CTD_human
C0026764	Multiple Myeloma	disease	BEFREE
C0027627	Neoplasm Metastasis	phenotype	BEFREE;CTD_human
C0027765	nervous system disorder	group	BEFREE;CTD_human
C0029463	Osteosarcoma	disease	BEFREE;CTD_human;LHGDN
C0029925	Ovarian Carcinoma	disease	BEFREE
C0030232	Pallor	phenotype	HPO
C0030312	Pancytopenia	disease	CTD_human;HPO
C0032285	Pneumonia	disease	BEFREE
C0035335	Retinoblastoma	disease	BEFREE
C0036220	Kaposi Sarcoma	disease	BEFREE
C0036341	Schizophrenia	disease	BEFREE
C0038279	Sterility, Postpartum	phenotype	CTD_human
C0040034	Thrombocytopenia	phenotype	HPO
C0040560	Toxoplasmosis, Congenital	disease	BEFREE
C0041755	Adverse reaction to drug	group	CTD_human
C0042769	Virus Diseases	group	BEFREE
C0080178	Spina Bifida	disease	BEFREE;LHGDN
C0085669	Acute leukemia	disease	BEFREE
C0153676	Secondary malignant neoplasm of lung	disease	BEFREE
C0154671	Degenerative brain disorder	group	HPO
C0158995	Congenital anemia	disease	GENOMICS_ENGLAND
C0232466	Feeding difficulties	phenotype	HPO
C0235946	Cerebral atrophy	disease	HPO
C0242510	Drug usage	phenotype	BEFREE
C0268135	Xeroderma pigmentosum, group A	disease	BEFREE
C0268608	Deficiency of dihydrofolate reductase	disease	BEFREE
C0276496	Familial Alzheimer Disease (FAD)	disease	BEFREE
C0276527	Pneumonia associated with AIDS	disease	BEFREE
C0278512	Metastatic osteosarcoma	disease	BEFREE
C0278996	Malignant Head and Neck Neoplasm	disease	BEFREE
C0280803	Primary central nervous system lymphoma	disease	BEFREE
C0302361	Disease caused by Shigella sonnei	disease	BEFREE
C0341869	Subfertility, Female	disease	CTD_human
C0343401	MRSA - Methicillin resistant Staphylococcus aureus infection	disease	BEFREE
C0392386	Decreased platelet count	phenotype	HPO
C0494165	Secondary malignant neoplasm of liver	disease	BEFREE
C0524910	Hepatitis C, Chronic	disease	BEFREE
C0557874	Global developmental delay	disease	HPO
C0584960	Factor V Leiden mutation	disease	BEFREE
C0585442	Osteosarcoma of bone	disease	BEFREE
C0677886	Epithelial ovarian cancer	disease	BEFREE
C0678222	Breast Carcinoma	disease	BEFREE;CTD_human
C0699790	Colon Carcinoma	disease	BEFREE
C0751349	Myoclonus, Eyelid	disease	HPO
C0751436	Hyperphenylalaninemia, Non-Phenylketonuric	disease	BEFREE
C0751606	Adult Acute Lymphocytic Leukemia	disease	BEFREE
C0851886	Pneumocystis Infections	group	BEFREE
C0856825	Acute GVH disease	disease	BEFREE
C0860207	Drug-Induced Liver Disease	disease	CTD_human
C0917730	Female sterility	phenotype	CTD_human
C1140680	Malignant neoplasm of ovary	disease	BEFREE
C1257931	Mammary Neoplasms, Human	group	CTD_human
C1261473	Sarcoma	group	BEFREE
C1262760	Hepatitis, Drug-Induced	disease	CTD_human
C1277241	Delayed myelination	phenotype	HPO
C1292753	Primary Effusion Lymphoma	disease	BEFREE
C1292769	Precursor B-cell lymphoblastic leukemia	disease	BEFREE
C1332986	Childhood Osteosarcoma	disease	BEFREE
C1458155	Mammary Neoplasms	group	BEFREE;CTD_human
C1527249	Colorectal Cancer	disease	BEFREE;CTD_human
C1535939	Pneumocystis jiroveci pneumonia	disease	BEFREE
C1833561	UV-Sensitive Syndrome	disease	BEFREE
C1836038	Poor head control	phenotype	HPO
C1847514	Postnatal microcephaly	phenotype	HPO
C1858120	Generalized hypotonia	phenotype	HPO
C1864897	Cognitive delay	phenotype	HPO
C1961099	Precursor T-Cell Lymphoblastic Leukemia-Lymphoma	disease	BEFREE
C1961102	Precursor Cell Lymphoblastic Leukemia Lymphoma	disease	BEFREE
C2751584	Neurodegeneration Due To Cerebral Folate Transport Deficiency	phenotype	BEFREE;GENOMICS_ENGLAND
C2752147	XERODERMA PIGMENTOSUM, COMPLEMENTATION GROUP C	disease	BEFREE
C2931822	Nasopharyngeal carcinoma	disease	BEFREE
C3151205	Megaloblastic Anemia due to Dihydrofolate Reductase Deficiency	disease	BEFREE;CLINVAR;CTD_human;ORPHANET;UNIPROT
C3469521	FANCONI ANEMIA, COMPLEMENTATION GROUP A (disorder)	disease	BEFREE
C3658290	Drug-Induced Acute Liver Injury	disease	CTD_human
C3714756	Intellectual Disability	group	GENOMICS_ENGLAND
C3826044	Lymphoblastic leukemia in children	disease	BEFREE
C3888194	MIXED LINEAGE LEUKEMIA	disease	BEFREE
C4020860	Supratentorial atrophy	disease	HPO
C4020875	Mental and motor retardation	phenotype	HPO
C4277682	Chemical and Drug Induced Liver Injury	disease	CTD_human
C4279912	Chemically-Induced Liver Toxicity	disease	CTD_human
C4316903	Absence Seizures	phenotype	HPO

Gene Ontology (GO)/biological pathways

GO:Molecular Function

GO ID	GO Term	Evidence
GO:0000900	translation repressor activity, mRNA regulatory element binding	IDA
GO:0003729	mRNA binding	IDA
GO:0004146	dihydrofolate reductase activity	ISS
GO:0004146	dihydrofolate reductase activity	IDA
GO:0004146	dihydrofolate reductase activity	IBA
GO:0004146	dihydrofolate reductase activity	NAS
GO:0005542	folic acid binding	IDA
GO:0008144	drug binding	IDA
GO:0050661	NADP binding	IBA
GO:0051870	methotrexate binding	IDA
GO:0070402	NADPH binding	IDA
GO:1990825	sequence-specific mRNA binding	IDA

GO:Biological Process

GO ID	GO Term	Evidence
GO:0000083	regulation of transcription involved in G1/S transition of mitotic cell cycle	TAS
GO:0006729	tetrahydrobiopterin biosynthetic process	ISS
GO:0006729	tetrahydrobiopterin biosynthetic process	IMP
GO:0006730	one-carbon metabolic process	IEA
GO:0017148	negative regulation of translation	IDA
GO:0031103	axon regeneration	ISS
GO:0031427	response to methotrexate	ISS
GO:0046452	dihydrofolate metabolic process	IBA
GO:0046452	dihydrofolate metabolic process	IDA
GO:0046653	tetrahydrofolate metabolic process	IDA
GO:0046654	tetrahydrofolate biosynthetic process	IEA
GO:0046654	tetrahydrofolate biosynthetic process	IBA
GO:0046654	tetrahydrofolate biosynthetic process	IDA
GO:0046655	folic acid metabolic process	ISS
GO:0046655	folic acid metabolic process	IBA
GO:0046655	folic acid metabolic process	TAS
GO:0051000	positive regulation of nitric-oxide synthase activity	ISS
GO:0055114	oxidation-reduction process	IDA
GO:2000121	regulation of removal of superoxide radicals	ISS

GO:Cellular Component

GO ID	GO Term	Evidence
GO:0005739	mitochondrion	IDA
GO:0005739	mitochondrion	IBA
GO:0005829	cytosol	TAS

Reactome Pathway

Reactome ID	Reactome Term	Evidence
R-HSA-1430728	Metabolism	IEA
R-HSA-1430728	Metabolism	TAS
R-HSA-1474151	Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation	IEA
R-HSA-1640170	Cell Cycle	TAS
R-HSA-196757	Metabolism of folate and pterines	TAS
R-HSA-196849	Metabolism of water-soluble vitamins and cofactors	TAS
R-HSA-196854	Metabolism of vitamins and cofactors	IEA
R-HSA-196854	Metabolism of vitamins and cofactors	TAS
R-HSA-453279	Mitotic G1 phase and G1/S transition	TAS
R-HSA-69205	G1/S-Specific Transcription	TAS
R-HSA-69206	G1/S Transition	TAS
R-HSA-69278	Cell Cycle, Mitotic	TAS
R-HSA-8978934	Metabolism of cofactors	IEA

Drugs and compounds information

ID	Drug Name	Action	PubMed
C090203	1,2-epoxy-3,4-dihydroxy-1,2,3,4-tetrahydrobenzo(c)phenanthrene	1,2-epoxy-3,4-dihydroxy-1,2,3,4-tetrahydrobenzo(c)phenanthrene results in increased mutagenesis of DHFR gene	1465420; 2062855; 2371281; 8417332;
C495626	14-deoxy-11,12-didehydroandrographolide	14-deoxy-11,12-didehydroandrographolide results in decreased expression of DHFR mRNA	22101062
D015655	1-Methyl-4-phenylpyridinium	1-Methyl-4-phenylpyridinium results in decreased expression of DHFR mRNA	24810058
C029497	2,3-bis(3'-hydroxybenzyl)butyrolactone	2,3-bis(3'-hydroxybenzyl)butyrolactone results in increased expression of DHFR mRNA	19167446
C029497	2,3-bis(3'-hydroxybenzyl)butyrolactone	[Coumestrol co-treated with 2,3-bis(3'-hydroxybenzyl)butyrolactone] results in increased expression of DHFR mRNA	19167446
C014024	2,4,5,2',4',5'-hexachlorobiphenyl	2,4,5,2',4',5'-hexachlorobiphenyl results in decreased expression of DHFR mRNA	20005886
C502239	2-amino-1-methyl-6-phenolimidazo(4,5-b)pyridine-DNA adduct	[2-hydroxyamino-1-methyl-6-phenylimidazo(4,5-b)pyridine results in increased abundance of 2-amino-1-methyl-6-phenolimidazo(4,5-b)pyridine-DNA adduct] which results in increased mutagenesis of DHFR gene	8199311
C006551	2-amino-2-methyl-1-propanol	2-amino-2-methyl-1-propanol results in increased expression of DHFR mRNA	25088246
C058706	2-desamino-2-methylaminopterin	2-desamino-2-methylaminopterin analog binds to and results in decreased activity of DHFR protein	1313737
C060533	2-hydroxyamino-1-methyl-6-phenylimidazo(4,5-b)pyridine	[2-hydroxyamino-1-methyl-6-phenylimidazo(4,5-b)pyridine results in increased abundance of 2-amino-1-methyl-6-phenolimidazo(4,5-b)pyridine-DNA adduct] which results in increased mutagenesis of DHFR gene	8199311
C060533	2-hydroxyamino-1-methyl-6-phenylimidazo(4,5-b)pyridine	[2-hydroxyamino-1-methyl-6-phenylimidazo(4,5-b)pyridine results in increased abundance of N-(deoxyguanosin-8-yl)-2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine] which results in increased mutagenesis of DHFR gene	8199311
C060533	2-hydroxyamino-1-methyl-6-phenylimidazo(4,5-b)pyridine	2-hydroxyamino-1-methyl-6-phenylimidazo(4,5-b)pyridine results in increased mutagenesis of DHFR gene	8199311
C076145	3-(1-deoxyribofuranosyl)benzamide	3-(1-deoxyribofuranosyl)benzamide results in decreased expression of DHFR protein	22954684
C028451	3,4,3',4'-tetrachlorobiphenyl	3,4,3',4'-tetrachlorobiphenyl inhibits the reaction [Dietary Fats results in increased expression of DHFR mRNA]	19467301
C529447	3-O-(3,4,5-trimethoxybenzoyl)epicatechin	3-O-(3,4,5-trimethoxybenzoyl)epicatechin binds to DHFR protein	20054477
C030371	5,6,7,8-tetrahydrofolic acid	DHFR protein results in increased chemical synthesis of 5,6,7,8-tetrahydrofolic acid	17413111
C483321	6-bromoindirubin-3'-oxime	[6-bromoindirubin-3'-oxime co-treated with DHFR mRNA] affects the expression of CTNNB1 protein	19727391
D015123	7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide results in decreased expression of DHFR mRNA	20018196
D015123	7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide results in increased expression of DHFR mRNA	19150397
C054852	7-hydroxystaurosporine	7-hydroxystaurosporine results in increased activity of DHFR protein	14653808
C054852	7-hydroxystaurosporine	7-hydroxystaurosporine results in increased expression of DHFR mRNA	14653808
C496492	abrine	abrine results in decreased expression of DHFR mRNA	31054353
C496492	abrine	abrine results in decreased expression of DHFR protein	31054353
D000082	Acetaminophen	Acetaminophen results in increased expression of DHFR mRNA	22230336
D000082	Acetaminophen	Acetaminophen affects the expression of DHFR mRNA	17562736
D016604	Aflatoxin B1	Aflatoxin B1 results in decreased methylation of DHFR gene	27153756
D016604	Aflatoxin B1	Aflatoxin B1 results in decreased expression of DHFR mRNA	19770486
D016607	Aflatoxin M1	Aflatoxin M1 results in decreased expression of DHFR mRNA	30928695
C000593263	afuresertib	afuresertib results in decreased expression of DHFR mRNA	28960945
D000393	Air Pollutants	Air Pollutants analog results in increased expression of DHFR mRNA	21757418
C025154	alpha-cobratoxin	alpha-cobratoxin inhibits the reaction [Nicotine results in decreased expression of DHFR mRNA]	12588870
C025154	alpha-cobratoxin	alpha-cobratoxin results in decreased expression of DHFR mRNA	12588870
D000630	Aminopterin	Aminopterin results in decreased activity of DHFR protein	24417268
D000643	Ammonium Chloride	Ammonium Chloride affects the expression of DHFR mRNA	16483693
D000952	Antigens, Polyomavirus Transforming	Antigens, Polyomavirus Transforming results in increased expression of DHFR mRNA	26680231
D000970	Antineoplastic Agents	Antineoplastic Agents results in decreased expression of DHFR mRNA	20652976
D000970	Antineoplastic Agents	Antineoplastic Agents results in decreased expression of DHFR protein	20652976
D001151	Arsenic	Arsenic affects the methylation of DHFR gene	25304211
D001151	Arsenic	DHFR gene SNP affects the susceptibility to Arsenic	25759212
C015001	arsenite	arsenite results in decreased expression of DHFR mRNA	18929588
D001280	Atrazine	Atrazine results in increased expression of DHFR mRNA	25929836
C100366	benzamide adenine nucleotide	benzamide adenine nucleotide results in decreased activity of DHFR protein	22954684
D001564	Benzo(a)pyrene	Benzo(a)pyrene results in decreased expression of DHFR mRNA	20064835; 26238291;
D001564	Benzo(a)pyrene	Benzo(a)pyrene results in increased expression of DHFR protein	18495319
C026487	benzo(e)pyrene	benzo(e)pyrene results in increased methylation of DHFR intron	30157460
C089231	benzo(g)chrysene-11,12-dihydrodiol-13,14-epoxide	benzo(g)chrysene-11,12-dihydrodiol-13,14-epoxide results in increased mutagenesis of DHFR exon	7586212
D019207	beta Carotene	[BCO1 protein affects the susceptibility to beta Carotene] which affects the expression of DHFR mRNA	24657404
C006780	bisphenol A	bisphenol A results in increased expression of DHFR mRNA	30248606
C006780	bisphenol A	bisphenol A affects the expression of DHFR mRNA	30903817
C006780	bisphenol A	bisphenol A results in decreased expression of DHFR mRNA	29275510
C006780	bisphenol A	bisphenol A results in decreased expression of DHFR mRNA	30816183
D002087	Butyrates	Butyrates results in decreased expression of DHFR mRNA	20072153
C055494	caffeic acid phenethyl ester	[Diethylnitrosamine co-treated with caffeic acid phenethyl ester] results in decreased expression of DHFR mRNA	20360939
D002220	Carbamazepine	Carbamazepine affects the expression of DHFR mRNA	24752500
D002251	Carbon Tetrachloride	Carbon Tetrachloride results in decreased expression of DHFR mRNA	17484886
D002251	Carbon Tetrachloride	Carbon Tetrachloride results in decreased expression of DHFR mRNA	31150632
D002251	Carbon Tetrachloride	schizandrin B inhibits the reaction [Carbon Tetrachloride results in decreased expression of DHFR mRNA]	31150632
D002437	Cefazolin	Cefazolin results in decreased activity of DHFR protein	25418905
D000077723	Cefepime	Cefepime results in decreased activity of DHFR protein	25418905
D002442	Ceftazidime	Ceftazidime results in decreased activity of DHFR protein	25418905
D015296	Ceftizoxime	Ceftizoxime results in decreased activity of DHFR protein	25418905
D002443	Ceftriaxone	Ceftriaxone results in decreased activity of DHFR protein	25418905
D002699	Chlorambucil	DHFR protein polymorphism results in decreased susceptibility to Chlorambucil	12872145
D002794	Choline	[Methionine deficiency co-treated with Choline deficiency co-treated with Folic Acid deficiency] results in decreased expression of DHFR mRNA	20938992
C074702	chromium hexavalent ion	chromium hexavalent ion affects the expression of DHFR mRNA	28472532
D002945	Cisplatin	Cisplatin promotes the reaction [Piroxicam results in decreased expression of DHFR mRNA]	21858171
D002945	Cisplatin	Cisplatin results in increased expression of DHFR mRNA	27594783
D002990	Clobetasol	Clobetasol results in decreased expression of DHFR mRNA	27462272
C018021	cobaltous chloride	cobaltous chloride results in decreased expression of DHFR mRNA	19376846
D003300	Copper	[NSC 689534 binds to Copper] which results in decreased expression of DHFR mRNA	20971185
D019327	Copper Sulfate	Copper Sulfate results in decreased expression of DHFR mRNA	19549813
D019327	Copper Sulfate	Copper Sulfate results in increased expression of DHFR mRNA	19549813
D003375	Coumestrol	[Coumestrol co-treated with 2,3-bis(3'-hydroxybenzyl)butyrolactone] results in increased expression of DHFR mRNA	19167446
D003375	Coumestrol	[Coumestrol co-treated with Resveratrol] results in increased expression of DHFR mRNA	19167446
D003375	Coumestrol	Coumestrol results in increased expression of DHFR mRNA	19167446
D016572	Cyclosporine	Cyclosporine results in decreased expression of DHFR mRNA	19770486; 23308384;
D003561	Cytarabine	Cytarabine results in increased expression of DHFR mRNA	19194470
D000069439	Dasatinib	Dasatinib results in decreased expression of DHFR mRNA	20579391
D003703	Demecolcine	Demecolcine results in decreased expression of DHFR mRNA	23649840
C041517	dibenzo(a,l)pyrene	dibenzo(a,l)pyrene results in decreased expression of DHFR protein	18495319
D003993	Dibutyl Phthalate	Dibutyl Phthalate results in decreased expression of DHFR mRNA	17361019; 21266533;
D004008	Diclofenac	Diclofenac affects the expression of DHFR mRNA	24752500
D004026	Dieldrin	Dieldrin results in decreased expression of DHFR mRNA	28385952
D004041	Dietary Fats	3,4,3',4'-tetrachlorobiphenyl inhibits the reaction [Dietary Fats results in increased expression of DHFR mRNA]	19467301
D004041	Dietary Fats	Dietary Fats results in increased expression of DHFR mRNA	19467301
D004051	Diethylhexyl Phthalate	Diethylhexyl Phthalate results in increased expression of DHFR mRNA	19850644
D004051	Diethylhexyl Phthalate	PPARA protein promotes the reaction [Diethylhexyl Phthalate results in increased expression of DHFR mRNA]	19850644
D004052	Diethylnitrosamine	[Diethylnitrosamine co-treated with caffeic acid phenethyl ester] results in decreased expression of DHFR mRNA	20360939
C010920	dihydrofolate	DHFR protein results in increased metabolism of dihydrofolate	17413111
D004317	Doxorubicin	Doxorubicin results in decreased expression of DHFR mRNA	29803840
D013759	Dronabinol	Dronabinol results in decreased expression of DHFR mRNA	18454173
D004642	Emodin	Emodin results in decreased expression of DHFR mRNA	16045814
D004726	Endosulfan	Endosulfan results in decreased expression of DHFR mRNA	29391264
C062669	epicatechin gallate	epicatechin gallate binds to and results in decreased activity of DHFR protein	20054477
C045651	epigallocatechin gallate	epigallocatechin gallate binds to and results in decreased activity of DHFR protein	20054477
C045651	epigallocatechin gallate	[potassium chromate(VI) co-treated with epigallocatechin gallate] results in increased expression of DHFR mRNA	22079256
D004958	Estradiol	Estradiol results in increased expression of DHFR mRNA	19167446
C007630	estradiol 17 beta-cypionate	estradiol 17 beta-cypionate results in increased expression of DHFR mRNA	22497863
D000431	Ethanol	Ethanol results in decreased expression of DHFR mRNA	28986285
D004997	Ethinyl Estradiol	Ethinyl Estradiol affects the expression of DHFR mRNA	17555576
D004997	Ethinyl Estradiol	Ethinyl Estradiol results in increased expression of DHFR mRNA	17942748
D004997	Ethinyl Estradiol	[Tetrachlorodibenzodioxin co-treated with Ethinyl Estradiol] results in increased expression of DHFR mRNA	17942748
D004997	Ethinyl Estradiol	Ethinyl Estradiol affects the expression of DHFR mRNA	23129252
D005020	Ethyl Methanesulfonate	Ethyl Methanesulfonate results in increased mutagenesis of DHFR gene	8417332
D005038	Ethylnitrosourea	Ethylnitrosourea results in increased mutagenesis of DHFR gene	8417332
D017313	Fenretinide	Fenretinide results in increased expression of DHFR mRNA	28973697
C004999	ferulic acid	ferulic acid results in decreased activity of DHFR protein	25418905
D005472	Fluorouracil	Fluorouracil affects the expression of DHFR mRNA	16557594
D005472	Fluorouracil	Fluorouracil results in increased expression of DHFR mRNA	15109396; 21814787;
D005492	Folic Acid	DHFR gene mutant form results in decreased abundance of Folic Acid	21310277
D005492	Folic Acid	Folic Acid affects the expression of DHFR mRNA	17311948
D005492	Folic Acid	[Folic Acid affects the susceptibility to Pemetrexed] which affects the expression of DHFR mRNA	22975265
D005492	Folic Acid	[Folic Acid deficiency co-treated with Methotrexate] results in decreased expression of DHFR mRNA	24657277
D005492	Folic Acid	Leucovorin inhibits the reaction [DHFR gene mutant form results in decreased abundance of Folic Acid]	21310277
D005492	Folic Acid	[Methionine deficiency co-treated with Choline deficiency co-treated with Folic Acid deficiency] results in decreased expression of DHFR mRNA	20938992
D005492	Folic Acid	Folic Acid inhibits the reaction [Methotrexate results in decreased expression of DHFR mRNA]	30502384
D005492	Folic Acid	DHFR protein results in increased reduction of Folic Acid	17413111
D005493	Folic Acid Antagonists	DHFR protein polymorphism results in decreased susceptibility to Folic Acid Antagonists	12872145
D005557	Formaldehyde	Formaldehyde results in decreased expression of DHFR mRNA	23649840
D019833	Genistein	Genistein results in decreased expression of DHFR mRNA	21048042
D005839	Gentamicins	Gentamicins results in decreased expression of DHFR mRNA	22061828
C000593030	GSK-J4	GSK-J4 results in decreased expression of DHFR mRNA	29301935
C545476	incobotulinumtoxinA	incobotulinumtoxinA results in decreased expression of DHFR mRNA	29522793
D007213	Indomethacin	Indomethacin results in increased expression of DHFR mRNA	18299717
D007213	Indomethacin	rebamipide inhibits the reaction [Indomethacin results in increased expression of DHFR mRNA]	18299717
D007529	Isoflavones	Isoflavones results in decreased expression of DHFR mRNA	17374662
D015474	Isotretinoin	Isotretinoin results in decreased expression of DHFR mRNA	20436886
C410337	K 7174	K 7174 results in decreased expression of DHFR mRNA	24086573
D019259	Lamivudine	[Zidovudine co-treated with Lamivudine] results in decreased expression of DHFR mRNA	15784690
D000077339	Leflunomide	Leflunomide results in increased expression of DHFR mRNA	24136188
D002955	Leucovorin	Leucovorin inhibits the reaction [DHFR gene mutant form results in decreased abundance of Folic Acid]	21310277
D002955	Leucovorin	Leucovorin results in increased expression of DHFR protein	16712799
D064704	Levofloxacin	Levofloxacin results in decreased activity of DHFR protein	25418905
D008464	Mecamylamine	Mecamylamine inhibits the reaction [Nicotine results in decreased expression of DHFR mRNA]	12588870
D008464	Mecamylamine	Mecamylamine results in decreased expression of DHFR mRNA	12588870
D008701	Methapyrilene	Methapyrilene results in increased methylation of DHFR intron	30157460
D008715	Methionine	[Methionine deficiency co-treated with Choline deficiency co-treated with Folic Acid deficiency] results in decreased expression of DHFR mRNA	20938992
D008727	Methotrexate	DHFR protein mutant form inhibits the reaction [Methotrexate results in decreased expression of CDK2 mRNA]	17519396
D008727	Methotrexate	DHFR protein mutant form inhibits the reaction [Methotrexate results in decreased expression of CYCE mRNA]	17519396
D008727	Methotrexate	DHFR protein mutant form inhibits the reaction [Methotrexate results in decreased expression of MCM6 mRNA]	17519396
D008727	Methotrexate	DHFR protein mutant form inhibits the reaction [Methotrexate results in decreased expression of MDR65 mRNA]	17519396
D008727	Methotrexate	DHFR protein mutant form inhibits the reaction [Methotrexate results in decreased expression of SLBP mRNA]	17519396
D008727	Methotrexate	DHFR protein mutant form inhibits the reaction [Methotrexate results in decreased expression of STAI mRNA]	17519396
D008727	Methotrexate	DHFR protein mutant form inhibits the reaction [Methotrexate results in increased expression of ANCE mRNA]	17519396
D008727	Methotrexate	DHFR protein mutant form inhibits the reaction [Methotrexate results in increased expression of OBP99A mRNA]	17519396
D008727	Methotrexate	DHFR protein mutant form results in decreased susceptibility to Methotrexate	17519396
D008727	Methotrexate	DHFR protein results in decreased susceptibility to Methotrexate	17519396
D008727	Methotrexate	[ADAR protein results in increased expression of DHFR protein] which results in decreased susceptibility to Methotrexate	28188287
D008727	Methotrexate	[DHFR 3' UTR SNP affects the expression of DHFR protein] which affects the susceptibility to Methotrexate	17686970; 17686970;
D008727	Methotrexate	[DHFR 3' UTR SNP affects the stability of DHFR mRNA] which affects the susceptibility to Methotrexate	17686970; 17686970;
D008727	Methotrexate	DHFR 3' UTR SNP affects the susceptibility to Methotrexate	17686970
D008727	Methotrexate	DHFR mRNA results in decreased susceptibility to Methotrexate	18694510; 19732436;
D008727	Methotrexate	DHFR protein results in decreased susceptibility to Methotrexate	14679136; 28188287;
D008727	Methotrexate	[Folic Acid deficiency co-treated with Methotrexate] results in decreased expression of DHFR mRNA	24657277
D008727	Methotrexate	Methotrexate results in decreased expression of DHFR mRNA	23897011; 24657277;
D008727	Methotrexate	Methotrexate results in increased expression of DHFR mRNA	23838799; 24736981;
D008727	Methotrexate	Methotrexate results in increased expression of DHFR protein	19570950; 22484375; 23799623; 24736981;
D008727	Methotrexate	[[MIR125A mRNA binds to DHFR 3' UTR] which results in decreased expression of DHFR protein] which results in increased susceptibility to Methotrexate	28188287; 28188287;
D008727	Methotrexate	[[MIR25 mRNA binds to DHFR 3' UTR] which results in decreased expression of DHFR protein] which results in increased susceptibility to Methotrexate	28188287; 28188287;
D008727	Methotrexate	Methotrexate results in decreased activity of DHFR protein	24417268
D008727	Methotrexate	DHFR mRNA results in decreased susceptibility to Methotrexate	16918715
D008727	Methotrexate	DHFR protein results in decreased susceptibility to Methotrexate	16918715
D008727	Methotrexate	Methotrexate promotes the reaction [E2F1 protein binds to DHFR promoter]	22484375
D008727	Methotrexate	Methotrexate results in decreased activity of DHFR protein	22806879
D008727	Methotrexate	Methotrexate results in decreased expression of DHFR mRNA	30502384
D008727	Methotrexate	Methotrexate results in decreased expression of DHFR protein	30502384
D008727	Methotrexate	Methotrexate results in increased expression of DHFR protein	22484375
D008727	Methotrexate	DHFR protein inhibits the reaction [Methotrexate results in decreased expression of CASP3 protein]	30502384
D008727	Methotrexate	DHFR protein inhibits the reaction [Methotrexate results in decreased expression of GFAP mRNA]	30502384
D008727	Methotrexate	DHFR protein inhibits the reaction [Methotrexate results in decreased expression of MTHFR mRNA]	30502384
D008727	Methotrexate	DHFR protein inhibits the reaction [Methotrexate results in decreased expression of MTRR mRNA]	30502384
D008727	Methotrexate	DHFR protein inhibits the reaction [Methotrexate results in increased cleavage of PARP protein]	30502384
D008727	Methotrexate	Folic Acid inhibits the reaction [Methotrexate results in decreased expression of DHFR mRNA]	30502384
D008727	Methotrexate	Methotrexate affects the activity of DHFR protein	1793349
D008727	Methotrexate	Methotrexate binds to DHFR protein	7057425
D008727	Methotrexate	Methotrexate results in decreased activity of DHFR protein	1363493; 17519396;
D008748	Methylcholanthrene	Methylcholanthrene results in increased expression of DHFR mRNA	20713471
C004925	methylmercuric chloride	methylmercuric chloride results in decreased expression of DHFR mRNA	28001369
D008767	Methylmercury Compounds	Methylmercury Compounds results in decreased expression of DHFR mRNA	18367466
D008767	Methylmercury Compounds	Methylmercury Compounds results in decreased expression of DHFR protein	26558463
D008741	Methyl Methanesulfonate	Methyl Methanesulfonate results in decreased expression of DHFR mRNA	26011545
C008493	methylselenic acid	methylselenic acid results in decreased expression of DHFR mRNA	12517777
C000622638	MLN7243	MLN7243 results in increased sumoylation of DHFR protein	31285264
D009249	NADP	NADP analog results in decreased activity of DHFR protein	22954684
D037742	Nanotubes, Carbon	Nanotubes, Carbon results in decreased expression of DHFR mRNA	25620056
C005274	naringin	naringin results in decreased activity of DHFR protein	25418905
C078255	N-(deoxyguanosin-8-yl)-2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine	[2-hydroxyamino-1-methyl-6-phenylimidazo(4,5-b)pyridine results in increased abundance of N-(deoxyguanosin-8-yl)-2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine] which results in increased mutagenesis of DHFR gene	8199311
D009532	Nickel	Nickel results in increased expression of DHFR mRNA	25583101
D009538	Nicotine	alpha-cobratoxin inhibits the reaction [Nicotine results in decreased expression of DHFR mRNA]	12588870
D009538	Nicotine	Mecamylamine inhibits the reaction [Nicotine results in decreased expression of DHFR mRNA]	12588870
D009538	Nicotine	Nicotine results in decreased expression of DHFR mRNA	12588870
D009538	Nicotine	Tubocurarine inhibits the reaction [Nicotine results in decreased expression of DHFR mRNA]	12588870
C012655	nimesulide	nimesulide results in decreased expression of DHFR mRNA	24136188
D009588	Nitrogen Mustard Compounds	DHFR protein polymorphism results in decreased susceptibility to Nitrogen Mustard Compounds	12872145
C558013	NSC 689534	[NSC 689534 binds to Copper] which results in decreased expression of DHFR mRNA	20971185
C437965	olmesartan	olmesartan results in increased expression of DHFR protein	17170375
C090046	olomoucine	olomoucine results in increased activity of DHFR protein	14653808
D000077150	Oxaliplatin	[Oxaliplatin co-treated with Topotecan] results in decreased expression of DHFR mRNA	25729387
D000077150	Oxaliplatin	Oxaliplatin results in decreased expression of DHFR mRNA	25729387
C016030	pantogab	pantogab results in decreased expression of DHFR mRNA	17379144
D000068437	Pemetrexed	[Folic Acid affects the susceptibility to Pemetrexed] which affects the expression of DHFR mRNA	22975265
D000068437	Pemetrexed	Pemetrexed results in decreased activity of DHFR protein	17465208
D010416	Pentachlorophenol	Pentachlorophenol results in decreased expression of DHFR mRNA	24642059
D010433	Pentylenetetrazole	[Pentylenetetrazole co-treated with Vigabatrin] affects the expression of DHFR mRNA	21503142
C023036	perfluorooctanoic acid	perfluorooctanoic acid results in decreased expression of DHFR mRNA	19162173
C023036	perfluorooctanoic acid	perfluorooctanoic acid results in decreased expression of DHFR mRNA	23978341
C027579	periodate-oxidized adenosine	periodate-oxidized adenosine affects the expression of DHFR mRNA	17097637
D010634	Phenobarbital	Phenobarbital affects the expression of DHFR mRNA	23091169
C006253	pirinixic acid	pirinixic acid results in decreased expression of DHFR mRNA	23811191
C006253	pirinixic acid	pirinixic acid results in increased expression of DHFR mRNA	17426115
D010894	Piroxicam	Cisplatin promotes the reaction [Piroxicam results in decreased expression of DHFR mRNA]	21858171
D010894	Piroxicam	Piroxicam results in decreased expression of DHFR mRNA	21858171
D059808	Polyphenols	Polyphenols results in decreased expression of DHFR mRNA	16293270
C027373	potassium chromate(VI)	[potassium chromate(VI) co-treated with epigallocatechin gallate] results in increased expression of DHFR mRNA	22079256
C027373	potassium chromate(VI)	potassium chromate(VI) results in increased expression of DHFR mRNA	22079256
D011192	Potassium Dichromate	Potassium Dichromate results in increased expression of DHFR mRNA	18332044
C005556	propionaldehyde	propionaldehyde results in decreased expression of DHFR mRNA	26079696
C052785	rebamipide	rebamipide inhibits the reaction [Indomethacin results in increased expression of DHFR mRNA]	18299717
D000077185	Resveratrol	[Coumestrol co-treated with Resveratrol] results in increased expression of DHFR mRNA	19167446
D000077185	Resveratrol	Resveratrol results in increased expression of DHFR protein	25505154
D000077546	Roscovitine	Roscovitine results in increased activity of DHFR protein	14653808
D012402	Rotenone	Rotenone results in decreased expression of DHFR mRNA	28374803
C015499	schizandrin B	schizandrin B inhibits the reaction [Carbon Tetrachloride results in decreased expression of DHFR mRNA]	31150632
D012822	Silicon Dioxide	Silicon Dioxide analog results in decreased expression of DHFR mRNA	25895662
C017947	sodium arsenite	sodium arsenite results in increased expression of DHFR mRNA	29361514
C017947	sodium arsenite	sodium arsenite results in increased mutagenesis of DHFR gene	12802802
C017947	sodium arsenite	sodium arsenite results in decreased expression of DHFR protein	19072884
C017947	sodium arsenite	sodium arsenite results in increased expression of DHFR protein	29459688
D053260	Soot	Soot results in increased expression of DHFR mRNA	26551751
C030000	stallimycin	stallimycin analog results in decreased expression of DHFR protein	21814787
C030000	stallimycin	stallimycin results in decreased expression of DHFR mRNA	21814787
C030000	stallimycin	stallimycin results in decreased expression of DHFR protein	21814787
D000077210	Sunitinib	Sunitinib results in decreased expression of DHFR mRNA	31533062
C001945	syringic acid	syringic acid results in decreased activity of DHFR protein	25418905
D013629	Tamoxifen	Tamoxifen results in increased expression of DHFR mRNA	15590111
D013629	Tamoxifen	Tamoxifen affects the expression of DHFR mRNA	17555576
D013749	Tetrachlorodibenzodioxin	Tetrachlorodibenzodioxin affects the expression of DHFR mRNA	21570461
D013749	Tetrachlorodibenzodioxin	[Tetrachlorodibenzodioxin co-treated with Ethinyl Estradiol] results in increased expression of DHFR mRNA	17942748
D013749	Tetrachlorodibenzodioxin	Tetrachlorodibenzodioxin results in increased expression of DHFR mRNA	17942748
D013749	Tetrachlorodibenzodioxin	Tetrachlorodibenzodioxin affects the expression of DHFR mRNA	22298810
D013749	Tetrachlorodibenzodioxin	Tetrachlorodibenzodioxin results in increased expression of DHFR mRNA	16054898
D014028	Tobacco Smoke Pollution	Tobacco Smoke Pollution results in decreased expression of DHFR mRNA	23724145; 28065790;
D014028	Tobacco Smoke Pollution	Tobacco Smoke Pollution results in increased methylation of DHFR promoter	31039056
D019772	Topotecan	[Oxaliplatin co-treated with Topotecan] results in decreased expression of DHFR mRNA	25729387
D019772	Topotecan	Topotecan results in decreased expression of DHFR mRNA	25729387
D014118	Toxins, Biological	Toxins, Biological affects the expression of DHFR mRNA	19682533
D000077606	Trabectedin	Trabectedin results in decreased expression of DHFR mRNA	15961672
D014212	Tretinoin	Tretinoin results in decreased expression of DHFR mRNA	18230668
D014260	Triclosan	Triclosan results in decreased expression of DHFR protein	30219713
C015559	trimellitic anhydride	trimellitic anhydride results in increased expression of DHFR mRNA	19042947
D014295	Trimethoprim	[Trimethoprim results in decreased activity of DHFR protein] which results in increased susceptibility to Valproic Acid	8318756
D016597	Trimetrexate	DHFR protein polymorphism results in decreased susceptibility to Trimetrexate	12872145
C016805	tris(1,3-dichloro-2-propyl)phosphate	tris(1,3-dichloro-2-propyl)phosphate results in decreased expression of DHFR mRNA	26179874
D014403	Tubocurarine	Tubocurarine inhibits the reaction [Nicotine results in decreased expression of DHFR mRNA]	12588870
D014403	Tubocurarine	Tubocurarine results in decreased expression of DHFR mRNA	12588870
D014520	Urethane	Urethane results in decreased expression of DHFR mRNA	28818685
D014635	Valproic Acid	Valproic Acid results in decreased methylation of DHFR gene	29154799
D014635	Valproic Acid	[Trimethoprim results in decreased activity of DHFR protein] which results in increased susceptibility to Valproic Acid	8318756
D001335	Vehicle Emissions	Vehicle Emissions results in decreased methylation of DHFR gene	25560391
D020888	Vigabatrin	[Pentylenetetrazole co-treated with Vigabatrin] affects the expression of DHFR mRNA	21503142
D014750	Vincristine	Vincristine results in decreased expression of DHFR mRNA	23649840
C029297	vinylidene chloride	vinylidene chloride results in decreased expression of DHFR mRNA	26682919
D000077337	Vorinostat	Vorinostat results in decreased expression of DHFR mRNA	20072153
D015215	Zidovudine	[Zidovudine co-treated with Lamivudine] results in decreased expression of DHFR mRNA	15784690

Functional annotations

Keywords

Keyword ID	Keyword Term
KW-0002	3D-structure
KW-0025	Alternative splicing
KW-0963	Cytoplasm
KW-0225	Disease mutation
KW-0487	Methotrexate resistance
KW-0496	Mitochondrion
KW-0521	NADP
KW-0554	One-carbon metabolism
KW-0560	Oxidoreductase
KW-1185	Reference proteome
KW-0694	RNA-binding

Interpro

InterPro ID	InterPro Term
IPR024072	DHFR-like_dom_sf
IPR017925	DHFR_CS
IPR001796	DHFR_dom

PROSITE

PROSITE ID	PROSITE Term
PS00075	DHFR_1
PS51330	DHFR_2

Pfam

Pfam ID	Pfam Term
PF00186	DHFR_1

Gene: DHFR

Basic information

Gene expression information

Gene expression in different tissues (GTEx V7)

Gene expression in different tissues (ENCODE)

Protein structural annotations

3D structure in PDB database

Protein disorder information

Orthologous information

There is no orthologous record for this gene !

Identified variants/mutations related to cleft phenotype

Other genetic variants/mutations

Disease or phenotype associated information

Gene Ontology (GO)/biological pathways

GO:Molecular Function

GO:Biological Process

GO:Cellular Component

Reactome Pathway

Drugs and compounds information

Functional annotations

Keywords

Interpro

PROSITE

Pfam

Protein-protein interaction

Protein-miRNA interaction