{{Rsnum
|rsid=734312
|Gene=WFS1
|Chromosome=4
|position=6301627
|Orientation=plus
|ReferenceAllele=G
|MissenseAllele=A
|GMAF=0.4803
|Assembly=GRCh38
|GenomeBuild=38.1
|dbSNPBuild=141
|geno1=(A;A)
|geno2=(A;G)
|geno3=(G;G)
|Gene_s=WFS1
}}{{ population diversity
| geno1=(A;A)
| geno2=(A;G)
| geno3=(G;G)
| CEU | 38.9 | 52.2 | 8.8
| HCB | 76.3 | 23.0 | 0.7
| JPT | 69.9 | 28.3 | 1.8
| YRI | 0.0 | 0.7 | 99.3
| ASW | 3.5 | 35.1 | 61.4
| CHB | 76.3 | 23.0 | 0.7
| CHD | 67.6 | 29.6 | 2.8
| GIH | 22.0 | 56.0 | 22.0
| LWK | 0.9 | 4.6 | 94.4
| MEX | 52.6 | 36.8 | 10.5
| MKK | 0.6 | 10.3 | 89.1
| TSI | 27.5 | 48.0 | 24.5
| HapMapRevision=28
}}[[rs734312]], or '''His611Arg''', is a SNP located in exon 8 of the [[WFS1]] gene. An A at this SNP encodes for histamine and a G encodes for arginine.

A single study {{PMID|17719176}} found this SNP to be associated with medication overuse headache (sample consisting of 82 MOH patients). Compared to the His/His genotypes, those carrying two Arg alleles had a significantly higher monthly drug consumption (p = 0.00075) and higher severe depressive scores on the Beck Depression Index (p = 0.003).

His611Arg is also potentially implicated in [[type-2 diabetes]]. In a sample of 3,234 high diabetes risk individuals, Arg/Arg carriers had a generally higher insulinogenic index and lower insulin sensitivity levels, while His allele carriers followed the opposite pattern. Arg/Arg carriers also responded strongly to [[metformin]] and lifestyle changes, with significantly elevated insulinogenic levels (p = 0.007 for metformin, p = 0.06 for lifestyle changes) and normalized insulin sensitivity. {{PMID|18060660|OA=1
}} [[http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2483955 |Full Text]]

{{PMID|18568334}} His allele associated with estimates of decreased beta cell function in individuals with abnormal glucose regulation

{{Venter SNP
|rsid=734312
|allele=A
|frequency=0.717
|uid=1103654325528
|type=homozygous_SNP
|hugo=WFS1
|ensembl gene=ENSG00000109501
|ensembl transcript=ENST00000382615
|sift=AFFECT FUNCTION
|disease=Defects in WFS1 are the cause of Wolfram syndrome (WFS) (MIM:222300); also known as diabetes insipidus and mellitus with optic atrophy and deafness syndrome (DIDMOAD). It is a rare autosomal recessive disorder characterized by juvenile diabetes mellitus, diabetes insipidus, optic atrophy, deafness and various neurological symptoms.
}}

{{ neighbor
| rsid = 28937892
| distance = 321
}}
{{ neighbor
| rsid = 28937891
| distance = 252
}}

{{PMID Auto
|PMID=19258739
|Title=Association study of the effect of WFS1 polymorphisms on risk of type 2 diabetes in Japanese population
}}

{{PMID|18040659|OA=1
}} Replication of the association between variants in WFS1 and risk of type 2 diabetes in European populations.

{{PMID|18991055}} Association between polymorphisms in SLC30A8, HHEX, CDKN2A/B, IGF2BP2, FTO, WFS1, CDKAL1, KCNQ1 and type 2 diabetes in the Korean population.

{{PMID|19115052}} Common variations in 4p locus are related to male completed suicide.

{{PMID|19401414|OA=1
}} Confirmation of multiple risk Loci and genetic impacts by a genome-wide association study of type 2 diabetes in the Japanese population.

{{PMID|19741467}} Association of common type 2 diabetes risk gene variants and posttransplantation diabetes mellitus in renal allograft recipients in Korea.

{{PMID|21127832}} Decreased insulin secretion and increased risk of type 2 diabetes associated with allelic variations of the WFS1 gene: the Data from Epidemiological Study on the Insulin Resistance Syndrome (DESIR) prospective study.

{{GET Evidence
|gene=WFS1
|aa_change=Arg611His
|aa_change_short=R611H
|impact=not reviewed
|qualified_impact=Low clinical importance, Uncertain not reviewed
|inheritance=recessive
|quality_scores=Array
|dbsnp_id=rs734312
|overall_frequency_n=4308
|overall_frequency_d=10758
|overall_frequency=0.400446
|n_genomes=29
|n_genomes_annotated=0
|n_haplomes=41
|n_articles=1
|n_articles_annotated=1
|qualityscore_in_silico=4
|qualitycomment_in_silico=Y
|qualityscore_in_vitro=1
|qualitycomment_in_vitro=Y
|qualityscore_case_control=2
|qualitycomment_case_control=Y
|qualityscore_severity=3
|qualitycomment_severity=Y
|qualityscore_treatability=4
|qualitycomment_treatability=Y
|gene_in_genetests=Y
|pph2_score=0.99
|genetests_testable=Y
|genetests_reviewed=Y
|nblosum100=1
|autoscore=4
|n_web_uneval=9
|summary_short=This nonsynonymous SNP is associated with Wolfram Syndrome (known as DIDMOAD), which is characterized by early-onset non-autoimmune diabetes mellitus, diabetes insipidus, optic atrophy, and deafness) and to adult Type Two Diabetes Mellitus.  The WFS1 gene maps to chromosome 4p16.3.  The variant has been shown to be statistically associated with type II diabetes in six UK studies and one study of Ashkenazi Jews (Sandhu, M., et al., Minton et al.).
}}

{{PMID Auto
|PMID=23257691
|Title=Association of rs734312 and rs10010131 polymorphisms in WFS1 gene with type 2 diabetes mellitus: a meta-analysis
}}

{{PMID Auto
|PMID=24477584
|Title=Genetic association of IDE, POU2F1, PON1, IL1α and IL1β with type 2 diabetes in Pakistani population
}}
{{on chip | 23andMe v1}}
{{on chip | 23andMe v2}}
{{on chip | 23andMe v3}}
{{on chip | 23andMe v4}}
{{on chip | FTDNA2}}
{{on chip | HumanOmni1Quad}}
{{on chip | Illumina Human 1M}}