NYX

Chr XXLR

nyctalopin

Also known as: CLRP, CSNB1, CSNB1A, CSNB4, NBM1

NYX encodes a small leucine-rich proteoglycan that functions as a scaffold for TRPM1 and GRM6 proteins and is required for TRPM1 trafficking to dendritic tips of ON-bipolar cells in the retina. Mutations cause X-linked congenital stationary night blindness type 1A, characterized by impaired night vision, nystagmus, myopia or hyperopia, and reduced visual acuity. This follows X-linked recessive inheritance, affecting primarily males with carrier females potentially having mild symptoms.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismXLRLOEUF 1.131 OMIM phenotype
Clinical SummaryNYX
🧬
Gene-Disease Validity (ClinGen)
NYX-related retinopathy · XLDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.13) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.13LOEUF
pLI 0.130
Z-score 1.39
OE 0.36 (0.151.13)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
2.11Z-score
OE missense 0.59 (0.510.69)
126 obs / 212.8 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.36 (0.151.13)
00.351.4
Missense OE0.59 (0.510.69)
00.61.4
Synonymous OE0.65
01.21.6
LoF obs/exp: 2 / 5.5Missense obs/exp: 126 / 212.8Syn Z: 2.77
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveNYX-related congenital stationary night blindnessLOFXLR
DN
0.6745th %ile
GOF
0.78top 25%
LOF
0.3261th %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.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

NYX · 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 →