TP73

Chr 1AR

tumor protein p73

Also known as: CILD47, P73

NCBI Gene: 7161 ENSG00000078900 UniProt: O15350 OMIM: 601990

This protein is a p53 family transcription factor that participates in apoptotic responses to DNA damage and serves as an essential regulator of ciliated cell differentiation in the lungs and other tissues. Mutations cause autosomal recessive primary ciliary dyskinesia and lissencephaly, affecting the respiratory system and brain development. The gene is highly constrained against loss-of-function variants (pLI 0.997, LOEUF 0.26), reflecting its critical developmental importance.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.261 OMIM phenotype

Clinical Summary— TP73

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Gene-Disease Validity (ClinGen)

ciliary dyskinesia, primary, 47, and lissencephaly · ARStrong

Strong evidence — appropriate for clinical testing

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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.

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ClinVar Variants

6 unique Pathogenic / Likely Pathogenic· 95 VUS of 144 total submissions

Explore recent and relevant literature in Research Assistant →

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GeneReview available — TP73

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

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?

1.85Z-score

OE missense 0.75 (0.68–0.82)

322 obs / 430.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.10 (0.04–0.26)

0≤0.351.4

Missense OE?0.75 (0.68–0.82)

0≤0.61.4

Synonymous OE?1.11

0≤1.21.6

LoF obs/exp: 3 / 30.3Missense obs/exp: 322 / 430.1Syn Z: -1.17

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

strongTP73-related ciliary dyskinesia and lissencephalyLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.4389th %ile

GOF

0.3491th %ile

LOF

0.76top 10%

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

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

144 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic5

Likely Pathogenic1

VUS95

Likely Benign18

Benign13

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	4	0	1	0	5
Likely Pathogenic	1	0	0	0	1
VUS	1	94	0	0	95
Likely Benign	0	15	0	3	18
Benign	0	1	4	8	13
Total	6	110	5	11	132

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

View in ClinVar →

94 pathogenic / likely-pathogenic (of 111) ClinVar copy-number / structural variants overlap TP73 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →