RCC1

Chr 1AR

regulator of chromosome condensation 1

Also known as: CHC1, IIAAN, RCC1-I

NCBI Gene: 1104ENSG00000180198UniProt: P18754OMIM: 179710

This protein functions as a guanine-nucleotide exchange factor that promotes RAN-GTP formation, playing a critical role in nuclear import and mitotic spindle assembly. Mutations cause autosomal recessive infection-induced acute-onset axonal neuropathy. The gene is highly constrained against loss-of-function variants (pLI=0.93, LOEUF=0.36), reflecting its essential cellular functions.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.361 OMIM phenotype
Clinical Summary— RCC1
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.93). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
12 unique Pathogenic / Likely Pathogenic· 52 VUS of 77 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.36LOEUF
pLI 0.931
Z-score 3.72
OE 0.14 (0.06–0.36)
Highly constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.68Z-score
OE missense 0.72 (0.64–0.81)
201 obs / 280.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.14 (0.06–0.36)
0≤0.351.4
Missense OE0.72 (0.64–0.81)
0≤0.61.4
Synonymous OE0.95
0≤1.21.6
LoF obs/exp: 3 / 21.7Missense obs/exp: 201 / 280.3Syn Z: 0.39
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
moderateRCC1-related infection-induced acute-onset axonal neuropathy with cerebral and cerebellar atrophyLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.4289th %ile
GOF
0.4282th %ile
LOF
0.64top 25%

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

77 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic9
Likely Pathogenic3
VUS52
Likely Benign2
9
Pathogenic
3
Likely Pathogenic
52
VUS
2
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
2
7
0
9
Likely Pathogenic
0
3
0
0
3
VUS
0
45
7
0
52
Likely Benign
0
2
0
0
2
Benign
0
0
0
0
0
Total05214066

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

View in ClinVar →

Protein Context — Lollipop Plot

RCC1 · 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.

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
Acute-onset axonal neuropathy following infection in children with biallelic RCC1 variants: a case series.
Harkness JR et al.·Lancet Neurol
2025Cohort
HERC5/ISG15 Enhances Glioblastoma Stemness and Tumor Progression by mediating SERBP1protein stability.
Li Z et al.·Neuromolecular Med
2025
RCC1 functions as a tumor facilitator in clear cell renal cell carcinoma by dysregulating cell cycle, apoptosis, and EZH2 stability.
Wu Y et al.·Cancer Med
2023
Identification and Validation of RPL7 and RCCD1 as Potential Biomarkers Associated with Immune Infiltration in Patients with Thin Endometrium.
Sun J et al.·Reprod Sci
2025Cohort
Variant Identification in BARD1, PRDM9, RCC1, and RECQL in Patients with Ovarian Cancer by Targeted Next-generation Sequencing of DNA Pools.
Suszynska M et al.·Cancer Prev Res (Phila)
2022Cohort
Top 5 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