TP53AIP1

Summary

TP53AIP1 (tumor protein p53 regulated apoptosis inducing protein 1, HGNC:29984) is a protein-coding gene on chromosome 11q24.3, encoding p53-regulated apoptosis-inducing protein 1 (Q9HCN2). May play an important role in mediating p53/TP53-dependent apoptosis.

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.

Source: NCBI Gene 63970 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 29 total
• MANE Select transcript: NM_022112

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29984
Approved symbol	TP53AIP1
Name	tumor protein p53 regulated apoptosis inducing protein 1
Location	11q24.3
Locus type	gene with protein product
Status	Approved
Aliases	p53AIP1
Ensembl gene	ENSG00000120471
Ensembl biotype	protein_coding
OMIM	605426
Entrez	63970

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 4 protein_coding, 1 retained_intron, 1 nonsense_mediated_decay

ENST00000458238, ENST00000525390, ENST00000527504, ENST00000530777, ENST00000531399, ENST00000602346

RefSeq mRNA: 4 — MANE Select: NM_022112 NM_001195194, NM_001195195, NM_001251964, NM_022112

CCDS: CCDS55797, CCDS55798, CCDS58195, CCDS8480

Canonical transcript exons

ENST00000531399 — 4 exons

Exon	Start	End
ENSE00001130929	128937678	128937894
ENSE00001330498	128936538	128936649
ENSE00002193750	128935370	128935712
ENSE00003913770	128942794	128942871

Expression profiles

Bgee: expression breadth ubiquitous, 159 present calls, max score 91.29.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.3560 / max 39.2189, expressed in 73 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
123118	0.3244	70
123119	0.0317	10

Top tissues by expression

272 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	91.29	gold quality
lower esophagus mucosa	UBERON:0035834	91.27	gold quality
cervix squamous epithelium	UBERON:0006922	88.68	gold quality
hair follicle	UBERON:0002073	88.34	gold quality
esophagus mucosa	UBERON:0002469	87.82	gold quality
gingival epithelium	UBERON:0001949	86.82	gold quality
skin of abdomen	UBERON:0001416	86.68	gold quality
gingiva	UBERON:0001828	84.94	gold quality
skin of leg	UBERON:0001511	84.10	gold quality
upper arm skin	UBERON:0004263	84.03	gold quality
zone of skin	UBERON:0000014	83.75	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.52	gold quality
tongue squamous epithelium	UBERON:0006919	83.00	gold quality
squamous epithelium	UBERON:0006914	82.33	gold quality
oviduct epithelium	UBERON:0004804	82.01	gold quality
cervix epithelium	UBERON:0004801	81.64	gold quality
esophagus squamous epithelium	UBERON:0006920	78.69	gold quality
vagina	UBERON:0000996	78.42	gold quality
epithelium of esophagus	UBERON:0001976	77.75	gold quality
mammalian vulva	UBERON:0000997	77.51	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	76.90	gold quality
thymus	UBERON:0002370	75.50	gold quality
right uterine tube	UBERON:0001302	75.02	gold quality
oral cavity	UBERON:0000167	73.26	gold quality
epithelium of nasopharynx	UBERON:0001951	73.18	silver quality
fallopian tube	UBERON:0003889	72.24	gold quality
sperm	CL:0000019	71.95	gold quality
penis	UBERON:0000989	71.86	gold quality
nasal cavity mucosa	UBERON:0001826	70.95	gold quality
mouth mucosa	UBERON:0003729	70.58	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	10.22

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TP53, TP73

miRNA regulators (miRDB)

15 targeting TP53AIP1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-6857-5P	99.87	65.32	985
HSA-MIR-2052	99.79	69.37	2031
HSA-MIR-3942-3P	99.57	69.03	2854
HSA-MIR-208A-5P	99.42	70.83	1913
HSA-MIR-208B-5P	99.42	70.83	1952
HSA-MIR-4652-3P	99.33	70.02	2742
HSA-MIR-504-3P	99.30	67.18	1745
HSA-MIR-3160-5P	99.28	69.07	1938
HSA-MIR-10524-5P	99.05	66.08	963
HSA-MIR-6887-5P	98.56	68.49	1295
HSA-MIR-6795-5P	98.52	68.51	1277
HSA-MIR-450A-2-3P	97.91	67.56	1459
HSA-MIR-505-5P	97.01	65.54	778

Literature-anchored findings (GeneRIF, showing 15)

• p53AIP1 regulates the mitochondrial apoptotic pathway. (PMID:12019168)
• The expression of Ki67 and p53 in various forms of leukoplakia point to the increasing instability of the genome in parallel with the severity of leukoplakia. (PMID:14707453)
• expression of the p53 mutant, R248Q, in liver cancer cells may enhance their drug resistance and upregulation of P-glycoprotein activity may contribute to this protective effect. (PMID:15004724)
• Roscovitine induced up-regulation of p53AIP1 protein and the depolarization of mitochondrial potential. (PMID:15657359)
• p53AIP1 gene is important for non-small cell lung cancer progression and may be a possible prognostic marker (PMID:17851056)
• Insufficient expression of p53AIP1 may play a role in gastric carcinogenesis in patients infected with H. pylori infection. (PMID:18277906)
• Insufficient expression of p53AIP1 may play a role in gastric carcinogenesis in patients infected with H. pylori infection. (PMID:18277909)
• Data suggest that the combination of p53AIP1 and survivin gene expression may be a powerful tool to stratify subgroups with better or worse prognosis from the variable non-small cell lung cancer population. (PMID:19228369)
• Apak competes with p53 for binding to inhibit p53AIP1 expression. (PMID:22334068)
• large sample size of the combined cohort rejects a high-risk effect greater than 2.2 and indicates a limited role of TP53AIP1 in prostate cancer predisposition (PMID:22457820)
• These studies indicate the critical role of p53AIP1 under DNA damaging stresses for cell fate determination in rheumatoid arthritis-fibroblast-like synovioctes containing the p53R248Q mutation. (PMID:24316591)
• Data indicate that p53-regulated apoptosis-inducing protein 1 (p53AIP1) inhibits the proliferation of PC-3M cells, arrests cell cycle at S/G2-M phase, decreases the abilities of invasion and migration and promotes cell apoptosis. (PMID:25108434)
• results show that constitutional truncating TP53AIP1 mutations predispose to CMM in the French population (PMID:29359367)
• Bioinformatic analysis identified TP53AIP1 as a direct target for miR-505. (PMID:30864684)
• TP53AIP1 induce autophagy via the AKT/mTOR signaling pathway in the breast cancer cells. (PMID:39223776)

Cross-species orthologs

0 orthologs

Protein

Protein identifiers

p53-regulated apoptosis-inducing protein 1 — Q9HCN2 (reviewed: Q9HCN2)

All UniProt accessions (1): Q9HCN2

UniProt curated annotations — full annotation on UniProt →

Function. May play an important role in mediating p53/TP53-dependent apoptosis.

Subcellular location. Mitochondrion.

Tissue specificity. Only found to be expressed in thymus.

Induction. By p53/TP53.

Miscellaneous. Dubious isoform. Could be a cloning artifact.

Isoforms (4)

UniProt ID	Names	Canonical?
Q9HCN2-1	1, Alpha	yes
Q9HCN2-2	2, Beta
Q9HCN2-3	3, Gamma
Q9HCN2-4	4

RefSeq proteins (4): NP_001182123, NP_001182124, NP_001238893, NP_071395* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR029284	TP53AIP1	Family

Pfam: PF15338

UniProt features (8 total): splice variant 4, chain 1, region of interest 1, compositionally biased region 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9HCN2-F1	47.79	0.00

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-6803204	TP53 Regulates Transcription of Genes Involved in Cytochrome C Release

MSigDB gene sets: 55 (showing top): JAEGER_METASTASIS_DN, BLALOCK_ALZHEIMERS_DISEASE_UP, NOJIMA_SFRP2_TARGETS_UP, GOCC_MITOCHONDRIAL_MATRIX, chr11q24, PID_P73PATHWAY, PID_P53_REGULATION_PATHWAY, REACTOME_TRANSCRIPTIONAL_REGULATION_BY_TP53, REACTOME_TP53_REGULATES_TRANSCRIPTION_OF_CELL_DEATH_GENES, REACTOME_TP53_REGULATES_TRANSCRIPTION_OF_GENES_INVOLVED_IN_CYTOCHROME_C_RELEASE, NFKBIA_TARGET_GENES, MIR4729, MIR8068, MIR205_3P, MIR3942_3P

GO Biological Process (1): apoptotic process (GO:0006915)

GO Molecular Function (0):

GO Cellular Component (2): mitochondrion (GO:0005739), mitochondrial matrix (GO:0005759)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
TP53 Regulates Transcription of Cell Death Genes	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
cytoplasm	1
intracellular membrane-bounded organelle	1
mitochondrion	1
intracellular organelle lumen	1

Protein interactions and networks

STRING

316 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TP53AIP1	TP53	P04637	718
TP53AIP1	PMAIP1	Q13794	663
TP53AIP1	TP53INP1	Q96A56	624
TP53AIP1	DYRK2	Q92630	622
TP53AIP1	BCL2	P10415	570
TP53AIP1	CDKN1A	P38936	563
TP53AIP1	HIPK2	Q9H2X6	522
TP53AIP1	RRM2B	Q7LG56	507
TP53AIP1	MDM2	Q00987	507
TP53AIP1	PRRG2	O14669	490
TP53AIP1	EP300	Q09472	470
TP53AIP1	TP73	O15350	462
TP53AIP1	BBC3	Q96PG8	447
TP53AIP1	YAP1	P46937	445
TP53AIP1	GADD45A	P24522	431

IntAct

2 interactions, top by confidence:

A	B	Type	Score
TP53AIP1	UBR3	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (3): UBR3 (Affinity Capture-MS), BCL2 (Affinity Capture-Western), UBR3 (Affinity Capture-MS)

ESM2 similar proteins: A0A1B0GUT2, A0A3Q1LFG5, A1L4Q6, A2RUQ5, A8MQB3, A8MU10, B1ANY3, C0HM98, H3BQW9, J3KSC0, P0C092, P0DMU3, P0DPA3, P24026, P59020, P59021, P59052, P87743, Q06250, Q0IIN9, Q0VFX4, Q14695, Q4R3X9, Q4VX62, Q52M75, Q5SR53, Q6ZUF6, Q6ZWC4, Q71F78, Q7Z4H9, Q8JMY5, Q8JMZ5, Q8JN06, Q8N2C9, Q8N2X6, Q8N3U1, Q8N9X3, Q8NAA6, Q8NBC4, Q8NDY4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

29 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	24
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

483 predictions. Top by Δscore:

Variant	Effect	Δscore
11:128942834:T:TA	donor_gain	0.9900
11:128936859:T:TC	acceptor_gain	0.9800
11:128942790:TCA:T	donor_loss	0.9800
11:128942792:A:T	donor_loss	0.9800
11:128942799:T:TA	donor_gain	0.9700
11:128936847:G:C	acceptor_gain	0.8900
11:128937894:ACT:A	acceptor_gain	0.8900
11:128937892:GGACT:G	acceptor_gain	0.8800
11:128936847:G:GC	acceptor_gain	0.8600
11:128936858:A:C	acceptor_gain	0.8600
11:128937893:GACTA:G	acceptor_gain	0.8600
11:128936859:T:C	acceptor_gain	0.8400
11:128940510:TCC:T	donor_gain	0.8400
11:128942796:G:A	donor_gain	0.8400
11:128937895:CTA:C	acceptor_gain	0.8300
11:128935791:C:CT	acceptor_gain	0.8200
11:128942791:CACCT:C	donor_gain	0.8200
11:128942792:ACCTG:A	donor_gain	0.8200
11:128942793:C:CG	donor_gain	0.8200
11:128942793:CCTGC:C	donor_gain	0.8200
11:128942250:T:TA	donor_gain	0.8100
11:128942387:G:T	donor_gain	0.8100
11:128942790:TCAC:T	donor_gain	0.8100
11:128937896:T:A	acceptor_gain	0.8000
11:128942792:ACCT:A	donor_gain	0.7900
11:128942793:CCTG:C	donor_gain	0.7900
11:128937163:T:TA	donor_gain	0.7800
11:128942792:A:AC	donor_gain	0.7800
11:128942793:C:CC	donor_gain	0.7800
11:128942794:C:T	donor_gain	0.7800

AlphaMissense

772 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:128937792:G:C	F9L	0.909
11:128937792:G:T	F9L	0.909
11:128937794:A:G	F9L	0.909
11:128935684:G:C	F94L	0.879
11:128935684:G:T	F94L	0.879
11:128935686:A:G	F94L	0.879
11:128936550:A:G	W81R	0.805
11:128936550:A:T	W81R	0.805
11:128936548:C:A	W81C	0.760
11:128936548:C:G	W81C	0.760
11:128935616:T:A	K117I	0.620
11:128936568:A:G	W75R	0.613
11:128936568:A:T	W75R	0.613
11:128936566:C:A	W75C	0.612
11:128936566:C:G	W75C	0.612
11:128937756:C:A	R21S	0.601
11:128937756:C:G	R21S	0.601
11:128935636:A:C	F110L	0.599
11:128935636:A:T	F110L	0.599
11:128935638:A:G	F110L	0.599
11:128937717:C:A	M34I	0.598
11:128937717:C:G	M34I	0.598
11:128937717:C:T	M34I	0.598
11:128937752:C:G	G23R	0.584
11:128936549:C:A	W81L	0.576
11:128935615:T:A	K117N	0.575
11:128935615:T:G	K117N	0.575
11:128937795:G:C	S8R	0.572
11:128937795:G:T	S8R	0.572
11:128937797:T:G	S8R	0.572

dbSNP variants (sampled 300 via entrez): RS1000012854 (11:128937139 C>A,G,T), RS1000848478 (11:128941285 C>G,T), RS1001007330 (11:128936068 T>C), RS1001263583 (11:128942076 G>A,C), RS1001455446 (11:128936965 G>A), RS1001614014 (11:128939355 C>T), RS1001739716 (11:128937125 C>A,T), RS1002820997 (11:128942975 C>T), RS1002883008 (11:128943439 C>G,T), RS1002935694 (11:128943170 A>G), RS1003152694 (11:128944213 C>T), RS1003267525 (11:128944489 G>C), RS1003462688 (11:128939270 T>A), RS1003504378 (11:128934886 C>A,T), RS1003584727 (11:128941222 A>G,T)

Disease associations

OMIM: gene MIM:605426 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST001820_13	Metabolite levels (5-HIAA)	5.000000e-07
GCST010002_202	Refractive error	1.000000e-17

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0005132	5-HIAA measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs118088833	Toxicity	3	cyclophosphamide;epirubicin;fluorouracil	Breast Neoplasms;Neutropenia

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs118088833	TP53AIP1	3	0.00	1	cyclophosphamide;epirubicin;fluorouracil

CTD chemical–gene interactions

22 total (human), top 22 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Arsenic Trioxide	affects binding, affects cotreatment, increases reaction, increases expression	3
2-(2-chloro-4-iodophenylamino)-N-cyclopropylmethoxy-3,4-difluorobenzamide	affects cotreatment, increases reaction, increases expression, affects binding	2
Air Pollutants	decreases expression, increases abundance, increases expression	2
Smoke	increases abundance, increases expression	2
naringenin	affects cotreatment, increases expression	1
bisphenol A	affects cotreatment, increases expression	1
CGP 52608	increases reaction, affects binding	1
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one	increases reaction, increases expression, affects binding, affects cotreatment	1
monomethylarsonous acid	decreases expression	1
theaflavin-3,3’-digallate	affects expression	1
Decitabine	affects reaction, increases expression, affects methylation	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Diazinon	increases methylation	1
Endosulfan	decreases expression	1
Fluorouracil	increases expression, increases reaction	1
Folic Acid	decreases expression	1
Gentian Violet	affects binding, increases reaction	1
Menthol	decreases expression	1
Nickel	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Lactic Acid	increases expression	1
Particulate Matter	decreases expression, increases abundance	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.