RCC1

Chr 1AR

regulator of chromosome condensation 1

Also known as: CHC1, IIAAN, RCC1-I

NCBI Gene: 1104 ENSG00000180198 UniProt: P18754 OMIM: 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.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

Enables several functions, including guanyl-nucleotide exchange factor activity; nucleosomal DNA binding activity; and protein heterodimerization activity. Involved in G1/S transition of mitotic cell cycle; regulation of mitotic nuclear division; and spindle organization. Located in chromatin; cytoplasm; and nuclear lumen. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2025]

OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.361 OMIM phenotype

Clinical Summary— RCC1

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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.

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ClinVar Variants

6 unique Pathogenic / Likely Pathogenic· 47 VUS of 66 total submissions

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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 OE?0.14 (0.06–0.36)

0≤0.351.4

Missense OE?0.72 (0.64–0.81)

0≤0.61.4

Synonymous OE?0.95

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

This gene — mechanism propensity

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

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

66 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic3

Likely Pathogenic3

VUS47

Likely Benign2

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Total
Pathogenic	2	1	3
Likely Pathogenic	3	0	3
VUS	47	0	47
Likely Benign	2	0	2
Benign	0	0	0
Total	54	1	55

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

View in ClinVar →

6 pathogenic / likely-pathogenic (of 14) ClinVar copy-number / structural variants overlap RCC1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →