NHS
Chr XXLDX-linkedNHS actin remodeling regulator
Also known as: CTRCT40, CXN
The NHS protein regulates actin remodeling and cell morphology, and controls development of the eye, teeth, brain, and craniofacial structures. Mutations cause Nance-Horan syndrome and X-linked cataract, both following X-linked inheritance patterns. This gene is highly constrained against loss-of-function variants (pLI 1.0, LOEUF 0.087), indicating that mutations typically have significant developmental consequences.
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
500 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 | 25 | 0 | 37 |
Likely Pathogenic | 16 | 0 | 1 | 0 | 17 |
VUS | 0 | 175 | 14 | 2 | 191 |
Likely Benign | 1 | 19 | 13 | 49 | 82 |
Benign | 0 | 6 | 10 | 10 | 26 |
Conflicting | — | 8 | |||
| Total | 29 | 200 | 63 | 61 | 361 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
NHS · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Scottish Advanced Fetal Research Study
RECRUITINGFollow-up Gene Therapy Trial for the Treatment of X-linked Retinitis Pigmentosa Associated With Variants in the RPGR Gene
ACTIVE NOT RECRUITINGThe BARCODE 2 Study - The Use of Genetic Profiling to Guide Prostate Cancer Treatment
ACTIVE NOT RECRUITINGMechanistic Study of Anti-Platelet Therapy in Atherosclerosis
NOT YET RECRUITINGMulti-omics Study in Citrin Deficiency
ACTIVE NOT RECRUITINGSafety and Efficacy of TSHA-102 in Pediatric Females With Rett Syndrome (REVEAL Pediatric Study)
ACTIVE NOT RECRUITINGStudy of RP3 Monotherapy and RP3 in Combination With Nivolumab in Patients With Solid Tumours
ACTIVE NOT RECRUITINGA Novel, Regulated Gene Therapy (NGN-401) Study for Females With Rett Syndrome
RECRUITINGA Study to Investigate the Safety and Effectiveness of a Coagulation Factor IX Gene Insertion Therapy (REGV131-LNP1265) in Pediatric, Adolescent and Adult Participants With Hemophilia B
RECRUITINGSusceptibility to Infectious Diseases in obEsity: an endocRine trAnslational socioLogic Evaluation, "SIDERALE"
RECRUITINGTrial of Perioperative Endocrine Therapy - Individualising Care
ACTIVE NOT RECRUITINGUnderstanding Beta Cell Disorders Through the Study of Rare Genotypes (ENDURE)
RECRUITINGExternal Resources
Links to major genomics databases and tools