RIMS2

Chr 8

regulating synaptic membrane exocytosis 2

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.

ResearchSummary from RefSeq, OMIM, UniProt

Rab effector involved in exocytosis. May act as scaffold protein. Plays a role in dendrite formation by melanocytes (PubMed:23999003)

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtCone-rod synaptic disorder syndrome, congenital non-progressive

Clinical highlights

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.21

LOEUF· LoF intol.

LOF

Mechanism· G2P

Some data sources returned errors (2)

ncbi: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi