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 ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• retinitis pigmentosa (Supportive), mode of inheritance: AD
• Oguchi disease (Supportive), mode of inheritance: AR
• Oguchi disease-1 (Definitive), mode of inheritance: AR
• retinitis pigmentosa 47 (Definitive), mode of inheritance: AD
• Oguchi disease-1 (Strong), mode of inheritance: AR
• retinitis pigmentosa 96 (Strong), mode of inheritance: AD

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 (12 variants)
• Oguchi disease (7 variants)
• Retinitis pigmentosa 47 (3 variants)
• Retinal dystrophy (3 variants)
• Oguchi disease-1 (2 variants)
• SAG-related disorder (2 variants)
• Oguchi disease-2 (2 variants)
• Oguchi disease-1;Retinitis pigmentosa 47 (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.

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			5	52	4	61
missense	1		178	1	3	183
nonsense	7	1				8
start loss						0
frameshift	7		2			9
inframe indel			1			1
splice donor/acceptor (+/-2bp)	2	15	1			18
splice region			12	14	2	28
non coding			11	47	41	99
Total	17	16	198	100	48

Highest pathogenic variant AF is 0.000197

Variants in SAG

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

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

Position	Type	Phenotype	Significance	ClinVar
2-233307828-C-G		Oguchi disease • Retinitis pigmentosa	Conflicting classifications of pathogenicity (Jan 13, 2018)
2-233307982-G-A		Retinitis pigmentosa • Oguchi disease	Conflicting classifications of pathogenicity (Jan 13, 2018)
2-233309152-A-G		Oguchi disease • Retinitis pigmentosa	Uncertain significance (Jan 13, 2018)
2-233309179-G-A		Oguchi disease • Retinitis pigmentosa	Uncertain significance (Jan 13, 2018)
2-233309185-A-G			Uncertain significance (Nov 25, 2022)
2-233309194-C-T			Uncertain significance (Jan 18, 2023)
2-233309195-A-G			Likely benign (Dec 20, 2023)
2-233309201-C-T		Retinal dystrophy	Conflicting classifications of pathogenicity (Oct 01, 2023)
2-233309202-G-A			Uncertain significance (Aug 08, 2023)
2-233309206-A-G			Uncertain significance (Jul 12, 2023)
2-233309208-A-C			Uncertain significance (Jul 20, 2023)
2-233309213-C-T			Uncertain significance (Jul 14, 2022)
2-233309219-C-T			Likely benign (Oct 13, 2022)
2-233309220-G-A		Retinitis pigmentosa • Oguchi disease • SAG-related disorder	Conflicting classifications of pathogenicity (Jan 19, 2024)
2-233309224-C-T			Likely benign (Nov 10, 2023)
2-233309225-G-A		Retinal dystrophy	Conflicting classifications of pathogenicity (Oct 01, 2023)
2-233309241-A-G			Uncertain significance (May 10, 2022)
2-233309253-C-T			Uncertain significance (Dec 22, 2023)
2-233309254-G-A			Uncertain significance (Nov 17, 2023)
2-233309255-G-A			Likely benign (Jan 12, 2023)
2-233309256-G-C			Uncertain significance (Aug 23, 2022)
2-233309256-GACAAATCGGTGAGTGGTGC-G			Likely pathogenic (Nov 07, 2022)
2-233309263-C-A			Pathogenic (Nov 28, 2021)
2-233309263-C-T			Uncertain significance (Nov 19, 2023)
2-233309264-G-A		Cone dystrophy	Conflicting classifications of pathogenicity (Aug 07, 2022)

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

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