SAG

Chr 2ARAD

S-antigen visual arrestin

Also known as: RP47, RP96, S-AG

NCBI Gene: 6295 ENSG00000130561 UniProt: P10523 OMIM: 181031

S-arrestin binds to photoactivated, phosphorylated rhodopsin and terminates rhodopsin signaling by competing with G-proteins, playing a critical role in desensitizing the photoactivated transduction cascade in retinal photoreceptors. Mutations cause Oguchi disease (a form of congenital stationary night blindness) and retinitis pigmentosa, inherited in autosomal recessive or autosomal dominant patterns depending on the specific condition. The gene shows high constraint against loss-of-function variants, indicating intolerance to protein-disrupting mutations.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

Members of arrestin/beta-arrestin protein family are thought to participate in agonist-mediated desensitization of G-protein-coupled receptors and cause specific dampening of cellular responses to stimuli such as hormones, neurotransmitters, or sensory signals. S-arrestin, also known as S-antigen, is a major soluble photoreceptor protein that is involved in desensitization of the photoactivated transduction cascade. It is expressed in the retina and the pineal gland and inhibits coupling of rhodopsin to transducin in vitro. Additionally, S-arrestin is highly antigenic, and is capable of inducing experimental autoimmune uveoretinitis. Mutations in this gene have been associated with Oguchi disease, a rare autosomal recessive form of night blindness. [provided by RefSeq, Jul 2008]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Oguchi disease-1MIM #258100

Retinitis pigmentosa 47, autosomal recessiveMIM #613758

Retinitis pigmentosa 96, autosomal dominantMIM #620228

UniProtNight blindness, congenital stationary, Oguchi type 1

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · retinitis pigmentosa 47 · AR · ClinGen 2026

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

398

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.44

LOEUF

LOF

Mechanism· G2P

📖

GeneReview available — SAG

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.44LOEUF

pLI 0.000

Z-score -0.10

OE 1.02 (0.74–1.44)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.68Z-score

OE missense 0.87 (0.78–0.98)

201 obs / 230.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?1.02 (0.74–1.44)

0≤0.351.4

Missense OE?0.87 (0.78–0.98)

0≤0.61.4

Synonymous OE?0.86

0≤1.21.6

LoF obs/exp: 24 / 23.5Missense obs/exp: 201 / 230.2Syn Z: 1.04

Background carrier burden — how many people carry a rare variant somewhere in SAG?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 62

584 rare PASS variants

Rare truncating (LoF)

1 in 820

102 rare PASS variants

Rare synonymous (reference)

1 in 190

235 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for SAG. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 80	1 in 1,100
South Asian	~43k	1 in 64	1 in 400
Remaining (unassigned)	~30k	1 in 51	1 in 940
European (Finnish)	~27k	1 in 140	none seen
Admixed American	~22k	1 in 67	1 in 460
African / African American	~21k	1 in 52	1 in 1,400
East Asian	~20k	1 in 87	1 in 1,200
Ashkenazi Jewish	~13k	1 in 270	1 in 1,100
Middle Eastern	~2,884	1 in 110	≈ 1 in 720

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 11 of 15 coding exons well covered in gnomAD exomes; exons 3, 6, 9, 16 marginal. Genomes: all 15.? see exons ↓