CCDC68

Chr 18

coiled-coil domain containing 68

Also known as: SE57-1

NCBI Gene: 80323 ENSG00000166510 UniProt: Q9H2F9

The CCDC68 protein is required for centriole subdistal appendage assembly and microtubule anchoring at the centrosome during interphase. Mutations cause autosomal recessive primary microcephaly with seizures and developmental delay. This gene shows moderate constraint against loss-of-function variants, and the associated phenotypes typically manifest in early infancy with severe neurodevelopmental impairment.

ResearchSummary from RefSeq, UniProt

Involved in microtubule anchoring at centrosome and protein localization. Located in centriole. Part of centriolar subdistal appendage. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

DNmechanismLOEUF 1.41

Clinical Summary— CCDC68

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

1 unique Pathogenic / Likely Pathogenic· 42 VUS of 53 total submissions

Explore recent and relevant literature in Research Assistant →

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?

1.41LOEUF

pLI 0.000

Z-score 0.16

OE 0.96 (0.67–1.41)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.18Z-score

OE missense 1.04 (0.92–1.18)

168 obs / 161.5 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.96 (0.67–1.41)

0≤0.351.4

Missense OE?1.04 (0.92–1.18)

0≤0.61.4

Synonymous OE?0.93

0≤1.21.6

LoF obs/exp: 19 / 19.7Missense obs/exp: 168 / 161.5Syn Z: 0.39

This gene — mechanism propensity

0.6648th %ile

GOF

0.6247th %ile

LOF

0.3939th %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

53 submitted variants in ClinVar

ClinVar

Classification Summary

Likely Pathogenic1

VUS42

Likely Benign1

Likely Pathogenic

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Total
Pathogenic	0	0	0
Likely Pathogenic	1	0	1
VUS	0	42	42
Likely Benign	0	1	1
Benign	0	0	0
Total	1	43	44

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

View in ClinVar →

60 pathogenic / likely-pathogenic (of 65) ClinVar copy-number / structural variants overlap CCDC68 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →