Fetal anomalies
Gene: USP14

USP14 (ubiquitin specific peptidase 14)
EnsemblGeneIds (GRCh38): ENSG00000101557
EnsemblGeneIds (GRCh37): ENSG00000101557
OMIM: 607274, Gene2Phenotype
USP14 is in 2 panels

2 reviews

Achchuthan Shanmugasundram (Genomics England Curator)

Green List (high evidence)

The rating of this gene has been updated to green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Created: 25 Feb 2025, 11:15 a.m. | Last Modified: 25 Feb 2025, 11:15 a.m.

Panel Version: 5.78

Comment on list classification: There are four unrelated families and functional evidence in support of the association of this gene to this panel. Hence, this gene can be promoted to green rating in the next GMS review.
Created: 26 Jun 2024, 12:32 p.m. | Last Modified: 26 Jun 2024, 12:32 p.m.

Panel Version: 4.23

PMID:35066879 reported the identification of a biallelic 4-bp deletion variant (p.Leu78Glnfs*11) in USP14 gene in three foetuses from two different branches of a consanguineous family, presenting with distal arthrogryposis, underdevelopment of the corpus callosum, and dysmorphic facial features. sp14-deficient mice show a phenotype similar to lethal human MCC phenotypes, with callosal anomalies, muscle wasting, and early lethality, attributed to neuromuscular junction defects due to decreased monomeric ubiquitin pool.

PMID:38469793 reported the identification of biallelic variants in four cases (one foetus, a newborn with a syndromic neurodevelopmental disorder and two siblings with a progressive neurological disease) from three unrelated families. The two siblings had compound heterozygous variants (p.Leu3Pro and p.Arg330Ter), whereas both foetus ( p.Lys300Serfs∗24) and newborn (p.Leu78Glnfs∗11) harboured different homozygous variants.

This gene has been associated with relevant phenotype in Gene2Phenotype (with 'limited' rating on the DD panel), but not yet in OMIM.
Created: 26 Jun 2024, 12:30 p.m. | Last Modified: 26 Jun 2024, 12:30 p.m.

Panel Version: 4.20

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
syndromic disease, MONDO:0002254; distal arthrogryposis, MONDO:0019942

Publications

Created: 26 Jun 2024, 12:30 p.m.
Last Modified: 26 Jun 2024, 12:32 p.m.
Panel version: 5.78

Zornitza Stark (Australian Genomics)

I don't know

PMID 38469793: biallelic USP14 variants in four individuals from three unrelated families: one fetus, a newborn with a syndromic NDD, and two siblings affected by a progressive neurological disease. Specifically, the two siblings from the latter family carried two compound heterozygous variants c.8T>C p.(Leu3Pro) and c.988C>T p.(Arg330*), while the fetus had a homozygous frameshift c.899_902del p.(Lys300Serfs*24) variant and the newborn patient harbored a homozygous frameshift c.233_236del p.(Leu78Glnfs*11) variant. The fetus and the newborn had extensive brain malformations.
Sources: Literature
Created: 23 Apr 2024, 8:47 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Syndromic disease MONDO:0002254, USP14-related

Publications

38469793

Created: 23 Apr 2024, 8:47 p.m.

Panel version: 3.157

Details

Mode of Inheritance

BIALLELIC, autosomal or pseudoautosomal

Sources

Expert Review Green
NHS GMS

Phenotypes

syndromic disease, MONDO:0002254
distal arthrogryposis, MONDO:0019942

Tags

gene-checked

OMIM

607274

Clinvar variants

Variants in USP14

Penetrance

None

Publications

Panels with this gene