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GeneBe

RS1

retinoschisin 1

Basic information

Region (hg38): X:18639687-18672108

Previous symbols: [ "RS" ]

Links

ENSG00000102104NCBI:6247OMIM:300839HGNC:10457Uniprot:O15537AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

Phenotypes

GenCC

Source: genCC

  • X-linked retinoschisis (Definitive), mode of inheritance: XL
  • X-linked retinoschisis (Supportive), mode of inheritance: XL
  • X-linked retinoschisis (Definitive), mode of inheritance: XL
  • X-linked retinoschisis (Definitive), mode of inheritance: XL
  • X-linked retinoschisis (Strong), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Retinoschisis 1, X-linked, juvenileXLGeneralGenetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testingOphthalmologic9326935; 9618178; 10636740; 10533068; 10922205; 10636421; 15531314; 15937075; 17304551; 17172462; 17296904; 20061330; 25999676

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the RS1 gene.

  • not provided (458 variants)
  • Juvenile retinoschisis (77 variants)
  • Developmental and epileptic encephalopathy, 2;Angelman syndrome-like (46 variants)
  • Angelman syndrome-like;Developmental and epileptic encephalopathy, 2 (40 variants)
  • not specified (35 variants)
  • Retinal dystrophy (29 variants)
  • CDKL5 disorder (14 variants)
  • Inborn genetic diseases (11 variants)
  • Developmental and epileptic encephalopathy, 2 (10 variants)
  • Retinoschisis (7 variants)
  • History of neurodevelopmental disorder (4 variants)
  • RS1-related condition (2 variants)
  • Epileptic encephalopathy (1 variants)
  • Developmental and epileptic encephalopathy, 1;Developmental and epileptic encephalopathy, 2;Angelman syndrome-like (1 variants)
  • Atypical Rett syndrome (1 variants)
  • West syndrome (1 variants)
  • Nicolaides-Baraitser syndrome (1 variants)
  • CDKL5-related condition (1 variants)
  • Juvenile retinoschisis;Macular schisis;Peripheral schisis (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RS1 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
61
clinvar
4
clinvar
65
missense
52
clinvar
46
clinvar
56
clinvar
3
clinvar
6
clinvar
163
nonsense
20
clinvar
10
clinvar
30
start loss
2
clinvar
2
frameshift
21
clinvar
6
clinvar
27
inframe indel
1
clinvar
4
clinvar
5
splice donor/acceptor (+/-2bp)
13
clinvar
7
clinvar
20
splice region
1
10
10
2
23
non coding
1
clinvar
46
clinvar
74
clinvar
28
clinvar
149
Total 109 70 106 138 38

Highest pathogenic variant AF is 0.00000902

Variants in RS1

This is a list of pathogenic ClinVar variants found in the RS1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position Type Phenotype Significance ClinVar
X-18641857-TA-T Benign (Oct 05, 2019)1272473
X-18641996-GGCAGGCATCAGGCACACTTGCTGAC-G not provided (-)99017
X-18642002-C-A RS1-related condition Likely benign (Aug 28, 2019)3035108
X-18642006-A-G Juvenile retinoschisis Likely pathogenic (Nov 04, 2016)371642
X-18642007-G-A Likely benign (Jan 16, 2024)1161501
X-18642011-C-T Pathogenic (Jul 17, 2023)372497
X-18642012-A-C Likely pathogenic (Aug 07, 2021)1511265
X-18642012-A-G Juvenile retinoschisis Pathogenic (Jul 12, 2021)9893
X-18642013-C-G not provided (-)99019
X-18642013-C-T Likely benign (Jul 03, 2021)1672537
X-18642015-T-TG Uncertain significance (-)68078
X-18642018-T-C Uncertain significance (Jan 30, 2024)1404057
X-18642022-GC-CT Pathogenic (Apr 09, 2022)2123578
X-18642023-C-T Pathogenic/Likely pathogenic (Mar 04, 2022)1700721
X-18642023-CA-C not provided (-)99018
X-18642024-A-C not provided (-)99016
X-18642024-A-G Retinal dystrophy Pathogenic/Likely pathogenic (Jan 25, 2020)99015
X-18642025-C-G Uncertain significance (Jun 18, 2021)1476227
X-18642028-C-T Likely benign (Jan 16, 2023)2827585
X-18642029-AG-A Juvenile retinoschisis Likely pathogenic (Jan 01, 2016)931958
X-18642031-C-T Likely benign (Oct 17, 2023)1977141
X-18642032-A-G Retinal dystrophy Pathogenic (Mar 24, 2023)99014
X-18642035-T-A Pathogenic (Jan 02, 2022)1359440
X-18642036-C-G not provided (-)99013
X-18642036-C-T not provided (-)99012

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
RS1protein_codingprotein_codingENST00000379984 632200
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
0.9570.0425125608011256090.00000398
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense0.969751030.7310.000009321450
Missense in Polyphen2036.6770.5453472
Synonymous0.9183441.50.8190.00000377418
Loss of Function2.9109.880.006.29e-7164

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.000.00
Ashkenazi Jewish0.000.00
East Asian0.000.00
Finnish0.000.00
European (Non-Finnish)0.00001220.00000881
Middle Eastern0.000.00
South Asian0.000.00
Other0.000.00

dbNSFP

Source: dbNSFP

Function
FUNCTION: Binds negatively charged membrane lipids, such as phosphatidylserine and phosphoinositides (By similarity). May play a role in cell-cell adhesion processes in the retina, via homomeric interaction between octamers present on the surface of two neighboring cells (PubMed:27114531). Required for normal structure and function of the retina (PubMed:19093009). {ECO:0000250|UniProtKB:Q9Z1L4, ECO:0000269|PubMed:19093009, ECO:0000305|PubMed:27114531}.;
Disease
DISEASE: Retinoschisis juvenile X-linked 1 (XLRS1) [MIM:312700]: A vitreo-retinal dystrophy characterized by macular pathology and by splitting of the superficial layer of the retina. Macular changes are present in almost all cases. In the fundi, radially oriented intraretinal foveomacular cysts are seen in a spoke-wheel configuration, with the absence of foveal reflex in most cases. In addition, approximately half of cases have bilateral peripheral retinoschisis in the inferotemporal part of the retina. Aside from the typical fundus appearance, strabismus, nystagmus, axial hyperopia, defective color vision and foveal ectopy can be present. The most important complications are vitreous hemorrhage, retinal detachment, and neovascular glaucoma. {ECO:0000269|PubMed:10079181, ECO:0000269|PubMed:10220153, ECO:0000269|PubMed:10234514, ECO:0000269|PubMed:10450864, ECO:0000269|PubMed:10533068, ECO:0000269|PubMed:17304551, ECO:0000269|PubMed:17615541, ECO:0000269|PubMed:17631851, ECO:0000269|PubMed:19093009, ECO:0000269|PubMed:19849666, ECO:0000269|PubMed:27798099, ECO:0000269|PubMed:9326935, ECO:0000269|PubMed:9760195, ECO:0000269|Ref.14}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway
Rac1-Pak1-p38-MMP-2 pathway (Consensus)

Recessive Scores

pRec
0.230

Intolerance Scores

loftool
rvis_EVS
0.3
rvis_percentile_EVS
72.01

Haploinsufficiency Scores

pHI
0.245
hipred
Y
hipred_score
0.728
ghis
0.398

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
N
gene_indispensability_pred
E
gene_indispensability_score
0.575

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Rs1
Phenotype
vision/eye phenotype; pigmentation phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan);

Gene ontology

Biological process
cell adhesion;multicellular organism development;visual perception;retina layer formation;adaptation of rhodopsin mediated signaling;protein homooligomerization
Cellular component
extracellular space;extrinsic component of plasma membrane
Molecular function
phosphatidylserine binding;phosphatidylinositol-4,5-bisphosphate binding;phosphatidylinositol-3,4,5-trisphosphate binding;phosphatidylinositol-5-phosphate binding;phosphatidylinositol-3-phosphate binding;phosphatidylinositol-3,4-bisphosphate binding;phosphatidylinositol-4-phosphate binding;phosphatidylinositol-3,5-bisphosphate binding