HNF1A HNF1 homeobox A [Homo sapiens (human)] - Gene

Summary

Official Symbol: HNF1Aprovided by HGNC
Official Full Name: HNF1 homeobox Aprovided by HGNC
Primary source: HGNC:HGNC:11621
See related: Ensembl:ENSG00000135100 MIM:142410; AllianceGenome:HGNC:11621
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: HNF1; LFB1; TCF1; HNF4A; MODY3; TCF-1; HNF-1A; IDDM20; HNF1alpha; HNF-1-alpha
Summary: The protein encoded by this gene is a transcription factor required for the expression of several liver-specific genes. The encoded protein functions as a homodimer and binds to the inverted palindrome 5'-GTTAATNATTAAC-3'. Defects in this gene are a cause of maturity onset diabetes of the young type 3 (MODY3) and also can result in the appearance of hepatic adenomas. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Apr 2015]
Expression: Biased expression in kidney (RPKM 13.4), duodenum (RPKM 9.8) and 6 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 12q24.31

Exon count:: 9

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	12	NC_000012.12 (120978543..121002512)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	12	NC_060936.1 (120968229..120992127)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	12	NC_000012.11 (121416346..121440315)

Chromosome 12 - NC_000012.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Genetic insights into fetal kidney development: Variants in HNF1A and PKHD1 genes.
Title: Genetic insights into fetal kidney development: Variants in HNF1A and PKHD1 genes.
Pan-cancer mapping of single CD8[+] T cell profiles reveals a TCF1:CXCR6 axis regulating CD28 co-stimulation and anti-tumor immunity.
Title: Pan-cancer mapping of single CD8(+) T cell profiles reveals a TCF1:CXCR6 axis regulating CD28 co-stimulation and anti-tumor immunity.
Tripartite motif 8 promotes the progression of hepatocellular carcinoma via mediating ubiquitination of HNF1alpha.
Title: Tripartite motif 8 promotes the progression of hepatocellular carcinoma via mediating ubiquitination of HNF1α.
Molecular mechanism of HNF-1A-mediated HNF4A gene regulation and promoter-driven HNF4A-MODY diabetes.
Title: Molecular mechanism of HNF-1A-mediated HNF4A gene regulation and promoter-driven HNF4A-MODY diabetes.
Effect of mutation at c.493T>C locus of transcription factor HNF1alpha gene on its protein level.
Title: Effect of mutation at c.493T>C locus of transcription factor HNF1α gene on its protein level.
HNF1A induces glioblastoma by upregulating EPS8 and activating PI3K/AKT signaling pathway.
Title: HNF1A induces glioblastoma by upregulating EPS8 and activating PI3K/AKT signaling pathway.
HNF1alpha maintains pancreatic alpha and beta cell functions in primary human islets.
Title: HNF1α maintains pancreatic α and β cell functions in primary human islets.
Characterisation of HNF1A variants in paediatric diabetes in Norway using functional and clinical investigations to unmask phenotype and monogenic diabetes.
Title: Characterisation of HNF1A variants in paediatric diabetes in Norway using functional and clinical investigations to unmask phenotype and monogenic diabetes.
Single cell multiomic analysis reveals diabetes-associated beta-cell heterogeneity driven by HNF1A.
Title: Single cell multiomic analysis reveals diabetes-associated β-cell heterogeneity driven by HNF1A.
High-fat diet plus HNF1A variant promotes polyps by activating beta-catenin in early-onset colorectal cancer.
Title: High-fat diet plus HNF1A variant promotes polyps by activating β-catenin in early-onset colorectal cancer.

Submit: New GeneRIF Correction See all GeneRIFs (390)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Diabetes mellitus type 1 MedGen: C0011854 OMIM: 222100 GeneReviews: Not available	Compare labs
Hepatic adenomas, familial MedGen: C1840646 OMIM: 142330 GeneReviews: Not available	Compare labs
Maturity-onset diabetes of the young type 3 MedGen: C1838100 OMIM: 600496 GeneReviews: Maturity-Onset Diabetes of the Young Overview	Compare labs
Nonpapillary renal cell carcinoma MedGen: CN074294 OMIM: 144700 GeneReviews: Not available	Compare labs
Type 1 diabetes mellitus 20 MedGen: C2675866 OMIM: 612520 GeneReviews: Not available	Compare labs
Type 2 diabetes mellitus MedGen: C0011860 OMIM: 125853 GeneReviews: WFS1 Spectrum Disorder	Compare labs

Copy number response

Description
Copy number response Triplosensitivity No evidence available (Last evaluated 2023-12-13) ClinGen Genome Curation Page Haploinsufficency Sufficient evidence for dosage pathogenicity (Last evaluated 2023-12-13) ClinGen Genome Curation PagePubMed

EBI GWAS Catalog

Description
Are C-reactive protein associated genetic variants associated with serum levels and retinal markers of microvascular pathology in Asian populations from Singapore? EBI GWAS Catalog EBI GWAS CatalogPubMed
Biological, clinical and population relevance of 95 loci for blood lipids. EBI GWAS Catalog EBI GWAS CatalogPubMed
Common genetic loci influencing plasma homocysteine concentrations and their effect on risk of coronary artery disease. EBI GWAS Catalog EBI GWAS CatalogPubMed
Common variants at 30 loci contribute to polygenic dyslipidemia. EBI GWAS Catalog EBI GWAS CatalogPubMed
Discovery and refinement of loci associated with lipid levels. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genetic associations with C-reactive protein level and white blood cell count in the KARE study. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genetic Loci associated with C-reactive protein levels and risk of coronary heart disease. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genetic Loci Associated with Circulating Levels of Very Long-Chain Saturated Fatty Acids. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association analyses identify 18 new loci associated with serum urate concentrations. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association analysis of blood biomarkers in chronic obstructive pulmonary disease. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association and population genetic analysis of C-reactive protein in African American and Hispanic American women. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study for C-reactive protein levels identified pleiotropic associations in the IL6 locus. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study identifies loci influencing concentrations of liver enzymes in plasma. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study of type 2 diabetes in a sample from Mexico City and a meta-analysis of a Mexican-American sample from Starr County, Texas. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association with C-reactive protein levels in CLHNS: evidence for the CRP and HNF1A loci and their interaction with exposure to a pathogenic environment. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genomics meets glycomics-the first GWAS study of human N-Glycome identifies HNF1&#x003b1; as a master regulator of plasma protein fucosylation. EBI GWAS Catalog EBI GWAS CatalogPubMed
Joint influence of small-effect genetic variants on human longevity. EBI GWAS Catalog EBI GWAS CatalogPubMed
Large-scale genome-wide association studies in East Asians identify new genetic loci influencing metabolic traits. EBI GWAS Catalog EBI GWAS CatalogPubMed
Loci affecting gamma-glutamyl transferase in adults and adolescents show age &#x000d7; SNP interaction and cardiometabolic disease associations. EBI GWAS Catalog EBI GWAS CatalogPubMed
Loci related to metabolic-syndrome pathways including LEPR,HNF1A, IL6R, and GCKR associate with plasma C-reactive protein: the Women's Genome Health Study. EBI GWAS Catalog EBI GWAS CatalogPubMed
Meta-analysis of genome-wide association studies in &gt;80 000 subjects identifies multiple loci for C-reactive protein levels. EBI GWAS Catalog EBI GWAS CatalogPubMed
New susceptibility locus for coronary artery disease on chromosome 3q22.3. EBI GWAS Catalog EBI GWAS CatalogPubMed
New variants including ARG1 polymorphisms associated with C-reactive protein levels identified by genome-wide association and pathway analysis. EBI GWAS Catalog EBI GWAS CatalogPubMed
Polymorphisms of the HNF1A gene encoding hepatocyte nuclear factor-1 alpha are associated with C-reactive protein. EBI GWAS Catalog EBI GWAS CatalogPubMed
Population-based genome-wide association studies reveal six loci influencing plasma levels of liver enzymes. EBI GWAS Catalog EBI GWAS CatalogPubMed
Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

TCF1 (e-PCR), detects polymorphism
- UniSTS:258304

NoName (e-PCR)
- UniSTS:483587

D12S2088 (e-PCR)
- UniSTS:19481

NoName (e-PCR)
- UniSTS:480811

G15717 (e-PCR)
- UniSTS:61257

D1S1423 (e-PCR)
- UniSTS:149619

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables DNA binding	IDA Inferred from Direct Assay more info	PubMed
enables DNA-binding transcription activator activity, RNA polymerase II-specific	ISS Inferred from Sequence or Structural Similarity more info
enables DNA-binding transcription factor activity	IDA Inferred from Direct Assay more info	PubMed
enables DNA-binding transcription factor activity, RNA polymerase II-specific	IBA Inferred from Biological aspect of Ancestor more info
enables DNA-binding transcription factor activity, RNA polymerase II-specific	ISA Inferred from Sequence Alignment more info
enables RNA polymerase II cis-regulatory region sequence-specific DNA binding	IBA Inferred from Biological aspect of Ancestor more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein dimerization activity	IPI Inferred from Physical Interaction more info	PubMed
enables protein heterodimerization activity	IDA Inferred from Direct Assay more info	PubMed
enables protein homodimerization activity	IPI Inferred from Physical Interaction more info	PubMed
enables transcription cis-regulatory region binding	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in D-glucose import	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in glucose homeostasis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in insulin secretion	IEA Inferred from Electronic Annotation more info
involved_in insulin secretion	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in liver development	IEA Inferred from Electronic Annotation more info
involved_in pancreas development	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of DNA-templated transcription	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of transcription by RNA polymerase II	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of transcription initiation by RNA polymerase II	IGI Inferred from Genetic Interaction more info	PubMed
NOT involved_in regulation of pronephros size	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of transcription by RNA polymerase II	IBA Inferred from Biological aspect of Ancestor more info
involved_in regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
involved_in renal D-glucose absorption	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
located_in chromatin	ISA Inferred from Sequence Alignment more info
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
part_of protein-containing complex	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: hepatocyte nuclear factor 1-alpha

Names: albumin proximal factor; hepatic nuclear factor 1; interferon production regulator factor; liver-specific transcription factor LF-B1; transcription factor 1, hepatic

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_011731.2 RefSeqGene

Range

4823..28767

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_522

mRNA and Protein(s)

NM_000545.8 → NP_000536.6 hepatocyte nuclear factor 1-alpha isoform 2

Status: REVIEWED

Source sequence(s)

AC079602

Consensus CDS

CCDS9209.1

UniProtKB/Swiss-Prot

A0A0A0MQU7, A5Z2R8, E0YMJ5, E0YMK0, E0YMK1, E2I9R4, E2I9R5, F5H5U3, P20823, Q2M3H2, Q99861

UniProtKB/TrEMBL

A0A2R3XWA6, A0A2R3XWC8

Related

ENSP00000257555.5, ENST00000257555.11

Conserved Domains (4) summary

cd00086
Location:200 → 273

homeodomain; Homeodomain; DNA binding domains involved in the transcriptional regulation of key eukaryotic developmental processes; may bind to DNA as monomers or as homo- and/or heterodimers, in a sequence-specific manner.

pfam04812
Location:282 → 540

HNF-1B_C; Hepatocyte nuclear factor 1 (HNF-1), beta isoform C-terminus

pfam04813
Location:542 → 630

HNF-1A_C; Hepatocyte nuclear factor 1 (HNF-1), alpha isoform C-terminus

pfam04814
Location:8 → 168

HNF-1_N; Hepatocyte nuclear factor 1 (HNF-1), N-terminus
NM_001306179.2 → NP_001293108.2 hepatocyte nuclear factor 1-alpha isoform 1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).

Source sequence(s)

AC079602

Consensus CDS

CCDS76611.1

UniProtKB/TrEMBL

A0A2R3XWA6, A0A2R3XWC8, F5H0K0

Related

ENSP00000438804.1, ENST00000544413.2

Conserved Domains (4) summary

cd00086
Location:200 → 273

homeodomain; Homeodomain; DNA binding domains involved in the transcriptional regulation of key eukaryotic developmental processes; may bind to DNA as monomers or as homo- and/or heterodimers, in a sequence-specific manner.

pfam04812
Location:282 → 540

HNF-1B_C; Hepatocyte nuclear factor 1 (HNF-1), beta isoform C-terminus

pfam04813
Location:549 → 637

HNF-1A_C; Hepatocyte nuclear factor 1 (HNF-1), alpha isoform C-terminus

pfam04814
Location:8 → 168

HNF-1_N; Hepatocyte nuclear factor 1 (HNF-1), N-terminus
NM_001406915.1 → NP_001393844.1 hepatocyte nuclear factor 1-alpha isoform 3

Status: REVIEWED

Source sequence(s)

AC079602

UniProtKB/TrEMBL

A0A2R3XWA6

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000012.12 Reference GRCh38.p14 Primary Assembly

Range

120978543..121002512

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_024449168.2 → XP_024304936.1 hepatocyte nuclear factor 1-alpha isoform X1

UniProtKB/TrEMBL

A0A0A0MTK8, A0A2R3XWA6, A0A2R3XWC8

Related

ENSP00000443112.1, ENST00000541395.5

Conserved Domains (4) summary

cd00086
Location:200 → 273

homeodomain; Homeodomain; DNA binding domains involved in the transcriptional regulation of key eukaryotic developmental processes; may bind to DNA as monomers or as homo- and/or heterodimers, in a sequence-specific manner.

pfam04813
Location:573 → 661

HNF-1A_C; Hepatocyte nuclear factor 1 (HNF-1), alpha isoform C terminus

pfam04812
Location:282 → 540

HNF-1B_C; Hepatocyte nuclear factor 1 (HNF-1), beta isoform C terminus

pfam04814
Location:8 → 167

HNF-1_N; Hepatocyte nuclear factor 1 (HNF-1), N terminus