LRCH1
Chr 13leucine rich repeats and calponin homology domain containing 1
Also known as: CHDC1, NP81
This protein acts as a negative regulator of the GTPase CDC42 by sequestering the CDC42-guanine exchange factor DOCK8, thereby inhibiting CD4+ T-cell migration. Mutations in LRCH1 cause neurodevelopmental disorders with intellectual disability and variable features including autism spectrum disorder, seizures, and motor delays. The gene shows autosomal dominant inheritance and is highly constrained against loss-of-function variants (pLI 0.996, LOEUF 0.279).
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to loss-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
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. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
LRCH1 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools