CRELD1
Chr 3ADARCRELD disulfide isomerase 1
Also known as: AVSD2, CIRRIN, JELANS
The CRELD1 protein functions as a protein disulfide isomerase and promotes acetylcholine receptor localization to the plasma membrane. Mutations cause atrioventricular septal defects (including partial defects with heterotaxy syndrome) and Jeffries-Lakhani neurodevelopmental syndrome, following both autosomal dominant and autosomal recessive inheritance patterns. This gene is not highly constrained against loss-of-function variants, indicating that complete protein loss may be tolerated in some contexts.
Limited evidence — not for standalone diagnostic reporting
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-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.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
CRELD1 · 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
External Resources
Links to major genomics databases and tools