THRA
  • 0
    Haplo
    Score
  • 0
    Triplo
    Score

Gene Facts External Data Attribution

HGNC Symbol
THRA (HGNC:11796) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
HGNC Name
thyroid hormone receptor alpha
Gene type
protein-coding gene
Locus type
gene with protein product
Previous symbols
THRA1, THRA2, ERBA1
Alias symbols
EAR-7.1/EAR-7.2, THRA3, AR7, ERBA, NR1A1, TRalpha, TRalpha1, TRalpha2, c-ERBA-1, c-erbA, THRalpha, THRalpha1, THRalpha2
%HI
3.21(Read more about the DECIPHER Haploinsufficiency Index)
pLI
1(Read more about gnomAD pLI score)
LOEUF
0.44(Read more about gnomAD LOEUF score)
Cytoband
17q21.1
Genomic Coordinates
GRCh37/hg19: chr17:38218446-38250120 NCBI Ensembl UCSC
GRCh38/hg38: chr17:40062193-40093867 NCBI Ensembl UCSC
MANE Select Transcript
NM_199334.5 ENST00000450525.7 (Read more about MANE Select)
Function
[Isoform Alpha-1]: Nuclear hormone receptor that can act as a repressor or activator of transcription. High affinity receptor for thyroid hormones, including triiodothyronine and thyroxine. {ECO:0000269|PubMed:12699376, ECO:0000269|PubMed:14673100, ECO:0000269|PubMed:18237438, ECO:0000269|PubMed:19926848}. [Isoform Alpha-2]: Does not bind thyroid hormone and functions as a weak dominant negative inhibitor of thyroid hormone action. {ECO:0000269|PubMed:8910441}. (Source: Uniprot)

Dosage Sensitivity Summary (Gene)

Dosage ID:
ISCA-27277
ClinGen Curation ID:
CCID:008004
Curation Status:
Complete
Issue Type:
Dosage Curation - Gene
Haploinsufficiency:
No Evidence for Haploinsufficiency (0)
Read full report...
Triplosensitivity:
No Evidence for Triplosensitivity (0)
Read full report...
Last Evaluated:
08/22/2013

Haploinsufficiency (HI) Score Details

HI Score:
0
HI Evidence Strength:
No Evidence for Haploinsufficiency (Disclaimer)
HI Evidence Comments:
Changes in THRA have been associated with nongoitrous congenital hypothyroidism. Evidence suggests that reported mutations act in a dominant negative manner. Buchokova et al. (2012) performed whole-exome sequencing on a 6-year-old girl of white European origin with congenital nongoitrous hypothyroidism and identified a de novo heterozygous E403X substitution in THRA, predicted to cause premature truncation with loss of the C-terminal alpha-helix. The mutation was not found in published normal genomes and exomes or in 200 ethnically matched control alleles. Functional analysis demonstrated that the mutant receptor did not activate a thyroid hormone-responsive reporter gene and mediated substantial repression of basal promoter activity, consistent with negligible binding of radiolabeled triiodothyronine to mutant TR-alpha. Coexpression studies showed that the E403X receptor strongly inhibited transcriptional activity by wildtype TR-alpha in a dominant-negative manner (PMID: 22168587). van Mullem et al. (2012) studied a father and daughter with congenital nongoitrous hypothyroidism and identified a frameshift predicted to result in premature termination (F397fs406X) in THRA. The mutation was not found in the unaffected mother, in 300 Caucasian controls, or in public databases. Transfection studies showed that the mutant receptor does not respond to stimulation by T3, and also exerts a strong dominant-negative effect on wildtype THRA (PMID: 22494134).

Triplosensitivity (TS) Score Details

TS Score:
0
TS Evidence Strength:
No Evidence for Triplosensitivity (Disclaimer)

Genomic View

Select assembly: (NC_000017.10) (NC_000017.11)