BCAT1

Chr 12

branched chain amino acid transaminase 1

Also known as: BCATC, BCT1, ECA39, MECA39, PNAS121, PP18

NCBI Gene: 586 ENSG00000060982 UniProt: P54687 OMIM: 113520

The protein is the cytosolic branched-chain amino acid transaminase that catalyzes the reversible transamination of branched-chain amino acids (leucine, isoleucine, and valine), which are essential for cell growth. Mutations cause hypervalinemia and hyperleucine-isoleucinemia with autosomal recessive inheritance. The gene shows no constraint against loss-of-function variants, indicating that complete loss of this cytosolic enzyme may be tolerated due to the presence of the mitochondrial isoform.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes the cytosolic form of the enzyme branched-chain amino acid transaminase. This enzyme catalyzes the reversible transamination of branched-chain alpha-keto acids to branched-chain L-amino acids essential for cell growth. Two different clinical disorders have been attributed to a defect of branched-chain amino acid transamination: hypervalinemia and hyperleucine-isoleucinemia. As there is also a gene encoding a mitochondrial form of this enzyme, mutations in either gene may contribute to these disorders. Alternatively spliced transcript variants have been described. [provided by RefSeq, May 2010]

OMIM ResearchGenerating clinical summary…

Active trials

110

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.02

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.02LOEUF

pLI 0.000

Z-score 1.48

OE 0.66 (0.44–1.02)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.22Z-score

OE missense 1.04 (0.93–1.17)

216 obs / 207.1 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.66 (0.44–1.02)

0≤0.351.4

Missense OE?1.04 (0.93–1.17)

0≤0.61.4

Synonymous OE?1.04

0≤1.21.6

LoF obs/exp: 15 / 22.6Missense obs/exp: 216 / 207.1Syn Z: -0.29

Background carrier burden — how many people carry a rare variant somewhere in BCAT1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 140

507 rare PASS variants

Rare truncating (LoF)

1 in 1,300

102 rare PASS variants

Rare synonymous (reference)

1 in 300

186 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for BCAT1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 180	1 in 1,500
South Asian	~43k	1 in 140	1 in 2,600
Remaining (unassigned)	~30k	1 in 120	1 in 2,300
European (Finnish)	~27k	1 in 280	≈ 1 in 13,000
Admixed American	~22k	1 in 110	1 in 1,300
African / African American	~21k	1 in 160	1 in 1,200
East Asian	~20k	1 in 92	1 in 1,100
Ashkenazi Jewish	~13k	1 in 250	1 in 2,600
Middle Eastern	~2,884	1 in 100	1 in 480

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 11 coding exons well covered in gnomAD exomes and genomes.? see exons ↓