HNF1B

Protein identityUniProt · HPA

UniProt accession

P35680

Gene

HNF1B

Ensembl

ENSG00000275410

Chromosome

17

Canonical length

557 aa

Protein class

Disease related genes, Human disease related genes, Predicted intracellular proteins, Transcription factors

Subcellular location

Nucleoplasm,Vesicles

Quaternary structure

Homodimer

OverviewNCBI Gene

This gene encodes a member of the homeodomain-containing superfamily of transcription factors. The protein binds to DNA as either a homodimer, or a heterodimer with the related protein hepatocyte nuclear factor 1-alpha. The gene has been shown to function in nephron development, and regulates development of the embryonic pancreas. Mutations in this gene result in renal cysts and diabetes syndrome and noninsulin-dependent diabetes mellitus, and expression of this gene is altered in some types of cancer. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Sep 2009]

Canonical amino-acid sequenceUniProt

557 residues, UniProt reviewed canonical sequence.

>P35680|HNF1B
     1  MVSKLTSLQQ ELLSALLSSG VTKEVLVQAL EELLPSPNFG VKLETLPLSP GSGAEPDTKP
    61  VFHTLTNGHA KGRLSGDEGS EDGDDYDTPP ILKELQALNT EEAAEQRAEV DRMLSEDPWR
   121  AAKMIKGYMQ QHNIPQREVV DVTGLNQSHL SQHLNKGTPM KTQKRAALYT WYVRKQREIL
   181  RQFNQTVQSS GNMTDKSSQD QLLFLFPEFS QQSHGPGQSD DACSEPTNKK MRRNRFKWGP
   241  ASQQILYQAY DRQKNPSKEE REALVEECNR AECLQRGVSP SKAHGLGSNL VTEVRVYNWF
   301  ANRRKEEAFR QKLAMDAYSS NQTHSLNPLL SHGSPHHQPS SSPPNKLSGV RYSQQGNNEI
   361  TSSSTISHHG NSAMVTSQSV LQQVSPASLD PGHNLLSPDG KMISVSGGGL PPVSTLTNIH
   421  SLSHHNPQQS QNLIMTPLSG VMAIAQSLNT SQAQSVPVIN SVAGSLAALQ PVQFSQQLHS
   481  PHQQPLMQQS PGSHMAQQPF MAAVTQLQNS HMYAHKQEPP QYSHTSRFPS AMVVTDTSSI
   541  STLTNMSSSK QCPLQAW

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against HNF1B 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)

0.58

Highest tissue expression

67 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about HNF1B.

Disease | AllUniProt

Conditions HNF1B is implicated in, by any mechanism.

• Renal cysts and diabetes syndrome (RCAD) MIM:137920
• Type 2 diabetes mellitus (T2D) MIM:125853
• Prostate cancer, hereditary, 11 (HPC11) MIM:611955

Disease | GeneticClinVar

281 pathogenic / likely-pathogenic of 909 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Renal cysts and diabetes syndrome
• Maturity-onset diabetes of the young
• Type 2 diabetes mellitus
• Nonpapillary renal cell carcinoma
• HNF1B-related disorder

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)

0.17

gnomAD pLI

1

gnomAD missense Z

1.73

DepMap mean gene effect

-0.32

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• anterior/posterior pattern specification
• branching morphogenesis of an epithelial tube
• embryonic digestive tract morphogenesis
• endocrine pancreas development
• endodermal cell fate specification
• epithelial cell proliferation
• gene expression
• genitalia development
• hepatoblast differentiation
• hindbrain development
• inner cell mass cell differentiation
• insulin secretion
• kidney development
• mesonephric duct formation
• negative regulation of mesenchymal cell apoptotic process involved in metanephros development
• negative regulation of transcription by RNA polymerase II
• Notch signaling pathway
• pancreas development
• positive regulation of DNA-templated transcription
• positive regulation of gene expression
• positive regulation of transcription initiation by RNA polymerase II
• pronephros development
• regulation of branch elongation involved in ureteric bud branching
• regulation of transcription by RNA polymerase II
• regulation of Wnt signaling pathway
• response to glucose
• mesenchymal cell apoptotic process involved in metanephros development
• negative regulation of mesenchymal cell apoptotic process involved in mesonephric nephron morphogenesis
• pronephric nephron tubule development
• regulation of pronephros size
• ureteric bud elongation

Molecular functions

• DNA binding
• DNA-binding transcription factor activity
• DNA-binding transcription factor activity, RNA polymerase II-specific
• identical protein binding
• promoter-specific chromatin binding
• protein homodimerization activity
• RNA polymerase II cis-regulatory region sequence-specific DNA binding
• transcription coregulator binding

Cellular components

• chromatin
• cytosol
• nucleoplasm
• nucleus
• transcription regulator complex

Protein domainsUniProt · Pfam · InterPro

• Homeodomain
• Hepatocyte nuclear factor 1, beta isoform, C-terminal
• Hepatocyte nuclear factor 1, N-terminal
• Homedomain-like superfamily
• Lambda repressor-like, DNA-binding domain superfamily
• Hepatocyte nuclear factor 1, N-terminal domain superfamily
• Hepatocyte nuclear factor 1
• HNF-1, dimerization domain
• HNF-1, POU-specific (POUs) atypical domain
• Hepatocyte nuclear factor 1 (HNF-1), beta isoform C terminus
• Hepatocyte nuclear factor 1 (HNF-1), N terminus

KeywordsUniProt

• Activator
• Diabetes mellitus
• DNA-binding
• Homeobox
• Nucleus
• Phosphoprotein
• Transcription
• Transcription regulation

InteractionsUniProt · HPA

Protein binding partners of HNF1B in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• PCBD1