RS1

retinoschisin 1

Basic information

Region (hg38): X:18639687-18672108

Previous symbols: [ "RS" ]

Links

ENSG00000102104

∙ NCBI:6247 ∙ OMIM:300839 ∙ HGNC:10457 ∙ Uniprot:O15537 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed

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

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Retinoschisis 1, X-linked, juvenile	XL	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Ophthalmologic	9326935; 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 (441 variants)
Juvenile retinoschisis (74 variants)
Developmental and epileptic encephalopathy, 2;Angelman syndrome-like (60 variants)
not specified (34 variants)
Retinal dystrophy (29 variants)
Angelman syndrome-like;Developmental and epileptic encephalopathy, 2 (26 variants)
Inborn genetic diseases (11 variants)
Developmental and epileptic encephalopathy, 2 (10 variants)
Retinoschisis (8 variants)
CDKL5 disorder (5 variants)
History of neurodevelopmental disorder (4 variants)
Atypical Rett syndrome (2 variants)
Epileptic encephalopathy (1 variants)
West syndrome (1 variants)
Nicolaides-Baraitser syndrome (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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous	1			57	4	62
missense	53	44	58	4	7	166
nonsense	18	9				27
start loss						0
frameshift	22	6	8			36
inframe indel	1	2				3
splice variant	12	7	10	9	2	40
non coding	2	2	48	71	27	150
Total	109	70	124	141	40

Highest pathogenic variant AF is 0.00000902

Variants in RS1

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

Position	Phenotype	Significance	ClinVar
X-18641857-TA-T		Benign (Oct 05, 2019)	link
X-18641996-GGCAGGCATCAGGCACACTTGCTGAC-G		not provided (-)	link
X-18642006-A-G	Juvenile retinoschisis	Likely pathogenic (Nov 04, 2016)	link
X-18642007-G-A		Likely benign (Oct 10, 2022)	link
X-18642011-C-T		Pathogenic (Jul 06, 2022)	link
X-18642012-A-C		Likely pathogenic (Aug 07, 2021)	link
X-18642012-A-G	Juvenile retinoschisis	Pathogenic (Sep 01, 2021)	link
X-18642013-C-G		not provided (-)	link
X-18642013-C-T		Likely benign (Jul 03, 2021)	link
X-18642015-T-TG		Uncertain significance (-)	link
X-18642018-T-C		Uncertain significance (Sep 12, 2022)	link
X-18642022-GC-CT		Pathogenic (Apr 09, 2022)	link
X-18642023-C-T		Pathogenic/Likely pathogenic (Mar 04, 2022)	link
X-18642023-CA-C		not provided (-)	link
X-18642024-A-C		not provided (-)	link
X-18642024-A-G	Retinal dystrophy	Pathogenic/Likely pathogenic (Aug 31, 2021)	link
X-18642025-C-G		Uncertain significance (Sep 24, 2021)	link
X-18642029-AG-A	Juvenile retinoschisis	Likely pathogenic (Jan 01, 2016)	link
X-18642031-C-T		Likely benign (Jul 23, 2022)	link
X-18642032-A-G	Retinal dystrophy	Pathogenic (Nov 19, 2018)	link
X-18642035-T-A		Pathogenic (Jan 02, 2022)	link
X-18642036-C-G		not provided (-)	link
X-18642036-C-T		not provided (-)	link
X-18642039-TC-T		Pathogenic (Jul 11, 2022)	link
X-18642041-C-A		Likely pathogenic (Jul 12, 2022)	link

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RS1	protein_coding	protein_coding	ENST00000379984	6	32200

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.957	0.0425	125608	0	1	125609	0.00000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.969	75	103	0.731	0.00000932	1450
Missense in Polyphen		20	36.677	0.5453		472
Synonymous	0.918	34	41.5	0.819	0.00000377	418
Loss of Function	2.91	0	9.88	0.00	6.29e-7	164

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000122	0.00000881
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

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

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

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