HNF1B
HNF1 homeobox B, the group of HNF class homeoboxes
Basic information
Region (hg38): 17:37686431-37745059
Previous symbols: [ "TCF2" ]
Links
Phenotypes
GenCC
Source:
- medullary sponge kidney (Supportive), mode of inheritance: AD
- renal hypomagnesemia 2 (Supportive), mode of inheritance: AD
- renal cysts and diabetes syndrome (Supportive), mode of inheritance: AD
- renal dysplasia, unilateral (Supportive), mode of inheritance: AD
- renal dysplasia, bilateral (Supportive), mode of inheritance: AD
- unilateral multicystic dysplastic kidney (Supportive), mode of inheritance: AD
- renal cysts and diabetes syndrome (Definitive), mode of inheritance: AD
- renal cysts and diabetes syndrome (Strong), mode of inheritance: AD
- renal cysts and diabetes syndrome (Definitive), mode of inheritance: AD
- transient neonatal diabetes mellitus (Strong), mode of inheritance: AD
- permanent neonatal diabetes mellitus (Strong), mode of inheritance: AD
- diabetes mellitus, noninsulin-dependent (Strong), mode of inheritance: AD
- renal cysts and diabetes syndrome (Strong), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Renal cell carcinoma, nonpapillary chromophobe | AD | Oncologic | Surveillance and early detection of and treatment for malignancy may decrease morbidity and mortality | Endocrine; Genitourinary; Oncologic; Renal | 7151342; 2624270; 9398836; 10484768; 11085914; 12161522; 12675839; 15068978; 16249435; 15649945; 21380624; 21617276; 21767339; 22587559; 22269832; 22432796; 22706971 |
ClinVar
This is a list of variants' phenotypes submitted to
- Renal cysts and diabetes syndrome (116 variants)
- not provided (27 variants)
- Maturity onset diabetes mellitus in young (10 variants)
- Nonpapillary renal cell carcinoma;Renal cysts and diabetes syndrome;Type 2 diabetes mellitus (4 variants)
- HNF1B-related disorder (2 variants)
- Type 2 diabetes mellitus (2 variants)
- Hyperechogenic kidneys (2 variants)
- Type 2 diabetes mellitus;Nonpapillary renal cell carcinoma;Renal cysts and diabetes syndrome (1 variants)
- Autosomal dominant medullary cystic kidney disease with or without hyperuricemia (1 variants)
- Chromophobe renal cell carcinoma (1 variants)
- Hyperuricemic nephropathy, familial juvenile type 3 (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the HNF1B gene is commonly pathogenic or not.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 67 | 70 | ||||
| missense | 13 | 61 | 143 | 226 | ||
| nonsense | 28 | 36 | ||||
| start loss | 2 | |||||
| frameshift | 59 | 20 | 80 | |||
| inframe indel | 6 | |||||
| splice donor/acceptor (+/-2bp) | 20 | 25 | ||||
| splice region | 1 | 3 | 4 | 8 | 16 | |
| non coding | 13 | 46 | 42 | 101 | ||
| Total | 125 | 94 | 162 | 119 | 46 |
Highest pathogenic variant AF is 0.00000657
Variants in HNF1B
This is a list of pathogenic ClinVar variants found in the HNF1B region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 17-37686434-T-C | Renal cysts and diabetes syndrome • Maturity onset diabetes mellitus in young | Conflicting classifications of pathogenicity (Jan 12, 2018) | ||
| 17-37686448-G-C | Renal cysts and diabetes syndrome | Benign (Jan 13, 2018) | ||
| 17-37686568-A-G | Renal cysts and diabetes syndrome • Maturity onset diabetes mellitus in young | Benign/Likely benign (Jan 12, 2018) | ||
| 17-37686583-A-G | Renal cysts and diabetes syndrome • Maturity onset diabetes mellitus in young | Conflicting classifications of pathogenicity (Jan 13, 2018) | ||
| 17-37686595-C-T | Renal cysts and diabetes syndrome • Maturity onset diabetes mellitus in young | Benign/Likely benign (Jan 12, 2018) | ||
| 17-37686671-C-T | Renal cysts and diabetes syndrome • Maturity onset diabetes mellitus in young | Conflicting classifications of pathogenicity (Jan 13, 2018) | ||
| 17-37686681-T-C | Renal cysts and diabetes syndrome • Maturity onset diabetes mellitus in young | Conflicting classifications of pathogenicity (Jan 13, 2018) | ||
| 17-37686689-C-T | Renal cysts and diabetes syndrome • Maturity onset diabetes mellitus in young | Benign/Likely benign (Jan 12, 2018) | ||
| 17-37686713-C-T | Renal cysts and diabetes syndrome • Maturity onset diabetes mellitus in young | Benign/Likely benign (Jan 13, 2018) | ||
| 17-37686743-G-A | Renal cysts and diabetes syndrome • Maturity onset diabetes mellitus in young | Conflicting classifications of pathogenicity (Jan 13, 2018) | ||
| 17-37686747-G-A | Renal cysts and diabetes syndrome • Maturity onset diabetes mellitus in young | Conflicting classifications of pathogenicity (Jan 12, 2018) | ||
| 17-37686787-A-G | Renal cysts and diabetes syndrome • Maturity onset diabetes mellitus in young | Uncertain significance (Jan 13, 2018) | ||
| 17-37686927-T-C | Renal cysts and diabetes syndrome • Maturity onset diabetes mellitus in young | Uncertain significance (Jan 13, 2018) | ||
| 17-37686928-T-T | Renal cysts and diabetes syndrome | Benign (Jan 12, 2018) | ||
| 17-37686963-T-C | Renal cysts and diabetes syndrome | Uncertain significance (Jan 13, 2018) | ||
| 17-37686963-T-G | Maturity onset diabetes mellitus in young | Uncertain significance (-) | ||
| 17-37686969-T-C | Renal cysts and diabetes syndrome • Maturity onset diabetes mellitus in young | Benign (Jan 13, 2018) | ||
| 17-37686988-T-C | Renal cysts and diabetes syndrome • Maturity onset diabetes mellitus in young | Benign (Jan 12, 2018) | ||
| 17-37687098-A-A | Renal cysts and diabetes syndrome | Benign (Jun 14, 2018) | ||
| 17-37687261-C-G | not specified | Uncertain significance (Jan 31, 2024) | ||
| 17-37687271-CT-C | Type 2 diabetes mellitus | Uncertain significance (-) | ||
| 17-37687272-T-T | Renal cysts and diabetes syndrome • not specified | Benign (Jun 26, 2018) | ||
| 17-37687273-G-T | Renal cysts and diabetes syndrome | Benign (Jun 14, 2018) | ||
| 17-37687284-T-C | Renal cysts and diabetes syndrome • Maturity onset diabetes mellitus in young • HNF1B-related disorder | Likely benign (Jan 12, 2018) | ||
| 17-37687305-C-T | HNF1B-related disorder | Uncertain significance (Feb 08, 2024) |
GnomAD
Source:
dbNSFP
Source:
- Function
- FUNCTION: Transcription factor, probably binds to the inverted palindrome 5'-GTTAATNATTAAC-3'.;
- Disease
- DISEASE: Renal cysts and diabetes syndrome (RCAD) [MIM:137920]: An autosomal dominant disorder comprising non-diabetic renal disease resulting from abnormal renal development, and diabetes, which in some cases occurs earlier than age 25 years and is thus consistent with a diagnosis of maturity-onset diabetes of the young (MODY5). The renal disease is highly variable and includes renal cysts, glomerular tufts, aberrant nephrogenesis, primitive tubules, irregular collecting systems, oligomeganephronia, enlarged renal pelves, abnormal calyces, small kidney, single kidney, horseshoe kidney, and hyperuricemic nephropathy. Affected individuals may also have abnormalities of the genital tract. {ECO:0000269|PubMed:10484768, ECO:0000269|PubMed:10672455, ECO:0000269|PubMed:11845238, ECO:0000269|PubMed:11918730, ECO:0000269|PubMed:14583183, ECO:0000269|PubMed:15001636, ECO:0000269|PubMed:15068978, ECO:0000269|PubMed:15181075, ECO:0000269|PubMed:15930087, ECO:0000269|PubMed:16249435}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Diabetes mellitus, non-insulin-dependent (NIDDM) [MIM:125853]: A multifactorial disorder of glucose homeostasis caused by a lack of sensitivity to the body's own insulin. Affected individuals usually have an obese body habitus and manifestations of a metabolic syndrome characterized by diabetes, insulin resistance, hypertension and hypertriglyceridemia. The disease results in long-term complications that affect the eyes, kidneys, nerves, and blood vessels. {ECO:0000269|PubMed:12161522}. Note=Disease susceptibility may be associated with variations affecting the gene represented in this entry.; DISEASE: Prostate cancer, hereditary, 11 (HPC11) [MIM:611955]: A condition associated with familial predisposition to cancer of the prostate. Most prostate cancers are adenocarcinomas that develop in the acini of the prostatic ducts. Other rare histopathologic types of prostate cancer that occur in approximately 5% of patients include small cell carcinoma, mucinous carcinoma, prostatic ductal carcinoma, transitional cell carcinoma, squamous cell carcinoma, basal cell carcinoma, adenoid cystic carcinoma (basaloid), signet-ring cell carcinoma and neuroendocrine carcinoma. {ECO:0000269|PubMed:18264097}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.;
- Pathway
- Maturity onset diabetes of the young - Homo sapiens (human);Anti-diabetic Drug Potassium Channel Inhibitors Pathway, Pharmacodynamics;Endoderm Differentiation
(Consensus)
Recessive Scores
- pRec
- 0.708
Intolerance Scores
- loftool
- 0.0380
- rvis_EVS
- -0.54
- rvis_percentile_EVS
- 20.26
Haploinsufficiency Scores
- pHI
- 0.393
- hipred
- Y
- hipred_score
- 0.837
- ghis
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.914
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Hnf1b
- Phenotype
- renal/urinary system phenotype; immune system phenotype; liver/biliary system phenotype; embryo phenotype; endocrine/exocrine gland phenotype; growth/size/body region phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); muscle phenotype; homeostasis/metabolism phenotype;
Zebrafish Information Network
- Gene name
- hnf1ba
- Affected structure
- hair cell
- Phenotype tag
- abnormal
- Phenotype quality
- mislocalised
Gene ontology
- Biological process
- negative regulation of transcription by RNA polymerase II;endodermal cell fate specification;kidney development;inner cell mass cell differentiation;regulation of transcription by RNA polymerase II;Notch signaling pathway;response to glucose;anterior/posterior pattern specification;response to organic cyclic compound;insulin secretion;regulation of Wnt signaling pathway;hindbrain development;pancreas development;circadian regulation of gene expression;regulation of pronephros size;pronephric nephron tubule development;response to drug;regulation of endodermal cell fate specification;positive regulation of transcription, DNA-templated;embryonic digestive tract morphogenesis;branching morphogenesis of an epithelial tube;pronephros development;epithelial cell proliferation;positive regulation of transcription initiation from RNA polymerase II promoter;ureteric bud elongation;hepatoblast differentiation;negative regulation of mesenchymal cell apoptotic process involved in mesonephric nephron morphogenesis;protein-DNA complex assembly;hepatocyte differentiation;regulation of branch elongation involved in ureteric bud branching;mesonephric duct formation;negative regulation of mesenchymal cell apoptotic process involved in metanephros development
- Cellular component
- nucleus;nucleoplasm;transcription factor complex
- Molecular function
- DNA-binding transcription factor activity, RNA polymerase II-specific;proximal promoter sequence-specific DNA binding;DNA-binding transcription factor activity;protein binding;protein homodimerization activity;protein-containing complex binding;protein heterodimerization activity