REM1

Chr 20

RRAD and GEM like GTPase 1

Also known as: GD:REM, GES

NCBI Gene: 28954ENSG00000088320UniProt: O75628

The REM1 protein is a RAS-like GTPase that promotes endothelial cell sprouting and reorganizes the actin cytoskeleton in endothelial cells, potentially functioning in angiogenesis and calcium signaling. Mutations cause autosomal recessive cerebroretinal microangiopathy with calcifications and cysts, a neurovascular disorder affecting the brain and retina. This gene is extremely intolerant to loss-of-function variants, indicating that complete loss of REM1 function is likely pathogenic.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
1
Pubs (1 yr)
16
P/LP submissions
0%
P/LP missense
1.44
LOEUF
Multiple*
Mechanism· predicted
Clinical Summary— REM1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
16 unique Pathogenic / Likely Pathogenic· 55 VUS of 92 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.44LOEUF
pLI 0.000
Z-score 0.38
OE 0.89 (0.57–1.44)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.67Z-score
OE missense 0.86 (0.76–0.98)
169 obs / 195.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.89 (0.57–1.44)
0≤0.351.4
Missense OE0.86 (0.76–0.98)
0≤0.61.4
Synonymous OE0.94
0≤1.21.6
LoF obs/exp: 12 / 13.5Missense obs/exp: 169 / 195.4Syn Z: 0.41
DN
0.75top 25%
GOF
0.73top 25%
LOF
0.3939th %ile

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.

DNprediction above median
GOFprediction above median

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

92 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic10
Likely Pathogenic6
VUS55
Likely Benign8
Benign1
10
Pathogenic
6
Likely Pathogenic
55
VUS
8
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
10
0
10
Likely Pathogenic
0
0
6
0
6
VUS
0
47
8
0
55
Likely Benign
0
2
6
0
8
Benign
0
1
0
0
1
Total05030080

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

View in ClinVar →

Protein Context — Lollipop Plot

REM1 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 4 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients