WFS1 wolframin ER transmembrane glycoprotein [Homo sapiens (human)] - Gene

Summary

Official Symbol: WFS1provided by HGNC
Official Full Name: wolframin ER transmembrane glycoproteinprovided by HGNC
Primary source: HGNC:HGNC:12762
See related: Ensembl:ENSG00000109501 MIM:606201; AllianceGenome:HGNC:12762
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: WFS; WFRS; WFSL; CTRCT41
Summary: This gene encodes a transmembrane protein, which is located primarily in the endoplasmic reticulum and ubiquitously expressed with highest levels in brain, pancreas, heart, and insulinoma beta-cell lines. Mutations in this gene are associated with Wolfram syndrome, also called DIDMOAD (Diabetes Insipidus, Diabetes Mellitus, Optic Atrophy, and Deafness), an autosomal recessive disorder. The disease affects the brain and central nervous system. Mutations in this gene can also cause autosomal dominant deafness 6 (DFNA6), also known as DFNA14 or DFNA38. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Mar 2009]
Expression: Ubiquitous expression in ovary (RPKM 44.4), fat (RPKM 34.2) and 24 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 4p16.1

Exon count:: 8

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	4	NC_000004.12 (6269850..6303265)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	4	NC_060928.1 (6243866..6277297)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	4	NC_000004.11 (6271577..6304992)

Chromosome 4 - NC_000004.12 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 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?

Characteristics of autosomal dominant WFS1-associated optic neuropathy and its comparability to OPA1-associated autosomal dominant optic atrophy.
Title: Characteristics of autosomal dominant WFS1-associated optic neuropathy and its comparability to OPA1-associated autosomal dominant optic atrophy.
Novel WFS1 Variants in Two Moroccan Families with Wolfram Syndrome.
Title: Novel WFS1 Variants in Two Moroccan Families with Wolfram Syndrome.
High Frequency of Recessive WFS1 Mutations Among Indian Children With Islet Antibody-negative Type 1 Diabetes.
Title: High Frequency of Recessive WFS1 Mutations Among Indian Children With Islet Antibody-negative Type 1 Diabetes.
The miR-668 binding site variant rs1046322 on WFS1 is associated with obesity in Southeast Asians.
Title: The miR-668 binding site variant rs1046322 on WFS1 is associated with obesity in Southeast Asians.
Selective proteasome degradation of C-terminally-truncated human WFS1 in pancreatic beta cells.
Title: Selective proteasome degradation of C-terminally-truncated human WFS1 in pancreatic beta cells.
Delineating Wolfram-like syndrome: A systematic review and discussion of the WFS1-associated disease spectrum.
Title: Delineating Wolfram-like syndrome: A systematic review and discussion of the WFS1-associated disease spectrum.
The genetic and clinical characteristics of WFS1 related diabetes in Chinese early onset type 2 diabetes.
Title: The genetic and clinical characteristics of WFS1 related diabetes in Chinese early onset type 2 diabetes.
Depletion of WFS1 compromises mitochondrial function in hiPSC-derived neuronal models of Wolfram syndrome.
Title: Depletion of WFS1 compromises mitochondrial function in hiPSC-derived neuronal models of Wolfram syndrome.
Genetic Variants of HNF4A, WFS1, DUSP9, FTO, and ZFAND6 Genes Are Associated with Prediabetes Susceptibility and Inflammatory Markers in the Saudi Arabian Population.
Title: Genetic Variants of HNF4A, WFS1, DUSP9, FTO, and ZFAND6 Genes Are Associated with Prediabetes Susceptibility and Inflammatory Markers in the Saudi Arabian Population.
Novel WFS1 mutations in patients with low-to-middle frequency hearing loss.
Title: Novel WFS1 mutations in patients with low-to-middle frequency hearing loss.

Submit: New GeneRIF Correction See all GeneRIFs (155)

Phenotypes

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Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Autosomal dominant nonsyndromic hearing loss 6 MedGen: C1833021 OMIM: 600965 GeneReviews: Genetic Hearing Loss Overview, WFS1 Spectrum Disorder	not available
Cataract 41 MedGen: C3805412 OMIM: 116400 GeneReviews: WFS1 Spectrum Disorder	not available
Type 2 diabetes mellitus MedGen: C0011860 OMIM: 125853 GeneReviews: WFS1 Spectrum Disorder	not available
Wolfram syndrome 1 MedGen: C4551693 OMIM: 222300 GeneReviews: WFS1 Spectrum Disorder	not available
Wolfram-like syndrome MedGen: C3280358 OMIM: 614296 GeneReviews: WFS1 Spectrum Disorder	not available

Copy number response

Description
Copy number response Haploinsufficency No evidence available (Last evaluated 2012-02-08) ClinGen Genome Curation Page Triplosensitivity No evidence available (Last evaluated 2012-02-08) ClinGen Genome Curation Page

EBI GWAS Catalog

Description
Genetic variant near IRS1 is associated with type 2 diabetes, insulin resistance and hyperinsulinemia. 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
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

D4S126 (e-PCR)
- UniSTS:147235

G01790 (e-PCR)
- UniSTS:11316

D4S3007 (e-PCR), detects polymorphism
- UniSTS:21865

D4S3023 (e-PCR), detects polymorphism
- UniSTS:9328

SHGC-59709 (e-PCR)
- UniSTS:79017

WI-21965 (e-PCR)
- UniSTS:26847

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ATPase binding	IPI Inferred from Physical Interaction more info	PubMed
enables DNA-binding transcription factor binding	IEA Inferred from Electronic Annotation more info
enables calcium-dependent protein binding	IEA Inferred from Electronic Annotation more info
enables calmodulin binding	IEA Inferred from Electronic Annotation more info
enables proteasome binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables ubiquitin protein ligase binding	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in ER overload response	IC Inferred by Curator more info	PubMed
involved_in ER overload response	TAS Traceable Author Statement more info	PubMed
involved_in ERAD pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in ERAD pathway	ISS Inferred from Sequence or Structural Similarity more info
involved_in calcium ion homeostasis	IBA Inferred from Biological aspect of Ancestor more info
involved_in calcium ion homeostasis	IDA Inferred from Direct Assay more info	PubMed
involved_in endoplasmic reticulum calcium ion homeostasis	IDA Inferred from Direct Assay more info	PubMed
involved_in endoplasmic reticulum unfolded protein response	IBA Inferred from Biological aspect of Ancestor more info
involved_in glucose homeostasis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in kidney development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of ATF6-mediated unfolded protein response	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of neuron apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of programmed cell death	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of response to endoplasmic reticulum stress	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of translation	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of type B pancreatic cell apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in nervous system process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in olfactory behavior	IEA Inferred from Electronic Annotation more info
involved_in pancreas development	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of ERAD pathway	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of calcium ion transport	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of growth	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of protein metabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of protein ubiquitination	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of protein ubiquitination	ISS Inferred from Sequence or Structural Similarity more info
involved_in protein maturation by protein folding	IC Inferred by Curator more info	PubMed
involved_in protein stabilization	IDA Inferred from Direct Assay more info	PubMed
involved_in protein stabilization	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in protein stabilization	ISS Inferred from Sequence or Structural Similarity more info
involved_in protein stabilization	TAS Traceable Author Statement more info	PubMed
involved_in renal water homeostasis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in response to endoplasmic reticulum stress	IDA Inferred from Direct Assay more info	PubMed
involved_in sensory perception of sound	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in visual perception	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
located_in dendrite	ISS Inferred from Sequence or Structural Similarity more info	PubMed
located_in endoplasmic reticulum	IDA Inferred from Direct Assay more info	PubMed
located_in endoplasmic reticulum	ISS Inferred from Sequence or Structural Similarity more info
located_in endoplasmic reticulum lumen	TAS Traceable Author Statement more info
is_active_in endoplasmic reticulum membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in endoplasmic reticulum membrane	IDA Inferred from Direct Assay more info	PubMed
located_in endoplasmic reticulum membrane	NAS Non-traceable Author Statement more info	PubMed
located_in endoplasmic reticulum membrane	TAS Traceable Author Statement more info
located_in secretory granule	IDA Inferred from Direct Assay more info	PubMed
located_in synaptic vesicle membrane	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: wolframin

Names: Wolfram syndrome 1 (wolframin)

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.