mutLBSgeneDB

mutLBSgeneDB
mutated Ligand Binding Site gene DataBase

Home

	Gene Summary
	Ligand Binding Site Mutation Information
	Protein Structure Related Information
	Gene Expression and Gene-Gene Network
	Phenotype Information
	Pharmacological Information
	Conservation Information for LBS

Gene summary for MTHFD1

Gene summary

Basic gene Info.	Gene symbol	MTHFD1
	Gene name	methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 1, methenyltetrahydrofolate cyclohydrolase, formyltetrahydrofolate synthetase
	Synonyms	MTHFC\|MTHFD
	Cytomap	UCSC genome browser: 14q24
	Type of gene	protein-coding
	RefGenes	NM_005956.3,
	Description	5,10-methylenetetrahydrofolate dehydrogenase, 5,10-methylenetetrahydrofolate cyclohydrolase, 10-formyltetrahydrofolate synthetaseC-1-tetrahydrofolate synthase, cytoplasmicC1-THF synthasecytoplasmic C-1-tetrahydrofolate synthase
	Modification date	20141207
dbXrefs	MIM : 172460
	HGNC : HGNC
	Ensembl : ENSG00000100714
	HPRD : 01403
	Vega : OTTHUMG00000141309
Protein	UniProt: P11586 go to UniProt's Cross Reference DB Table
Expression	CleanEX: HS_MTHFD1
	BioGPS: 4522
Pathway	NCI Pathway Interaction Database: MTHFD1
	KEGG: MTHFD1
	REACTOME: MTHFD1
	Pathway Commons: MTHFD1
Context	iHOP: MTHFD1
	ligand binding site mutation search in PubMed: MTHFD1
	UCL Cancer Institute: MTHFD1
Assigned class in mutLBSgeneDB	C: This gene just belongs to mutLBSgenes.

Gene ontology having evidence of Inferred from Direct Assay (IDA) from Entrez

GO ID

GO Term

PubMed ID

Top

Ligand binding site mutations for MTHFD1

Cancer type specific mutLBS sorted by frequency

LBS	AAchange of nsSNV	Cancer type	# samples
M221	E220G	COAD	1
D125	V124M	KIRC	1
P272	V271F	KIRC	1
M221	E220G	OV	1
Y52	Y52H	STAD	1

cf) Cancer type abbreviation. BLCA: Bladder urothelial carcinoma, BRCA: Breast invasive carcinoma, CESC: Cervical squamous cell carcinoma and endocervical adenocarcinoma, COAD: Colon adenocarcinoma, GBM: Glioblastoma multiforme, LGG: Brain lower grade glioma, HNSC: Head and neck squamous cell carcinoma, KICH: Kidney chromophobe, KIRC: Kidney renal clear cell carcinoma, KIRP: Kidney renal papillary cell carcinoma, LAML: Acute myeloid leukemia, LUAD: Lung adenocarcinoma, LUSC: Lung squamous cell carcinoma, OV: Ovarian serous cystadenocarcinoma, PAAD: Pancreatic adenocarcinoma, PRAD: Prostate adenocarcinoma, SKCM: Skin cutaneous melanoma, STAD: Stomach adenocarcinoma, THCA: Thyroid carcinoma, UCEC: Uterine corpus endometrial carcinoma.

Top

Protein structure related information for MTHFD1

Relative protein structure stability change (ΔΔE) using Mupro 1.1
Mupro score denotes assessment of the effect of mutations on thermodynamic stability.
(ΔΔE<0: mutation decreases stability, ΔΔE>0: mutation increases stability)

: nsSNV at non-LBS

: nsSNV at LBS

nsSNVs sorted by the relative stability change of protein structure by each mutation
Blue: mutations of positive stability change. and red : the most recurrent mutation for this gene.

LBS	AAchange of nsSNV	Relative stability change
Y52	Y52H	-1.5182422
M221	E220G	-1.1897978
D125	V124M	-1.163824
P272	V271F	-1.06966

(MuPro1.1: Jianlin Cheng et al., Prediction of Protein Stability Changes for Single-Site Mutations Using Support Vector Machines, PROTEINS: Structure, Function, and Bioinformatics. 2006, 62:1125-1132)

Structure image for MTHFD1 from PDB

Top

Differential gene expression and gene-gene network for MTHFD1

Differential gene expression between mutated and non-mutated LBS samples in all 16 major cancer types

Differential co-expressed gene network based on protein-protein interaction data (CePIN)

* Left PPI network was created from samples with mutations in the LBS of MTHFD1 and the right PPI network was created from samples without mutations in the LBS of MTHFD1. Only genes with p-value < 0.05 are shown.
Red circle: input gene. Orange circle: LBSgene. Blue circle: other gene.

Top

Phenotype information for MTHFD1

Gene level disease information (DisGeNet)

Disease ID	Disease name	# PubMed	Association type
umls:C0027794	Neural Tube Defects	5	Biomarker, GeneticVariation
umls:C0000832	Abruptio Placentae	2	Biomarker, GeneticVariation

Mutation level pathogenic information (ClinVar annotation)

Allele ID

AA change

Clinical significance

Origin

Phenotype IDs

Top

Pharmacological information for MTHFD1

Gene expression profile of anticancer drug treated cell-lines (CCLE)
Heatmap showing the correlation between gene expression and drug response across all the cell-lines. We chose the top 20 among 138 drugs.We used Pearson's correlation coefficient.

Gene-centered drug-gene interaction network

Drug information targeting mutLBSgene (Approved drugs only)

Drug status	DrugBank ID	Name	Type	Drug structure
Approved\|nutraceutical	DB00116	Tetrahydrofolic acid	Small molecule
Nutraceutical	DB00157	NADH	Small molecule
Experimental	DB02358	LY374571	Small molecule
Experimental	DB03461	2'-Monophosphoadenosine 5'-Diphosphoribose	Small molecule
Experimental	DB04322	LY249543	Small molecule

Gene-centered ligand-gene interaction network

Ligands binding to mutated ligand binding site of MTHFD1 go to BioLip

Ligand ID	Ligand short name	Ligand long name	PDB ID	PDB name	mutLBS
NDP		NADPH	1a4i	A	M221
NDP		NADPH	1a4i	B	M221
NAP		NADP ZWITTERION	1dia	A	M221
NAP		NADP ZWITTERION	1dib	A	M221
NAP		NADP ZWITTERION	1dig	A	M221
L34		LY345899	1dib	A	Y52 D125
L24		LY249543	1dia	A	Y52 P272

Top

Conservation information for LBS of MTHFD1

Multiple alignments for P11586 in multiple species

LBS	AA sequence	# species	Species
A215	DILVVATGQPE	3	Homo sapiens, Mus musculus, Rattus norvegicus
A215	DIVVVAIGQPE	1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
A215	DILVVGIGVAE	1	Drosophila melanogaster
A215	DIVVAAIGIPH	1	Schizosaccharomyces pombe (strain 972 / ATCC 24843)
A215	-----------	1	Arabidopsis thaliana
C236	AVVIDCGINYV	2	Mus musculus, Rattus norvegicus
C236	AIVIDCGINYV	1	Homo sapiens
C236	TVVIDVGTNYV	1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
C236	AVVIDCGINVK	1	Drosophila melanogaster
C236	VVAIDVGINSI	1	Schizosaccharomyces pombe (strain 972 / ATCC 24843)
C236	-----------	1	Arabidopsis thaliana
D125	PEKDVDGLTSI	2	Homo sapiens, Rattus norvegicus
D125	AEKDVDGFGPT	1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
D125	PEKDVDGLHTV	1	Drosophila melanogaster
D125	PEKDVDGFCET	1	Schizosaccharomyces pombe (strain 972 / ATCC 24843)
D125	-----------	1	Arabidopsis thaliana
D125	PEKDVDGLTSV	1	Mus musculus
G172	HAVVVGRSKIV	3	Homo sapiens, Mus musculus, Rattus norvegicus
G172	RSVVIGRSDIV	1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
G172	RAVVLGRSKIV	1	Drosophila melanogaster
G172	HAVVIGRSNIV	1	Schizosaccharomyces pombe (strain 972 / ATCC 24843)
G172	-----------	1	Arabidopsis thaliana
G217	LVVATGQPEMV	3	Homo sapiens, Mus musculus, Rattus norvegicus
G217	VVVAIGQPEFV	1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
G217	LVVGIGVAEMV	1	Drosophila melanogaster
G217	VVAAIGIPHFV	1	Schizosaccharomyces pombe (strain 972 / ATCC 24843)
G217	-----------	1	Arabidopsis thaliana
G237	VVIDCGINYVP	2	Mus musculus, Rattus norvegicus
G237	IVIDCGINYVP	1	Homo sapiens
G237	VVIDVGTNYVA	1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
G237	VVIDCGINVKP	1	Drosophila melanogaster
G237	VAIDVGINSIP	1	Schizosaccharomyces pombe (strain 972 / ATCC 24843)
G237	-----------	1	Arabidopsis thaliana
G273	ITPVPGGVGPM	4	Homo sapiens, Saccharomyces cerevisiae (strain ATCC 204508 / S288c), Mus musculus, Rattus norvegicus
G273	LTPVPGGVGPM	1	Drosophila melanogaster
G273	ITPVPGSVGPM	1	Schizosaccharomyces pombe (strain 972 / ATCC 24843)
G273	-----------	1	Arabidopsis thaliana
G274	TPVPGGVGPMT	5	Homo sapiens, Saccharomyces cerevisiae (strain ATCC 204508 / S288c), Drosophila melanogaster, Mus musculus, Rattus norvegicus
G274	TPVPGSVGPMT	1	Schizosaccharomyces pombe (strain 972 / ATCC 24843)
G274	-----------	1	Arabidopsis thaliana
G276	VPGGVGPMTVA	5	Homo sapiens, Saccharomyces cerevisiae (strain ATCC 204508 / S288c), Drosophila melanogaster, Mus musculus, Rattus norvegicus
G276	VPGSVGPMTVA	1	Schizosaccharomyces pombe (strain 972 / ATCC 24843)
G276	-----------	1	Arabidopsis thaliana
H196	TVTTCHSKTAH	1	Homo sapiens
H196	TVTITHSKTRD	1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
H196	TVTVCHSKTRN	1	Drosophila melanogaster
H196	TVTLCHSKTES	1	Schizosaccharomyces pombe (strain 972 / ATCC 24843)
H196	-----------	1	Arabidopsis thaliana
H196	TVTTCHSKTAN	1	Mus musculus
H196	TVTTCHSKTAD	1	Rattus norvegicus
I238	VIDCGINYVPD	3	Homo sapiens, Mus musculus, Rattus norvegicus
I238	VIDVGTNYVAD	1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
I238	VIDCGINVKPD	1	Drosophila melanogaster
I238	AIDVGINSIPD	1	Schizosaccharomyces pombe (strain 972 / ATCC 24843)
I238	-----------	1	Arabidopsis thaliana
K56	LYINVKLKAAE	2	Homo sapiens, Mus musculus
K56	TYVRMKRKAAE	1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
K56	VYIRMKIKAAT	1	Drosophila melanogaster
K56	VYVRMKTRAAN	1	Schizosaccharomyces pombe (strain 972 / ATCC 24843)
K56	-----------	1	Arabidopsis thaliana
K56	LYINVKLKAAQ	1	Rattus norvegicus
L101	GIIVQLPLPAH	2	Saccharomyces cerevisiae (strain ATCC 204508 / S288c), Schizosaccharomyces pombe (strain 972 / ATCC 24843)
L101	GFIVQLPLDSE	2	Mus musculus, Rattus norvegicus
L101	GFLVQLPLDSE	1	Homo sapiens
L101	GIIVQMPLDCD	1	Drosophila melanogaster
L101	-----------	1	Arabidopsis thaliana
L202	SKTAHLDEEVN	1	Homo sapiens
L202	SKTRDIASYLH	1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
L202	SKTRNLEEITR	1	Drosophila melanogaster
L202	SKTESIADIVR	1	Schizosaccharomyces pombe (strain 972 / ATCC 24843)
L202	-----------	1	Arabidopsis thaliana
L202	SKTANLDKEVN	1	Mus musculus
L202	SKTADLDKEVN	1	Rattus norvegicus
L98	TVHGFLVQLPL	1	Homo sapiens
L98	HTHGIIVQLPL	1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
L98	RVHGIIVQMPL	1	Drosophila melanogaster
L98	TVHGIIVQLPL	1	Schizosaccharomyces pombe (strain 972 / ATCC 24843)
L98	-----------	1	Arabidopsis thaliana
L98	SVHGFIVQLPL	1	Mus musculus
L98	TVHGFIVQLPL	1	Rattus norvegicus
M221	TGQPEMVKGEW	3	Homo sapiens, Mus musculus, Rattus norvegicus
M221	IGQPEFVKGEW	1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
M221	IGVAEMVKGSW	1	Drosophila melanogaster
M221	IGIPHFVKADW	1	Schizosaccharomyces pombe (strain 972 / ATCC 24843)
M221	-----------	1	Arabidopsis thaliana
P272	FITPVPGGVGP	3	Homo sapiens, Mus musculus, Rattus norvegicus
P272	LITPVPGGVGP	1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
P272	HLTPVPGGVGP	1	Drosophila melanogaster
P272	AITPVPGSVGP	1	Schizosaccharomyces pombe (strain 972 / ATCC 24843)
P272	-----------	1	Arabidopsis thaliana
P277	PGGVGPMTVAM	5	Homo sapiens, Saccharomyces cerevisiae (strain ATCC 204508 / S288c), Drosophila melanogaster, Mus musculus, Rattus norvegicus
P277	PGSVGPMTVAM	1	Schizosaccharomyces pombe (strain 972 / ATCC 24843)
P277	-----------	1	Arabidopsis thaliana
Q100	HGIIVQLPLPA	2	Saccharomyces cerevisiae (strain ATCC 204508 / S288c), Schizosaccharomyces pombe (strain 972 / ATCC 24843)
Q100	HGFIVQLPLDS	2	Mus musculus, Rattus norvegicus
Q100	HGFLVQLPLDS	1	Homo sapiens
Q100	HGIIVQMPLDC	1	Drosophila melanogaster
Q100	-----------	1	Arabidopsis thaliana
Q218	VVATGQPEMVK	3	Homo sapiens, Mus musculus, Rattus norvegicus
Q218	VVAIGQPEFVK	1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Q218	VVGIGVAEMVK	1	Drosophila melanogaster
Q218	VAAIGIPHFVK	1	Schizosaccharomyces pombe (strain 972 / ATCC 24843)
Q218	-----------	1	Arabidopsis thaliana
R173	AVVVGRSKIVG	3	Homo sapiens, Mus musculus, Rattus norvegicus
R173	SVVIGRSDIVG	1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
R173	AVVLGRSKIVG	1	Drosophila melanogaster
R173	AVVIGRSNIVG	1	Schizosaccharomyces pombe (strain 972 / ATCC 24843)
R173	-----------	1	Arabidopsis thaliana
S174	VVVGRSKIVGA	3	Homo sapiens, Mus musculus, Rattus norvegicus
S174	VVIGRSDIVGS	1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
S174	VVLGRSKIVGT	1	Drosophila melanogaster
S174	VVIGRSNIVGR	1	Schizosaccharomyces pombe (strain 972 / ATCC 24843)
S174	-----------	1	Arabidopsis thaliana
S197	VTTCHSKTAHL	1	Homo sapiens
S197	VTITHSKTRDI	1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
S197	VTVCHSKTRNL	1	Drosophila melanogaster
S197	VTLCHSKTESI	1	Schizosaccharomyces pombe (strain 972 / ATCC 24843)
S197	-----------	1	Arabidopsis thaliana
S197	VTTCHSKTANL	1	Mus musculus
S197	VTTCHSKTADL	1	Rattus norvegicus
T148	CFIPCTPKGCL	3	Homo sapiens, Mus musculus, Rattus norvegicus
T148	FFLPCTPKGII	1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
T148	-FLPCTPWGCL	1	Drosophila melanogaster
T148	LFTACTPKGIM	1	Schizosaccharomyces pombe (strain 972 / ATCC 24843)
T148	-----------	1	Arabidopsis thaliana
T216	ILVVATGQPEM	3	Homo sapiens, Mus musculus, Rattus norvegicus
T216	IVVVAIGQPEF	1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
T216	ILVVGIGVAEM	1	Drosophila melanogaster
T216	IVVAAIGIPHF	1	Schizosaccharomyces pombe (strain 972 / ATCC 24843)
T216	-----------	1	Arabidopsis thaliana
T279	GVGPMTVAMLM	5	Homo sapiens, Saccharomyces cerevisiae (strain ATCC 204508 / S288c), Drosophila melanogaster, Mus musculus, Rattus norvegicus
T279	SVGPMTVAMLL	1	Schizosaccharomyces pombe (strain 972 / ATCC 24843)
T279	-----------	1	Arabidopsis thaliana
V171	RHAVVVGRSKI	3	Homo sapiens, Mus musculus, Rattus norvegicus
V171	SRSVVIGRSDI	1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
V171	ARAVVLGRSKI	1	Drosophila melanogaster
V171	KHAVVIGRSNI	1	Schizosaccharomyces pombe (strain 972 / ATCC 24843)
V171	-----------	1	Arabidopsis thaliana
V177	GRSKIVGAPMH	3	Homo sapiens, Mus musculus, Rattus norvegicus
V177	GRSDIVGSPVA	1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
V177	GRSKIVGTPAA	1	Drosophila melanogaster
V177	GRSNIVGRPMS	1	Schizosaccharomyces pombe (strain 972 / ATCC 24843)
V177	-----------	1	Arabidopsis thaliana
V275	PVPGGVGPMTV	5	Homo sapiens, Saccharomyces cerevisiae (strain ATCC 204508 / S288c), Drosophila melanogaster, Mus musculus, Rattus norvegicus
V275	PVPGSVGPMTV	1	Schizosaccharomyces pombe (strain 972 / ATCC 24843)
V275	-----------	1	Arabidopsis thaliana
V280	VGPMTVAMLMQ	4	Homo sapiens, Saccharomyces cerevisiae (strain ATCC 204508 / S288c), Mus musculus, Rattus norvegicus
V280	VGPMTVAMLMK	1	Drosophila melanogaster
V280	VGPMTVAMLLQ	1	Schizosaccharomyces pombe (strain 972 / ATCC 24843)
V280	-----------	1	Arabidopsis thaliana
V55	NLYINVKLKAA	3	Homo sapiens, Mus musculus, Rattus norvegicus
V55	ATYVRMKRKAA	1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
V55	NVYIRMKIKAA	1	Drosophila melanogaster
V55	NVYVRMKTRAA	1	Schizosaccharomyces pombe (strain 972 / ATCC 24843)
V55	-----------	1	Arabidopsis thaliana
V99	VHGFIVQLPLD	2	Mus musculus, Rattus norvegicus
V99	VHGFLVQLPLD	1	Homo sapiens
V99	THGIIVQLPLP	1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
V99	VHGIIVQMPLD	1	Drosophila melanogaster
V99	VHGIIVQLPLP	1	Schizosaccharomyces pombe (strain 972 / ATCC 24843)
V99	-----------	1	Arabidopsis thaliana
Y52	DDSNLYINVKL	3	Homo sapiens, Mus musculus, Rattus norvegicus
Y52	PDSATYVRMKR	1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Y52	EDSNVYIRMKI	1	Drosophila melanogaster
Y52	EDSNVYVRMKT	1	Schizosaccharomyces pombe (strain 972 / ATCC 24843)
Y52	-----------	1	Arabidopsis thaliana