PDHB

Chr 3AR

pyruvate dehydrogenase E1 subunit beta

Also known as: E1beta, PDHBD, PDHE1-B, PDHE1B, PHE1B

NCBI Gene: 5162 ENSG00000168291 UniProt: P11177 OMIM: 179060

The protein encodes the E1 beta subunit of the pyruvate dehydrogenase complex, which catalyzes the conversion of pyruvate to acetyl-CoA in mitochondria, linking glycolysis to the tricarboxylic acid cycle. Mutations cause pyruvate dehydrogenase E1-beta deficiency through an autosomal recessive inheritance pattern. The pathogenic mechanism involves dominant-negative effects of mutant proteins on the enzymatic complex.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

The pyruvate dehydrogenase (PDH) complex is a nuclear-encoded mitochondrial multienzyme complex that catalyzes the overall conversion of pyruvate to acetyl-CoA and carbon dioxide, and provides the primary link between glycolysis and the tricarboxylic acid (TCA) cycle. The PDH complex is composed of multiple copies of three enzymatic components: pyruvate dehydrogenase (E1), dihydrolipoamide acetyltransferase (E2) and lipoamide dehydrogenase (E3). The E1 enzyme is a heterotetramer of two alpha and two beta subunits. This gene encodes the E1 beta subunit. Mutations in this gene are associated with pyruvate dehydrogenase E1-beta deficiency. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Mar 2012]

GeneReviews OMIM ResearchGenerating clinical summary…

DNmechanismARLOEUF 0.551 OMIM phenotype

Clinical Summary— PDHB

🧬

Gene-Disease Validity (ClinGen)

Leigh syndrome · ARModerate

Moderate evidence — consider for supplementary testing

⚡

Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.26) despite low pLI — interpret in context.

📋

ClinVar Variants

44 unique Pathogenic / Likely Pathogenic· 101 VUS of 445 total submissions

Explore recent and relevant literature in Research Assistant →

📖

GeneReview available — PDHB

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.55LOEUF

pLI 0.152

Z-score 2.98

OE 0.26 (0.14–0.55)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.57Z-score

OE missense 0.69 (0.60–0.79)

139 obs / 201.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.26 (0.14–0.55)

0≤0.351.4

Missense OE?0.69 (0.60–0.79)

0≤0.61.4

Synonymous OE?1.13

0≤1.21.6

LoF obs/exp: 5 / 19.0Missense obs/exp: 139 / 201.6Syn Z: -0.85

This gene — mechanism propensity

0.74top 25%

GOF

0.6052th %ile

LOF

0.3162th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

445 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic18

Likely Pathogenic26

VUS101

Likely Benign249

Benign27

Conflicting11

Pathogenic

Likely Pathogenic

101

VUS

249

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	13	5	0	0	18
Likely Pathogenic	21	5	0	0	26
VUS	1	78	17	5	101
Likely Benign	0	3	113	133	249
Benign	0	0	25	2	27
Conflicting	—				11
Total	35	91	155	140	432

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

9 pathogenic / likely-pathogenic (of 10) ClinVar copy-number / structural variants overlap PDHB — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →