SAG

S-antigen visual arrestin, the group of Classical arrestins

Basic information

Region (hg38): 2:233307815-233347055

Links

ENSG00000130561

∙ NCBI:6295 ∙ OMIM:181031 ∙ HGNC:10521 ∙ Uniprot:P10523 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed

Phenotypes

GenCC

Source: genCC

retinitis pigmentosa (Supportive), mode of inheritance: AD
Oguchi disease (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Retinitis pigmentosa 96; Retinitis pigmentosa 47; Oguchi disease 1	AD/AR	General	Manifesting heterozygotes have been described; 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	7670478; 9565049; 21447990; 21494281; 21987685; 22665972; 28549094; 33047631

ClinVar

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

not provided (363 variants)
Oguchi disease (54 variants)
Retinitis pigmentosa (50 variants)
not specified (10 variants)
Retinal dystrophy (6 variants)
Oguchi disease-1 (5 variants)
Inborn genetic diseases (5 variants)
Retinitis pigmentosa 47 (3 variants)
Oguchi disease-1;Retinitis pigmentosa 47 (2 variants)
Oguchi disease-2 (2 variants)
Retinitis pigmentosa 47;Oguchi disease-1 (2 variants)
Cone dystrophy (1 variants)
SAG-Related Disorders (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SAG gene is commonly pathogenic or not.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	55	4	60
missense	1		153	8	6	168
nonsense	6					6
start loss						0
frameshift	7	1	2			10
inframe indel			1			1
splice variant	2	10	13	17	3	45
non coding			8	42	40	90
Total	16	11	178	122	53

Highest pathogenic variant AF is 0.000460

Variants in SAG

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

Position	Phenotype	Significance	ClinVar
2-233307828-C-G	Oguchi disease • Retinitis pigmentosa	Conflicting interpretations of pathogenicity (Jan 13, 2018)	link
2-233307982-G-A	Oguchi disease • Retinitis pigmentosa	Conflicting interpretations of pathogenicity (Jan 13, 2018)	link
2-233309152-A-G	Oguchi disease • Retinitis pigmentosa	Uncertain significance (Jan 13, 2018)	link
2-233309179-G-A	Oguchi disease • Retinitis pigmentosa	Uncertain significance (Jan 13, 2018)	link
2-233309185-A-G		Uncertain significance (Nov 25, 2022)	link
2-233309195-A-G		Likely benign (Jul 12, 2022)	link
2-233309201-C-T		Likely benign (Jun 10, 2022)	link
2-233309202-G-A		Uncertain significance (Aug 09, 2022)	link
2-233309206-A-G		Uncertain significance (Jun 27, 2022)	link
2-233309213-C-T		Uncertain significance (Jul 14, 2022)	link
2-233309219-C-T		Likely benign (Oct 13, 2022)	link
2-233309220-G-A	Retinitis pigmentosa • Oguchi disease	Conflicting interpretations of pathogenicity (Nov 01, 2022)	link
2-233309224-C-T		Likely benign (Nov 01, 2022)	link
2-233309225-G-A		Likely benign (Oct 01, 2022)	link
2-233309241-A-G		Uncertain significance (May 10, 2022)	link
2-233309253-C-T		Uncertain significance (Oct 03, 2022)	link
2-233309254-G-A		Uncertain significance (Jul 30, 2022)	link
2-233309256-G-C		Uncertain significance (Aug 23, 2022)	link
2-233309256-GACAAATCGGTGAGTGGTGC-G		Likely pathogenic (Aug 28, 2021)	link
2-233309263-C-A		Pathogenic (Nov 28, 2021)	link
2-233309263-C-T		Uncertain significance (Nov 01, 2022)	link
2-233309264-G-A	Cone dystrophy	Conflicting interpretations of pathogenicity (Aug 07, 2022)	link
2-233309271-G-T	Oguchi disease • Retinitis pigmentosa	Conflicting interpretations of pathogenicity (Oct 10, 2022)	link
2-233309276-A-C		Likely benign (Aug 20, 2022)	link
2-233309280-G-A		Likely benign (Sep 12, 2022)	link

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SAG	protein_coding	protein_coding	ENST00000409110	15	39240

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.49e-16	0.00634	124882	0	112	124994	0.000448

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.685	201	230	0.873	0.0000135	2613
Missense in Polyphen		73	86.476	0.84417		1029
Synonymous	1.04	81	93.9	0.863	0.00000602	767
Loss of Function	-0.101	24	23.5	1.02	0.00000123	281

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00197	0.00170
Ashkenazi Jewish	0.000398	0.000397
East Asian	0.000556	0.000552
Finnish	0.00	0.00
European (Non-Finnish)	0.000271	0.000265
Middle Eastern	0.000556	0.000552
South Asian	0.00102	0.00101
Other	0.000497	0.000493

dbNSFP

Source: dbNSFP

Function: FUNCTION: Binds to photoactivated, phosphorylated RHO and terminates RHO signaling via G-proteins by competing with G- proteins for the same binding site on RHO (By similarity). May play a role in preventing light-dependent degeneration of retinal photoreceptor cells (PubMed:9565049). {ECO:0000250|UniProtKB:P08168, ECO:0000305|PubMed:9565049}.;
Disease: DISEASE: Night blindness, congenital stationary, Oguchi type 1 (CSNBO1) [MIM:258100]: A non-progressive retinal disorder characterized by impaired night vision, often associated with nystagmus and myopia. Congenital stationary night blindness Oguchi type is an autosomal recessive form associated with fundus discoloration and abnormally slow dark adaptation. {ECO:0000269|PubMed:7670478}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Retinitis pigmentosa 47 (RP47) [MIM:613758]: A retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well. {ECO:0000269|PubMed:9565049}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway: Phototransduction - Homo sapiens (human);Signaling by GPCR;Signal Transduction;Visual signal transduction: Rods;G alpha (i) signalling events;Activation of the phototransduction cascade;Inactivation, recovery and regulation of the phototransduction cascade;The phototransduction cascade;Visual phototransduction;GPCR downstream signalling (Consensus)

Recessive Scores

pRec: 0.463

Intolerance Scores

loftool: 0.882
rvis_EVS: 0.29
rvis_percentile_EVS: 71.57

Haploinsufficiency Scores

pHI: 0.248
hipred: N
hipred_score: 0.331
ghis

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.591

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Sag
Phenotype: vision/eye 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); homeostasis/metabolism phenotype;

Gene ontology

Biological process: cell surface receptor signaling pathway;rhodopsin mediated signaling pathway;regulation of rhodopsin mediated signaling pathway;negative regulation of phosphoprotein phosphatase activity
Cellular component: photoreceptor outer segment;photoreceptor inner segment;cytosol;membrane
Molecular function: opsin binding;protein phosphatase inhibitor activity;phosphoprotein binding