RS1

retinoschisin 1

Basic information

Region (hg38): X:18639688-18672108

Previous symbols: [ "RS" ]

Links

ENSG00000102104 ∙ NCBI:6247 ∙ OMIM:300839 ∙ HGNC:10457 ∙ Uniprot:O15537 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

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

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 (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)
• CDKL5-related_disorder (4 variants)
• History_of_neurodevelopmental_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.

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

Highest pathogenic variant AF is 0.000020059942

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

• 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