RMC1

Chr 18

regulator of MON1-CCZ1

Also known as: C18orf8, HsT2591, MIC1, Mic-1, WDR98

NCBI Gene: 29919ENSG00000141452UniProt: Q96DM3

This protein functions as a component of the CCZ1-MON1 RAB7A guanine exchange factor complex, acting as a positive regulator necessary for endosomal and autophagic flux and efficient RAB7A localization. Mutations cause autosomal recessive neurodegeneration with brain iron accumulation, typically presenting in childhood with progressive movement disorders and cognitive decline. The gene is highly constrained against loss-of-function variants, indicating that functional copies are critical for normal cellular function.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
3
Pubs (1 yr)
36
P/LP submissions
0%
P/LP missense
0.30
LOEUF· LoF intol.
—
Mechanism
Clinical Summary— RMC1
⚡
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
34 unique Pathogenic / Likely Pathogenic· 16 VUS of 86 total submissions
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.30LOEUF
pLI 0.988
Z-score 5.19
OE 0.16 (0.09–0.30)
Highly constrained

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

Missense Constraint
1.74Z-score
OE missense 0.75 (0.68–0.82)
281 obs / 375.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.16 (0.09–0.30)
0≤0.351.4
Missense OE0.75 (0.68–0.82)
0≤0.61.4
Synonymous OE0.96
0≤1.21.6
LoF obs/exp: 7 / 44.3Missense obs/exp: 281 / 375.8Syn Z: 0.35

ClinVar Variant Classifications

86 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic33
Likely Pathogenic1
VUS16
Likely Benign4
Benign4
33
Pathogenic
1
Likely Pathogenic
16
VUS
4
Likely Benign
4
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
33
0
33
Likely Pathogenic
0
0
1
0
1
VUS
1
6
9
0
16
Likely Benign
0
1
2
1
4
Benign
0
0
0
4
4
Total1745558

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

View in ClinVar →

Protein Context — Lollipop Plot

RMC1 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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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 3 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