HNF1B

Chr 17

HNF1 homeobox B

Also known as: ADTKD3, FJHN, HNF-1-beta, HNF-1B, HNF1beta, HNF2, HPC11, LF-B3

NCBI Gene: 6928 ENSG00000275410 UniProt: P35680

This transcription factor binds DNA as a homodimer or heterodimer with hepatocyte nuclear factor 1-alpha and regulates nephron development and embryonic pancreas development. Loss-of-function mutations cause renal cysts and diabetes syndrome and type 2 diabetes mellitus through autosomal dominant inheritance. The gene is highly intolerant to loss-of-function variants, consistent with haploinsufficiency as the underlying disease mechanism.

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

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]

GeneReviews ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtRenal cysts and diabetes syndrome

UniProtType 2 diabetes mellitus

UniProtProstate cancer, hereditary, 11

Clinical highlights

Gene-disease validity (ClinGen)

renal cysts and diabetes syndrome · ADDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

126

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.17

LOEUF· LoF intol.

LOF

Mechanism· G2P

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