CDKN2B

Chr 9

cyclin dependent kinase inhibitor 2B

Also known as: CDK4I, INK4B, MTS2, P15, TP15, p15INK4b

CDKN2B encodes a cyclin-dependent kinase inhibitor that forms complexes with CDK4 or CDK6 to regulate cell cycle G1 progression and functions as a cell growth regulator. The gene is not highly constrained against loss-of-function variants and has an associated GeneReviews entry, indicating established clinical significance. Mutations cause disease with autosomal inheritance patterns.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 1.83
Clinical SummaryCDKN2B
Population Constraint (gnomAD)
Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.83LOEUF
pLI 0.007
Z-score 0.11
OE 0.93 (0.411.83)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.70Z-score
OE missense 1.20 (1.031.41)
112 obs / 93.1 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.93 (0.411.83)
00.351.4
Missense OE1.20 (1.031.41)
00.61.4
Synonymous OE1.09
01.21.6
LoF obs/exp: 3 / 3.2Missense obs/exp: 112 / 93.1Syn Z: -0.48
DN
0.6358th %ile
GOF
0.78top 25%
LOF
0.3067th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

CDKN2B · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold
Clinical Literature
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