BCO1

protein-coding

beta-carotene oxygenase 1

Gene summary

Vitamin A metabolism is important for vital processes such as vision, embryonic development, cell differentiation, and membrane and skin protection. The protein encoded by this gene is a key enzyme in beta-carotene metabolism to vitamin A. It catalyzes the oxidative cleavage of beta,beta-carotene into two retinal molecules. [provided by RefSeq, Jul 2008]

Previous symbols:

BCDO
BCDO1
BCMO1

MANE transcript

NM_017429.3

Inheritance

ClinVar variants

U:105B:32

Top phenotype

Hypercarotenemia and vitamin A deficiency, autosomal dominant

gnomAD constraint

pLI —, LoF o/e 0.81

Max pathogenic AF

—

Genomic locus

chr16:81,238,689-81,291,142

External References & Databases

Ensembl (ENSG00000135697)

Transcript & Mutation Effects

hg38 • Region Span ~52.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

hereditary hypercarotenemia and vitamin A deficiencySUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0007272

Submitter: Orphanet

hereditary hypercarotenemia and vitamin A deficiencyLIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0007272

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Hypercarotenemia and vitamin A deficiency, autosomal dominantAD

Manifestation: Biochemical

Intervention: Biochemical; Gastrointestinal

Rationale: Dietary precautions may be beneficial, as individuals may have manifestations of hypercarotenemia/hypovitaminosis A with a carotenoid-containing/retinol-inadequate diet

Refs: 5453458; 17951468

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to BCO1 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 131

not providedTotal: 10

BCO1-related disorderTotal: 9

Hereditary hypercarotenemia and vitamin A deficiencyTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_017429.3. 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				17 clinvar		17
missense			105 clinvar	14 clinvar	1 clinvar	120
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	105	31	1	137

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 20 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_017429.3	RefSeq	NP_059125.2	11	MANE Select
ENST00000258168.7	Ensembl	ENSP00000258168.2	11	MANE Select
ENST00000563804.5	Ensembl	ENSP00000457910.1	3	Standard
ENST00000564552.1	Ensembl	ENSP00000455219.1	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Retinol metabolism - Homo sapiens (human)
Vitamin A Deficiency
Retinol Metabolism
Vitamin A and Carotenoid Metabolism
Signaling by GPCR

Biological Process

retinoid metabolic process
carotene catabolic process
vitamin A biosynthetic process
retinol metabolic process
retinal metabolic process

Molecular Function

beta-carotene 15,15'-monooxygenase activity
retinal isomerase activity
carotenoid dioxygenase activity
metal ion binding

Cellular Component

cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000258168
Coding exons: 11
Length: 52695
Individuals with no LoFs: 125632
Homozygous LoFs: 1
Heterozygous LoFs: 115
Defined: 125748
p: 0.000461

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.898	346	302	1.15	0.0000181	3615
Missense (PolyPhen)		109	106.19	1.0264		1321
Synonymous	-1.88	153	126	1.21	0.00000920	1029
Loss of Function	0.866	20	24.6	0.812	0.00000117	302

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00018	0.00018	rare
Latino/Admixed American	0.00012	0.00012	rare
Ashkenazi Jewish	0.00020	0.00020	rare
East Asian	0.00022	0.00022	rare
Finnish	0.00018	0.00018	rare
European (Non-Finnish)	0.00052	0.00052	rare
South Asian	0.0013	0.0013	notable
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Symmetrically cleaves beta-carotene into two molecules of retinal using a dioxygenase mechanism. {ECO:0000269|PubMed:24668807}.;
Disease: DISEASE: Hypercarotenemia and vitamin A deficiency, autosomal dominant (HCVAD) [MIM:115300]: A disorder characterized by increased serum beta-carotene, decreased conversion of beta- carotene to vitamin A and decreased serum vitamin A. {ECO:0000269|PubMed:17951468}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Intolerance Scores

RVIS EVS: 0.4
RVIS percentile EVS: 76.49

Essentials

Essential (gene trap): N