NHS
Chr XXLDX-linkedNHS actin remodeling regulator
Also known as: CTRCT40, CXN
This gene encodes a protein containing four conserved nuclear localization signals. The encoded protein functions in eye, tooth, craniofacial and brain development, and it can regulate actin remodeling and cell morphology. Mutations in this gene have been shown to cause Nance-Horan syndrome, and also X-linked cataract-40. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, May 2014]
Primary Disease Associations & Inheritance
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Among the most LoF-intolerant genes (~top 3%)
Mild missense constraint
The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).
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
359 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 12 | 0 | 22 | 0 | 34 |
Likely Pathogenic | 10 | 0 | 3 | 0 | 13 |
VUS | 0 | 169 | 16 | 1 | 186 |
Likely Benign | 1 | 24 | 10 | 55 | 90 |
Benign | 0 | 11 | 4 | 16 | 31 |
Conflicting | — | 5 | |||
| Total | 23 | 204 | 55 | 72 | 359 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →NHS · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
Gene2Phenotype Curations
NHS-related Nance-Horan syndrome
definitiveGene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
The Effect of Time-Restricted Eating in Cardiometabolic Health
RECRUITINGHypertension in Children and Young People at Risk of Autosomal Dominant Polycystic Kidney Disease
RECRUITINGA Gene Transfer Study for Late-Onset Pompe Disease (RESOLUTE)
ACTIVE NOT RECRUITINGUnderstanding Beta Cell Disorders Through the Study of Rare Genotypes (ENDURE)
RECRUITINGGenetic Carbohydrate Maldigestion as a Model to Study Food Hypersensitivity
ACTIVE NOT RECRUITINGLentiviral Gene Therapy for p47 AR-CGD
RECRUITINGIntensive Weight Loss Intervention Versus Usual Care for Adults With Severe and Complex Obesity
RECRUITINGFrequency of Selected Single Nucleotide Polymorphisms in Huntington Disease Gene Expansion Carriers
RECRUITINGHCMR - Novel Markers of Prognosis in Hypertrophic Cardiomyopathy
ACTIVE NOT RECRUITINGNeuralNET Cerebral Palsy Pilot Study
ACTIVE NOT RECRUITINGEstablishing the Salience of Type 1 Interferon Pathway Blockade in the Central Mechanisms of SLE Related Fatigue
NOT YET RECRUITINGA Phase 1/2/3 Study of UX701 Gene Therapy in Adults With Wilson Disease
ACTIVE NOT RECRUITINGExternal Resources
Links to major genomics databases and tools