CDCA8

Chr 1

cell division cycle associated 8

Also known as: BOR, BOREALIN, DasraB, MESRGP

NCBI Gene: 55143 ENSG00000134690 UniProt: Q53HL2 OMIM: 609977

The protein is a component of the chromosomal passenger complex that regulates mitosis by ensuring correct chromosome alignment and segregation and is required for chromatin-induced microtubule stabilization and spindle assembly. Mutations cause autosomal recessive primary microcephaly with seizures and developmental delay, with onset in infancy. The gene is moderately constrained against loss-of-function variants.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a component of the chromosomal passenger complex. This complex is an essential regulator of mitosis and cell division. This protein is cell-cycle regulated and is required for chromatin-induced microtubule stabilization and spindle formation. Alternate splicing results in multiple transcript variants. Pseudgenes of this gene are found on chromosomes 7, 8 and 16. [provided by RefSeq, Apr 2013]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 0.68

Clinical Summary— CDCA8

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Population Constraint (gnomAD)

Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

26 VUS of 51 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.68LOEUF

pLI 0.007

Z-score 2.59

OE 0.36 (0.21–0.68)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.02Z-score

OE missense 0.77 (0.67–0.90)

126 obs / 162.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.36 (0.21–0.68)

0≤0.351.4

Missense OE?0.77 (0.67–0.90)

0≤0.61.4

Synonymous OE?0.77

0≤1.21.6

LoF obs/exp: 7 / 19.2Missense obs/exp: 126 / 162.8Syn Z: 1.38

This gene — mechanism propensity

0.6840th %ile

GOF

0.1999th %ile

LOF

0.3841th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

51 submitted variants in ClinVar

ClinVar

Classification Summary

VUS26

Likely Benign5

Conflicting1

VUS

Likely Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	0	0	0	0	0
VUS	0	26	0	0	26
Likely Benign	0	4	0	1	5
Benign	0	0	0	0	0
Conflicting	—				1
Total	0	30	0	1	32

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

View in ClinVar →

5 pathogenic / likely-pathogenic (of 11) ClinVar copy-number / structural variants overlap CDCA8 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →