HNF4A
Hepatocyte nuclear factor 4-alpha
Also known as: HNF4, HNF4A_HUMAN, MODY, MODY1, NR2A1, TCF14
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- P41235
- Gene
- HNF4A
- Ensembl
- ENSG00000101076
- Chromosome
- 20
- Canonical length
- 474 aa
- Protein class
- Disease related genes, Human disease related genes, Nuclear receptors, Predicted intracellular proteins, Transcription factors
- Subcellular location
- Nucleoplasm
- Quaternary structure
- Homodimer
OverviewNCBI Gene
The protein encoded by this gene is a nuclear transcription factor which binds DNA as a homodimer. The encoded protein controls the expression of several genes, including hepatocyte nuclear factor 1 alpha, a transcription factor which regulates the expression of several hepatic genes. This gene may play a role in development of the liver, kidney, and intestines. Mutations in this gene have been associated with monogenic autosomal dominant non-insulin-dependent diabetes mellitus type I. Alternative splicing of this gene results in multiple transcript variants encoding several different isoforms. [provided by RefSeq, Apr 2012]
Canonical amino-acid sequenceUniProt
474 residues, UniProt reviewed canonical sequence.
>P41235|HNF4A
1 MRLSKTLVDM DMADYSAALD PAYTTLEFEN VQVLTMGNDT SPSEGTNLNA PNSLGVSALC
61 AICGDRATGK HYGASSCDGC KGFFRRSVRK NHMYSCRFSR QCVVDKDKRN QCRYCRLKKC
121 FRAGMKKEAV QNERDRISTR RSSYEDSSLP SINALLQAEV LSRQITSPVS GINGDIRAKK
181 IASIADVCES MKEQLLVLVE WAKYIPAFCE LPLDDQVALL RAHAGEHLLL GATKRSMVFK
241 DVLLLGNDYI VPRHCPELAE MSRVSIRILD ELVLPFQELQ IDDNEYAYLK AIIFFDPDAK
301 GLSDPGKIKR LRSQVQVSLE DYINDRQYDS RGRFGELLLL LPTLQSITWQ MIEQIQFIKL
361 FGMAKIDNLL QEMLLGGSPS DAPHAHHPLH PHLMQEHMGT NVIVANTMPT HLSNGQMCEW
421 PRPRGQAATP ETPQPSPPGG SGSEPYKLLP GAVATIVKPL SAIPQPTITK QEVILocalizationUniProt · AlphaFold · HPA
Whether an antibody against HNF4A can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.
- Antibody reachability
- Intracellular
- Secreted
- No
- Transmembrane segments
- 0
- Mean surface accessibility (rSASA)
- 0.43
- Highest tissue expression
- 113 nTPM
Expression across tissuesHPA
Tissue
- liver: 113 nTPM
- duodenum: 96 nTPM
- small intestine: 79 nTPM
- colon: 54 nTPM
- rectum: 45 nTPM
- kidney: 43 nTPM
Single-cell type
- colonocytes: 444 nCPM
- enteric stem cells: 433 nCPM
- paneth cells: 356 nCPM
- enteric transient amplifying cells: 348 nCPM
- enterocytes: 333 nCPM
- hepatocytes: 282 nCPM
Immune cell
- basophil: 1.8 nTPM
- NK-cell: 0.5 nTPM
- neutrophil: 0.4 nTPM
- naive B-cell: 0.2 nTPM
- classical monocyte: 0.1 nTPM
- eosinophil: 0.1 nTPM
Brain region
- choroid plexus: 32 nTPM
- cerebral cortex: 3.3 nTPM
- hippocampal formation: 3.2 nTPM
- cerebellum: 3.1 nTPM
- basal ganglia: 3 nTPM
- white matter: 2.8 nTPM
DiseaseUniProt · ClinVar · IEDB · PubMed
Four sources answering four different questions about HNF4A.
Disease | AllUniProt
Conditions HNF4A is implicated in, by any mechanism.
- Maturity-onset diabetes of the young 1 (MODY1) MIM:125850
- Type 2 diabetes mellitus (T2D) MIM:125853
- Fanconi renotubular syndrome 4 with maturity-onset diabetes of the young (FRTS4) MIM:616026
Disease | GeneticClinVar
159 pathogenic / likely-pathogenic of 766 ClinVar records.
Conditions with pathogenic or likely-pathogenic variants.
- Monogenic diabetes
- Maturity-onset diabetes of the young type 1
- Maturity-onset diabetes of the young
- Fanconi renotubular syndrome 4 with maturity-onset diabetes of the young
- Type 2 diabetes mellitus
Genetic constraint and essentialitygnomAD · DepMap
Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.
- gnomAD LOEUF (loss-of-function intolerance)
- 0.51
- gnomAD pLI
- 0.15
- gnomAD missense Z
- 1.81
- DepMap mean gene effect
- 0.03
- DepMap dependency class
- selective
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 6% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- blood coagulation
- cell differentiation
- cholesterol homeostasis
- glucose homeostasis
- lipid homeostasis
- lipid metabolic process
- negative regulation of cell growth
- negative regulation of cell population proliferation
- negative regulation of DNA-templated transcription
- phospholipid homeostasis
- positive regulation of DNA-templated transcription
- positive regulation of transcription by RNA polymerase II
- regulation of circadian rhythm
- regulation of gastrulation
- regulation of insulin secretion
- regulation of lipid metabolic process
- regulation of transcription by RNA polymerase II
- response to glucose
- rhythmic process
- sex differentiation
- signal transduction involved in regulation of gene expression
- transcription by RNA polymerase II
- triglyceride homeostasis
- xenobiotic metabolic process
- regulation of growth hormone receptor signaling pathway
- regulation of ornithine metabolic process
Molecular functions
- chromatin binding
- DNA binding
- DNA-binding transcription activator activity, RNA polymerase II-specific
- DNA-binding transcription factor activity
- DNA-binding transcription factor activity, RNA polymerase II-specific
- fatty acid binding
- nuclear receptor activity
- protein homodimerization activity
- RNA polymerase II cis-regulatory region sequence-specific DNA binding
- RNA polymerase II-specific DNA-binding transcription factor binding
- sequence-specific double-stranded DNA binding
- signaling receptor binding
- transcription cis-regulatory region binding
- zinc ion binding
Cellular components
Protein domainsUniProt · Pfam · InterPro
- Nuclear hormone receptor, ligand-binding domain
- Zinc finger, nuclear hormone receptor-type
- Nuclear hormone receptor
- Zinc finger, NHR/GATA-type
- Nuclear hormone receptor-like domain superfamily
- Hepatocyte nuclear factor 4, ligand-binding domain
- Hepatocyte nuclear factor 4-like, DNA-binding domain
- Nuclear hormone receptor family NR2 subfamily
- Ligand-binding domain of nuclear hormone receptor
- Double treble clef zinc finger, C4 type
KeywordsUniProt
InteractionsUniProt · HPA
Protein binding partners of HNF4A in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads HNF4A as an antibody target. Whether an autoantibody or antibody against HNF4A could matter depends on whether native HNF4A is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
HNF4A is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.
Annotation status
The present source text does not explicitly label HNF4A as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
Loading the interactive Seroatlas protein explorer...