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…

Primary Disease Associations & Inheritance

Ciliary dyskinesia, primary, 47, and lissencephalyMIM #619466

Clinical highlights

Gene–disease validity (ClinGen)

Strong · ciliary dyskinesia, primary, 47, and lissencephaly · AR · ClinGen 2023

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

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Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.26

LOEUF· LoF intol.

LOF

Mechanism· G2P

📖

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

Background carrier burden — how many people carry a rare variant somewhere in TP73?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 71

867 rare PASS variants

Rare truncating (LoF)

1 in 4,000

82 rare PASS variants

Rare synonymous (reference)

1 in 78

408 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for TP73. 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 90	1 in 4,800
South Asian	~43k	1 in 51	1 in 3,800
Remaining (unassigned)	~30k	1 in 70	≈ 1 in 10,000
European (Finnish)	~27k	1 in 160	≈ 1 in 13,000
Admixed American	~22k	1 in 64	1 in 2,000
African / African American	~21k	1 in 67	1 in 2,500
East Asian	~20k	1 in 59	≈ 1 in 4,800
Ashkenazi Jewish	~13k	1 in 370	1 in 1,900
Middle Eastern	~2,884	1 in 74	≈ 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): 12 of 13 coding exons well covered in gnomAD exomes; exon 2 marginal. Genomes: all 13.? see exons ↓