GPR179

Chr 17AR

G protein-coupled receptor 179

Also known as: CSNB1E, GPR158L, GPR158L1

NCBI Gene: 440435 ENSG00000277399 UniProt: Q6PRD1

This gene encodes a member of the glutamate receptor subfamily of G protein-coupled receptors. The encoded protein has an EGF-like calcium binding domain and a seven transmembrane domain in the N-terminal region of the protein. Mutations in this gene are associated with congenital stationary night blindness type 1E. [provided by RefSeq, Apr 2012]

Primary Disease Associations & Inheritance

Night blindness, congenital stationary (complete), 1E, autosomal recessiveMIM #614565

Active trials

Pathogenic / LP

398

ClinVar variants

Pubs (1 yr)

0.8

Missense Z

0.82

LOEUF

Clinical Summary— GPR179

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Gene-Disease Validity (ClinGen)

GPR179-related retinopathy · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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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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ClinVar Variants

13 Pathogenic / Likely Pathogenic· 231 VUS of 398 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.

0.82LOEUF

pLI 0.000

Z-score 2.95

OE 0.66 (0.53–0.82)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.

0.84Z-score

OE missense 0.94 (0.89–0.98)

1225 obs / 1310.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.

LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.66 (0.53–0.82)

0≤0.351.4

Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.94 (0.89–0.98)

0≤0.61.4

Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.97

0≤1.21.6

LoF obs/exp: 56 / 85.5Missense obs/exp: 1225 / 1310.1Syn Z: 0.55

0.6455th %ile

GOF

0.6833th %ile

LOF

0.3066th %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.