PDHA2

pyruvate dehydrogenase E1 subunit alpha 2

Basic information

Region (hg38): 4:95840093-95841464

Previous symbols: [ "PDHAL" ]

Links

ENSG00000163114 ∙ NCBI:5161 ∙ OMIM:179061 ∙ HGNC:8807 ∙ Uniprot:P29803 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• spermatogenic failure 70 (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Spermatogenic failure 70	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Genitourinary	29581481; 35172124

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PDHA2 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PDHA2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous						0
missense			27		2	29
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	27	0	2

Variants in PDHA2

This is a list of pathogenic ClinVar variants found in the PDHA2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
4-95840164-T-C		not specified	Uncertain significance (Jan 21, 2025)
4-95840166-A-T		not specified	Uncertain significance (Apr 18, 2023)
4-95840172-C-A		not specified	Uncertain significance (Dec 16, 2023)
4-95840175-G-A		not specified	Uncertain significance (Oct 25, 2023)
4-95840185-G-A		not specified	Uncertain significance (Jan 25, 2025)
4-95840203-C-T		not specified	Uncertain significance (Oct 04, 2022)
4-95840212-T-A			Benign (May 01, 2023)
4-95840245-C-T		not specified	Uncertain significance (May 24, 2023)
4-95840338-A-G		not specified	Uncertain significance (Jan 22, 2025)
4-95840424-T-G		not specified	Uncertain significance (Jun 17, 2024)
4-95840443-G-A		not specified	Uncertain significance (Jan 08, 2025)
4-95840451-G-C		not specified	Uncertain significance (Oct 20, 2023)
4-95840463-G-A		not specified	Uncertain significance (May 26, 2023)
4-95840464-G-C		not specified	Uncertain significance (Jul 16, 2024)
4-95840497-A-G		not specified	Uncertain significance (Dec 27, 2023)
4-95840523-C-T		not specified	Uncertain significance (Oct 20, 2023)
4-95840554-A-G		not specified	Uncertain significance (Dec 23, 2024)
4-95840577-T-C		not specified	Uncertain significance (Apr 20, 2024)
4-95840626-A-G		not specified	Uncertain significance (Jan 21, 2025)
4-95840638-G-A		not specified	Uncertain significance (Dec 03, 2024)
4-95840668-C-G		not specified	Uncertain significance (Dec 14, 2024)
4-95840706-G-A		not specified	Uncertain significance (Sep 16, 2021)
4-95840718-A-C		not specified	Uncertain significance (Feb 03, 2022)
4-95840718-A-G		not specified	Uncertain significance (Feb 28, 2023)
4-95840740-C-T		not specified	Uncertain significance (Apr 24, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PDHA2	protein_coding	protein_coding	ENST00000295266	1	1387

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.93e-9	0.0561	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.260	242	231	1.05	0.0000141	2518
Missense in Polyphen		105	96.764	1.0851		1071
Synonymous	-0.435	94	88.8	1.06	0.00000573	786
Loss of Function	-0.455	12	10.4	1.15	7.11e-7	131

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: 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:16436377}.
• Pathway: Citrate cycle (TCA cycle) - Homo sapiens (human);Pyruvate metabolism - Homo sapiens (human);Glycolysis / Gluconeogenesis - Homo sapiens (human);Central carbon metabolism in cancer - Homo sapiens (human);HIF-1 signaling pathway - Homo sapiens (human);Glucagon signaling pathway - Homo sapiens (human);Hereditary Leiomyomatosis and Renal Cell Carcinoma Pathway;Acetylcholine Synthesis;Glycolysis and Gluconeogenesis;Signal Transduction;Regulation of pyruvate dehydrogenase (PDH) complex;Pyruvate metabolism;Pyruvate metabolism and Citric Acid (TCA) cycle;Metabolism of amino acids and derivatives;The citric acid (TCA) cycle and respiratory electron transport;Glycolysis and Gluconeogenesis;Metabolism;pyruvate decarboxylation to acetyl CoA;Glyoxylate metabolism and glycine degradation;Pyruvate metabolism;Signaling by Retinoic Acid;Signaling by Nuclear Receptors;superpathway of conversion of glucose to acetyl CoA and entry into the TCA cycle (Consensus)

Recessive Scores

• pRec: 0.275

Intolerance Scores

• loftool: 0.270
• rvis_EVS: 0.33
• rvis_percentile_EVS: 73.61

Haploinsufficiency Scores

• pHI: 0.258
• hipred: N
• hipred_score: 0.173

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.981

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Pdha2

Gene ontology

• Biological process: glucose metabolic process;acetyl-CoA biosynthetic process from pyruvate;pyruvate metabolic process;tricarboxylic acid cycle
• Cellular component: nucleus;nucleolus;mitochondrion;mitochondrial matrix;pyruvate dehydrogenase complex
• Molecular function: pyruvate dehydrogenase (acetyl-transferring) activity;pyruvate dehydrogenase (NAD+) activity