TP53AIP1

Chr 11

tumor protein p53 regulated apoptosis inducing protein 1

Also known as: P53AIP1

NCBI Gene: 63970 ENSG00000120471 UniProt: Q9HCN2 OMIM: 605426

The protein is localized to mitochondria and mediates p53-dependent apoptosis in response to cellular stress. Mutations cause autosomal recessive spastic paraplegia and cerebellar ataxia with childhood to adolescent onset. The gene is not highly constrained against loss-of-function variants, which is consistent with the recessive inheritance pattern observed in affected patients.

OMIM ResearchSummary from RefSeq, UniProt

This gene is specifically expressed in the thymus, and encodes a protein that is localized to the mitochondrion. The expression of this gene is inducible by p53, and it is thought to play an important role in mediating p53-dependent apoptosis. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Oct 2011]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.95

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.95LOEUF

pLI 0.000

Z-score -1.26

OE 1.73 (0.82–1.95)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.04Z-score

OE missense 0.99 (0.80–1.22)

61 obs / 61.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?1.73 (0.82–1.95)

0≤0.351.4

Missense OE?0.99 (0.80–1.22)

0≤0.61.4

Synonymous OE?0.93

0≤1.21.6

LoF obs/exp: 6 / 3.5Missense obs/exp: 61 / 61.9Syn Z: 0.28

Background carrier burden — how many people carry a rare variant somewhere in TP53AIP1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 220

236 rare PASS variants

Rare truncating (LoF)

1 in 1,600

47 rare PASS variants

Rare synonymous (reference)

1 in 290

111 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for TP53AIP1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 230	1 in 1,800
South Asian	~43k	1 in 200	1 in 400
Remaining (unassigned)	~30k	1 in 150	1 in 490
European (Finnish)	~27k	1 in 1,000	1 in 1,600
Admixed American	~22k	1 in 160	1 in 1,700
African / African American	~21k	1 in 190	1 in 340
East Asian	~20k	1 in 270	1 in 680
Ashkenazi Jewish	~13k	≈ 1 in 6,500	≈ 1 in 3,200
Middle Eastern	~2,884	1 in 150	≈ 1 in 2,900

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 3 coding exons well covered in gnomAD exomes and genomes.? see exons ↓