GPR143

Chr XXLRX-linked

G protein-coupled receptor 143

Also known as: NYS6, OA1

This protein functions as a G protein-coupled receptor for tyrosine, L-DOPA and dopamine that regulates melanosome biogenesis, organization and transport in pigment cells. Mutations cause X-linked recessive ocular albinism type 1 (Nettleship-Falls type) and congenital nystagmus, presenting as severe visual disorders affecting pigmentation and eye movement control. The gene is highly constrained against loss-of-function variation, indicating critical developmental importance.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismXLR/X-linkedLOEUF 0.372 OMIM phenotypes
Clinical SummaryGPR143
🧬
Gene-Disease Validity (ClinGen)
GPR143-related foveal hypoplasia · XLDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.93). One damaged copy is likely sufficient to cause disease.
📖
GeneReview available — GPR143
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.37LOEUF
pLI 0.925
Z-score 3.04
OE 0.08 (0.030.37)
Highly constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
0.88Z-score
OE missense 0.79 (0.680.93)
111 obs / 140.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.08 (0.030.37)
00.351.4
Missense OE0.79 (0.680.93)
00.61.4
Synonymous OE1.03
01.21.6
LoF obs/exp: 1 / 12.7Missense obs/exp: 111 / 140.3Syn Z: -0.16
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveGPR143-related ocular albinismLOFXLR
DN
0.4884th %ile
GOF
0.6736th %ile
LOF
0.53top 25%

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and loss-of-function). 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
LOFLOEUF 0.37

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. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

GPR143 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC