HNF1A
HNF1 homeobox A, the group of HNF class homeoboxes
Basic information
Region (hg38): 12:120978542-121002512
Previous symbols: [ "MODY3", "TCF1" ]
Links
Phenotypes
GenCC
Source:
- nonpapillary renal cell carcinoma (No Known Disease Relationship), mode of inheritance: Unknown
- type 1 diabetes mellitus 20 (Strong), mode of inheritance: AD
- diabetes mellitus, noninsulin-dependent (Strong), mode of inheritance: AD
- maturity-onset diabetes of the young type 3 (Strong), mode of inheritance: AD
- maturity-onset diabetes of the young (Supportive), mode of inheritance: AD
- hyperinsulinism due to HNF1A deficiency (Supportive), mode of inheritance: AD
- type 1 diabetes mellitus 20 (Definitive), mode of inheritance: AD
- maturity-onset diabetes of the young type 3 (Strong), mode of inheritance: AD
- monogenic diabetes (Definitive), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Renal cell carcinoma, nonpapillary clear cell; Liver adenomatosis; Maturity onset diabetes of the young, type 3 | AD | Endocrine; Oncologic | Surveillance and early detection of and treatment for neoplasms (eg, including renal and/or hepatic neoplasms) may decrease morbidity and mortality; Individuals with Maturity onset diabetes of the young, type 3 have been reported as presenting in childhood with macrosomia and hyperinsulinism, which has been reported as diazoxide-responsive | Endocrine; Oncologic | 8945470; 9313763; 10482964; 11058894; 10649494; 11575290; 11668618; 11904371; 12050210; 12355088; 12355088; 14598263; 15001650; 15649945; 21120312; 21683639; 22517943; 22802087 |
ClinVar
This is a list of variants' phenotypes submitted to
- not provided (465 variants)
- Maturity onset diabetes mellitus in young (343 variants)
- Monogenic diabetes (328 variants)
- Maturity-onset diabetes of the young type 3 (201 variants)
- not specified (136 variants)
- 6 conditions (60 variants)
- Nonpapillary renal cell carcinoma (16 variants)
- Type 1 diabetes mellitus 20 (14 variants)
- HNF1A-related condition (11 variants)
- Type 2 diabetes mellitus (10 variants)
- Diabetes mellitus (7 variants)
- Diabetes mellitus type 1 (3 variants)
- Ovarian cancer (3 variants)
- Clear cell carcinoma of kidney (2 variants)
- DiGeorge syndrome (1 variants)
- Keratoderma-ichthyosis-deafness syndrome, autosomal recessive (1 variants)
- Hyperinsulinism due to HNF1A deficiency (1 variants)
- Chromophobe renal cell carcinoma (1 variants)
- Breast carcinoma (1 variants)
- Diabetes mellitus type 1;Type 2 diabetes mellitus;Type 1 diabetes mellitus 20;Maturity-onset diabetes of the young type 3 (1 variants)
- Diabetes mellitus type 2, susceptibility to (1 variants)
- Diabetes mellitus type 1;Type 2 diabetes mellitus;Maturity-onset diabetes of the young type 3;Type 1 diabetes mellitus 20 (1 variants)
- Maturity-onset diabetes of the young type 3;Type 2 diabetes mellitus;Diabetes mellitus type 1;Type 1 diabetes mellitus 20 (1 variants)
- Diabetes mellitus type 1;Type 1 diabetes mellitus 20;Type 2 diabetes mellitus;Maturity-onset diabetes of the young type 3 (1 variants)
- Reduced delayed hypersensitivity (1 variants)
- Hepatic adenomas, familial (1 variants)
- Maturity-onset diabetes of the young type 1 (1 variants)
- Diabetes mellitus type 1;Maturity-onset diabetes of the young type 3;Type 1 diabetes mellitus 20;Type 2 diabetes mellitus (1 variants)
- Symphalangism affecting the proximal phalanx of the 4th finger (1 variants)
- Insulin-resistant diabetes mellitus (1 variants)
- Diabetes mellitus type 1;Type 1 diabetes mellitus 20;Maturity-onset diabetes of the young type 3;Type 2 diabetes mellitus (1 variants)
- SERUM HDL CHOLESTEROL LEVEL, MODIFIER OF (1 variants)
- Insulin resistance, susceptibility to (1 variants)
- Gestational diabetes (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the HNF1A 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 | 85 | 99 | ||||
| missense | 39 | 59 | 228 | 13 | 11 | 350 |
| nonsense | 31 | 10 | 42 | |||
| start loss | 4 | |||||
| frameshift | 52 | 37 | 94 | |||
| inframe indel | 10 | |||||
| splice donor/acceptor (+/-2bp) | 17 | 27 | ||||
| splice region ? | 1 | 4 | 5 | 8 | 1 | 19 |
| non coding ? | 18 | 32 | 39 | 92 | ||
| Total | 142 | 123 | 268 | 130 | 55 |
Highest pathogenic variant AF is 0.00000659
Variants in HNF1A
This is a list of pathogenic ClinVar variants found in the HNF1A region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 12-120978551-T-C | Monogenic diabetes • HNF1A-related disorder | Uncertain significance (Aug 11, 2021) | ||
| 12-120978554-A-G | Monogenic diabetes | Uncertain significance (Mar 31, 2024) | ||
| 12-120978582-C-A | Monogenic diabetes | Uncertain significance (Aug 18, 2021) | ||
| 12-120978582-C-T | Monogenic diabetes | Uncertain significance (Aug 18, 2021) | ||
| 12-120978588-G-A | HNF1A-related disorder | Conflicting classifications of pathogenicity (Aug 26, 2022) | ||
| 12-120978597-A-AGGGTTGG | Monogenic diabetes • Maturity onset diabetes mellitus in young • 6 conditions | Benign (Apr 12, 2022) | ||
| 12-120978621-C-A | not specified | Uncertain significance (Jan 09, 2024) | ||
| 12-120978643-TG-T | Maturity-onset diabetes of the young type 3 | Pathogenic (Jan 01, 2000) | ||
| 12-120978645-G-A | Uncertain significance (Jan 18, 2022) | |||
| 12-120978645-G-C | not specified | Conflicting classifications of pathogenicity (Jan 31, 2024) | ||
| 12-120978646-G-A | Likely benign (Oct 31, 2023) | |||
| 12-120978673-T-G | not specified • HNF1A-related disorder | Conflicting classifications of pathogenicity (Jul 01, 2023) | ||
| 12-120978680-T-C | not specified • HNF1A-related disorder | Conflicting classifications of pathogenicity (Sep 08, 2020) | ||
| 12-120978707-C-G | Uncertain significance (Apr 18, 2022) | |||
| 12-120978708-G-A | Uncertain significance (Jul 21, 2022) | |||
| 12-120978740-G-A | not specified | Benign/Likely benign (Mar 07, 2024) | ||
| 12-120978763-C-T | Maturity-onset diabetes of the young type 3 • Monogenic diabetes • Maturity onset diabetes mellitus in young | Uncertain significance (Mar 04, 2022) | ||
| 12-120978764-G-A | not specified • Maturity onset diabetes mellitus in young | Uncertain significance (Nov 14, 2019) | ||
| 12-120978765-A-G | not specified • Maturity-onset diabetes of the young type 3 • Maturity onset diabetes mellitus in young • Nonpapillary renal cell carcinoma | Conflicting classifications of pathogenicity (Jul 07, 2023) | ||
| 12-120978769-A-C | Monogenic diabetes | Likely pathogenic (Mar 04, 2022) | ||
| 12-120978769-A-G | Maturity-onset diabetes of the young type 3 • Monogenic diabetes • Maturity onset diabetes mellitus in young | Pathogenic (Mar 04, 2022) | ||
| 12-120978769-A-T | Monogenic diabetes | Pathogenic (Mar 04, 2022) | ||
| 12-120978770-T-C | Monogenic diabetes • Maturity onset diabetes mellitus in young | Pathogenic (Aug 26, 2022) | ||
| 12-120978770-TG-T | Monogenic diabetes • Maturity onset diabetes mellitus in young | Pathogenic (Feb 22, 2022) | ||
| 12-120978772-G-A | Uncertain significance (Jun 01, 2021) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| HNF1A | protein_coding | protein_coding | ENST00000257555 | 10 | 23970 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.961 | 0.0389 | 125710 | 0 | 8 | 125718 | 0.0000318 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 1.14 | 318 | 380 | 0.836 | 0.0000240 | 4043 |
| Missense in Polyphen | 80 | 114.45 | 0.69898 | 1266 | ||
| Synonymous | -1.42 | 201 | 177 | 1.14 | 0.0000124 | 1361 |
| Loss of Function | 4.18 | 4 | 27.8 | 0.144 | 0.00000154 | 278 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000580 | 0.0000580 |
| Ashkenazi Jewish | 0.000101 | 0.0000992 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000466 | 0.0000440 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Transcriptional activator that regulates the tissue specific expression of multiple genes, especially in pancreatic islet cells and in liver. Required for the expression of several liver specific genes. Binds to the inverted palindrome 5'- GTTAATNATTAAC-3'. {ECO:0000269|PubMed:10966642, ECO:0000269|PubMed:12453420}.;
- Disease
- DISEASE: Hepatic adenomas familial (HEPAF) [MIM:142330]: Rare benign liver tumors of presumable epithelial origin that develop in an otherwise normal liver. Hepatic adenomas may be single or multiple. They consist of sheets of well-differentiated hepatocytes that contain fat and glycogen and can produce bile. Bile ducts or portal areas are absent. Kupffer cells, if present, are reduced in number and are non-functional. Conditions associated with adenomas are insulin-dependent diabetes mellitus and glycogen storage diseases (types 1 and 3). Note=The disease is caused by mutations affecting the gene represented in this entry. Bi-allelic inactivation of HNF1A, whether sporadic or associated with MODY3, may be an early step in the development of some hepatocellular carcinomas.; DISEASE: Maturity-onset diabetes of the young 3 (MODY3) [MIM:600496]: A form of diabetes that is characterized by an autosomal dominant mode of inheritance, onset in childhood or early adulthood (usually before 25 years of age), a primary defect in insulin secretion and frequent insulin-independence at the beginning of the disease. {ECO:0000269|PubMed:10078571, ECO:0000269|PubMed:10102714, ECO:0000269|PubMed:10482964, ECO:0000269|PubMed:10588527, ECO:0000269|PubMed:10966642, ECO:0000269|PubMed:12453420, ECO:0000269|PubMed:17573900, ECO:0000269|PubMed:8945470, ECO:0000269|PubMed:9032114, ECO:0000269|PubMed:9075818, ECO:0000269|PubMed:9075819, ECO:0000269|PubMed:9097962, ECO:0000269|PubMed:9166684, ECO:0000269|PubMed:9287053, ECO:0000269|PubMed:9392505, ECO:0000269|PubMed:9626139, ECO:0000269|PubMed:9754819}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Diabetes mellitus, insulin-dependent, 20 (IDDM20) [MIM:612520]: A multifactorial disorder of glucose homeostasis that is characterized by susceptibility to ketoacidosis in the absence of insulin therapy. Clinical features are polydipsia, polyphagia and polyuria which result from hyperglycemia-induced osmotic diuresis and secondary thirst. These derangements result in long-term complications that affect the eyes, kidneys, nerves, and blood vessels. {ECO:0000269|PubMed:10333057, ECO:0000269|PubMed:9313763, ECO:0000269|PubMed:9867222}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.;
- Pathway
- Maturity onset diabetes of the young - Homo sapiens (human);Signaling pathways regulating pluripotency of stem cells - Homo sapiens (human);Anti-diabetic Drug Potassium Channel Inhibitors Pathway, Pharmacodynamics;WNT-Core;Adipogenesis;Vitamin D Receptor Pathway;Hepatitis C and Hepatocellular Carcinoma;Development and heterogeneity of the ILC family;ESC Pluripotency Pathways;Role of Osx and miRNAs in tooth development;wnt signaling pathway;growth hormone signaling pathway;role of mal in rho-mediated activation of srf;FOXA2 and FOXA3 transcription factor networks;Presenilin action in Notch and Wnt signaling
(Consensus)
Intolerance Scores
- loftool
- 0.0579
- rvis_EVS
- -0.44
- rvis_percentile_EVS
- 24.6
Haploinsufficiency Scores
- pHI
- 0.866
- hipred
- Y
- hipred_score
- 0.835
- ghis
- 0.458
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.991
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | High | High | High |
| Primary Immunodeficiency | High | High | High |
| Cancer | High | High | High |
Mouse Genome Informatics
- Gene name
- Hnf1a
- Phenotype
- adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); endocrine/exocrine gland phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); muscle phenotype; homeostasis/metabolism phenotype; cellular phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); liver/biliary system 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); reproductive system phenotype; digestive/alimentary phenotype; renal/urinary system phenotype; skeleton phenotype;
Zebrafish Information Network
- Gene name
- hnf1a
- Affected structure
- pancreatic B cell
- Phenotype tag
- abnormal
- Phenotype quality
- decreased area
Gene ontology
- Biological process
- natural killer cell differentiation;liver development;regulation of transcription by RNA polymerase II;insulin secretion;pancreas development;regulation of pronephros size;renal glucose absorption;glucose homeostasis;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;glucose import;positive regulation of transcription initiation from RNA polymerase II promoter
- Cellular component
- nucleus;cytoplasm;protein-containing complex
- Molecular function
- DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription activator activity, RNA polymerase II-specific;DNA binding;DNA-binding transcription factor activity;protein binding;transcription regulatory region DNA binding;protein dimerization activity