RIMS2
Chr 8ARregulating synaptic membrane exocytosis 2
Also known as: CRSDS, OBOE, RAB3IP3, RIM2
RIMS2 encodes a presynaptic scaffold protein that regulates neurotransmitter release by interacting with RAB3 and other synaptic proteins involved in exocytosis. Biallelic mutations cause cone-rod synaptic disorder syndrome, a congenital nonprogressive condition affecting retinal photoreceptor synapses and leading to visual impairment from birth. This gene is highly constrained against loss-of-function variants (pLI ~1.0, LOEUF 0.21) and follows autosomal recessive inheritance.
Primary Disease Associations & Inheritance
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Mild missense constraint
Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.
The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.
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
294 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 | 1 | 0 | 43 | 0 | 44 |
Likely Pathogenic | 1 | 0 | 1 | 0 | 2 |
VUS | 1 | 191 | 11 | 1 | 204 |
Likely Benign | 0 | 3 | 7 | 9 | 19 |
Benign | 0 | 3 | 0 | 4 | 7 |
Conflicting | — | 2 | |||
| Total | 3 | 197 | 62 | 14 | 278 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
RIMS2 · 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