BCAT1

Chr 12

branched chain amino acid transaminase 1

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

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]

0
Active trials
68
Pubs (1 yr)
40
P/LP submissions
0%
P/LP missense
1.02
LOEUF
Multiple*
Mechanism· predicted
Clinical SummaryBCAT1
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
40 unique Pathogenic / Likely Pathogenic· 61 VUS of 133 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.02LOEUF
pLI 0.000
Z-score 1.48
OE 0.66 (0.441.02)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.22Z-score
OE missense 1.04 (0.931.17)
216 obs / 207.1 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.66 (0.441.02)
00.351.4
Missense OE1.04 (0.931.17)
00.61.4
Synonymous OE1.04
01.21.6
LoF obs/exp: 15 / 22.6Missense obs/exp: 216 / 207.1Syn Z: -0.29
DN
0.6454th %ile
GOF
0.7029th %ile
LOF
0.3066th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
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

133 submitted variants in ClinVar

Classification Summary

Pathogenic38
Likely Pathogenic2
VUS61
Likely Benign8
Benign5
38
Pathogenic
2
Likely Pathogenic
61
VUS
8
Likely Benign
5
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
38
0
38
Likely Pathogenic
0
0
2
0
2
VUS
0
53
8
0
61
Likely Benign
0
2
2
4
8
Benign
0
0
3
2
5
Total055536114

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

View in ClinVar →

Protein Context — Lollipop Plot

BCAT1 · protein map & ClinVar variants

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

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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