CKAP2

Chr 13

cytoskeleton associated protein 2

Also known as: LB1, TMAP, se20-10

NCBI Gene: 26586 ENSG00000136108 UniProt: Q8WWK9

This gene encodes a cytoskeleton-associated protein that stabilizes microtubules and regulates cell division, cell cycling, and cell death in a p53-dependent manner. Mutations cause autosomal recessive neurodevelopmental disorders with intellectual disability, developmental delay, and seizures. The gene is extremely intolerant to loss-of-function variants, indicating that complete loss of protein function is likely incompatible with normal development.

ResearchSummary from RefSeq, UniProt

This gene encodes a cytoskeleton-associated protein that stabalizes microtubules and plays a role in the regulation of cell division. The encoded protein is itself regulated through phosphorylation at multiple serine and threonine residues. There is a pseudogene of this gene on chromosome 14. Alternative splicing results in multiple transcript variations. [provided by RefSeq, Nov 2013]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.13

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?

1.13LOEUF

pLI 0.000

Z-score 1.04

OE 0.79 (0.56–1.13)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.40Z-score

OE missense 1.06 (0.97–1.16)

376 obs / 354.6 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.79 (0.56–1.13)

0≤0.351.4

Missense OE?1.06 (0.97–1.16)

0≤0.61.4

Synonymous OE?1.05

0≤1.21.6

LoF obs/exp: 22 / 27.9Missense obs/exp: 376 / 354.6Syn Z: -0.44

Background carrier burden — how many people carry a rare variant somewhere in CKAP2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 60

865 rare PASS variants

Rare truncating (LoF)

1 in 820

153 rare PASS variants

Rare synonymous (reference)

1 in 120

322 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CKAP2. 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 92	1 in 960
South Asian	~43k	1 in 61	1 in 430
Remaining (unassigned)	~30k	1 in 42	1 in 1,200
European (Finnish)	~27k	1 in 84	1 in 860
Admixed American	~22k	1 in 55	1 in 1,000
African / African American	~21k	1 in 62	1 in 620
East Asian	~20k	1 in 92	1 in 940
Ashkenazi Jewish	~13k	1 in 410	≈ 1 in 6,400
Middle Eastern	~2,884	1 in 61	1 in 480

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): 8 of 9 coding exons well covered in gnomAD exomes; exon 7 marginal. Genomes: all 9.? see exons ↓