HNF1A
  • 3
    Haplo
    Score
  • 0
    Triplo
    Score

Gene Facts External Data Attribution

HGNC Symbol
HNF1A (HGNC:11621) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
HGNC Name
HNF1 homeobox A
Gene type
protein-coding gene
Locus type
gene with protein product
Previous symbols
MODY3, TCF1
Alias symbols
HNF1, LFB1, HNF1α
%HI
35.48(Read more about the DECIPHER Haploinsufficiency Index)
pLI
0.99(Read more about gnomAD pLI score)
LOEUF
0.48(Read more about gnomAD LOEUF score)
Cytoband
12q24.31
Genomic Coordinates
GRCh37/hg19: chr12:121416346-121440315 NCBI Ensembl UCSC
GRCh38/hg38: chr12:120978543-121002512 NCBI Ensembl UCSC
MANE Select Transcript
NM_000545.8 ENST00000257555.11 (Read more about MANE Select)
Function
Transcriptional activator that regulates the tissue specific expression of multiple genes, especially in pancreatic islet cells and in liver (By similarity). Binds to the inverted palindrome 5'- GTTAATNATTAAC-3' (PubMed:12453420, PubMed:10966642). Activates the transcription of CYP1A2, CYP2E1 and CYP3A11 (By similarity). {ECO:0000250|UniProtKB:P22361, ECO:0000269|PubMed:10966642, ECO:0000269|PubMed:12453420}. (Microbial infection) Plays a crucial role for hepatitis B virus gene transcription and... (Source: Uniprot)

Dosage Sensitivity Summary (Gene)

Dosage ID:
ISCA-8517
ClinGen Curation ID:
CCID:007288
Curation Status:
Complete
Issue Type:
Dosage Curation - Gene
Haploinsufficiency:
Sufficient Evidence for Haploinsufficiency (3)
Read full report...
Triplosensitivity:
No Evidence for Triplosensitivity (0)
Read full report...
Last Evaluated:
12/13/2023

Haploinsufficiency (HI) Score Details

HI Score:
3
HI Evidence Strength:
Sufficient Evidence for Haploinsufficiency (Disclaimer)
HI Disease:
HI Evidence:
  • PUBMED: 12574234
    Bjorkhaug et al. (2003) detected a novel 4-bp deletion in exon 3 of the HNF1A gene NM_000545.8:c.587_590del - frameshift variant - (p.T196fsdelCCAA). In a Norwegian family with MODY3 (600496), and a novel splice site mutation in intron 3 of the HNF1A gene, NM_000545.8:c.714-1G>A, a novel 2-bp deletion in exon 7 of the HNF1A gene NM_000545.8:c.1333_1334del - frameshift variant , (p.S445fsdelAG) in 3 members of a Norwegian family with MODY3 .
  • PUBMED: 11668618
    Yoshiuchi et al. (2001) identified a 142delG frameshift mutation NM_000545.8(HNF1A):c.142del, p.Glu48fs in the HNF1A gene in a family with a strong history of type 1 diabetes (T1D20; 612520). Reporter gene analysis indicated that the mutant protein had no transactivation activity in HeLa and other cells. Haploinsufficiency for the HNF1A gene is indicated to lead to severe forms of diabetes resembling type I
  • PUBMED: 8945470
    K Yamagata (1996): Three frameshift variants were identified in 3 families with MODY3, c.895insC at codon 291, deletion of CT at codon 379, deletion of TG at codon547/548, (unknown transcript in the paper).
  • PUBMED: 9097962
    Vaxillaire et al. (1997): In a family in which 4 members of 3 generations had MODY3 (600496), a deletion of guanine from codon glycine-292 (G292fsdelG), resulting in a frameshift in the HNF1A gene: NM_000545.8:c.876del - frameshift variant.
  • PUBMED: 9166684
    Glucksmann et al (1997): four frameshift variants were identified in 6 families (C,E,F,G,H,K) with MODY3, c.895insC (unknown transcript in the paper), at codon 291.
HI Evidence Comments:
Heterozygous damaging mutations or gene/exon deletions in HNF1A have a strong literature of being overwhelmingly associated with MODY3 (Maturity-Onset Diabetes of the Young, Type 3). However, there are other diseases and conditions that are also associated with HFN1A mutations or deletions, such as cancers (including renal cancers, hepatocellular carcinomas, and liver adenomas). For these conditions, it is less clear if HNF1A haploinsufficiency is causal.

Triplosensitivity (TS) Score Details

TS Score:
0
TS Evidence Strength:
No Evidence for Triplosensitivity (Disclaimer)

Genomic View

Select assembly: (NC_000012.11) (NC_000012.12)