BCO1

beta-carotene oxygenase 1

Basic information

Region (hg38): 16:81238689-81291142

Previous symbols: [ "BCDO", "BCDO1", "BCMO1" ]

Links

ENSG00000135697 ∙ NCBI:53630 ∙ OMIM:605748 ∙ HGNC:13815 ∙ Uniprot:Q9HAY6 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hereditary hypercarotenemia and vitamin A deficiency (Limited), mode of inheritance: Unknown
• hereditary hypercarotenemia and vitamin A deficiency (Supportive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hypercarotenemia and vitamin A deficiency, autosomal dominant	AD	Biochemical; Gastrointestinal	Dietary precautions may be beneficial, as individuals may have manifestations of hypercarotenemia/hypovitaminosis A with a carotenoid-containing/retinol-inadequate diet	Biochemical	5453458; 17951468

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the BCO1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the BCO1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				5	3	8
missense			35	4	3	42
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding				1	24	25
Total	0	0	35	10	30

Variants in BCO1

This is a list of pathogenic ClinVar variants found in the BCO1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
16-81238935-G-C		not specified	Uncertain significance (Jan 23, 2023)
16-81239023-T-A			Benign (Jun 18, 2021)
16-81239178-G-A			Benign (Jun 18, 2021)
16-81245485-A-T		BCO1-related disorder	Likely benign (Dec 03, 2019)
16-81245515-T-C			Benign (Nov 10, 2018)
16-81245516-G-A		not specified	Uncertain significance (Feb 21, 2024)
16-81245559-G-T		not specified	Uncertain significance (May 31, 2024)
16-81245566-C-T		BCO1-related disorder	Likely benign (Apr 11, 2019)
16-81245773-C-G			Benign (Nov 10, 2018)
16-81245829-A-G			Benign (Nov 10, 2018)
16-81245849-CTTTTTT-C			Benign (Jun 19, 2021)
16-81245849-CTTTTTTTT-C			Benign (Jun 21, 2021)
16-81245849-C-CT			Benign (Jun 20, 2021)
16-81245877-T-C			Benign (Nov 10, 2018)
16-81259438-G-A			Benign (Jun 21, 2021)
16-81259457-A-G			Benign (Jun 19, 2021)
16-81259602-A-G			Benign (Jun 19, 2021)
16-81259694-G-A		not specified	Uncertain significance (Jun 11, 2024)
16-81259740-C-G		not specified	Uncertain significance (Jun 29, 2022)
16-81259778-C-A		not specified	Uncertain significance (May 09, 2023)
16-81260064-G-A			Benign (Jun 19, 2021)
16-81262138-C-G		not specified	Uncertain significance (Oct 12, 2021)
16-81262175-C-A		BCO1-related disorder	Benign (Jun 09, 2021)
16-81262224-A-G		not specified	Uncertain significance (Apr 19, 2024)
16-81262237-A-G		Hereditary hypercarotenemia and vitamin A deficiency	Uncertain significance (Mar 29, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
BCO1	protein_coding	protein_coding	ENST00000258168	11	52695

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
5.50e-12	0.206	125632	1	115	125748	0.000461

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.898	346	302	1.15	0.0000181	3615
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000300	0.000300
Ashkenazi Jewish	0.000198	0.000198
East Asian	0.000217	0.000217
Finnish	0.000185	0.000185
European (Non-Finnish)	0.000519	0.000519
Middle Eastern	0.000217	0.000217
South Asian	0.00131	0.00127
Other	0.000163	0.000163

dbNSFP

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.
• Pathway: Retinol metabolism - Homo sapiens (human);Vitamin A Deficiency;Retinol Metabolism;Vitamin A and Carotenoid Metabolism;Signaling by GPCR;Signal Transduction;Metabolism of fat-soluble vitamins;Metabolism;Metabolism of vitamins and cofactors;Retinoid metabolism and transport;G alpha (i) signalling events;Visual phototransduction;GPCR downstream signalling (Consensus)

Intolerance Scores

• rvis_EVS: 0.4
• rvis_percentile_EVS: 76.49

Haploinsufficiency Scores

• pHI: 0.0927
• hipred: N
• hipred_score: 0.216

Essentials

• essential_gene_gene_trap: N

Mouse Genome Informatics

• Gene name: Bco1
• Phenotype: liver/biliary system phenotype; growth/size/body region phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: retinoid metabolic process;carotene catabolic process;vitamin A biosynthetic process;retinol metabolic process;retinal metabolic process;oxidation-reduction process;beta-carotene metabolic process
• Cellular component: cytosol
• Molecular function: beta-carotene 15,15'-monooxygenase activity;retinal isomerase activity;carotenoid dioxygenase activity;metal ion binding