Intellectual disability
Gene: TP73

TP73 (tumor protein p73)
EnsemblGeneIds (GRCh38): ENSG00000078900
EnsemblGeneIds (GRCh37): ENSG00000078900
OMIM: 601990, Gene2Phenotype
TP73 is in 5 panels

3 reviews

Sarah Leigh (Genomics England Curator)

The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Created: 14 Mar 2022, 2:22 p.m. | Last Modified: 14 Mar 2022, 2:22 p.m.

Panel Version: 3.1519

Created: 14 Mar 2022, 2:22 p.m.
Last Modified: 14 Mar 2022, 2:22 p.m.
Panel version: 3.1519

Arina Puzriakova (Genomics England Curator)

Green List (high evidence)

Comment on list classification: There is now sufficient evidence to promote this gene to Green at the next GMS panel review - at least 7 unrelated families with distinct variants and relevant phenotypes. Supported by some functional data.

TP73 is also now associated with a relevant phenotype in OMIM (MIM# 619466) but is not yet listed in G2P.
Created: 21 Sep 2021, 2:09 p.m. | Last Modified: 21 Sep 2021, 2:09 p.m.

Panel Version: 3.1295

PMID: 34077761 (2021) - Further 7 individuals from 5 families identified with different homozygous variants in this gene. All affected individuals exhibited cortical malformations characterised by lissencephaly, central muscular hypotonia and moderate to severe cognitive dysfunction.
Created: 21 Sep 2021, 2:06 p.m. | Last Modified: 21 Sep 2021, 2:06 p.m.

Panel Version: 3.1294

Comment on list classification: Rating Red as gene only distinguished due to multiple hits in same candidate gene - patients display discordant phenotype and DD only reported in one patient.
Created: 27 Aug 2020, 3:06 p.m. | Last Modified: 27 Aug 2020, 3:06 p.m.

Panel Version: 3.272

PMID: 31130284 (2019) - Two individuals with homozygous variants in this gene identified as part of a large candidate gene discovery study. Phenotype in one patient included lissencephaly and hypotonia; while the other, a 19-month-old female, presented motor delay, speech delay, cleft lip and/or palate, cortical dysplasia, pachygyria, and strabismus.
Created: 27 Aug 2020, 3:04 p.m. | Last Modified: 27 Aug 2020, 3:04 p.m.

Panel Version: 3.271

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Ciliary dyskinesia, primary, 47, and lissencephaly, OMIM:619466

Publications

Created: 27 Aug 2020, 3:04 p.m.
Last Modified: 27 Aug 2020, 3:04 p.m.
Panel version: 3.1294

Zornitza Stark (Australian Genomics)

Green List (high evidence)

New publication adds further evidence for gene-disease association, PMID 34077761:

- Seven individuals from five unrelated families homozygous for TP73 variants (includes 1x large deletion, 1x splice variant, 1x frameshift and 2x nonsense variants) and cortical malformations/ID
- In vitro ciliogenesis experiments demonstrated that epithelial cells from TP73 variant carriers had reduced number of ciliated cells and shortened cilia resulting in abnormal ciliary clearance of the airways compared to healthy controls
Created: 7 Aug 2021, 7:29 a.m. | Last Modified: 7 Aug 2021, 7:29 a.m.

Panel Version: 3.1216

Two unrelated families, no functional data.
Sources: Expert list
Created: 1 Mar 2020, 8:45 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Intellectual disability; lissencephaly

Publications

Created: 1 Mar 2020, 8:45 a.m.

Panel version: 3.1216

Details

Mode of Inheritance

BIALLELIC, autosomal or pseudoautosomal

Sources

Expert Review Green

Phenotypes

Ciliary dyskinesia, primary, 47, and lissencephaly, OMIM:619466

OMIM

601990

Clinvar variants

Variants in TP73

Penetrance

None

Publications

Panels with this gene

History Filter Activity

14 Mar 2022, Gel status: 3

Removed Tag

Ivone Leong (Genomics England Curator)

Tag Q3_21_rating was removed from gene: TP73.

14 Mar 2022, Gel status: 3

Added New Source, Status Update

Ivone Leong (Genomics England Curator)

Source Expert Review Green was added to TP73. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)

21 Sep 2021, Gel status: 2