HADHB

Chr 2AR

hydroxyacyl-CoA dehydrogenase trifunctional multienzyme complex subunit beta

Also known as: ECHB, MSTP029, MTPB, MTPD, MTPD2, TP-BETA

The beta subunit of mitochondrial trifunctional protein catalyzes 3-ketoacyl-CoA thiolase activity in the final three steps of long-chain fatty acid beta-oxidation and also functions as an RNA-binding protein that destabilizes certain mRNAs. Autosomal recessive mutations cause mitochondrial trifunctional protein deficiency, a disorder of fatty acid oxidation. The pathogenic mechanism involves dominant-negative effects where mutant protein disrupts normal enzyme function.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
DNmechanismARLOEUF 1.041 OMIM phenotype
Clinical SummaryHADHB
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Gene-Disease Validity (ClinGen)
mitochondrial trifunctional protein deficiency · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.04LOEUF
pLI 0.000
Z-score 1.39
OE 0.72 (0.511.04)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.65Z-score
OE missense 0.89 (0.800.99)
234 obs / 263.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.72 (0.511.04)
00.351.4
Missense OE0.89 (0.800.99)
00.61.4
Synonymous OE0.95
01.21.6
LoF obs/exp: 21 / 29.1Missense obs/exp: 234 / 263.7Syn Z: 0.39
DN
0.73top 25%
GOF
0.6051th %ile
LOF
0.4135th %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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

HADHB · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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