CDKN1B

Chr 12AD

cyclin dependent kinase inhibitor 1B

Also known as: CDKN4, KIP1, MEN1B, MEN4, P27KIP1

This gene encodes a cyclin-dependent kinase inhibitor, which shares a limited similarity with CDK inhibitor CDKN1A/p21. The encoded protein binds to and prevents the activation of cyclin E-CDK2 or cyclin D-CDK4 complexes, and thus controls the cell cycle progression at G1. The degradation of this protein, which is triggered by its CDK dependent phosphorylation and subsequent ubiquitination by SCF complexes, is required for the cellular transition from quiescence to the proliferative state. Mutations in this gene are associated with multiple endocrine neoplasia type IV (MEN4). [provided by RefSeq, Apr 2014]

GeneReviewsOMIMResearchGenerating clinical summary…
LOFmechanismADLOEUF 0.651 OMIM phenotype
Clinical SummaryCDKN1B
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Gene-Disease Validity (ClinGen)
multiple endocrine neoplasia type 4 · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

2 total gene-disease associations curated

Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.62) — some intolerance to loss-of-function variants.
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ClinVar Variants
121 unique Pathogenic / Likely Pathogenic· 602 VUS of 1121 total submissions
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GeneReview available — CDKN1B
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint?
0.65LOEUF
pLI 0.624
Z-score 2.17
OE 0.14 (0.050.65)
Moderately constrained

Typical tolerance to LoF variation

Missense Constraint?
-1.85Z-score
OE missense 1.50 (1.321.70)
164 obs / 109.6 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?
LoF OE?0.14 (0.050.65)
00.351.4
Missense OE?1.50 (1.321.70)
00.61.4
Synonymous OE?1.99
01.21.6
LoF obs/exp: 1 / 7.4Missense obs/exp: 164 / 109.6Syn Z: -5.17
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongCDKN1B-related multiple endocrine neoplasiaLOFAD

This gene — mechanism propensity

DN
0.3793th %ile
GOF
0.3491th %ile
LOF
0.66top 25%

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

LOFprediction above median · 1 literature citation · 97% of P/LP variants are LoF · ClinGen HI: Sufficient evidence for dosage pathogenicity

Literature Evidence

LOFClinical Features of Multiple Endocrine Neoplasia Type 4: Novel Pathogenic Variant and Review of Published Cases1

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

References

  1. 1.PMID 30990521

ClinVar Variant Classifications

1121 submitted variants in ClinVar

Classification Summary

Pathogenic100
Likely Pathogenic21
VUS602
Likely Benign267
Benign20
Conflicting106
100
Pathogenic
21
Likely Pathogenic
602
VUS
267
Likely Benign
20
Benign
106
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
97
0
3
0
100
Likely Pathogenic
20
0
1
0
21
VUS
39
505
56
2
602
Likely Benign
0
10
47
210
267
Benign
0
3
15
2
20
Conflicting
106
Total1565181222141,116

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

View in ClinVar →

47 pathogenic / likely-pathogenic (of 52) ClinVar copy-number / structural variants overlap CDKN1B — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

CDKN1B · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →