NYX

Chr XXLR

nyctalopin

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

NCBI Gene: 60506ENSG00000188937UniProt: Q9GZU5

The product of this gene belongs to the small leucine-rich proteoglycan (SLRP) family of proteins. Defects in this gene are the cause of congenital stationary night blindness type 1 (CSNB1), also called X-linked congenital stationary night blindness (XLCSNB). CSNB1 is a rare inherited retinal disorder characterized by impaired scotopic vision, myopia, hyperopia, nystagmus and reduced visual acuity. The role of other SLRP proteins suggests that mutations in this gene disrupt developing retinal interconnections involving the ON-bipolar cells, leading to the visual losses seen in patients with complete CSNB. [provided by RefSeq, Oct 2008]

Primary Disease Associations & Inheritance

Night blindness, congenital stationary (complete), 1A, X-linkedMIM #310500
XLR
497
ClinVar variants
99
Pathogenic / LP
0.13
pLI score
0
Active trials
Clinical Summary— NYX
🧬
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.
📋
ClinVar Variants
99 Pathogenic / Likely Pathogenic· 284 VUS of 497 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.
1.13LOEUF
pLI 0.130
Z-score 1.39
OE 0.36 (0.15–1.13)
Tolerant

Highly tolerant — LoF variants common in population

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.
2.11Z-score
OE missense 0.59 (0.51–0.69)
126 obs / 212.8 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

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.0.36 (0.15–1.13)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.59 (0.51–0.69)
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.0.65
0≤1.21.6
LoF obs/exp: 2 / 5.5Missense obs/exp: 126 / 212.8Syn Z: 2.77

ClinVar Variant Classifications

497 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic80
Likely Pathogenic19
VUS284
Likely Benign99
Benign7
Conflicting8
80
Pathogenic
19
Likely Pathogenic
284
VUS
99
Likely Benign
7
Benign
8
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
18
1
61
0
80
Likely Pathogenic
5
8
6
0
19
VUS
3
259
22
0
284
Likely Benign
0
1
6
92
99
Benign
0
3
1
3
7
Conflicting
—8
Total262729695497

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View 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.

Gene2Phenotype Curations

NYX-related congenital stationary night blindness

definitive
Monoallelic X HemizygousLoss Of FunctionAbsent Gene Product
Dev. DisordersEye
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
NYCTALOPIN; NYX
MIM #300278 · *

Night blindness, congenital stationary (complete), 1A, X-linked

MIM #310500

Molecular basis of disorder known

X-linked recessive
📖
GeneReview available — NYX
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Cognitive Impairment in Parkinson's Disease: An Updated Overview Focusing on Emerging Pharmaceutical Treatment Approaches.
Degirmenci Y et al.·Medicina (Kaunas)
2023Review
The X-linked retinopathies: Physiological insights, pathogenic mechanisms, phenotypic features and novel therapies.
De Silva SR et al.·Prog Retin Eye Res
2021Review
A Description of the Yield of Genetic Reinvestigation in Patients with Inherited Retinal Dystrophies and Previous Inconclusive Genetic Testing.
Areblom M et al.·Genes (Basel)
2023Cohort
Familial Whole Exome Sequencing Study of 30 Families With Early-Onset High Myopia.
Yang E et al.·Invest Ophthalmol Vis Sci
2023
Congenital Stationary Night Blindness: Structure, Function and Genotype-Phenotype Correlations in a Cohort of 122 Patients.
Katta M et al.·Ophthalmol Retina
2024Cohort
NYX mutations in four families with high myopia with or without CSNB1.
Zhou L et al.·Mol Vis
2015
NYX-related Congenital Stationary Night Blindness in Two Siblings due to Probable Maternal Germline Mosaicism.
Scanga HL et al.·Ophthalmic Genet
2021Case report
Inherited Retinal Diseases with High Myopia: A Review.
Liu C et al.·Genes (Basel)
2025Review
Congenital Stationary Night Blindness: Clinical and Genetic Features.
Kim AH et al.·Int J Mol Sci
2022
Refractive Error in Inherited Retinal Disease.
Yassin SH et al.·Am J Ophthalmol
2025
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools