PDHA1 |
- 3
Haplo
Score - 0
Triplo
Score
Gene Facts External Data Attribution
- HGNC Symbol
- PDHA1 (HGNC:8806) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
- HGNC Name
- pyruvate dehydrogenase E1 subunit alpha 1
- Gene type
- protein-coding gene
- Locus type
- gene with protein product
- Previous symbols
- PDHA
- Alias symbols
- E1alpha
- %HI
- 35.05(Read more about the DECIPHER Haploinsufficiency Index)
- pLI
- 0.99(Read more about gnomAD pLI score)
- LOEUF
- 0.27(Read more about gnomAD LOEUF score)
- Cytoband
- Xp22.12
- Genomic Coordinates
-
GRCh37/hg19: chrX:19362045-19379836 NCBI Ensembl UCSC GRCh38/hg38: chrX:19343927-19361718 NCBI Ensembl UCSC - MANE Select Transcript
- NM_000284.4 ENST00000422285.7 (Read more about MANE Select)
- Function
- The pyruvate dehydrogenase complex catalyzes the overall conversion of pyruvate to acetyl-CoA and CO(2), and thereby links the glycolytic pathway to the tricarboxylic cycle. {ECO:0000269|PubMed:19081061, ECO:0000269|PubMed:7782287}. (Source: Uniprot)
Dosage Sensitivity Summary (Gene)
Haploinsufficiency (HI) Score Details
- pyruvate dehydrogenase deficiency Monarch
-
PUBMED:
21914562
Imbard et al (2014) sequenced PDHA1 in 82 individuals with pyruvate dehydrogenase complex deficiency and identified 4 truncating variants in PDHA1 in three females (p.Ser312ArgfsX13, p.Arg304X, p.Gln84ThrfsX12) and one mosaic male (p.Arg283X). Affected individuals were all found to have reduced PDHc enzyme activity in fibroblasts. Two of the truncating variants detected in females were de novo. The inheritance of the other two variants was unknown. Two additional individuals were found to have large deletions (3.4 MB and 2.1 MB) containing PDHA1.
-
PUBMED:
33504798
Martin et al (2021) analyzed exome sequencing data from 11,044 families in the Deciphering Developmental Disorders study to study the contribution of X-liked causes of developmental disorders in males and females. In this study they detected 2 de novo frameshift variants and 1 de novo nonsense variant in PDHA1 in female probands.
-
PUBMED:
18709504
Ridout et al (2008) detected a mosaic splice site variant in a female with clinical features of pyruvate dehydrogenase complex deficiency, including brain abnormalities, developmental delay, and elevated lactate. Immunocytochemistry showed 40% of fibroblasts were deficient for E1alpha protein. Mutant cDNA was not detected suggesting the abnormal transcript was degraded. The splice site variant was not present in either parent.
-
PUBMED:
15384102
Cameron et al (2004) detected a 4 basepair duplication in exon 9 of PDHA1 in a female with severe lactic acidosis, prenatal hydrocephalus, and died at 1 month of age. Western blot demonstrated reduced E1alph protein and very low PDHc enzyme activity was detected in fibroblasts. The variant was not present in an unaffected female sibling.
-
PUBMED:
20002125
Barnerias et al (2010) reported a 4 basepair deletion in a female with encephalopathy, seizures, brain abnormalities, elevated lactate, and reduced PDHc activity.
The loss-of-function and triplosensitivity ratings for genes on the X chromosome are made in the context of a male genome to account for the effects of hemizygous duplications or nullizygous deletions. In contrast, disruption of some genes on the X chromosome causes male lethality and the ratings of dosage sensitivity instead take into account the phenotype in female individuals. Factors that may affect the severity of phenotypes associated with X-linked disorders include the presence of variable copies of the X chromosome (i.e. 47,XXY or 45,X) and skewed X-inactivation in females.
Triplosensitivity (TS) Score Details
The loss-of-function and triplosensitivity ratings for genes on the X chromosome are made in the context of a male genome to account for the effects of hemizygous duplications or nullizygous deletions. In contrast, disruption of some genes on the X chromosome causes male lethality and the ratings of dosage sensitivity instead take into account the phenotype in female individuals. Factors that may affect the severity of phenotypes associated with X-linked disorders include the presence of variable copies of the X chromosome (i.e. 47,XXY or 45,X) and skewed X-inactivation in females.