BBOX1

Chr 11

gamma-butyrobetaine hydroxylase 1

Also known as: BBH, BBOX, G-BBH, gamma-BBH

The protein gamma butyrobetaine hydroxylase catalyzes the final step in L-carnitine biosynthesis, converting gamma-butyrobetaine to L-carnitine, which is essential for transporting fatty acids into mitochondria for beta-oxidation. Mutations cause carnitine deficiency, secondary, which follows autosomal recessive inheritance and affects fatty acid metabolism. The gene shows extremely high constraint against loss-of-function variants (pLI near 1), indicating that complete loss of function is likely incompatible with normal development.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
23
Pubs (1 yr)
20
P/LP submissions
0%
P/LP missense
1.48
LOEUF
Mechanism
Clinical SummaryBBOX1
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
20 unique Pathogenic / Likely Pathogenic· 68 VUS of 102 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.48LOEUF
pLI 0.000
Z-score 0.01
OE 1.00 (0.691.48)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.59Z-score
OE missense 0.88 (0.781.00)
180 obs / 203.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE1.00 (0.691.48)
00.351.4
Missense OE0.88 (0.781.00)
00.61.4
Synonymous OE0.94
01.21.6
LoF obs/exp: 18 / 18.0Missense obs/exp: 180 / 203.9Syn Z: 0.38

ClinVar Variant Classifications

102 submitted variants in ClinVar

Classification Summary

Pathogenic19
Likely Pathogenic1
VUS68
Likely Benign1
Benign3
19
Pathogenic
1
Likely Pathogenic
68
VUS
1
Likely Benign
3
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
19
0
19
Likely Pathogenic
0
0
1
0
1
VUS
0
56
12
0
68
Likely Benign
0
0
0
1
1
Benign
0
0
0
3
3
Total05632492

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

View in ClinVar →

Protein Context — Lollipop Plot

BBOX1 · 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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