RBM44
Chr 2RNA binding motif protein 44
RBM44 encodes a protein that functions as a component of intercellular bridges during meiosis, structures that connect differentiating germ cells, and is predicted to be involved in mRNA splicing via the spliceosome. Pathogenic variants in RBM44 cause neurodevelopmental disorder with seizures and nonepileptic paroxysms, which follows an autosomal dominant inheritance pattern. This gene is highly constrained against loss-of-function variants, indicating intolerance to protein-truncating mutations.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
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
231 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 | 0 | 0 | 78 | 0 | 78 |
Likely Pathogenic | 0 | 0 | 1 | 0 | 1 |
VUS | 0 | 121 | 10 | 0 | 131 |
Likely Benign | 0 | 15 | 0 | 1 | 16 |
Benign | 0 | 0 | 0 | 0 | 0 |
| Total | 0 | 136 | 89 | 1 | 226 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
RBM44 · 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