CDK16

Chr X

cyclin dependent kinase 16

Also known as: PCTAIRE, PCTAIRE1, PCTGAIRE, PCTK1

NCBI Gene: 5127 ENSG00000102225 UniProt: Q00536 OMIM: 311550

This X-linked serine/threonine protein kinase regulates vesicle-mediated transport, exocytosis, neuron differentiation, and insulin secretion, with particular roles in growth hormone release and spermatogenesis. Mutations cause X-linked intellectual disability with variable features that may include metabolic dysfunction and developmental delays. The gene is highly constrained against loss-of-function variants, indicating that such mutations are likely to cause significant clinical phenotypes.

OMIM ResearchSummary from RefSeq, UniProt

The protein encoded by this gene belongs to the cdc2/cdkx subfamily of the ser/thr family of protein kinases. It may play a role in signal transduction cascades in terminally differentiated cells; in exocytosis; and in transport of secretory cargo from the endoplasmic reticulum. This gene is thought to escape X inactivation. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2009]

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.26

Clinical Summary— CDK16

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Gene-Disease Validity (ClinGen)

X-linked complex neurodevelopmental disorder · XLLimited

Limited evidence — not for standalone diagnostic reporting

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.99). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

1 unique Pathogenic / Likely Pathogenic· 55 VUS of 154 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.26LOEUF

pLI 0.995

Z-score 4.20

OE 0.08 (0.03–0.26)

Highly constrained

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

Missense Constraint?

2.91Z-score

OE missense 0.48 (0.42–0.56)

122 obs / 252.0 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.08 (0.03–0.26)

0≤0.351.4

Missense OE?0.48 (0.42–0.56)

0≤0.61.4

Synonymous OE?0.83

0≤1.21.6

LoF obs/exp: 2 / 24.4Missense obs/exp: 122 / 252.0Syn Z: 1.32

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

limitedCDK16-related intellectual disabilityLOFmonoallelic_X_heterozygous

This gene — mechanism propensity

0.4289th %ile

GOF

0.4973th %ile

LOF

0.72top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.26

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

154 submitted variants in ClinVar

ClinVar

Classification Summary

Likely Pathogenic1

VUS55

Likely Benign5

Benign4

Likely Pathogenic

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	0	1	0	0	1
VUS	3	50	1	1	55
Likely Benign	0	2	0	3	5
Benign	0	2	1	1	4
Total	3	55	2	5	65

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

View in ClinVar →

55 pathogenic / likely-pathogenic (of 63) ClinVar copy-number / structural variants overlap CDK16 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →