CDK13

Chr 7

cyclin dependent kinase 13

Also known as: CDC2L, CDC2L5, CHDFIDD, CHED, hCDK13

NCBI Gene: 8621 ENSG00000065883 UniProt: Q14004

The protein is a cyclin-dependent serine/threonine kinase that localizes to nuclear speckles and likely functions in mRNA processing. Loss-of-function mutations cause an autosomal dominant syndrome characterized by congenital heart defects, dysmorphic facial features, and intellectual developmental disorder. The gene is highly intolerant to loss-of-function variants, supporting haploinsufficiency as the disease mechanism.

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

The protein encoded by this gene is a member of the cyclin-dependent serine/threonine protein kinase family. Members of this family are well known for their essential roles as master switches in cell cycle control. The exact function of this protein has not yet been determined, but it may play a role in mRNA processing and may be involved in regulation of hematopoiesis. Alternatively spliced transcript variants have been described.[provided by RefSeq, Dec 2009]

GeneReviews ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtCongenital heart defects, dysmorphic facial features, and intellectual developmental disorder

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · syndromic intellectual disability · AD · ClinGen 2021

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.32

LOEUF· LoF intol.

Multiple*

Mechanism· predicted

📖

GeneReview available — CDK13

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.32LOEUF

pLI 0.908

Z-score 5.58

OE 0.20 (0.12–0.32)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

2.35Z-score

OE missense 0.75 (0.69–0.80)

510 obs / 682.6 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.20 (0.12–0.32)

0≤0.351.4

Missense OE?0.75 (0.69–0.80)

0≤0.61.4

Synonymous OE?1.12

0≤1.21.6

LoF obs/exp: 11 / 56.2Missense obs/exp: 510 / 682.6Syn Z: -1.51

Background carrier burden — how many people carry a rare variant somewhere in CDK13?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 38

1,906 rare PASS variants

Rare truncating (LoF)

1 in 850

135 rare PASS variants

Rare synonymous (reference)

1 in 47

947 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CDK13. 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 51	1 in 1,400
South Asian	~43k	1 in 28	1 in 560
Remaining (unassigned)	~30k	1 in 36	1 in 1,100
European (Finnish)	~27k	1 in 100	1 in 900
Admixed American	~22k	1 in 33	1 in 470
African / African American	~21k	1 in 35	1 in 420
East Asian	~20k	1 in 35	1 in 850
Ashkenazi Jewish	~13k	1 in 270	1 in 370
Middle Eastern	~2,884	1 in 36	1 in 400

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): 8 of 14 coding exons well covered in gnomAD exomes; exons 1, 6, 7, 9, 10, 11 marginal. Genomes: all 14.? see exons ↓