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Skeletal dysplasia

Gene: UNC45A

Amber List (moderate evidence)

UNC45A (unc-45 myosin chaperone A)
EnsemblGeneIds (GRCh38): ENSG00000140553
EnsemblGeneIds (GRCh37): ENSG00000140553
OMIM: 611219, Gene2Phenotype
UNC45A is in 3 panels

3 reviews

Eleanor Williams (Genomics England Curator)

Green List (high evidence)

Copied this gene from the Osteogenesis imperfecta panel, as all green genes on that panel should also be green on the Skeletal dysplasia panel
Created: 25 Sep 2021, 1:43 p.m. | Last Modified: 25 Sep 2021, 1:43 p.m.
Panel Version: 2.126
Comment on list classification: Promoting this gene from grey to amber, with recommendation for green rating following GMS review. 2 unrelated families with bone fragility and biallelic variants in this gene reported in the literature, plus another case reported by an NHS laboratory.
Created: 18 Aug 2021, 3:43 p.m. | Last Modified: 18 Aug 2021, 3:43 p.m.
Panel Version: 2.19
Associated with Osteootohepatoenteric syndrome #619377 (AR) in OMIM.

As expert reviewers note, PMID: 29429573 (Esteve et al 2018) report 4 individuals from 3 families with compound het missense and nonsense variants in UNC45A. In 2 of the families bone fragility is reported as part of the phenotype. Patient lymphoblastoid cells showed a 70-93% decrease in abundance in UNC45A protein compared to controls.

Additional case with bone fragility/osteopenia reported by Julia Baptista brings the number of cases with this phenotype to three.
Created: 18 Aug 2021, 3:42 p.m. | Last Modified: 18 Aug 2021, 3:42 p.m.
Panel Version: 2.18

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Osteootohepatoenteric syndrome, OMIM:619377


Julia Baptista (Royal Devon and Exeter NHS Foundation Trust)

Green List (high evidence)

In addition to the three families reported by Esteve et al 2018, we are aware of two additional patients with biallelic UNC45A variants. Only one had bone fragility/osteopenia, but both presented with cholestasis and diarrhoea (in one case this was congenital whereas in the other it developed early in life).
Created: 19 Feb 2021, 6:07 p.m. | Last Modified: 19 Feb 2021, 6:07 p.m.
Panel Version: 2.13

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

cholestasis; diarrhea; bone fragility


Variants in this GENE are reported as part of current diagnostic practice

Zornitza Stark (Australian Genomics)

I don't know

Bone fragility is present in 3 cases from two families and is not present in another case with biallelic variants. In vitro functional assays suggest loss-of-function mechanism of disease. In vivo zebrafish assays demonstrate defects in gut development and bone fragility doesn't appear to be assessed. Emerging gene-disease association, uncertain if bone fragility is a consistent/prominent feature of the phenotype yet.
Sources: Expert list
Created: 27 Jul 2020, 12:16 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

cholestasis; congenital diarrhea; impaired hearing; bone fragility



Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
  • Expert Review Amber
  • Expert list
  • Osteootohepatoenteric syndrome, OMIM:619377
Q3_21_rating Q3_21_NHS_review
Clinvar variants
Variants in UNC45A
Panels with this gene

History Filter Activity

25 Sep 2021, Gel status: 2

Created, Added New Source, Added Tag, Set mode of inheritance, Set publications, Set Phenotypes

Eleanor Williams (Genomics England Curator)

gene: UNC45A was added gene: UNC45A was added to Skeletal dysplasia. Sources: Expert list,Expert Review Amber Q3_21_rating, Q3_21_NHS_review tags were added to gene: UNC45A. Mode of inheritance for gene: UNC45A was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: UNC45A were set to 29429573 Phenotypes for gene: UNC45A were set to Osteootohepatoenteric syndrome, OMIM:619377