CDKN1A

Chr 6

cyclin dependent kinase inhibitor 1A

Also known as: CAP20, CDKN1, CIP1, MDA-6, P21, SDI1, WAF1, p21CIP1

This gene encodes a potent cyclin-dependent kinase inhibitor. The encoded protein binds to and inhibits the activity of cyclin-cyclin-dependent kinase2 or -cyclin-dependent kinase4 complexes, and thus functions as a regulator of cell cycle progression at G1. The expression of this gene is tightly controlled by the tumor suppressor protein p53, through which this protein mediates the p53-dependent cell cycle G1 phase arrest in response to a variety of stress stimuli. This protein can interact with proliferating cell nuclear antigen, a DNA polymerase accessory factor, and plays a regulatory role in S phase DNA replication and DNA damage repair. This protein was reported to be specifically cleaved by CASP3-like caspases, which thus leads to a dramatic activation of cyclin-dependent kinase2, and may be instrumental in the execution of apoptosis following caspase activation. Mice that lack this gene have the ability to regenerate damaged or missing tissue. Multiple alternatively spliced variants have been found for this gene. [provided by RefSeq, Sep 2015]

ResearchGenerating clinical summary…
5
Active trials
545
Pubs (1 yr)
P/LP submissions
P/LP missense
1.38
LOEUF
Mechanism
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint?
1.38LOEUF
pLI 0.002
Z-score 0.87
OE 0.66 (0.341.38)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?
0.42Z-score
OE missense 0.89 (0.761.05)
104 obs / 116.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.66 (0.341.38)
00.351.4
Missense OE?0.89 (0.761.05)
00.61.4
Synonymous OE?0.88
01.21.6
LoF obs/exp: 5 / 7.6Missense obs/exp: 104 / 116.7Syn Z: 0.64

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

CDKN1A · protein map & ClinVar variants

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