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)
Triplosensitivity:
No Evidence for Triplosensitivity
(0)
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)