CCDC68

Chr 18

coiled-coil domain containing 68

Also known as: SE57-1

NCBI Gene: 80323 ENSG00000166510 UniProt: Q9H2F9 OMIM: 616909

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.

OMIM ResearchSummary from RefSeq, UniProt

Involved in intracellular protein localization and microtubule anchoring at centrosome. Located in centriole. Part of centriolar subdistal appendage. [provided by Alliance of Genome Resources, Jun 2026]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.41

LOEUF

Mechanism· predicted

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

Background carrier burden — how many people carry a rare variant somewhere in CCDC68?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 120

387 rare PASS variants

Rare truncating (LoF)

1 in 1,000

96 rare PASS variants

Rare synonymous (reference)

1 in 330

138 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CCDC68. 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 200	1 in 960
South Asian	~43k	1 in 150	1 in 1,300
Remaining (unassigned)	~30k	1 in 110	1 in 850
European (Finnish)	~27k	1 in 1,100	1 in 3,300
Admixed American	~22k	1 in 180	1 in 2,200
African / African American	~21k	1 in 130	1 in 690
East Asian	~20k	1 in 110	1 in 2,000
Ashkenazi Jewish	~13k	1 in 900	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 140	≈ 1 in 2,900

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): 6 of 10 coding exons well covered in gnomAD exomes; exons 3, 8, 10, 11 marginal. Genomes: all 10.? see exons ↓