OPN3

Chr 1

opsin 3

Also known as: ECPN, PPP1R116

NCBI Gene: 23596 ENSG00000054277 UniProt: Q9H1Y3 OMIM: 606695

Opsin 3 encodes a G protein-coupled receptor that functions as a non-visual photoreceptor, binding retinal and responding to ultraviolet A and blue light to regulate melanogenesis, food intake via hypothalamic signaling, and various cellular processes including apoptosis and metabolism. The gene shows low constraint against loss-of-function variants (pLI 0.001, LOEUF 0.89), and currently no established human diseases are associated with OPN3 mutations. This opsin is expressed in multiple tissues including brain, skin, and testis, distinguishing it from the visual opsins found in the eye.

OMIM ResearchSummary from RefSeq, UniProt

Opsins are members of the guanine nucleotide-binding protein (G protein)-coupled receptor superfamily. In addition to the visual opsins, mammals possess several photoreceptive non-visual opsins that are expressed in extraocular tissues. This gene, opsin 3, is strongly expressed in brain and testis and weakly expressed in liver, placenta, heart, lung, skeletal muscle, kidney, and pancreas. The gene may also be expressed in the retina. The protein has the canonical features of a photoreceptive opsin protein. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 0.89

Clinical Summary— OPN3

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.89LOEUF

pLI 0.001

Z-score 1.86

OE 0.48 (0.27–0.89)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.10Z-score

OE missense 0.79 (0.69–0.90)

168 obs / 213.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.48 (0.27–0.89)

0≤0.351.4

Missense OE?0.79 (0.69–0.90)

0≤0.61.4

Synonymous OE?0.99

0≤1.21.6

LoF obs/exp: 7 / 14.7Missense obs/exp: 168 / 213.0Syn Z: 0.07

This gene — mechanism propensity

0.77top 25%

GOF

0.83top 10%

LOF

0.2581th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.