RS1

retinoschisin 1

Basic information

Region (hg38): X:18639688-18672108

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 (Strong), mode of inheritance: XL
  • X-linked retinoschisis (Definitive), mode of inheritance: XL
  • retinoschisis (Definitive), 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 (540 variants)
  • Juvenile_retinoschisis (176 variants)
  • Developmental_and_epileptic_encephalopathy,_2 (123 variants)
  • Angelman_syndrome-like (118 variants)
  • Retinal_dystrophy (97 variants)
  • not_specified (47 variants)
  • CDKL5_disorder (27 variants)
  • Inborn_genetic_diseases (26 variants)
  • Retinoschisis (11 variants)
  • RS1-related_disorder (7 variants)
  • History_of_neurodevelopmental_disorder (4 variants)
  • CDKL5-related_disorder (4 variants)
  • Atypical_Rett_syndrome (2 variants)
  • Peripheral_schisis (1 variants)
  • Macular_schisis (1 variants)
  • Epileptic_encephalopathy (1 variants)
  • West_syndrome (1 variants)
  • Nicolaides-Baraitser_syndrome (1 variants)
  • Developmental_and_epileptic_encephalopathy,_1 (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. These statistics are base on transcript: NM_000000330.4. Only rare variants are included in the table.

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.

EffectPLPVUSLBBSum
synonymous
1
clinvar
86
clinvar
5
clinvar
92
missense
76
clinvar
84
clinvar
106
clinvar
7
clinvar
4
clinvar
277
nonsense
34
clinvar
11
clinvar
4
clinvar
49
start loss
2
2
4
frameshift
41
clinvar
9
clinvar
10
clinvar
60
splice donor/acceptor (+/-2bp)
21
clinvar
7
clinvar
5
clinvar
33
Total 174 111 128 93 9

Highest pathogenic variant AF is 0.0000200599

Loading clinvar variants...

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