TP73

Chr 1AR

tumor protein p73

Also known as: CILD47, P73

NCBI Gene: 7161ENSG00000078900UniProt: O15350

This gene encodes a member of the p53 family of transcription factors involved in cellular responses to stress and development. It maps to a region on chromosome 1p36 that is frequently deleted in neuroblastoma and other tumors, and thought to contain multiple tumor suppressor genes. The demonstration that this gene is monoallelically expressed (likely from the maternal allele), supports the notion that it is a candidate gene for neuroblastoma. Many transcript variants resulting from alternative splicing and/or use of alternate promoters have been found for this gene, but the biological validity and the full-length nature of some variants have not been determined. [provided by RefSeq, Feb 2011]

Primary Disease Associations & Inheritance

Ciliary dyskinesia, primary, 47, and lissencephalyMIM #619466
AR
238
ClinVar variants
97
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— TP73
🧬
Gene-Disease Validity (ClinGen)
ciliary dyskinesia, primary, 47, and lissencephaly · ARStrong

Strong evidence — appropriate for clinical testing

⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
97 Pathogenic / Likely Pathogenic· 109 VUS of 238 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.26LOEUF
pLI 0.997
Z-score 4.59
OE 0.10 (0.04–0.26)
Highly constrained

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

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.85Z-score
OE missense 0.75 (0.68–0.82)
322 obs / 430.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.10 (0.04–0.26)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.75 (0.68–0.82)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.11
0≤1.21.6
LoF obs/exp: 3 / 30.3Missense obs/exp: 322 / 430.1Syn Z: -1.17

ClinVar Variant Classifications

238 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic94
Likely Pathogenic3
VUS109
Likely Benign18
Benign14
94
Pathogenic
3
Likely Pathogenic
109
VUS
18
Likely Benign
14
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
0
92
0
94
Likely Pathogenic
1
0
2
0
3
VUS
0
92
16
1
109
Likely Benign
0
15
0
3
18
Benign
0
1
5
8
14
Total310811512238

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

View in ClinVar →

Protein Context — Lollipop Plot

TP73 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

TP73-related ciliary dyskinesia and lissencephaly

strong
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
TUMOR PROTEIN p73; TP73
MIM #601990 · *

Ciliary dyskinesia, primary, 47, and lissencephaly

MIM #619466

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — TP73
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Comprehensive genomic profiles of small cell lung cancer.
George J et al.·Nature
2015
Long Non-Coding TP73-AS1: A Potential Biomarker and Therapeutic Target in Cancer.
Li K et al.·Int J Mol Sci
2025Review
Long non-coding RNA TP73-AS1 in cancers.
Gong CY et al.·Clin Chim Acta
2020Review
Clinical implications of the deregulated TP73 isoforms expression in cancer.
Rodríguez N et al.·Clin Transl Oncol
2018Review
The TP73 complex network: ready for clinical translation in cancer?
Soldevilla B et al.·Genes Chromosomes Cancer
2013Review
TAp73 and ΔTAp73 isoforms show cell-type specific distributions and alterations in cancer.
Hrabal V et al.·Sci Rep
2024
Association between TP73 G4C14-A4T14 polymorphism and different cancer types: an updated meta-analysis of 55 case-control studies.
Jafrin S et al.·J Int Med Res
2022Meta-analysis
TP73-AS1 promotes breast cancer cell proliferation through miR-200a-mediated TFAM inhibition.
Yao J et al.·J Cell Biochem
2018
Pathogenic TP73 variants may lead to premature ovarian insufficiency by hyperactivating primordial follicles via the PI3K/AKT/FOXO3A pathway.
Hu Z et al.·Maturitas
2025
Patient-derived response estimates from zero-passage organoids of luminal breast cancer.
Przanowska RK et al.·Breast Cancer Res
2024
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools