LYRM4
Chr 6ARLYR motif containing 4
Also known as: C6orf149, CGI-203, COXPD19, ISD11
This protein stabilizes the core iron-sulfur cluster assembly complex and regulates the cysteine desulfurase activity of NFS1, participating in the synthesis of [2Fe-2S] clusters essential for mitochondrial and cytoplasmic iron-sulfur protein biogenesis. Mutations cause autosomal recessive defects in iron-sulfur cluster assembly, leading to mitochondrial dysfunction affecting multiple organ systems. The gene shows moderate constraint against loss-of-function variants, consistent with its essential role in cellular iron metabolism.
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 (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative 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
LYRM4 · 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
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools