{{Rsnum
|rsid=10490924
|Gene=ARMS2
|Chromosome=10
|position=122454932
|Orientation=plus
|ReferenceAllele=G
|MissenseAllele=T
|GMAF=0.2736
|Assembly=GRCh38
|GenomeBuild=38.1
|dbSNPBuild=141
|Summary=age related macular degeneration
|geno1=(G;G)
|geno2=(G;T)
|geno3=(T;T)
|Gene_s=ARMS2
}}{{ population diversity
| geno1=(G;G)
| geno2=(G;T)
| geno3=(T;T)
| CEU | 61.1 | 38.1 | 0.9
| HCB | 28.5 | 56.9 | 14.6
| JPT | 38.9 | 43.4 | 17.7
| YRI | 56.5 | 38.8 | 4.8
| ASW | 57.9 | 40.4 | 1.8
| CHB | 28.5 | 56.9 | 14.6
| CHD | 33.0 | 53.2 | 13.8
| GIH | 41.6 | 45.5 | 12.9
| LWK | 49.1 | 40.9 | 10.0
| MEX | 51.7 | 43.1 | 5.2
| MKK | 49.4 | 44.9 | 5.8
| TSI | 71.6 | 28.4 | 0.0
| HapMapRevision=28
}}{{CPMC SNP
|link=https://cpmc.coriell.org/v/Report/TesticularCancer
}}

[[rs10490924]] was identified as a risk factor from chromosome 10 related to [[age related macular degeneration]]. The risk allele is (T). Odds ratios for heterozygotes and homozygotes are, respectively, 2.69 (CI: 2.22-3.27) and 8.21 (CI: 5.79-11.65).{{PMID|16174643}}

Disease risk in combination with the [[rs1061170]] SNP in the [[CFH]] gene is dramatically increased. Homozygotes for both the rare/risk alleles at both loci are estimated to be at 57 fold higher risk for [[age related macular degeneration]] than individuals homozygous for the common alleles at both loci. {{PMID|16174643}}

A subsequent study indicated that the risk based on solely the [[ARMS2]] SNP [[rs10490924]] is significantly higher in smokers than in non-smokers. {{PMID|16642439|OA=1
}}

Based on a study of ~750 patients, [[rs10490924]] is significantly higher in participants with choroidal neovascularization than in those with geographic atrophy (odds ratio 1.37, CI: 1.21-1.54, p = 4.2 × 10(-7)).{{PMID|21122828|OA=1
}}

Note that this SNP is completely predictive (ie is in perfect linkage disequilibrium) with [[rs11200638]], thus the status of one predicts the status of the other.

{{PMID|17884985|OA=1
}} A likely biological mechanism is that the A69S change in the LOC387715/ARMS2 protein affects its presumptive function in mitochondria.

{{PMID|18164066}} [[rs10490924]] and [[rs11200638]] defined 2 significant haplotypes associated with increased risk of neovascular AMD.

{{PMID|18400199}} In comparison with wild-type homozygosity (G;G), homozygosity for the at-risk allele genotype (T;T) increased the likelihood for polypoidal choroidal vasculopathy (PCV) 8.4-fold (CI: 3.6-19.5) and heterozygosity for the at-risk allele genotype (G;T) increased the risk for PCV 4x (CI: 1.9-8.4), based on a study of ~100 Japanese patients.

{{PMID|18682806|OA=1
}} An analysis of the joint effects of [[rs1061170]], [[rs11200638]] and [[rs10490924]] on [[AMD]]

{{ neighbor
| rsid = 11200638
| distance = 6096
}}

{{PMID Auto
|PMID=19268887
|Title=ARMS2 (LOC387715) Variants in Japanese Patients with Exudative Age-related Macular Degeneration and Polypoidal Choroidal Vasculopathy.
}}
{{PMID Auto
|PMID=19259132
|Title=Multilocus analysis of age-related macular degeneration.
|OA=1
}}
{{PMID Auto
|PMID=19255159
|Title=Age-Related Macular Degeneration Associated ARMS2 is not a Mitochondrial but Cytosolic Protein.
|OA=1
}}

{{omim
|id=611313
|desc=LOC387715 GENE
|rsnum=10490924
}}

{{omim
|id=610149
|desc=MACULAR DEGENERATION, AGE-RELATED, 7; ARMD7
|rsnum=10490924
}}

{{omim
|id=602194
|desc=HTRA SERINE PEPTIDASE 1; HTRA1
|rsnum=10490924
}}
{{PMID Auto
|PMID=19680273
|Title=ARMS2/HTRA1 and CFH polymorphisms are not associated with choroidal neovascularization in highly myopic eyes of the elderly Japanese population
}}
{{PMID Auto
|PMID=19797206
|Title=Susceptibility genes and progression in age-related maculopathy - a study of single eyes. The prospective Muenster Ageing and Retina Study (MARS)
}}
{{PMID Auto
|PMID=19796758
|Title=Comprehensive Analysis of Complement Factor H and LOC387715/ARMS2/HTRA1 Variants with Respect to Phenotype in Advanced Age-related Macular Degeneration
|OA=1
}}
{{PMID Auto
|PMID=19491722
|Title=Analyses of single nucleotide polymorphisms and haplotype linkage of LOC387715 and the HTRA1 gene in exudative age-related macular degeneration in a Chinese cohort
}}
{{PMID Auto
|PMID=19898184
|Title=Angiographic lesion size associated with loc387715 a69s genotype in subfoveal polypoidal choroidal vasculopathy
}}

{{PMID Auto
|PMID=19933195
|Title=Analysis of six genetic risk factors highly associated with AMD in the region surrounding ARMS2 and HTRA1 on chromosome 10q26
}}

{{PharmGKB
|RSID=rs10490924
|Name_s=
|Gene_s=ARMS2, HTRA1
|Feature=
|Evidence=PubMed ID:17053109
|Annotation=In confirmation of other studies, rs10490924 was found to be significantly associated with risk of Age-related Macular degeneration in a Caucasian (White) case-control study.
|Drugs=
|Drug Classes=
|Diseases=Macular Degeneration
|Curation Level=Curated
|PharmGKB Accession ID=PA161889387
}}

{{PMID Auto
|PMID=20157352
|Title=Genetic analysis of typical wet-type age-related macular degeneration and polypoidal choroidal vasculopathy in Japanese population
|OA=1
}}

{{PMID Auto
|PMID=20182747
|Title=Analysis of the indel at the ARMS2 3'UTR in age-related macular degeneration
|OA=1
}}

{{PMID Auto
|PMID=20381870
|Title=Progression of Geographic Atrophy and Genotype in Age-Related Macular Degeneration
|OA=1
}}
{{PMID Auto GWAS
|PMID=20385826
|Trait=Age-related macular degeneration
|Title=Genome-wide association study of advanced age-related macular degeneration identifies a role of the hepatic lipase gene (LIPC)
|RiskAllele=
|Pval=5E-119
|OR=None
|ORtxt=None
|OA=1
}}
{{PMID Auto
|PMID=20664795
|Title=R102G polymorphism of the C3 gene associated with exudative age-related macular degeneration in a French population
|OA=1
}}
{{PMID Auto
|PMID=20688737
|Title=Joint Effect of Cigarette Smoking, CFH and LOC387715/HTRA1 Polymorphisms on Polypoidal Choroidal Vasculopathy
}}
{{PMID Auto GWAS
|PMID=20861866
|Trait=None
|Title=Genome-wide association identifies SKIV2L and MYRIP as protective factors for age-related macular degeneration
|RiskAllele=T
|Pval=1E-60
|OR=2.75
|ORtxt=[NR]
|OA=1
}}
{{PMID Auto
|PMID=21067572
|Title=Association Analysis of Nine Candidate Gene Polymorphisms in Indian Patients with Type 2 Diabetic Retinopathy
|OA=1
}}

{{omim
|id=611313
|rsnum=10490924
|variant=0001
}}

{{PMID Auto
|PMID=21621535
|Title=No association between the T280M polymorphism of the CX3CR1 gene and exudative AMD
}}

{{PMID Auto GWAS
|PMID=21665990
|Trait=None
|Title=Common variants near FRK/COL10A1 and VEGFA are associated with advanced age-related macular degeneration.
|RiskAllele=T
|Pval=0
|OR=2.9400
|ORtxt=[NR]
|OA=1
}}

{{PMID Auto
|PMID=21825189
|Title=Complement Factor H 402H Variant and Reticular Macular Disease
|OA=1
}}

{{PMID Auto
|PMID=21878851
|Title=ASSOCIATION BETWEEN HIGH-RISK DISEASE LOCI AND RESPONSE TO ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR TREATMENT FOR WET AGE-RELATED MACULAR DEGENERATION
}}

{{PMID Auto
|PMID=21882634
|Title=[Influence of genetic mutations on clinical presentation of subretinal neovascularization. Report 2: The impact of HTRA and VEGF genes polymorphism]
}}

{{PMID Auto
|PMID=22049084
|Title=HTRA1 regulates angiogenesis through TGF-? family member GDF6
|OA=1
}}

{{PMID Auto
|PMID=22509112
|Title=Genetic associations in polypoidal choroidal vasculopathy: A systematic review and meta-analysis
|OA=1
}}

{{PMID Auto
|PMID=22552255
|Title=Retinal function and CFH-ARMS2 polymorphisms analysis: a pilot study in Italian AMD patients
}}

{{PMID Auto
|PMID=21959923
|Title=Association of ARMS2/HTRA1 variants with polypoidal choroidal vasculopathy phenotype in a Korean population
}}

{{PMID Auto
|PMID=22594510
|Title=Association of genetic polymorphisms with response to bevacizumab for neovascular age-related macular degeneration in the Chinese population
}}

{{PMID Auto
|PMID=22699975
|Title=Genetic analysis of simultaneous geographic atrophy and choroidal neovascularization
|OA=1
}}

{{ClinVar
|rsid=10490924
|Reversed=0
|FwdREF=G
|FwdALT=T
|REF=G
|ALT=T
|RSPOS=124214448
|CHROM=10
|GMAF=0.2734
|dbSNPBuildID=119
|SSR=0
|SAO=1
|VP=0x05016800000017051f130100
|GENEINFO=ARMS2:387715
|GENE_NAME=ARMS2
|GENE_ID=387715
|WGT=0
|VC=SNV
|CLNALLE=1
|CLNHGVS=NC_000010.10:g.124214448G>T
|CLNSRC=GTR; OMIM Allelic Variant
|CLNORIGIN=1
|CLNSRCID=GTR000325422; 611313.0001
|CLNSIG=255
|CLNCUI=C3151070
|CLNDBN=Age-related macular degeneration 8
|Disease=Age-related macular degeneration 8
|CLNACC=RCV000001030.2
|Tags=PM;PMC;SLO;VLD;G5A;G5;HD;GNO;KGPhase1;KGPilot123;KGPROD;OTHERKG;PH3;LSD;MTP;OM
|CAF=0.7264; 0.2736
|CLNDSDB=MedGen:OMIM
|CLNDSDBID=C3151070:613778
|COMMON=1
}}

{{PMID|16080115|OA=1
}} Susceptibility genes for age-related maculopathy on chromosome 10q26.

{{PMID|17210853}} Neovascular age-related macular degeneration and its association with LOC387715 and complement factor H polymorphism.

{{PMID|17325155|OA=1
}} The LOC387715 polymorphism and age-related macular degeneration: replication in three case-control samples.

{{PMID|17327825|OA=1
}} An update on the genetics of age-related macular degeneration.

{{PMID|17347568}} The LOC387715 gene, smoking, body mass index, environmental associations with advanced age-related macular degeneration.

{{PMID|17426452}} HTRA1 variant confers similar risks to geographic atrophy and neovascular age-related macular degeneration.

{{PMID|17438519|OA=1
}} HTRA1 promoter polymorphism predisposes Japanese to age-related macular degeneration.

{{PMID|17692272}} LOC387715/HTRA1 variants in polypoidal choroidal vasculopathy and age-related macular degeneration in a Japanese population.

{{PMID|17903296|OA=1
}} Genome-wide association with bone mass and geometry in the Framingham Heart Study.

{{PMID|17903296|OA=1
}} Genome-wide association with bone mass and geometry in the Framingham Heart Study.

{{PMID|17917691|OA=1
}} Genetic markers and biomarkers for age-related macular degeneration.

{{PMID|18043728|OA=1
}} Haplotypes in the complement factor H (CFH) gene: associations with drusen and advanced age-related macular degeneration.

{{PMID|18061132}} Phenotype analysis of patients with the risk variant LOC387715 (A69S) in age-related macular degeneration.

{{PMID|18079691}} PLEKHA1-LOC387715-HTRA1 polymorphisms and exudative age-related macular degeneration in the French population.

{{PMID|18162041|OA=1
}} Neovascular age-related macular degeneration risk based on CFH, LOC387715/HTRA1, and smoking.

{{PMID|18248681|OA=1
}} Prevalence of common disease-associated variants in Asian Indians.

{{PMID|18301036}} HTRA1 polymorphism in dry and wet age-related macular degeneration.

{{PMID|18423869}} CFH and LOC387715/ARMS2 genotypes and treatment with antioxidants and zinc for age-related macular degeneration.

{{PMID|18436811}} Variants in the 10q26 gene cluster (LOC387715 and HTRA1) exhibit enhanced risk of age-related macular degeneration along with CFH in Indian patients.

{{PMID|18493315|OA=1
}} C2 and CFB genes in age-related maculopathy and joint action with CFH and LOC387715 genes.

{{PMID|18515590}} Association analysis of CFH, C2, BF, and HTRA1 gene polymorphisms in Chinese patients with polypoidal choroidal vasculopathy.

{{PMID|18535016|OA=1
}} Rhesus monkeys and humans share common susceptibility genes for age-related macular disease.

{{PMID|18601744|OA=1
}} Combining identity by descent and association in genetic case-control studies.

{{PMID|18682812|OA=1
}} Association of CFH, LOC387715, and HTRA1 polymorphisms with exudative age-related macular degeneration in a northern Chinese population.

{{PMID|18688167}} Polymorphisms in the LOC387715/ARMS2 putative gene and the risk for Alzheimer's disease.

{{PMID|19026761|OA=1
}} Molecular pathology of age-related macular degeneration.

{{PMID|19048105|OA=1
}} Multifactor effects and evidence of potential interaction between complement factor H Y402H and LOC387715 A69S in age-related macular degeneration.

{{PMID|19065273|OA=1
}} Sequence variants in HTRA1 and LOC387715/ARMS2 and phenotype and response to photodynamic therapy in neovascular age-related macular degeneration in populations from Israel.

{{PMID|19169232}} Variations in five genes and the severity of age-related macular degeneration: results from the Muenster aging and retina study.

{{PMID|19202148|OA=1
}} Assessing susceptibility to age-related macular degeneration with proteomic and genomic biomarkers.

{{PMID|19661236|OA=1
}} Plasma complement components and activation fragments: associations with age-related macular degeneration genotypes and phenotypes.

{{PMID|19806217|OA=1
}} rs5888 variant of SCARB1 gene is a possible susceptibility factor for age-related macular degeneration.

{{PMID|19823576|OA=1
}} CFH, C3 and ARMS2 are significant risk loci for susceptibility but not for disease progression of geographic atrophy due to AMD.

{{PMID|19958499|OA=1
}} A particle swarm based hybrid system for imbalanced medical data sampling.

{{PMID|20140183|OA=1
}} Genetic and functional dissection of HTRA1 and LOC387715 in age-related macular degeneration.

{{PMID|20157618|OA=1
}} Complement component 3: an assessment of association with AMD and analysis of gene-gene and gene-environment interactions in a Northern Irish cohort.

{{PMID|20339564|OA=1
}} Risk factors for age-related maculopathy.

{{PMID|20346514|OA=1
}} C-reactive protein and CFH, ARMS2/HTRA1 gene variants are independently associated with risk of macular degeneration.

{{PMID|20378180|OA=1
}} Three major loci involved in age-related macular degeneration are also associated with polypoidal choroidal vasculopathy.

{{PMID|20456446}} LOC387715/HTRA1 polymorphisms, smoking and combined effects on exudative age-related macular degeneration in a Korean population.

{{PMID|20664794|OA=1
}} Age-related macular degeneration-associated variants at chromosome 10q26 do not significantly alter ARMS2 and HTRA1 transcript levels in the human retina.

{{PMID|20689796|OA=1
}} Monozygotic twins with polypoidal choroidal vasuculopathy.

{{PMID|20881291|OA=1
}} Persons with age-related maculopathy risk genotypes and clinically normal eyes have reduced mesopic vision.

{{PMID|21203342|OA=1
}} Elevated C-reactive protein levels and ARMS2/HTRA1 gene variants in subjects without age-related macular degeneration.

{{PMID|21397333}} Role of complement factor H I62V and age-related maculopathy susceptibility 2 A69S variants in the clinical expression of polypoidal choroidal vasculopathy.

{{PMID|21402993}} Assessing susceptibility to age-related macular degeneration with genetic markers and environmental factors.

{{PMID|21455292|OA=1
}} Using genetic variation and environmental risk factor data to identify individuals at high risk for age-related macular degeneration.

{{PMID|21896867}} Associations of complement factor H (CFH) and age-related maculopathy susceptibility 2 (ARMS2) genotypes with subtypes of polypoidal choroidal vasculopathy.

{{PMID|22293892|OA=1
}} A69S and R38X ARMS2 and Y402H CFH gene polymorphisms as risk factors for neovascular age-related macular degeneration in Poland - a brief report.

{{PMID|22491416}} Differentiation of exudative age-related macular degeneration and polypoidal choroidal vasculopathy in the ARMS2/HTRA1 locus.

{{PMID|22618592}} Association of genetic polymorphisms and age-related macular degeneration in chinese population.

{{PMID Auto GWAS
|PMID=22705344
|Trait=None
|Title=Heritability and Genome-Wide Association Study to Assess Genetic Differences between Advanced Age-Related Macular Degeneration Subtypes.
|RiskAllele=T
|Pval=0
|OR=3.6700
|ORtxt=None
|OA=1
}}

{{PMID Auto GWAS
|PMID=22694956
|Trait=None
|Title=Genome-wide association study of age-related macular degeneration identifies associated variants in the TNXB-FKBPL-NOTCH4 region of chromosome 6p21.3.
|RiskAllele=T
|Pval=3E-72
|OR=3.0000
|ORtxt=None
|OA=1
}}

{{PMID Auto
|PMID=22977134
|Title=Single nucleotide polymorphism in the cholesterol-24S-hydroxylase (CYP46A1) gene and its association with CFH and LOC387715 gene polymorphisms in AMD
}}

{{GET Evidence
|gene=ARMS2
|aa_change=Ala69Ser
|aa_change_short=A69S
|impact=pathogenic
|qualified_impact=Insufficiently evaluated pathogenic
|inheritance=unknown
|quality_scores=Array
|dbsnp_id=rs10490924
|overall_frequency_n=2100
|overall_frequency_d=10124
|overall_frequency=0.207428
|n_genomes=37
|n_genomes_annotated=0
|n_haplomes=44
|n_articles=3
|n_articles_annotated=3
|qualityscore_in_silico=1
|qualitycomment_in_silico=Y
|qualityscore_case_control=3
|qualityscore_severity=2
|gene_in_genetests=Y
|in_pharmgkb=Y
|genetests_testable=Y
|nblosum100=-1
|autoscore=3
|webscore=N
|n_web_uneval=10
|summary_short=associated wuth polypoidal choroidal vasculopathy (PCV) and age-related macular degeneration (AMD)
}}

{{PMID Auto
|PMID=23337555
|Title=Pharmacogenetics for Genes Associated with Age-Related Macular Degeneration in the Comparison of AMD Treatments Trials (CATT)
|OA=1
}}

{{PMID Auto
|PMID=23111182
|Title=Prevalence and genomic association of reticular pseudodrusen in age-related macular degeneration
}}

{{PMID Auto
|PMID=23302509
|Title=Mitochondrial DNA haplogroups confer differences in risk for age-related macular degeneration: a case control study
|OA=1
}}

{{PMID Auto
|PMID=23098369
|Title=ARMS2 increases the risk of early and late age-related macular degeneration in the European Eye Study
}}

{{PMID Auto
|PMID=23582991
|Title=Genetic Influences on the Outcome of Anti-Vascular Endothelial Growth Factor Treatment in Neovascular Age-related Macular Degeneration
}}

{{PMID Auto
|PMID=23644223
|Title=Variants at chromosome 10q26 locus and the expression of HTRA1 in the retina
}}

{{PMID Auto GWAS
  |PMID=23455636
  |Trait=Age-related macular degeneration
  |Title=Seven new loci associated with age-related macular degeneration.
  |RiskAllele=T
  |Pval=4E-540
  |OR=2.76
  |ORtxt=[2.72-2.80]
  |OA=1
}}

{{PMID Auto
|PMID=23938121
|Title=Associations of Candidate Genes to Age-Related Macular Degeneration Among Racial/Ethnic Groups in the Multi-Ethnic Study of Atherosclerosis
}}

{{PMID Auto GWAS
  |PMID=23577725
  |Trait=Age-related macular degeneration
  |Title=Genetic factors in nonsmokers with age-related macular degeneration revealed through genome-wide gene-environment interaction analysis.
  |RiskAllele=A
  |Pval=8E-27
  |OR=2.28
  |ORtxt=[1.96-2.65]
  |OA=1
}}

{{PMID Auto
|PMID=24332537
|Title=Incidence and Progression of Reticular Drusen in Age-Related Macular Degeneration: Findings from an Older Australian Cohort
}}

{{PMID Auto
|PMID=23103884
|Title=Age-related macular degeneration and coronary heart disease: evaluation of genetic and environmental associations.
}}

{{PMID Auto
|PMID=23204795
|Title=Pharmacogenetic influence of LOC387715/HTRA1 on the efficacy of bevacizumab treatment for age-related macular degeneration in a Korean population.
|OA=1
}}

{{PMID Auto
|PMID=23289807
|Title=Gene-gene interactions of CFH and LOC387715/ARMS2 with Korean exudative age-related macular degeneration patients.
}}

{{PMID Auto
|PMID=23289808
|Title=The association of age-related maculopathy susceptibility 2 (ARMS2) and complement factor H (CFH) variants with two angiographic subtypes of polypoidal choroidal vasculopathy.
}}

{{PMID Auto
|PMID=24865190
|Title=Association of Specific Genetic Polymorphisms with Age-related Macular Degeneration in a Northern Chinese Population
}}

{{PMID Auto
|PMID=24865191
|Title=Genetic Variants in the SKIV2L Gene in Exudative Age-related Macular Degeneration in the Japanese Population
}}

{{PMID Auto
|PMID=24970616
|Title=The contribution of genetic factors to phenotype and progression of drusen in early age-related macular degeneration
}}

{{PMID Auto
|PMID=24067115
|Title=Functional effect of Saffron supplementation and risk genotypes in early age-related macular degeneration: a preliminary report
}}
{{on chip | 23andMe v2}}
{{on chip | 23andMe v3}}
{{on chip | 23andMe v4}}
{{on chip | Affy GenomeWide 6}}
{{on chip | HumanOmni1Quad}}