RAB5IF
Chr 20ARRAB5 interacting factor
Also known as: C20orf24, CFSMR2, OPTI, PNAS-11, RCAF1, RIP5
The protein is a component of the multi-pass translocon complex that mediates insertion of multi-pass membrane proteins into the ER membrane and acts as an assembly factor for mitochondrial respiratory complexes. Autosomal recessive mutations cause craniofacial dysmorphism, skeletal anomalies, and impaired intellectual development syndrome 2. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.602), and the condition involves craniofacial, skeletal, and neurodevelopmental systems.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
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
RAB5IF · 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