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mutLBSgeneDB |
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| Gene summary for HNF4A |
 Gene summary |
| Basic gene Info. | Gene symbol | HNF4A |
| Gene name | hepatocyte nuclear factor 4, alpha | |
| Synonyms | FRTS4|HNF4|HNF4a7|HNF4a8|HNF4a9|HNF4alpha|MODY|MODY1|NR2A1|NR2A21|TCF|TCF14 | |
| Cytomap | UCSC genome browser: 20q13.12 | |
| Type of gene | protein-coding | |
| RefGenes | NM_000457.4, NM_001030003.2,NM_001030004.2,NM_001258355.1,NM_001287182.1, NM_001287183.1,NM_001287184.1,NM_175914.4,NM_178849.2, NM_178850.2, | |
| Description | HNF4alpha10/11/12TCF-14hepatic nuclear factor 4 alphahepatocyte nuclear factor 4-alphanuclear receptor subfamily 2 group A member 1transcription factor 14transcription factor HNF-4 | |
| Modification date | 20141222 | |
| dbXrefs | MIM : 600281 | |
| HGNC : HGNC | ||
| Ensembl : ENSG00000101076 | ||
| HPRD : 02612 | ||
| Vega : OTTHUMG00000032531 | ||
| Protein | UniProt: P41235 go to UniProt's Cross Reference DB Table | |
| Expression | CleanEX: HS_HNF4A | |
| BioGPS: 3172 | ||
| Pathway | NCI Pathway Interaction Database: HNF4A | |
| KEGG: HNF4A | ||
| REACTOME: HNF4A | ||
| Pathway Commons: HNF4A | ||
| Context | iHOP: HNF4A | |
| ligand binding site mutation search in PubMed: HNF4A | ||
| UCL Cancer Institute: HNF4A | ||
| Assigned class in mutLBSgeneDB | A: This gene has a literature evidence and it belongs to targetable_mutLBSgenes. | |
| References showing study about ligand binding site mutation for HNF4A. | 1. "Arya VB, Rahman S, Senniappan S, Flanagan SE, Ellard S, Hussain K. HNF4A mutation: switch from hyperinsulinaemic hypoglycaemia to maturity-onset diabetes of the young, and incretin response. Diabet Med. 2014 Mar;31(3):e11-5. doi:10.1111/dme.12369. PubMed PMID: 24299156; PubMed Central PMCID: PMC4305198. " 24299156 | |
| Gene ontology having evidence of Inferred from Direct Assay (IDA) from Entrez |
| GO ID | GO Term | PubMed ID | GO:0006357 | regulation of transcription from RNA polymerase II promoter | 10330009 | GO:0007596 | blood coagulation | 12911579 | GO:0019216 | regulation of lipid metabolic process | 10551874 | GO:0045893 | positive regulation of transcription, DNA-templated | 16488887 | GO:0045944 | positive regulation of transcription from RNA polymerase II promoter | 7615825 |
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| Ligand binding site mutations for HNF4A |
| Lollipop-style diagram of mutations at LBS in amino-acid sequence. We represented ligand binding site mutations only. (You can see big image via clicking.)  : non-synonymous mutation on LBS, Circle size denotes number of samples. |
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| Cancer type specific mutLBS sorted by frequency |
| LBS | AAchange of nsSNV | Cancer type | # samples | V199 | E200K | BLCA | 1 | R113 | R113G | BRCA | 1 | G69 | T68M | COAD | 1 | R109 | D107Y | COAD | 1 | V199 | V199I | COAD | 1 | R89 | V88L | LUAD | 1 | H92 | H92N | LUAD | 1 | C63 | G64V | LUAD | 1 | L213 | L213M | LUAD | 1 | C60 | A61P | LUAD | 1 | C60 | A58V | LUAD | 1 | H92,K90 | N91K | OV | 1 | R89 | R89Q | SKCM | 1 | D135 | D135N | SKCM | 1 | C60 | A58T | STAD | 1 | H92 | Y94H | STAD | 1 | V199,K203 | W201R | THCA | 1 | H92 | Y94C | UCEC | 1 | R116 | C115W | UCEC | 1 | D9 | D9N | UCEC | 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. |
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| Protein structure related information for HNF4A |
| 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 |
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| 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 | R113 | R113G | -1.7656923 | H92 | Y94H | -1.4297622 | R89 | R89Q | -1.2431329 | H92 | Y94C | -1.1743606 | V199 | E200K | -1.1544839 | V199 | W201R | -1.073723 | K203 | W201R | -1.073723 | K90 | N91K | -1.0527065 | H92 | N91K | -1.0527065 | L213 | L213M | -0.97293049 | D9 | D9N | -0.97266091 | R109 | D107Y | -0.95366755 | H92 | H92N | -0.89794906 | C60 | A58T | -0.6543048 | C60 | A61P | -0.64222332 | D135 | D135N | -0.56276856 | G69 | T68M | -0.50804122 | R89 | V88L | -0.48239106 | R116 | C115W | -0.42649148 | V199 | V199I | -0.36762108 | C60 | A58V | -0.33282158 | C63 | G64V | -0.16182682 |
| (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 HNF4A from PDB |
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| Differential gene expression and gene-gene network for HNF4A |
| 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) |
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| Phenotype information for HNF4A |
| Gene level disease information (DisGeNet) |
| Disease ID | Disease name | # PubMed | Association type |
| umls:C0011860 | Diabetes Mellitus, Type 2 | 141 | Biomarker, GeneticVariation |
| umls:C0342276 | Mason-Type Diabetes | 83 | Biomarker |
| umls:C1852093 | Maturity-Onset Diabetes of the Young, Type 1 | 7 | Biomarker, GeneticVariation |
| umls:C0009324 | Colitis, Ulcerative | 7 | Biomarker, GeneticVariation |
| Mutation level pathogenic information (ClinVar annotation) |
| Allele ID | AA change | Clinical significance | Origin | Phenotype IDs |
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| Pharmacological information for HNF4A |
| 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. |
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| Gene-centered drug-gene interaction network |
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| Drug information targeting mutLBSgene (Approved drugs only) |
| Drug status | DrugBank ID | Name | Type | Drug structure |
| Investigational | DB05447 | AVI-4557 | Small molecule |  |
| Experimental | DB08231 | MYRISTIC ACID | Small molecule |  |
| Gene-centered ligand-gene interaction network |
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| Ligands binding to mutated ligand binding site of HNF4A go to BioLip |
| Ligand ID | Ligand short name | Ligand long name | PDB ID | PDB name | mutLBS |
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| Conservation information for LBS of HNF4A |
| Multiple alignments for P41235 in multiple species |
| LBS | AA sequence | # species | Species | C60 | GVSALCAICGD | 3 | Homo sapiens, Mus musculus, Rattus norvegicus | C63 | ALCAICGDRAT | 3 | Homo sapiens, Mus musculus, Rattus norvegicus | C77 | YGASSCDGCKG | 3 | Homo sapiens, Mus musculus, Rattus norvegicus | C80 | SSCDGCKGFFR | 3 | Homo sapiens, Mus musculus, Rattus norvegicus | D135 | VQNERDRISTR | 3 | Homo sapiens, Mus musculus, Rattus norvegicus | D214 | CELLLDDQVAL | 2 | Mus musculus, Rattus norvegicus | D214 | CELPLDDQVAL | 1 | Homo sapiens | D78 | GASSCDGCKGF | 3 | Homo sapiens, Mus musculus, Rattus norvegicus | D9 | SKTLVDMDMAD | 1 | Homo sapiens | D9 | SKTLAGMDMAD | 1 | Mus musculus | D9 | SKTLADMDMAD | 1 | Rattus norvegicus | E133 | EAVQNERDRIS | 3 | Homo sapiens, Mus musculus, Rattus norvegicus | E27 | AYTTLEFENVQ | 3 | Homo sapiens, Mus musculus, Rattus norvegicus | E372 | DNLLQEMLLGG | 3 | Homo sapiens, Mus musculus, Rattus norvegicus | F208 | KYIPAFCELLL | 2 | Mus musculus, Rattus norvegicus | F208 | KYIPAFCELPL | 1 | Homo sapiens | F83 | DGCKGFFRRSV | 3 | Homo sapiens, Mus musculus, Rattus norvegicus | G377 | EMLLGGSASDA | 2 | Mus musculus, Rattus norvegicus | G377 | EMLLGGSPSDA | 1 | Homo sapiens | G69 | GDRATGKHYGA | 3 | Homo sapiens, Mus musculus, Rattus norvegicus | G79 | ASSCDGCKGFF | 3 | Homo sapiens, Mus musculus, Rattus norvegicus | H71 | RATGKHYGASS | 3 | Homo sapiens, Mus musculus, Rattus norvegicus | H92 | SVRKNHMYSCR | 3 | Homo sapiens, Mus musculus, Rattus norvegicus | I137 | NERDRISTRRS | 3 | Homo sapiens, Mus musculus, Rattus norvegicus | K203 | LVEWAKYIPAF | 3 | Homo sapiens, Mus musculus, Rattus norvegicus | K70 | DRATGKHYGAS | 3 | Homo sapiens, Mus musculus, Rattus norvegicus | K81 | SCDGCKGFFRR | 3 | Homo sapiens, Mus musculus, Rattus norvegicus | K90 | RRSVRKNHMYS | 3 | Homo sapiens, Mus musculus, Rattus norvegicus | L196 | MKEQLLVLVEW | 3 | Homo sapiens, Mus musculus, Rattus norvegicus | L213 | FCELLLDDQVA | 2 | Mus musculus, Rattus norvegicus | L213 | FCELPLDDQVA | 1 | Homo sapiens | L220 | DQVALLRAHAG | 3 | Homo sapiens, Mus musculus, Rattus norvegicus | L369 | AKIDNLLQEML | 3 | Homo sapiens, Mus musculus, Rattus norvegicus | M373 | NLLQEMLLGGS | 3 | Homo sapiens, Mus musculus, Rattus norvegicus | N110 | DKDKRNQCRYC | 3 | Homo sapiens, Mus musculus, Rattus norvegicus | N368 | MAKIDNLLQEM | 3 | Homo sapiens, Mus musculus, Rattus norvegicus | Q131 | KKEAVQNERDR | 3 | Homo sapiens, Mus musculus, Rattus norvegicus | Q216 | LLLDDQVALLR | 2 | Mus musculus, Rattus norvegicus | Q216 | LPLDDQVALLR | 1 | Homo sapiens | R109 | VDKDKRNQCRY | 3 | Homo sapiens, Mus musculus, Rattus norvegicus | R113 | KRNQCRYCRLK | 3 | Homo sapiens, Mus musculus, Rattus norvegicus | R116 | QCRYCRLKKCF | 3 | Homo sapiens, Mus musculus, Rattus norvegicus | R134 | AVQNERDRIST | 3 | Homo sapiens, Mus musculus, Rattus norvegicus | R136 | QNERDRISTRR | 3 | Homo sapiens, Mus musculus, Rattus norvegicus | R221 | QVALLRAHAGE | 3 | Homo sapiens, Mus musculus, Rattus norvegicus | R66 | AICGDRATGKH | 3 | Homo sapiens, Mus musculus, Rattus norvegicus | R85 | CKGFFRRSVRK | 3 | Homo sapiens, Mus musculus, Rattus norvegicus | R86 | KGFFRRSVRKN | 3 | Homo sapiens, Mus musculus, Rattus norvegicus | R89 | FRRSVRKNHMY | 3 | Homo sapiens, Mus musculus, Rattus norvegicus | S138 | ERDRISTRRSS | 3 | Homo sapiens, Mus musculus, Rattus norvegicus | S4 | 3 | Homo sapiens, Mus musculus, Rattus norvegicus | V130 | MKKEAVQNERD | 3 | Homo sapiens, Mus musculus, Rattus norvegicus | V199 | QLLVLVEWAKY | 3 | Homo sapiens, Mus musculus, Rattus norvegicus | V217 | LLDDQVALLRA | 2 | Mus musculus, Rattus norvegicus | V217 | PLDDQVALLRA | 1 | Homo sapiens | Y72 | ATGKHYGASSC | 3 | Homo sapiens, Mus musculus, Rattus norvegicus |
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