# BCO2

> Gene · canonical: https://sugi.bio/atlas/gene/BCO2/
> Atlas v1.12.2 · generated 2026-10-13T13:32:47+00:00

## 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](https://www.ncbi.nlm.nih.gov/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](https://www.ebi.ac.uk/gxa/sc/experiments/E-GEOD-137537) | yes | 14.08 |
| [E-ANND-3](https://www.ebi.ac.uk/gxa/sc/experiments/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](https://gnomad.broadinstitute.org/)

**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](https://www.informatics.jax.org/marker/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](https://www.uniprot.org/uniprotkb/Q9XT71/entry) | 99.6% | Diamond |
| Bos taurus | [Q28175](https://www.uniprot.org/uniprotkb/Q28175/entry) | 98.7% | Diamond |
| Canis lupus familiaris | [Q9TVB8](https://www.uniprot.org/uniprotkb/Q9TVB8/entry) | 98.5% | Diamond |
| Pongo abelii | [Q5RF16](https://www.uniprot.org/uniprotkb/Q5RF16/entry) | 98.0% | Diamond |
| Macaca fascicularis | [Q8HXG8](https://www.uniprot.org/uniprotkb/Q8HXG8/entry) | 95.5% | Diamond |
| Cynops pyrrhogaster | [Q8AXN9](https://www.uniprot.org/uniprotkb/Q8AXN9/entry) | 92.5% | Diamond |
| Ambystoma tigrinum | [Q9YI25](https://www.uniprot.org/uniprotkb/Q9YI25/entry) | 92.5% | Diamond |
| Gallus gallus | [Q9YGX2](https://www.uniprot.org/uniprotkb/Q9YGX2/entry) | 90.6% | Diamond |
| Mustela putorius furo | [Q6QT07](https://www.uniprot.org/uniprotkb/Q6QT07/entry) | 84.5% | Diamond |
| Arabidopsis thaliana | [Q8VY26](https://www.uniprot.org/uniprotkb/Q8VY26/entry) | 65.4% | Diamond |
| Galleria mellonella | [A8Y9I2](https://www.uniprot.org/uniprotkb/A8Y9I2/entry) | 49.1% | Diamond |
| Fusarium fujikuroi IMI 58289 | [S0ENQ2](https://www.uniprot.org/uniprotkb/S0ENQ2/entry) | 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](/atlas/gene/PLET1/) | protein-coding | 349633 |
| [PTS](/atlas/gene/PTS/) | protein-coding | 5805 |
| [TEX12-AS1](/atlas/gene/TEX12-AS1/) | ncRNA | 107987164 |
| [TEX12](/atlas/gene/TEX12/) | protein-coding | 56158 |
| [IL18](/atlas/gene/IL18/) | protein-coding | 3606 |
| [SDHD](/atlas/gene/SDHD/) | protein-coding | 6392 |

<a id="protein-Q9BYV7"></a>

## 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 →](https://www.uniprot.org/uniprotkb/Q9BYV7/entry)

**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](https://amigo.geneontology.org/amigo/term/GO:0016121) | BP | direct assay |
| [carotene metabolic process](https://amigo.geneontology.org/amigo/term/GO:0016119) | BP | direct assay |
| [oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen](https://amigo.geneontology.org/amigo/term/GO:0016702) | 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](#clinvar) (0 pathogenic / likely pathogenic); [5 GWAS associations](#gwas-assoc).

#### 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 |

## Related Atlas pages

*No linked Atlas pages yet — the cross-entity mesh grows as the corpus expands.*