Genes in panel
STRs in panel
Prev Next
Regions in panel
Prev Next

Intellectual disability syndromic and non-syndromic

Gene: THRA

Green List (high evidence)

THRA (thyroid hormone receptor, alpha)
EnsemblGeneIds (GRCh38): ENSG00000126351
EnsemblGeneIds (GRCh37): ENSG00000126351
OMIM: 190120, Gene2Phenotype
THRA is in 7 panels

1 review

Hnin Aung (Other)

Green List (high evidence)

Over 10 sequence variants (including truncating nonsense and frameshift as well as missense) have been reported in the literature in association with consistent phenotype of mild hypothyroidism (growth retardation, relatively high birth length and weight, mild-to-moderate mental retardation, mild skeletal dysplasia, delayed dentition and constipation) and specific facial features. Milder outcomes for missense variants and more severe phenotype manifestations for truncating variants have been observed.

Most of the variants are located in the last exon of the THRA isoform 1 (NM_199334.5; a shorter isoform) affecting the C-terminal ligand binding domain with nonsense and frameshift variants predicted to escape nonsense mediated decay. These variants are either de novo or inherited from an affected parent. A few pedigrees are also available with segregation data. Truncating variants appear to have near complete penetrance whereas missense variants may be associated with variable expressivity (Family C - PMID: 27144938).

Functional evidence suggests altered gene product with possible dominant negative effect (PMID: 22168587, 28471274). Knock in mouse model available for E403X presenting with similar phenotype as seen in the human patients, including growth retardation and variable presentation of psychomotor deficit (PMID: 32924834). A small number THRA sequence variant (missense) reported among autism cohort [PMID: 28856816, 25621899].
Created: 22 May 2024, 3:41 a.m. | Last Modified: 22 May 2024, 3:47 a.m.
Panel Version: 0.5881

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Hypothyroidism congenital nongoitrous 6 (MIM 614450); Intellectual disability syndromic; Growth retardation; Facial dysmorphism; Constipation

Publications

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • Genetic Health Queensland
Phenotypes
  • Hypothyroidism congenital nongoitrous 6 (MIM 614450)
OMIM
190120
Clinvar variants
Variants in THRA
Penetrance
None
Publications
Panels with this gene

History Filter Activity

27 May 2024, Gel status: 3

Entity classified by Genomics England curator

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Gene: thra has been classified as Green List (High Evidence).

27 May 2024, Gel status: 3

Set Phenotypes

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Phenotypes for gene: THRA were changed from to Hypothyroidism congenital nongoitrous 6 (MIM 614450)

27 May 2024, Gel status: 3

Set publications

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Publications for gene: THRA were set to

27 May 2024, Gel status: 3

Set mode of inheritance

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Mode of inheritance for gene: THRA was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

22 Nov 2019, Gel status: 3

Created, Added New Source, Set mode of inheritance

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

gene: THRA was added gene: THRA was added to Intellectual disability, syndromic and non-syndromic_GHQ. Sources: Expert Review Green,Genetic Health Queensland Mode of inheritance for gene: THRA was set to Unknown