CEP295

Chr 11AR

centrosomal protein 295

Also known as: KIAA1731, SCKL11

NCBI Gene: 85459 ENSG00000166004 UniProt: Q9C0D2 OMIM: 617728

Enables microtubule binding activity. Involved in several processes, including centriole replication; positive regulation of protein acetylation; and regulation of centrosome duplication. Located in cytoplasm and microtubule cytoskeleton. [provided by Alliance of Genome Resources, Jul 2025]

OMIM Research

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Seckel syndrome 11MIM #620767

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Seckel syndrome 11; no ClinGen or GenCC tier

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.49

LOEUF

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.49LOEUF

pLI 0.000

Z-score 6.13

OE 0.38 (0.30–0.49)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.66Z-score

OE missense 0.86 (0.82–0.91)

999 obs / 1157.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.38 (0.30–0.49)

0≤0.351.4

Missense OE?0.86 (0.82–0.91)

0≤0.61.4

Synonymous OE?0.83

0≤1.21.6

LoF obs/exp: 43 / 113.4Missense obs/exp: 999 / 1157.8Syn Z: 2.75

Background carrier burden — how many people carry a rare variant somewhere in CEP295?

gnomAD v4 · ~728k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 16

3,147 rare PASS variants

Rare truncating (LoF)

1 in 230

567 rare PASS variants

Rare synonymous (reference)

1 in 47

1,071 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CEP295. 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)	~554k	1 in 27	1 in 250
South Asian	~43k	1 in 14	1 in 160
Remaining (unassigned)	~30k	1 in 16	1 in 230
European (Finnish)	~27k	1 in 68	1 in 550
Admixed American	~22k	1 in 14	1 in 170
African / African American	~21k	1 in 18	1 in 210
East Asian	~20k	1 in 19	1 in 180
Ashkenazi Jewish	~13k	1 in 50	1 in 500
Middle Eastern	~2,882	1 in 14	1 in 280

Each group is summed over the variants that are rare in that group. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 19 of 29 coding exons well covered in gnomAD exomes; exons 2, 4, 6, 11, 12 and 5 more marginal. Genomes: all 29.? see exons ↓