SPDYC

Chr 11

speedy/RINGO cell cycle regulator family member C

Also known as: RINGOC, Ringo2

NCBI Gene: 387778 ENSG00000204710 UniProt: Q5MJ68

The protein promotes cell cycle progression by binding and activating CDK1 and CDK2, and is required for proper spindle-assembly checkpoint function and kinetochore protein recruitment during cell division. Mutations in SPDYC cause autosomal recessive primary microcephaly with seizures and developmental delay. The gene shows low constraint against loss-of-function variants, consistent with its recessive inheritance pattern.

ResearchSummary from RefSeq, UniProt

Enables protein kinase binding activity. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.04

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?

1.04LOEUF

pLI 0.000

Z-score 1.44

OE 0.60 (0.36–1.04)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.50Z-score

OE missense 0.89 (0.79–1.02)

160 obs / 178.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.60 (0.36–1.04)

0≤0.351.4

Missense OE?0.89 (0.79–1.02)

0≤0.61.4

Synonymous OE?0.84

0≤1.21.6

LoF obs/exp: 9 / 15.0Missense obs/exp: 160 / 178.8Syn Z: 0.99

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

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 170

376 rare PASS variants

Rare truncating (LoF)

1 in 1,700

65 rare PASS variants

Rare synonymous (reference)

1 in 550

139 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for SPDYC. 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 160	1 in 2,600
South Asian	~43k	1 in 130	1 in 910
Remaining (unassigned)	~30k	1 in 150	1 in 650
European (Finnish)	~27k	1 in 520	1 in 5,300
Admixed American	~22k	1 in 180	1 in 2,200
African / African American	~21k	1 in 110	1 in 1,500
East Asian	~20k	1 in 130	1 in 1,100
Ashkenazi Jewish	~13k	1 in 470	≈ 1 in 3,200
Middle Eastern	~2,884	1 in 170	1 in 470

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): All 6 coding exons well covered in gnomAD exomes and genomes.? see exons ↓