RIMS1

Chr 6

regulating synaptic membrane exocytosis 1

Also known as: CORD7, RAB3IP2, RIM, RIM1

NCBI Gene: 22999ENSG00000079841UniProt: Q86UR5

The protein encoded by this gene is a RAS gene superfamily member that regulates synaptic vesicle exocytosis. This gene also plays a role in the regulation of voltage-gated calcium channels during neurotransmitter and insulin release. Mutations have suggested a role cognition and have been identified as the cause of cone-rod dystrophy type 7. Multiple transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Mar 2012]

690
ClinVar variants
7
Pathogenic / LP
0.99
pLI score· haploinsufficient
1
Active trials
Clinical Summary— RIMS1
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.99). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
7 Pathogenic / Likely Pathogenic· 401 VUS of 690 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.28LOEUF
pLI 0.990
Z-score 7.38
OE 0.19 (0.14–0.28)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
2.01Z-score
OE missense 0.82 (0.77–0.87)
767 obs / 940.3 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.19 (0.14–0.28)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.82 (0.77–0.87)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.98
0≤1.21.6
LoF obs/exp: 19 / 97.7Missense obs/exp: 767 / 940.3Syn Z: 0.29

ClinVar Variant Classifications

690 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic4
Likely Pathogenic3
VUS401
Likely Benign269
Benign12
Conflicting1
4
Pathogenic
3
Likely Pathogenic
401
VUS
269
Likely Benign
12
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
4
0
4
Likely Pathogenic
1
0
2
0
3
VUS
6
352
39
4
401
Likely Benign
0
6
116
147
269
Benign
0
0
11
1
12
Conflicting
—1
Total7358172152690

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

RIMS1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

RIMS1-related cone-rod dystrophy

limited
ADUndeterminedAltered Gene Product Structure
Eye
G2P ↗
missense variantinframe deletioninframe insertion

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Precision risk stratification of primary gastric cancer after eradication of H. pylori by a DNA methylation marker: a multicentre prospective study.
Yamada H et al.·Gut
2025
A clinical and electrophysiological case study of a child with a novel frame shift mutation in the CACNA1F and missense variation of RIMS1 genes.
Weston P et al.·Doc Ophthalmol
2022Case report
Dominant Cone Rod Dystrophy, Previously Assigned to a Missense Variant in RIMS1, Is Fully Explained by Co-Inheritance of a Dominant Allele of PROM1.
Martin-Gutierrez MP et al.·Invest Ophthalmol Vis Sci
2022
Genome-wide association study in NSAID-induced acute urticaria/angioedema in Spanish and Han Chinese populations.
Cornejo-García JA et al.·Pharmacogenomics
2013Meta-analysis
The human cognition-enhancing CORD7 mutation increases active zone number and synaptic release.
Paul MM et al.·Brain
2022
RIM genes differentially contribute to organizing presynaptic release sites.
Kaeser PS et al.·Proc Natl Acad Sci U S A
2012
Whole exome sequencing identified genetic variations in Chinese hemangioblastoma patients.
Ma D et al.·Am J Med Genet A
2017Cohort
Whole Genome Messenger RNA Profiling Identifies a Novel Signature to Predict Gastric Cancer Survival.
Dai J et al.·Clin Transl Gastroenterol
2019
Clinical features and linkage analysis for a Chinese family with autosomal dominant central areolar choroidal dystrophy.
Ma K et al.·Chin Med J (Engl)
2009
Functional characteristics of patients with retinal dystrophy that manifest abnormal parafoveal annuli of high density fundus autofluorescence; a review and update.
Robson AG et al.·Doc Ophthalmol
2008Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
16P11.2 Deletion Syndrome16p11.2 Duplications1Q21.1 Deletion

Online Study of People Who Have Genetic Changes and Features of Autism: Simons Searchlight

RECRUITING
NCT01238250Simons SearchlightStarted 2010-10

External Resources

Links to major genomics databases and tools