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Skeletal dysplasia

Gene: TMEM251

Amber List (moderate evidence)

TMEM251 (transmembrane protein 251)
EnsemblGeneIds (GRCh38): ENSG00000153485
EnsemblGeneIds (GRCh37): ENSG00000153485
TMEM251 is in 1 panel

2 reviews

Eleanor Williams (Genomics England Curator)

I don't know

Comment on list classification: Promoting from grey to amber. 2 cases reported.
Created: 20 Oct 2021, 10:40 a.m. | Last Modified: 20 Oct 2021, 10:40 a.m.
Panel Version: 2.139
Associated with Dysostosis multiplex, Ain-Naz type #619345 (AR) in OMIM.

As reviewer states, PMID:33252156 (Ain et al 2021), reports two unrelated families (from Pakistan and Iran) with individuals presenting with a severe skeletal disorder. WES identified two homozygous variants (missense and nonsense) in TMEM251. The candidate variants segregated with 5 affected members of the first family. In the second family there was only 1 affected individual who was homozygous for the variant, 22 other unaffected members were either heterozygous or and wild type alleles. The affected patient from the second family had developmental delay and craniosynostosis in addition to skeletal abnormalities. Abnormal activities of three lysosomal enzymes detected from the sample of the patient from one family suggest that TMEM251 may have a metabolic role. (It was not possible to perform these tests in affected individuals in the other family). Some functional data (p.Arg45Trp mutant TMEM251 protein was targeted less efficiently and the localization was punctate in Golgi in osteosarcoma cells, and Tmem251 knockdown by small interfering RNA induced dedifferentiation of rat primary chondrocytes).
Created: 20 Oct 2021, 10:32 a.m. | Last Modified: 20 Oct 2021, 10:32 a.m.
Panel Version: 2.137

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Dysostosis multiplex, Ain-Naz type, OMIM:19345

Publications

Zornitza Stark (Australian Genomics)

I don't know

Two unrelated consanguineous families with homozygous variants (c.133C>T; p.Arg45Trp and c.215dupA; p.Tyr72Ter), with co-segregation data in one family. Preliminary in vitro functional assays conducted - Tmem251 knockdown by small interfering RNA induced dedifferentiation of rat primary chondrocytes.
Sources: Literature
Created: 21 Jan 2021, 9:19 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Dysostosis multiplex‐like skeletal dysplasia; severe short stature

Publications

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
Phenotypes
  • Dysostosis multiplex, Ain-Naz type, OMIM:19345
  • severe short stature
Clinvar variants
Variants in TMEM251
Penetrance
None
Publications
Panels with this gene

History Filter Activity

20 Oct 2021, Gel status: 2

Entity classified by Genomics England curator

Eleanor Williams (Genomics England Curator)

Gene: tmem251 has been classified as Amber List (Moderate Evidence).

20 Oct 2021, Gel status: 0

Set Phenotypes

Eleanor Williams (Genomics England Curator)

Phenotypes for gene: TMEM251 were changed from Dysostosis multiplex‐like skeletal dysplasia; severe short stature to Dysostosis multiplex, Ain-Naz type, OMIM:19345; severe short stature

21 Jan 2021, Gel status: 0

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

Zornitza Stark (Australian Genomics)

gene: TMEM251 was added gene: TMEM251 was added to Skeletal dysplasia. Sources: Literature Mode of inheritance for gene: TMEM251 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TMEM251 were set to 33252156 Phenotypes for gene: TMEM251 were set to Dysostosis multiplex‐like skeletal dysplasia; severe short stature Review for gene: TMEM251 was set to AMBER