CDKN2AIP

Chr 4

CDKN2A interacting protein

Also known as: XTBD2

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.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
1
Pubs (1 yr)
98
P/LP submissions
0%
P/LP missense
0.33
LOEUF· LoF intol.
LOF
Mechanism· predicted
Clinical SummaryCDKN2AIP
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.
📋
ClinVar Variants
98 unique Pathogenic / Likely Pathogenic· 94 VUS of 198 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.33LOEUF
pLI 0.964
Z-score 3.63
OE 0.10 (0.040.33)
Highly constrained

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

Missense Constraint
0.54Z-score
OE missense 0.91 (0.821.01)
271 obs / 297.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.10 (0.040.33)
00.351.4
Missense OE0.91 (0.821.01)
00.61.4
Synonymous OE0.99
01.21.6
LoF obs/exp: 2 / 19.1Missense obs/exp: 271 / 297.1Syn Z: 0.06
DN
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.

ClinVar Variant Classifications

198 submitted variants in ClinVar

Classification Summary

Pathogenic90
Likely Pathogenic8
VUS94
Likely Benign1
90
Pathogenic
8
Likely Pathogenic
94
VUS
1
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
90
0
90
Likely Pathogenic
0
0
8
0
8
VUS
0
88
6
0
94
Likely Benign
0
0
0
1
1
Benign
0
0
0
0
0
Total0881041193

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

View in ClinVar →

Protein Context — Lollipop Plot

CDKN2AIP · 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.

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Clinical Literature
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