HNF1B

HNF1 homeobox B, the group of HNF class homeoboxes

Basic information

Region (hg38): 17:37686431-37745059

Previous symbols: [ "TCF2" ]

Links

ENSG00000275410 ∙ NCBI:6928 ∙ OMIM:189907 ∙ HGNC:11630 ∙ Uniprot:P35680 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• 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 (Strong), mode of inheritance: AD
• renal cysts and diabetes syndrome (Definitive), 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: CGD

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 ClinVar and linked to the HNF1B gene.

• not_provided (414 variants)
• Renal_cysts_and_diabetes_syndrome (391 variants)
• Maturity_onset_diabetes_mellitus_in_young (175 variants)
• Type_2_diabetes_mellitus (113 variants)
• Nonpapillary_renal_cell_carcinoma (110 variants)
• HNF1B-related_disorder (74 variants)
• not_specified (65 variants)
• Monogenic_diabetes (7 variants)
• Autosomal_dominant_polycystic_liver_disease (4 variants)
• Hyperechogenic_kidneys (3 variants)
• Congenital_anomaly_of_kidney_and_urinary_tract (3 variants)
• Hyperuricemic_nephropathy,_familial_juvenile_type_3 (2 variants)
• Ovarian_cancer (2 variants)
• Autosomal_dominant_medullary_cystic_kidney_disease_with_or_without_hyperuricemia (1 variants)
• Renal_cyst (1 variants)
• Inborn_genetic_diseases (1 variants)
• See_cases (1 variants)
• Diabetes_mellitus (1 variants)
• Chromophobe_renal_cell_carcinoma (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. These statistics are base on transcript: NM_000000458.4. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous	1		2	127	1	131
missense	17	79	239	20	3	358
nonsense	33	12				45
start loss	2					2
frameshift	71	34	2			107
splice donor/acceptor (+/-2bp)	23	6				29
Total	147	131	243	147	4

Highest pathogenic variant AF is 0.0000332314

GnomAD

Source: gnomAD

dbNSFP

Source: dbNSFP

• 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

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