TP53I3

protein-coding

tumor protein p53 inducible protein 3

Gene summary

The protein encoded by this gene is similar to oxidoreductases, which are enzymes involved in cellular responses to oxidative stresses and irradiation. This gene is induced by the tumor suppressor p53 and is thought to be involved in p53-mediated cell death. It contains a p53 consensus binding site in its promoter region and a downstream pentanucleotide microsatellite sequence. P53 has been shown to transcriptionally activate this gene by interacting with the downstream pentanucleotide microsatellite sequence. The microsatellite is polymorphic, with a varying number of pentanucleotide repeats directly correlated with the extent of transcriptional activation by p53. It has been suggested that the microsatellite polymorphism may be associated with differential susceptibility to cancer. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2011]

MANE transcript

NM_004881.5

Inheritance

—

ClinVar variants

U:47B:17

Top phenotype

TP53I3-related disorder

gnomAD constraint

pLI —, LoF o/e 1.09

Max pathogenic AF

—

Genomic locus

chr2:24,077,433-24,085,861

External References & Databases

Ensembl (ENSG00000115129)

Transcript & Mutation Effects

hg38 • Region Span ~8.4 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TP53I3 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 41

TP53I3-related disorderTotal: 23

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004881.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				6 clinvar	3 clinvar	9
missense			42 clinvar	5 clinvar		47
nonsense			3 clinvar	3 clinvar		6
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	47	14	3	64

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 25 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_004881.5	RefSeq	NP_004872.2	5	MANE Select
ENST00000238721.9	Ensembl	ENSP00000238721.4	5	MANE Select
NM_001206802.2	RefSeq	NP_001193731.1	4	Standard
NM_147184.4	RefSeq	NP_671713.1	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

p53 signaling pathway - Homo sapiens (human)
TP53 Regulates Transcription of Cell Death Genes
Gene expression (Transcription)
Generic Transcription Pathway
TP53 Regulates Transcription of Cell Death Genes

Biological Process

NADP metabolic process
regulation of apoptotic process
oxidation-reduction process

Molecular Function

NADPH:quinone reductase activity
protein homodimerization activity
quinone binding
NADPH binding

Cellular Component

cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000238721
Coding exons: 5
Length: 8429
Individuals with no LoFs: 125185
Homozygous LoFs: 0
Heterozygous LoFs: 562
Defined: 125747
p: 0.00224

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.512	166	186	0.894	0.00000945	2126
Missense (PolyPhen)		47	56.436	0.8328		677
Synonymous	0.394	74	78.4	0.943	0.00000428	711
Loss of Function	-0.310	15	13.8	1.09	7.35e-7	151

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0067	0.0067	notable
Latino/Admixed American	0.0010	0.0010	notable
Ashkenazi Jewish	0.00099	0.00099	rare
East Asian	0.00033	0.00033	rare
Finnish	0.0011	0.0011	notable
European (Non-Finnish)	0.0030	0.0030	notable
South Asian	0.0010	0.0010	notable
Other	0.0016	0.0015	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May be involved in the generation of reactive oxygen species (ROS). Has low NADPH-dependent beta-naphthoquinone reductase activity, with a preference for 1,2-beta-naphthoquinone over 1,4-beta-naphthoquinone. Has low NADPH-dependent diamine reductase activity (in vitro). {ECO:0000269|PubMed:19349281}.;

Recessive Scores

pRec: 0.139

Intolerance Scores

LoFtool: 0.879
RVIS EVS: 0.55
RVIS percentile EVS: 81.48

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.925

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium