CDK15

Chr 2

cyclin dependent kinase 15

Also known as: ALS2CR7, PFTAIRE2, PFTK2

NCBI Gene: 65061 ENSG00000138395 UniProt: Q96Q40 OMIM: 616147

CDK15 encodes a serine/threonine protein kinase that phosphorylates BIRC5 and acts as an antiapoptotic protein by countering TRAIL-induced apoptosis. The gene shows minimal constraint against loss-of-function variants (pLI near zero), and no established Mendelian diseases have been definitively linked to CDK15 mutations in the current literature. Further research is needed to determine if CDK15 variants cause human disease.

OMIM ResearchSummary from RefSeq, UniProt

Enables protein serine/threonine kinase activity. Predicted to be involved in regulation of cell cycle phase transition. Predicted to be active in cytosol and nucleus. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 1.35

Clinical Summary— CDK15

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

56 VUS of 65 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.35LOEUF

pLI 0.000

Z-score 0.13

OE 0.97 (0.71–1.35)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.00Z-score

OE missense 1.00 (0.90–1.11)

239 obs / 238.8 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.97 (0.71–1.35)

0≤0.351.4

Missense OE?1.00 (0.90–1.11)

0≤0.61.4

Synonymous OE?1.05

0≤1.21.6

LoF obs/exp: 26 / 26.7Missense obs/exp: 239 / 238.8Syn Z: -0.36

This gene — mechanism propensity

0.6358th %ile

GOF

0.6150th %ile

LOF

0.4429th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

65 submitted variants in ClinVar

ClinVar

Classification Summary

VUS56

VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	56	56
Likely Benign	0	0
Benign	0	0
Total	56	56

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

View in ClinVar →

31 pathogenic / likely-pathogenic (of 37) ClinVar copy-number / structural variants overlap CDK15 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →