HNF1B
  • 3
    Haplo
    Score
  • 0
    Triplo
    Score

Gene Facts External Data Attribution

HGNC Symbol
HNF1B (HGNC:11630) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
HGNC Name
HNF1 homeobox B
Gene type
protein-coding gene
Locus type
gene with protein product
Previous symbols
TCF2
Alias symbols
LFB3, VHNF1, HNF1beta, MODY5, HNF1β
%HI
0.76(Read more about the DECIPHER Haploinsufficiency Index)
pLI
1(Read more about gnomAD pLI score)
LOEUF
0.24(Read more about gnomAD LOEUF score)
Cytoband
17q12
Genomic Coordinates
GRCh37/hg19: chr17:36046434-36105050 NCBI Ensembl UCSC
GRCh38/hg38: chr17:37686431-37745059 NCBI Ensembl UCSC
MANE Select Transcript
NM_000458.4 ENST00000617811.5 (Read more about MANE Select)
Function
Transcription factor that binds to the inverted palindrome 5'-GTTAATNATTAAC-3' (PubMed:7900999, PubMed:17924661). Binds to the FPC element in the cAMP regulatory unit of the PLAU gene (By similarity). Transcriptional activity is increased by coactivator PCBD1 (PubMed:24204001). {ECO:0000250|UniProtKB:Q03365, ECO:0000269|PubMed:17924661, ECO:0000269|PubMed:24204001, ECO:0000269|PubMed:7900999}. (Source: Uniprot)

Dosage Sensitivity Summary (Gene)

Dosage ID:
ISCA-3955
ClinGen Curation ID:
CCID:007289
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...
Related Links:
Last Evaluated:
12/21/2020

Haploinsufficiency (HI) Score Details

HI Score:
3
HI Evidence Strength:
Sufficient Evidence for Haploinsufficiency (Disclaimer)
HI Disease:
  • renal cysts and diabetes syndrome Monarch
HI Evidence:
  • PUBMED: 10720943
    Bingham et al. (2000) sequenced HNF1B in 6 patients with maturity-onset diabetes of the young (MODY) and found a de novo 5 bp deletion in exon 4 in one proband. The proband was also found to have small renal cysts and impaired renal function. The HNF1B variant was present in the proband's son who had multicystic, dysplastic kidneys.
  • PUBMED: 15068978
    Bellanné-Chantelot et al. (2004) report 8 new variants in HNF1B in patients with MODY5. Two nonsense variants (one was de novo) and one de novo splice site mutation were identified. All probands were found to have renal involvement including structural abnormalities and impaired kidney function. Mutations were not detected in 212 normal control chromosomes.
  • PUBMED: 9398836
    Horikawa et al. (1997) sequenced HNF1B in 57 probands with MODY. They found a nonsense variant (R177X) in a proband and the affected sister and mother. The variant was not found in 53 unrelated normal controls.
HI Evidence Comments:
Loss of function variants in HNF1 have been associated with renal cysts and diabetes syndrome. Additional cases: PMID 15930087 Edghill et al. (2006) identified 13 new probands with HNF1B variants from a cohort 160 patients with unexplained renal disease, with or without diabetes. Seven variants were predicted to be loss of function, including 3 nonsense, 2 frameshift and 2 splice site variants. Familial studies were performed for 6 of the probands with loss of function variants. HNF1B variants were detected in 10 affected family members across the 6 families with at least one segregation per family. Variants were absent in 6 unaffected family members.

Triplosensitivity (TS) Score Details

TS Score:
0
TS Evidence Strength:
No Evidence for Triplosensitivity (Disclaimer)
TS Evidence Comments:
Located within the 17q12 duplication syndrome (614526). Note: Mefford et al. (2007) PMID:17924346 idenfied a complex duplication in a patient with intellectual disability and seizures. A 27 kb duplication involves LHX1 and a second 259 kb duplication includes HNF1B. Both duplications are present in the unaffected mother.

Genomic View

Select assembly: (NC_000017.10) (NC_000017.11)