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BCKDHB

branched chain keto acid dehydrogenase E1 subunit beta

The BCKDHB gene provides instructions for a key component of an enzyme complex essential for breaking down certain amino acids in the body. The BCKDHB gene is crucial for normal metabolic function, specifically in the breakdown of branched-chain amino acids.

Chromosome 6q14.1 Autosomal recessive HGNC:987 Tier C
BCKDHB 6q14.1 p arm q arm 6

BCKDHB is located on the long (q) arm of chromosome 6, at band 6q14.1. Arm ratio per GRCh38 - banding schematic.

Explore chromosome 6 in the library →

Available at Jeen Health

Clinical tests that include this

Carrier Screening panel
BCKDHB is 1 of 1,008 genes on this panel
Expanded carrier screening for recessive and X-linked conditions
Newborn Genetic Screening panel
BCKDHB is 1 of 258 genes on this panel
Genomic newborn screening for actionable paediatric conditions

Overview

The BCKDHB gene encodes a subunit of the branched-chain alpha-keto acid dehydrogenase (BCKD) enzyme complex. This complex plays a vital role in metabolising branched-chain amino acids, which are obtained from dietary protein.

Disruptions to the BCKDHB gene can impair the function of the BCKD enzyme complex, leading to the accumulation of these amino acids and their by-products. This accumulation can result in serious health conditions, notably Maple Syrup Urine Disease.

What the gene does

The BCKDHB gene provides the blueprint for the beta subunit of the E1 component within the branched-chain alpha-keto acid dehydrogenase (BCKD) enzyme complex. Two beta subunits, along with two alpha subunits (encoded by the BCKDHA gene), form the complete E1 component. This E1 component is a critical part of the larger BCKD enzyme complex, which resides within the mitochondria, the cell's energy-producing centres.

The primary function of the BCKD enzyme complex is to catalyse a step in the breakdown pathway of three specific branched-chain amino acids: leucine, isoleucine, and valine. These amino acids are obtained through the diet, particularly from protein-rich foods. Their breakdown generates molecules that can be utilised by the body for energy production.

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Chromosome location

The BCKDHB gene is located on chromosome 6, specifically at position 6q14.1. This genomic address pinpoints its precise location within the human genome.

Protein structure

The BCKDHB gene produces a protein composed of 392 amino acids. This protein forms the beta subunit, a key component of the branched-chain alpha-keto acid dehydrogenase (BCKD) enzyme complex.

Key variants

Variants within the BCKDHB gene can alter the structure or function of the beta subunit, thereby affecting the overall activity of the BCKD enzyme complex. More than 90 distinct genetic changes have been identified in individuals with conditions associated with this gene.

The table below shows the top 10 pathogenic or likely-pathogenic variants currently classified in ClinVar for BCKDHB.
View all on ClinVar →

Sample of pathogenic variants

10 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.

Variant (HGVS) Protein change Classification Evidence Associated condition
c.1007dup
Duplication
 p.Phe337fs Pathogenic/Likely pathogenic ★★☆☆ Maple syrup urine disease
c.1095_1096del
Microsatellite
 p.Pro366fs Pathogenic/Likely pathogenic ★★☆☆ Maple syrup urine disease
c.199C>T
single nucleotide variant
 p.Gln67Ter Pathogenic/Likely pathogenic ★★☆☆ Maple syrup urine disease type 1B
c.274+1G>T
single nucleotide variant
 - Pathogenic/Likely pathogenic ★★☆☆ Maple syrup urine disease type 1A
c.360dup
Duplication
 p.Asn121Ter Pathogenic/Likely pathogenic ★★☆☆ Maple syrup urine disease type 1B
c.532G>T
single nucleotide variant
 p.Gly178Ter Pathogenic/Likely pathogenic ★★☆☆ Maple syrup urine disease type 1A
c.550del
Deletion
 p.Ser184fs Pathogenic ★★☆☆ Maple syrup urine disease type 1B
c.580C>T
single nucleotide variant
 p.Leu194Phe Pathogenic/Likely pathogenic ★★☆☆ Maple syrup urine disease
c.756_759del
Deletion
 p.Ile253fs Pathogenic/Likely pathogenic ★★☆☆ Maple syrup urine disease type 1B
c.75del
Deletion
 p.Leu26fs Pathogenic ★★☆☆ Maple syrup urine disease

Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.

Associated conditions

Pathogenic variants in the BCKDHB gene are primarily associated with Maple Syrup Urine Disease, which is inherited in an autosomal recessive pattern. This condition typically manifests as the severe, classic form shortly after birth. The disease is named for the distinctive sweet odour of affected infants' urine, which is a characteristic symptom.

Inheritance pattern

Conditions caused by pathogenic BCKDHB variants typically follow autosomal recessive inheritance.

♀ Carrier parent 1 altered copy ♂ Carrier parent 1 altered copy Affected Carrier Carrier Unaffected Affected Carrier Unaffected Circles = females · Squares = males

When both parents are carriers, each child has a 25% chance of being affected, 50% of being a carrier, and 25% of being unaffected.

Carrier frequency by population How common is heterozygous BCKDHB carrier status across ancestry groups?

UK clinical status

The BCKDHB gene is recognised within the NHS Genomic Medicine Service due to its clinical significance. It is listed on several NHS England National Genomic Test Directory panels, including those for Early onset or syndromic epilepsy, Hereditary neuropathy, Hereditary neuropathy or pain disorder (R78), Hyperammonaemia, Intellectual disability, Likely inborn error of metabolism (R98), and Undiagnosed metabolic disorders. It is also included in the DDG2P database.

Green-listed
High evidence · clinically actionable in NHS testing
Included in NHS GMS signed-off panels
Hereditary neuropathy or pain disorder · R78 NHS GMS → Likely inborn error of metabolism · R98 NHS GMS → DDG2P NHS GMS → Early onset or syndromic epilepsy NHS GMS → Intellectual disability NHS GMS →
NHS Genomic Medicine Service Jeen carrier screening

Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory

Frequently asked questions

What is the main role of the BCKDHB gene?

The BCKDHB gene provides instructions for creating a component of the BCKD enzyme complex, which is essential for breaking down specific branched-chain amino acids (leucine, isoleucine, and valine) obtained from food.

How is Maple Syrup Urine Disease related to the BCKDHB gene?

Maple Syrup Urine Disease is caused by pathogenic variants in genes like BCKDHB. These variants impair the function of the BCKD enzyme complex, leading to an accumulation of branched-chain amino acids and their by-products, which causes the symptoms of the disease.

Is Maple Syrup Urine Disease inherited?

Yes, Maple Syrup Urine Disease is inherited in an autosomal recessive manner. This means an individual must inherit two copies of a pathogenic variant (one from each parent) to develop the condition.

References

  1. Quental S, Macedo-Ribeiro S, Matos R. Molecular and structural analyses of maple syrup urine disease and identification of a founder mutation in a Portuguese Gypsy community. Molecular genetics and metabolism. 2008. PMID: 18378174
  2. Flaschker N, Feyen O, Fend S. Description of the mutations in 15 subjects with variant forms of maple syrup urine disease. Journal of inherited metabolic disease. 2007. PMID: 17922217
  3. Rodríguez-Pombo P, Navarrete R, Merinero B. Mutational spectrum of maple syrup urine disease in Spain. Human mutation. 2006. PMID: 16786533
  4. Henneke M, Flaschker N, Helbling C. Identification of twelve novel mutations in patients with classic and variant forms of maple syrup urine disease. Human mutation. 2003. PMID: 14517957
  5. Nellis MM, Danner DJ. Gene preference in maple syrup urine disease. American journal of human genetics. 2001. PMID: 11112664
  6. Edelmann L, Wasserstein MP, Kornreich R. Maple syrup urine disease: identification and carrier-frequency determination of a novel founder mutation in the Ashkenazi Jewish population. American journal of human genetics. 2001. PMID: 11509994
  7. Adam MP, Bick S, Mirzaa GM. Maple Syrup Urine Disease. 1993. PMID: 20301495
Educational content. This page is not medical or genetic advice, is not individually reviewed by a clinician for each reader, and should not replace a consultation with a qualified healthcare professional or genetic counsellor. If you are considering genetic testing or acting on a test result, book a consultation.
Data sources Last updated 13 September 2026. Content compiled from HGNC · MedlinePlus Genetics · ClinGen · Genomics England PanelApp · NHS National Genomic Test Directory · ClinVar · UniProt · AlphaFold .