NDP

Chr XXLDXLR

norrin cystine knot growth factor NDP

Also known as: EVR2, FEVR, ND

NCBI Gene: 4693ENSG00000124479UniProt: Q00604

This gene encodes a secreted protein with a cystein-knot motif that activates the Wnt/beta-catenin pathway. The protein forms disulfide-linked oligomers in the extracellular matrix. Mutations in this gene result in Norrie disease and X-linked exudative vitreoretinopathy. [provided by RefSeq, Feb 2009]

Primary Disease Associations & Inheritance

Exudative vitreoretinopathy 2, X-linkedMIM #305390
XLDXLR
Norrie diseaseMIM #310600
XLR
UniProtVitreoretinopathy, exudative 2
0
Active trials
161
Pathogenic / LP
295
ClinVar variants
60
Pubs (1 yr)
1.0
Missense Z
0.88
LOEUF
Clinical Summary— NDP
🧬
Gene-Disease Validity (ClinGen)
Norrie disease · XLDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.65) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
161 Pathogenic / Likely Pathogenic· 73 VUS of 295 total submissions
📖
GeneReview available — NDP
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint
0.88LOEUF
pLI 0.650
Z-score 1.71
OE 0.00 (0.00–0.88)
Moderately constrained

Typical tolerance to LoF variation

Missense Constraint
0.97Z-score
OE missense 0.62 (0.46–0.83)
31 obs / 50.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.00 (0.00–0.88)
0≤0.351.4
Missense OE0.62 (0.46–0.83)
0≤0.61.4
Synonymous OE1.21
0≤1.21.6
LoF obs/exp: 0 / 3.4Missense obs/exp: 31 / 50.4Syn Z: -0.76

ClinVar Variant Classifications

295 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic126
Likely Pathogenic35
VUS73
Likely Benign41
Benign12
Conflicting8
126
Pathogenic
35
Likely Pathogenic
73
VUS
41
Likely Benign
12
Benign
8
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
10
12
104
0
126
Likely Pathogenic
7
19
9
0
35
VUS
1
51
21
0
73
Likely Benign
0
1
16
24
41
Benign
0
1
9
2
12
Conflicting
—8
Total188415926295

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

View in ClinVar →

NDP · protein map & ClinVar variants

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

Gene2Phenotype Curations

NDP-related Norrie disease

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

NDP-related exudative vitreoretinopathy

definitive
Monoallelic X HemizygousUndeterminedAltered Gene Product Structure
Eye
G2P ↗
missense variantinframe deletioninframe insertion

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Landmark / reviewRecent case evidence
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients