BCO2

Summary

BCO2 (beta-carotene oxygenase 2, HGNC:18503) is a protein-coding gene on chromosome 11q23.1, encoding Carotenoid-cleaving dioxygenase, mitochondrial (Q9BYV7). Broad specificity mitochondrial dioxygenase that mediates the asymmetric oxidative cleavage of carotenoids.

This gene encodes an enzyme which oxidizes carotenoids such as beta-carotene during the biosynthesis of vitamin A. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 83875 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 89 total
• GTEx eGene: eQTL in 47 tissues, sQTL in 39 (q < 0.05)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.05 (unconstrained)
• MANE Select transcript: NM_031938
• Notable: 89 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18503
Approved symbol	BCO2
Name	beta-carotene oxygenase 2
Location	11q23.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ34464, B-DIOX-II
Ensembl gene	ENSG00000197580
Ensembl biotype	protein_coding
OMIM	611740
Entrez	83875

Gene structure

Transcript identifiers

Ensembl transcripts: 58 — 36 protein_coding, 15 nonsense_mediated_decay, 7 retained_intron

MANE Select: ENST00000357685

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 5, TSL 2: 6, TSL 3: 4, TSL 4: 2, TSL 5: 2

ENST00000357685, ENST00000361053, ENST00000438022, ENST00000460924, ENST00000461480, ENST00000494860, ENST00000525175, ENST00000526088, ENST00000527198, ENST00000527939, ENST00000530677, ENST00000531003, ENST00000531169, ENST00000532593, ENST00000532612, ENST00000532673, ENST00000532716, ENST00000534122, ENST00000534550, ENST00000856015, ENST00000856016, ENST00000856017, ENST00000856018, ENST00000856019, ENST00000856020, ENST00000856021, ENST00000856022, ENST00000856023, ENST00000856024, ENST00000856025, ENST00000856026, ENST00000856027, ENST00000958912, ENST00000958913, ENST00000958914, ENST00000958915, ENST00000958916, ENST00000958917, ENST00000958918, ENST00000958919, ENST00000958920, ENST00000958921, ENST00000974889, ENST00000974890, ENST00000974891, ENST00000974892, ENST00000974893, ENST00000974894, ENST00000974895, ENST00000974896, ENST00001029715, ENST00001029716, ENST00001029719, ENST00001029720, ENST00001029722, ENST00001029723, ENST00001122653, ENST00001142136

RefSeq mRNA: 5 — MANE Select: NM_031938 NM_001037290, NM_001256397, NM_001256398, NM_001256400, NM_031938

CCDS: CCDS41716, CCDS58181, CCDS58182, CCDS58183, CCDS8358

Canonical transcript exons

ENST00000357685 — 12 exons

Exon	Start	End
ENSE00001865060	112217761	112218946
ENSE00002140404	112175512	112175689
ENSE00003496031	112213724	112213861
ENSE00003497402	112200613	112200773
ENSE00003517751	112202023	112202190
ENSE00003542671	112193879	112193994
ENSE00003575644	112194653	112194755
ENSE00003644131	112216220	112216330
ENSE00003711640	112179278	112179482
ENSE00003721487	112199699	112199827
ENSE00003742170	112193474	112193697
ENSE00003789952	112214762	112214944

Expression profiles

Bgee: expression breadth ubiquitous, 210 present calls, max score 97.25.

FANTOM5 (CAGE): breadth broad, TPM avg 2.4625 / max 163.2011, expressed in 469 samples.

Highest expression (Bgee): lobe of liver, apex of heart, ventricle myocardium, heart left ventricle, cardiac ventricle.

Genetic regulation across tissues (GTEx eQTL / sQTL)

BCO2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 47 tissues and its splicing (sQTL) in 39 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 86 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Nerve Tibial	sqtl	4.6e-95	-1.28	11:112195020:CTATCT:C
Thyroid	sqtl	6.1e-62	-1.05	11:112210485:A:C
Heart Left Ventricle	eqtl	4.3e-53	-0.56	11:112210485:A:C
Adrenal Gland	eqtl	8.3e-46	-0.75	11:112210485:A:C
Pituitary	sqtl	1.1e-44	-1.45	11:112187553:C:T
Muscle Skeletal	eqtl	2.3e-41	-0.40	11:112210485:A:C
Heart Atrial Appendage	eqtl	1.4e-39	-0.54	11:112210485:A:C
Heart Atrial Appendage	sqtl	4.3e-39	-1.02	11:112210485:A:C
Adipose Subcutaneous	sqtl	1.1e-34	-0.84	11:112188554:C:T
Brain Cerebellum	sqtl	1.0e-33	-1.30	11:112199451:G:A
Thyroid	eqtl	1.9e-33	+0.47	11:112212373:C:T
Skin Not Sun Exposed Suprapubic	sqtl	2.4e-33	-0.89	11:112199451:G:A
Brain Cerebellar Hemisphere	sqtl	1.8e-32	-1.40	11:112199451:G:A
Testis	eqtl	4.7e-32	-0.44	11:112199451:G:A
Skin Sun Exposed Lower leg	eqtl	1.1e-31	+0.48	11:112194760:A:C
Esophagus Gastroesophageal Junction	sqtl	3.2e-31	-1.03	11:112210485:A:C
Brain Nucleus accumbens basal ganglia	sqtl	1.6e-29	-1.28	11:112187685:G:A
Colon Sigmoid	sqtl	3.2e-29	-1.11	11:112210485:A:C
Brain Nucleus accumbens basal ganglia	eqtl	5.4e-28	-0.65	11:112187685:G:A
Adipose Visceral Omentum	eqtl	2.2e-27	-0.30	11:112210485:A:C

FANTOM5 promoters

3 alternative TSS:

Promoter ID	TPM avg	Samples expressed
116712	1.4488	354
116713	0.9368	305
116714	0.0769	33

Top tissues by expression

showing 100 of 248 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	97.25	gold quality
apex of heart	UBERON:0002098	96.50	gold quality
left ventricle myocardium	UBERON:0006566	96.24	gold quality
heart left ventricle	UBERON:0002084	96.02	gold quality
cardiac ventricle	UBERON:0002082	95.83	gold quality
right atrium auricular region	UBERON:0006631	95.80	gold quality
cardiac atrium	UBERON:0002081	95.46	gold quality
left adrenal gland cortex	UBERON:0035825	94.58	gold quality
left adrenal gland	UBERON:0001234	94.56	gold quality
right adrenal gland	UBERON:0001233	94.45	gold quality
right uterine tube	UBERON:0001302	94.15	gold quality
adrenal cortex	UBERON:0001235	93.08	gold quality
heart	UBERON:0000948	93.01	gold quality
liver	UBERON:0002107	92.47	gold quality
myocardium	UBERON:0002349	92.19	gold quality
adrenal gland	UBERON:0002369	92.14	gold quality
adrenal tissue	UBERON:0018303	91.56	gold quality
right adrenal gland cortex	UBERON:0035827	91.23	gold quality
cardiac muscle of right atrium	UBERON:0003379	90.03	gold quality
heart right ventricle	UBERON:0002080	89.65	gold quality
hindlimb stylopod muscle	UBERON:0004252	89.15	gold quality
oviduct epithelium	UBERON:0004804	88.70	gold quality
lower esophagus mucosa	UBERON:0035834	87.05	gold quality
hypothalamus	UBERON:0001898	86.09	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	85.84	gold quality
adenohypophysis	UBERON:0002196	85.72	gold quality
bronchial epithelial cell	CL:0002328	85.30	gold quality
pituitary gland	UBERON:0000007	84.98	gold quality
muscle of leg	UBERON:0001383	84.92	gold quality
gall bladder	UBERON:0002110	84.77	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	84.73	gold quality
bronchus	UBERON:0002185	84.32	gold quality
gastrocnemius	UBERON:0001388	84.22	gold quality
spinal cord	UBERON:0002240	83.86	gold quality
caudate nucleus	UBERON:0001873	83.39	gold quality
fallopian tube	UBERON:0003889	83.24	gold quality
nucleus accumbens	UBERON:0001882	83.05	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.41	gold quality
vagina	UBERON:0000996	82.15	gold quality
substantia nigra	UBERON:0002038	82.09	gold quality
muscle tissue	UBERON:0002385	82.01	gold quality
biceps brachii	UBERON:0001507	81.64	gold quality
Brodmann (1909) area 9	UBERON:0013540	81.63	gold quality
epithelial cell of pancreas	CL:0000083	81.61	gold quality
skeletal muscle tissue	UBERON:0001134	81.54	gold quality
corpus callosum	UBERON:0002336	81.44	gold quality
putamen	UBERON:0001874	81.43	gold quality
primary visual cortex	UBERON:0002436	81.14	gold quality
right frontal lobe	UBERON:0002810	80.98	gold quality
omental fat pad	UBERON:0010414	80.90	gold quality
peritoneum	UBERON:0002358	80.86	gold quality
esophagus mucosa	UBERON:0002469	80.81	gold quality
anterior cingulate cortex	UBERON:0009835	80.74	gold quality
tibial nerve	UBERON:0001323	80.58	gold quality
midbrain	UBERON:0001891	80.16	gold quality
cerebellar hemisphere	UBERON:0002245	80.08	gold quality
body of uterus	UBERON:0009853	80.05	gold quality
right hemisphere of cerebellum	UBERON:0014890	80.02	gold quality
cerebellar cortex	UBERON:0002129	79.99	gold quality
pancreatic ductal cell	CL:0002079	79.88	silver quality
parietal pleura	UBERON:0002400	79.64	gold quality
thyroid gland	UBERON:0002046	79.34	gold quality
vastus lateralis	UBERON:0001379	79.31	gold quality
left lobe of thyroid gland	UBERON:0001120	79.29	gold quality
quadriceps femoris	UBERON:0001377	79.24	silver quality
muscle layer of sigmoid colon	UBERON:0035805	79.21	gold quality
endothelial cell	CL:0000115	79.06	gold quality
metanephros cortex	UBERON:0010533	78.95	gold quality
germinal epithelium of ovary	UBERON:0001304	78.89	gold quality
adipose tissue of abdominal region	UBERON:0007808	78.74	gold quality
cerebellum	UBERON:0002037	78.64	gold quality
deltoid	UBERON:0001476	78.56	silver quality
esophagus	UBERON:0001043	78.44	gold quality
right testis	UBERON:0004534	78.36	gold quality
amygdala	UBERON:0001876	78.18	gold quality
forebrain	UBERON:0001890	78.18	gold quality
left testis	UBERON:0004533	78.05	gold quality
right lobe of thyroid gland	UBERON:0001119	77.99	gold quality
ectocervix	UBERON:0012249	77.87	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	77.86	gold quality
brain	UBERON:0000955	77.85	gold quality
prefrontal cortex	UBERON:0000451	77.78	gold quality
buccal mucosa cell	CL:0002336	77.75	silver quality
dorsolateral prefrontal cortex	UBERON:0009834	77.73	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	77.71	gold quality
sperm	CL:0000019	77.39	silver quality
esophagus squamous epithelium	UBERON:0006920	77.28	gold quality
endocervix	UBERON:0000458	77.11	gold quality
cortex of kidney	UBERON:0001225	77.00	gold quality
occipital lobe	UBERON:0002021	76.89	gold quality
small intestine Peyer’s patch	UBERON:0003454	76.89	gold quality
Ammon’s horn	UBERON:0001954	76.69	gold quality
neocortex	UBERON:0001950	76.60	gold quality
testis	UBERON:0000473	76.34	gold quality
uterine cervix	UBERON:0000002	76.33	gold quality
calcaneal tendon	UBERON:0003701	76.30	gold quality
frontal cortex	UBERON:0001870	76.25	gold quality
left uterine tube	UBERON:0001303	76.16	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	76.05	gold quality
lower esophagus	UBERON:0013473	75.93	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-137537	yes	14.08
E-ANND-3	yes	6.05

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 78 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Retina	tissue	51.8	high
Liver	tissue	48.9	medium
Heart muscle	tissue	31.4	not detected
Skeletal muscle	tissue	20.1	not detected
Choroid plexus	tissue	19.1
Tongue	tissue	13.3
Locus coeruleus	tissue	12.6
Adrenal gland	tissue	12.0	medium
Postcentral gyrus	tissue	10.1
Nucleus accumbens	tissue	9.7
Fallopian tube	tissue	9.1	high
Hippocampus	tissue	6.7	not detected
Caudate putamen	tissue	5.9
Frontal cortex	tissue	5.2
Gallbladder	tissue	4.8	high
Vagina	tissue	4.7	not detected
Pituitary gland	tissue	4.2
Periaqueductal gray	tissue	4.0
Basal ganglia	tissue	3.9	not detected
Cerebral cortex	tissue	3.7	not detected
Amygdala	tissue	3.7
Retrosplenial cortex	tissue	3.7
Placenta	tissue	3.6	low
Substantia nigra	tissue	3.6
Insular cortex	tissue	3.6
Putamen	tissue	3.5
Ventral forebrain	tissue	3.5
Olfactory bulb	tissue	3.4
Hippocampal formation	tissue	3.3
Entorhinal cortex	tissue	3.3
Temporal cortex	tissue	3.3
Corpus callosum	tissue	3.2
Hypothalamus	tissue	3.1
Spinal cord	tissue	3.1
Retrosplenial and cingulate cortex	tissue	3.1
Occipital cortex	tissue	3.0
Prefrontal cortex	tissue	2.9
Midbrain	tissue	2.9
Cerebellum	tissue	2.9	not detected
Septum	tissue	2.9
Somatosensory cortex	tissue	2.8
Motor cortex	tissue	2.7
Medulla oblongata	tissue	2.7
Thalamus	tissue	2.6
Superior colliculi	tissue	2.6
Pons	tissue	2.1
Testis	tissue	2.0	low
Endometrium 1	tissue	1.4	high
Esophagus	tissue	1.3	not detected
Urinary bladder	tissue	1.3	low
Thyroid gland	tissue	1.3	low
Lung	tissue	1.2	medium
Smooth muscle	tissue	1.0	not detected
Epididymis	tissue	1.0	high
Small intestine	tissue	1.0	high
Kidney	tissue	1.0	high
Skin 1	tissue	0.9	not detected
Seminal vesicle	tissue	0.8	medium
Tonsil	tissue	0.8	medium
Pancreas	tissue	0.7	medium

Brain sub-regions (HPA Brain Atlas): detected in 191; highest nTPM — Parieto-temporal junction (white matter) (14.5), Nucleus tractus solitarii (14.0), Corpus callosum, genu (white matter) (12.8), Periaquaductal grey, anterior (12.7), Principal sensory trigeminal nucleus (12.6).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting BCO2 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 82 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-3065-3P	99.87	70.25	1407
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-4760-5P	99.80	69.88	1619
HSA-MIR-3913-5P	99.78	67.26	968
HSA-MIR-26A-5P	99.78	73.52	2303
HSA-MIR-26B-5P	99.78	73.51	2305
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-556-3P	99.74	68.75	1203
HSA-MIR-4755-5P	99.71	70.34	2716
HSA-MIR-5006-3P	99.71	70.26	2728
HSA-MIR-4465	99.71	72.56	2096
HSA-MIR-30B-3P	99.70	65.76	2325
HSA-MIR-3689A-3P	99.70	65.73	2306
HSA-MIR-3689B-3P	99.70	65.71	2311
HSA-MIR-3689C	99.70	65.71	2311
HSA-MIR-6779-5P	99.70	65.76	2363
HSA-MIR-6892-3P	99.68	66.40	1178

Functional genomics

gnomAD constraint: pLI 8.04e-13, LOEUF 1.05, missense Z 0.592 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000357685 — one region, missense o/e 0.97.

Literature-anchored findings (GeneRIF, showing 11)

• we found that the third family member, beta,beta-carotene-9’,10’-oxygenase (BCDO2), is a mitochondrial carotenoid-oxygenase with broad substrate specificity (PMID:21106934)
• The gene encoding beta-carotene-9’,10’-oxygenase, which cleaves the 9’,10’ double bond in beta-carotene into beta-apo-10’-carotenal, was cloned and expressed in Escherichia coli. (PMID:21302131)
• a stepwise cleavage by BCO2 and BCO1 with APO10ol as an intermediate could provide a mechanism to tailor asymmetric carotenoids such as beta-cryptoxanthin for vitamin A production. (PMID:24106281)
• Inactivity of human beta,beta-carotene-9’,10’-dioxygenase (BCO2) underlies retinal accumulation of the human macular carotenoid pigment. (PMID:24982131)
• Role of beta-Carotene 9,10-Dioxygenase in Macular Pigment Metabolism (PMID:26307071)
• review of molecular aspects in carotenoid metabolism and diseases (PMID:27390265)
• Study identifies BCO2 as a tumor suppressor in prostate cancer which mediates inhibition of NF-kB signaling. Its expression is decreased in human prostate cancer. (PMID:27406826)
• Associations for BCO2, PCSK9, and TR1B1 Polymorphism and Lifestyle Factors with Ischemic Stroke (PMID:31250580)
• Enzymology of vertebrate carotenoid oxygenases. (PMID:32035229)
• Evolutionary aspects and enzymology of metazoan carotenoid cleavage oxygenases. (PMID:32061750)
• The human mitochondrial enzyme BCO2 exhibits catalytic activity toward carotenoids and apocarotenoids. (PMID:32873706)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	bco2l	ENSDARG00000027620
danio_rerio	bco2b	ENSDARG00000041715
danio_rerio	bco2a	ENSDARG00000055722
mus_musculus	Bco2	ENSMUSG00000032066
rattus_norvegicus	Bco2	ENSRNOG00000038746
drosophila_melanogaster	ninaB	FBGN0002937

Paralogs (2): RPE65 (ENSG00000116745), BCO1 (ENSG00000135697)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:2177469) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 13 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal adipose tissue morphology	1
abnormal liver morphology	1
enlarged spleen	1
small testis	1
abnormal homeostasis	1
decreased testis weight	1
decreased seminal vesicle weight	1
increased spleen weight	1
increased liver triglyceride level	1
abnormal blood homeostasis	1
abnormal hepatocyte physiology	1
abnormal aerobic respiration	1
macrovesicular hepatic steatosis	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Chlorocebus aethiops	Q9XT71	99.6%	Diamond
Bos taurus	Q28175	98.7%	Diamond
Canis lupus familiaris	Q9TVB8	98.5%	Diamond
Pongo abelii	Q5RF16	98.0%	Diamond
Macaca fascicularis	Q8HXG8	95.5%	Diamond
Cynops pyrrhogaster	Q8AXN9	92.5%	Diamond
Ambystoma tigrinum	Q9YI25	92.5%	Diamond
Gallus gallus	Q9YGX2	90.6%	Diamond
Mustela putorius furo	Q6QT07	84.5%	Diamond
Arabidopsis thaliana	Q8VY26	65.4%	Diamond
Galleria mellonella	A8Y9I2	49.1%	Diamond
Fusarium fujikuroi IMI 58289	S0ENQ2	43.0%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
PLET1	protein-coding	349633
PTS	protein-coding	5805
TEX12-AS1	ncRNA	107987164
TEX12	protein-coding	56158
IL18	protein-coding	3606
SDHD	protein-coding	6392

Protein

Protein identifiers

Carotenoid-cleaving dioxygenase, mitochondrial — Q9BYV7 (reviewed: Q9BYV7)

Alternative names: B-diox-II, Beta,beta-carotene 9’,10’-oxygenase, Beta-carotene dioxygenase 2

All UniProt accessions (6): E9PPP9, E9PS89, Q9BYV7, H0YCL7, H0YCN8, V9GYA9

UniProt curated annotations — full annotation on UniProt →

Function. Broad specificity mitochondrial dioxygenase that mediates the asymmetric oxidative cleavage of carotenoids. Cleaves carotenes (pure hydrocarbon carotenoids) such as all-trans-beta-carotene and lycopene as well as xanthophylls (oxygenated carotenoids) such as zeaxanthin, lutein and beta-cryptoxanthin at both the 9,10 and the 9’,10’ carbon-carbon double bond. Through its function in carotenoids metabolism regulates oxidative stress and the production of important signaling molecules.

Subcellular location. Mitochondrion.

Tissue specificity. Highly expressed in retinal pigment epithelium. Also expressed in stomach, small intestine, liver, testis, kidney, adrenal gland, pancreas, heart, skeletal muscle and prostate (at protein level).

Cofactor. Binds 1 Fe(2+) ion per subunit.

Similarity. Belongs to the carotenoid oxygenase family.

Isoforms (5)

UniProt ID	Names	Canonical?
Q9BYV7-1	1	yes
Q9BYV7-2	2
Q9BYV7-4	4
Q9BYV7-5	5
Q9BYV7-6	6

RefSeq proteins (5): NP_001032367, NP_001243326, NP_001243327, NP_001243329, NP_114144* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004294	Carotenoid_Oase	Family

Pfam: PF03055

Enzyme classification (BRENDA)

• EC 1.13.11.71 — carotenoid-9’,10’-cleaving dioxygenase (BRENDA: 11 organisms, 24 substrates, 6 inhibitors, 5 Km, 4 kcat entries)

Substrate kinetics (BRENDA)

4 substrates with measured Km, best-characterized 4. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
BETA-CAROTENE	0.0152–0.067	2
ALL-TRANS-BETA-CAROTENE	0.037	1
ALPHA-CAROTENE	0.048	1
LUTEIN	0.105	1

Catalyzed reactions (Rhea)

• all-trans-beta-carotene + O2 = beta-ionone + all-trans-10’-apo-beta-carotenal (RHEA:26389)
• all-trans-zeaxanthin + 2 O2 = 4,9-dimethyldodeca-2,4,6,8,10-pentaenedial + 2 (3R)-hydroxy-beta-ionone (RHEA:26393)
• all-trans-zeaxanthin + O2 = (3R)-3-hydroxy-10’-apo-beta-carotenal + (3R)-hydroxy-beta-ionone (RHEA:68104)
• (3R)-3-hydroxy-10’-apo-beta-carotenal + O2 = 4,9-dimethyldodeca-2,4,6,8,10-pentaenedial + (3R)-hydroxy-beta-ionone (RHEA:68424)
• lutein + O2 = (3R,6R)-hydroxy-alpha-ionone + (3R)-3-hydroxy-10’-apo-beta-carotenal (RHEA:68428)
• lutein + O2 = (3R,6R)-3-hydroxy-10’-apo-alpha-carotenal + (3R)-hydroxy-beta-ionone (RHEA:68432)
• (3R,6R)-3-hydroxy-10’-apo-alpha-carotenal + O2 = (3R,6R)-hydroxy-alpha-ionone + 4,9-dimethyldodeca-2,4,6,8,10-pentaenedial (RHEA:68436)
• beta-cryptoxanthin + O2 = all-trans-10’-apo-beta-carotenal + (3R)-hydroxy-beta-ionone (RHEA:68440)
• 5-cis-lycopene + O2 = 5-cis-10’-apo-lycopenal + (3E,5E)-6,10-dimethylundeca-3,5,9-trien-2-one (RHEA:68444)
• 13-cis-lycopene + O2 = 13-cis-10’-apo-lycopenal + (3E,5E)-6,10-dimethylundeca-3,5,9-trien-2-one (RHEA:68448)
• all-trans-10’-apo-beta-carotenal + O2 = beta-ionone + 4,9-dimethyldodeca-2,4,6,8,10-pentaenedial (RHEA:68452)

UniProt features (17 total): sequence conflict 5, binding site 4, splice variant 4, sequence variant 3, chain 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BYV7-F1	88.41	0.78

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Oxidoreductases, Metabolic proteins, Predicted intracellular proteins

Protein evidence: Evidence at protein level

Antibody reliability (HPA): IH supported

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (4)

Position	Role
226	Fe cation
286	Fe cation
357	Fe cation
573	Fe cation

Function

Pathways and Gene Ontology

Reactome pathways

1 curated (TAS) of 6; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

6 pathways:

ID	Pathway	Evidence
R-HSA-975634	Retinoid metabolism and transport	curated
R-HSA-1430728	Metabolism	—
R-HSA-6806667	Metabolism of fat-soluble vitamins	—
R-HSA-196854	Metabolism of vitamins and cofactors	—
R-HSA-9709957	Sensory Perception	—
R-HSA-2187338	Visual phototransduction	—

MSigDB gene sets: 141 (showing top): SHEPARD_BMYB_MORPHOLINO_UP, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN, GOBP_REGULATION_OF_REACTIVE_OXYGEN_SPECIES_METABOLIC_PROCESS, GOBP_RETINAL_METABOLIC_PROCESS, GOBP_RETINOIC_ACID_METABOLIC_PROCESS, GOBP_LIPID_METABOLIC_PROCESS, GOBP_ORGANIC_ACID_METABOLIC_PROCESS, GOBP_ALDEHYDE_METABOLIC_PROCESS, GOBP_REGULATION_OF_MITOCHONDRIAL_MEMBRANE_POTENTIAL, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN, MCCABE_HOXC6_TARGETS_CANCER_UP, GOBP_LIPID_CATABOLIC_PROCESS

GO Biological Process (12): carotenoid metabolic process (GO:0016116), carotene metabolic process (GO:0016119), carotene catabolic process (GO:0016121), xanthophyll catabolic process (GO:0016124), retinoic acid metabolic process (GO:0042573), retinal metabolic process (GO:0042574), regulation of mitochondrial membrane potential (GO:0051881), lutein catabolic process (GO:0062172), lycopene catabolic process (GO:1901176), zeaxanthin catabolic process (GO:1901826), regulation of reactive oxygen species metabolic process (GO:2000377), lipid metabolic process (GO:0006629)

GO Molecular Function (8): beta-carotene 15,15’-dioxygenase activity (GO:0003834), carotenoid dioxygenase activity (GO:0010436), 9,10 (9’, 10’)-carotenoid-cleaving dioxygenase activity (GO:0010437), oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen (GO:0016702), metal ion binding (GO:0046872), beta,beta-carotene-9’,10’-cleaving oxygenase activity (GO:0102076), oxidoreductase activity (GO:0016491), dioxygenase activity (GO:0051213)

GO Cellular Component (2): mitochondrion (GO:0005739), mitochondrial matrix (GO:0005759)

Reactome top-level categories

5 top-level categories:

Category	Pathways
Visual phototransduction	1
Metabolism of fat-soluble vitamins	1
Metabolism	1
Sensory Perception	1
Metabolism of vitamins and cofactors	1

GO top-level categories

28 GO namespaces:

Category	Terms
oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen	3
retinoid metabolic process	2
xanthophyll catabolic process	2
terpenoid metabolic process	1
terpene metabolic process	1
carotene metabolic process	1
terpene catabolic process	1
carotenoid catabolic process	1
xanthophyll metabolic process	1
monocarboxylic acid metabolic process	1
hormone metabolic process	1
aldehyde metabolic process	1
olefinic compound metabolic process	1
regulation of membrane potential	1
carotene catabolic process	1
regulation of metabolic process	1
reactive oxygen species metabolic process	1
primary metabolic process	1
carotenoid dioxygenase activity	1
oxidoreductase activity, acting on single donors with incorporation of molecular oxygen	1
dioxygenase activity	1
cation binding	1
catalytic activity	1
oxidoreductase activity	1
cytoplasm	1
intracellular membrane-bounded organelle	1
mitochondrion	1
intracellular organelle lumen	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 3 of 22 annotations. The rest are phylogenetic / computational / electronic (IEA).

3 experimentally-supported GO terms:

GO term	NS	Evidence
carotene catabolic process	BP	direct assay
carotene metabolic process	BP	direct assay
oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 702 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BCO2	STARD3	Q14849	648
BCO2	ISX	Q2M1V0	644
BCO2	ASIP	P42127	571
BCO2	RARS1	P54136	569
BCO2	LRAT	O95237	559
BCO2	SCARB1	Q8WTV0	545
BCO2	GSTP1	P09211	504
BCO2	RDH14	Q9HBH5	497
BCO2	RDH13	Q8NBN7	496
BCO2	CYP26A1	O43174	462
BCO2	SPR	P35270	461
BCO2	MITF	O75030	454
BCO2	MC1R	Q01726	453
BCO2	RDH10	Q8IZV5	451
BCO2	STRA6	Q9BX79	441

IntAct

BioGRID (2 interactions; top human partners by supporting records): DPF3 (Cross-Linking-MS (XL-MS)), NUDT1 (Cross-Linking-MS (XL-MS))

Disease & clinical

Genetic variants

Variant evidence for BCO2: 89 ClinVar records (0 pathogenic / likely pathogenic); 5 GWAS associations.

ClinVar

89 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	74
Likely benign	9
Benign	0

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 27 predictions of 1,284):

Position(s)	Effect	Δscore	Sites
11:112177595	donor_gain	1.0000
11:112179479	donor_gain	1.0000
11:112200784	donor_gain	1.0000
11:112202021–112202022	acceptor_loss	1.0000	6
11:112202167	donor_gain	1.0000
11:112202191–112202192	donor_loss	1.0000	5
11:112216209	acceptor_gain	1.0000
11:112216331–112216332	donor_loss	1.0000	5
11:112217759–112217760	acceptor_loss	1.0000	5
11:112177603	donor_gain	0.9900

AlphaMissense

974 missense substitutions predicted likely pathogenic (of 3,835 scored), across 279 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
D104	8	0.972	0.988
D371	8	0.967	0.981
H286	8	0.946	0.982
H357	8	0.930	0.981
H573	8	0.930	0.981
H226	8	0.926	0.981
F103	8	0.909	0.980
F288	8	0.905	0.987
D176	8	0.880	0.973
H101	8	0.852	0.952
W325	7	0.933	0.982
F411	7	0.929	0.984
N177	7	0.924	0.985
R410	7	0.923	0.979
F92	7	0.915	0.975
W507	7	0.908	0.954
F125	7	0.894	0.970
F145	7	0.889	0.973
F519	7	0.880	0.954
F333	7	0.876	0.992

HPA cancer prognostics

RNA cancer specificity: Cancer enhanced (Kidney Chromophobe)

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

2 prognostic cancer types:

Cancer	Prognostic	p-value
Liver Hepatocellular Carcinoma (validation)	favorable	6.24e-06
Pancreatic Adenocarcinoma (validation)	unfavorable	0.000866

Disease associations

OMIM: gene MIM:611740 | disease phenotypes:

GWAS associations

5 associations:

Study	Trait	p-value
GCST002255_1	Inflammatory biomarkers	2e-32
GCST009736_1	Interleukin-18 levels	2e-32
GCST000590_1	Interleukin-18 levels	4e-9
GCST000590_2	Interleukin-18 levels	1e-8
GCST001537_1	Immune reponse to smallpox (secreted IL-12p40)	1e-8

EFO canonical traits (from GWAS)

4 canonical traits:

EFO ID	Trait name
EFO:0004581	interleukin 18 measurement
EFO:0004645	response to vaccine
EFO:0004873	cytokine measurement
EFO:0004812	interleukin-1 beta measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Cyclosporine	decreases expression	2
sotorasib	decreases expression, affects cotreatment	1
methylmercuric chloride	decreases expression	1
propionaldehyde	increases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
sodium arsenite	decreases expression	1
abrine	decreases expression	1
bisphenol S	increases methylation	1
jinfukang	affects cotreatment, increases expression	1
trametinib	affects cotreatment, decreases expression	1
NVP-BKM120	affects cotreatment, decreases expression	1
Sunitinib	decreases expression	1
Arsenic	affects methylation	1
Atrazine	increases expression	1
Cisplatin	affects cotreatment, increases expression	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Succimer	affects cotreatment, decreases expression	1
Tetrachlorodibenzodioxin	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	increases expression	1
Valproic Acid	decreases methylation	1
Aflatoxin B1	decreases expression	1
Copper Sulfate	increases expression	1
Acrylamide	increases expression	1
Particulate Matter	decreases expression	1
Magnetite Nanoparticles	affects cotreatment, decreases expression	1

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

1 trials:

NCT	Phase	Status	Title
NCT05257005	Not specified	UNKNOWN	Natural History Study of Pyruvate Dehydrogenase Deficiency