BBOX1

protein-coding

gamma-butyrobetaine hydroxylase 1

Gene summary

This gene encodes gamma butyrobetaine hydroxylase which catalyzes the formation of L-carnitine from gamma-butyrobetaine, the last step in the L-carnitine biosynthetic pathway. Carnitine is essential for the transport of activated fatty acids across the mitochondrial membrane during mitochondrial beta-oxidation. [provided by RefSeq, Jul 2008]

Previous symbols:

BBOX

MANE transcript

NM_003986.3

Inheritance

—

ClinVar variants

U:59B:4

Top phenotype

BBOX1-related disorder

gnomAD constraint

pLI —, LoF o/e 1

Max pathogenic AF

—

Genomic locus

chr11:27,040,725-27,127,809

External References & Databases

Ensembl (ENSG00000129151)

Transcript & Mutation Effects

hg38 • Region Span ~87.1 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to BBOX1 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 56

not providedTotal: 3

BBOX1-related disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_003986.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				1 clinvar	3 clinvar	4
missense			56 clinvar			56
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	59	1	3	63

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 41 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_003986.3	RefSeq	NP_003977.1	7	MANE Select
ENST00000263182.8	Ensembl	ENSP00000263182.3	7	MANE Select
NM_001376258.1	RefSeq	NP_001363187.1	7	Standard
NM_001376259.1	RefSeq	NP_001363188.1	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Lysine degradation - Homo sapiens (human)
Carnitine Synthesis
Branched-chain amino acid catabolism
Metabolism of amino acids and derivatives
Metabolism

Biological Process

carnitine biosynthetic process
oxidation-reduction process

Molecular Function

iron ion binding
protein binding
zinc ion binding
gamma-butyrobetaine dioxygenase activity
oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen

Cellular Component

mitochondrion
cytosol
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000263182
Coding exons: 7
Length: 87085
Individuals with no LoFs: 125619
Homozygous LoFs: 0
Heterozygous LoFs: 128
Defined: 125747
p: 0.000509

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.594	180	204	0.883	0.0000101	2559
Missense (PolyPhen)		77	78.646	0.97907		933
Synonymous	0.376	66	70.0	0.943	0.00000354	690
Loss of Function	0.0109	18	18.1	0.997	8.46e-7	228

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00037	0.00037	rare
Latino/Admixed American	0.00023	0.00023	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00055	0.00049	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00073	0.00071	rare
South Asian	0.00078	0.00072	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Catalyzes the formation of L-carnitine from gamma- butyrobetaine.;

Recessive Scores

pRec: 0.191

Intolerance Scores

LoFtool: 0.363
RVIS EVS: -0.56
RVIS percentile EVS: 19.54

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Indispensability pred.: E
Indispensability score: 0.993

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium