CDKN2AIP

Chr 4

CDKN2A interacting protein

Also known as: XTBD2

NCBI Gene: 55602 ENSG00000168564 UniProt: Q9NXV6 OMIM: 615914

The protein regulates DNA damage response through multiple signaling pathways involved in cell proliferation, apoptosis and senescence, including the p53-HDM2-p21 pathway. Mutations cause familial melanoma-pancreatic cancer syndrome, characterized by increased susceptibility to melanoma and pancreatic adenocarcinoma with autosomal dominant inheritance. This gene is highly constrained against loss-of-function variants, indicating that complete loss of protein function is likely not tolerated.

OMIM ResearchSummary from RefSeq, UniProt

The protein encoded by this gene regulates the DNA damage response through several different signaling pathways. One such pathway is the p53-HDM2-p21(WAF1) pathway, which is critical to the DNA damage response. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2015]

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.33

Clinical Summary— CDKN2AIP

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.96). One damaged copy is likely sufficient to cause disease.

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.33LOEUF

pLI 0.964

Z-score 3.63

OE 0.10 (0.04–0.33)

Highly constrained

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

Missense Constraint?

0.54Z-score

OE missense 0.91 (0.82–1.01)

271 obs / 297.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.10 (0.04–0.33)

0≤0.351.4

Missense OE?0.91 (0.82–1.01)

0≤0.61.4

Synonymous OE?0.99

0≤1.21.6

LoF obs/exp: 2 / 19.1Missense obs/exp: 271 / 297.1Syn Z: 0.06

This gene — mechanism propensity

0.2798th %ile

GOF

0.2895th %ile

LOF

0.80top 5%

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

LOFprediction above median · LOEUF 0.33

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