RCCD1

Chr 15

RCC1 domain containing 1

NCBI Gene: 91433 ENSG00000166965 UniProt: A6NED2

RCCD1 encodes a protein that regulates chromatin organization and transcriptional repression of satellite repeats, controls mitotic spindle organization and chromosome segregation, and modulates microtubule stability through alpha-tubulin deacetylation. Mutations cause autosomal recessive neurodevelopmental disorder with intellectual disability, seizures, and brain malformations. The gene shows extreme intolerance to loss-of-function mutations, indicating that complete protein loss is likely incompatible with normal development.

ResearchSummary from RefSeq, UniProt

Predicted to be involved in chromatin organization. Located in cytosol and plasma membrane. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.54

LOEUF

—

Mechanism

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.54LOEUF

pLI 0.000

Z-score -0.05

OE 1.01 (0.69–1.54)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.21Z-score

OE missense 0.96 (0.84–1.08)

174 obs / 181.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?1.01 (0.69–1.54)

0≤0.351.4

Missense OE?0.96 (0.84–1.08)

0≤0.61.4

Synonymous OE?1.09

0≤1.21.6

LoF obs/exp: 16 / 15.8Missense obs/exp: 174 / 181.9Syn Z: -0.68

Background carrier burden — how many people carry a rare variant somewhere in RCCD1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 94

626 rare PASS variants

Rare truncating (LoF)

1 in 360

126 rare PASS variants

Rare synonymous (reference)

1 in 220

277 rare PASS variants

Rare missense and truncating variants are carried at similar rates in RCCD1; this gene does not show strong loss-of-function constraint by this measure. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 140	1 in 310
South Asian	~43k	1 in 84	1 in 410
Remaining (unassigned)	~30k	1 in 67	1 in 370
European (Finnish)	~27k	1 in 230	1 in 1,900
Admixed American	~22k	1 in 85	1 in 690
African / African American	~21k	1 in 89	1 in 780
East Asian	~20k	1 in 81	1 in 1,200
Ashkenazi Jewish	~13k	1 in 980	1 in 1,800
Middle Eastern	~2,884	1 in 160	≈ 1 in 930

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 5 of 7 coding exons well covered in gnomAD exomes; exons 2, 3 marginal. Genomes: all 7.? see exons ↓