CYP27C1

Summary

CYP27C1 (cytochrome P450 family 27 subfamily C member 1, HGNC:33480) is a protein-coding gene on chromosome 2q14.3, encoding Cytochrome P450 27C1 (Q4G0S4). A cytochrome P450 monooxygenase that catalyzes the 3,4 desaturation of all-trans-retinol (also called vitamin A1) to all-trans-3,4-didehydroretinol (also called vitamin A2) in the skin.

This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids.

Source: NCBI Gene 339761 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 66 total
• MANE Select transcript: NM_001367502

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:33480
Approved symbol	CYP27C1
Name	cytochrome P450 family 27 subfamily C member 1
Location	2q14.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ16008
Ensembl gene	ENSG00000186684
Ensembl biotype	protein_coding
OMIM	620605
Entrez	339761

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000335247, ENST00000409327, ENST00000664447, ENST00000911450

RefSeq mRNA: 3 — MANE Select: NM_001367502 NM_001001665, NM_001367501, NM_001367502

CCDS: CCDS33285, CCDS92857

Canonical transcript exons

ENST00000664447 — 9 exons

Exon	Start	End
ENSE00001338178	127193094	127193297
ENSE00001338183	127193789	127193867
ENSE00001338188	127195335	127195501
ENSE00001338189	127199376	127199539
ENSE00001338190	127201122	127201331
ENSE00003852213	127203372	127203571
ENSE00003866439	127205900	127206090
ENSE00003888564	127219989	127220299
ENSE00003888805	127183832	127187387

Expression profiles

Bgee: expression breadth ubiquitous, 147 present calls, max score 91.90.

FANTOM5 (CAGE): breadth broad, TPM avg 0.2884 / max 10.1649, expressed in 187 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
30513	0.2884	187

Top tissues by expression

226 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
tendon of biceps brachii	UBERON:0008188	91.90	gold quality
cartilage tissue	UBERON:0002418	79.96	silver quality
layer of synovial tissue	UBERON:0007616	76.77	gold quality
synovial joint	UBERON:0002217	76.72	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	74.29	gold quality
tibia	UBERON:0000979	72.35	gold quality
ventricular zone	UBERON:0003053	71.74	gold quality
ectocervix	UBERON:0012249	70.47	gold quality
skin of leg	UBERON:0001511	69.47	gold quality
palpebral conjunctiva	UBERON:0001812	69.25	gold quality
skin of abdomen	UBERON:0001416	69.19	gold quality
zone of skin	UBERON:0000014	68.67	gold quality
ganglionic eminence	UBERON:0004023	67.79	gold quality
endocervix	UBERON:0000458	67.31	gold quality
skin of hip	UBERON:0001554	66.35	gold quality
vagina	UBERON:0000996	65.74	gold quality
uterine cervix	UBERON:0000002	64.36	gold quality
upper leg skin	UBERON:0004262	63.87	gold quality
buccal mucosa cell	CL:0002336	63.58	gold quality
pigmented layer of retina	UBERON:0001782	63.20	gold quality
gingival epithelium	UBERON:0001949	62.55	silver quality
esophagus mucosa	UBERON:0002469	61.90	gold quality
gingiva	UBERON:0001828	60.22	silver quality
endometrium	UBERON:0001295	59.92	gold quality
muscle layer of sigmoid colon	UBERON:0035805	59.78	gold quality
tibial nerve	UBERON:0001323	59.72	gold quality
tendon	UBERON:0000043	59.40	silver quality
right atrium auricular region	UBERON:0006631	58.41	gold quality
lower esophagus mucosa	UBERON:0035834	58.36	gold quality
cardiac atrium	UBERON:0002081	57.94	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.21

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

97 targeting CYP27C1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-767-5P	99.95	70.85	993
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-4495	99.82	72.08	3080
HSA-MIR-4760-5P	99.80	69.88	1619
HSA-MIR-4694-3P	99.79	69.53	2640
HSA-MIR-323A-3P	99.79	70.30	1739
HSA-MIR-577	99.78	69.13	2479
HSA-MIR-3934-3P	99.76	65.51	1351
HSA-MIR-623	99.76	68.16	1170
HSA-MIR-6885-3P	99.75	70.36	3187
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-1976	99.74	65.48	1127
HSA-MIR-4306	99.72	70.50	3630

Literature-anchored findings (GeneRIF, showing 2)

• Data suggest that the most likely catalytic mechanism for conversion of all-trans-retinol to 3,4-dehydroretinol by CYP27C1 begins with abstraction of a hydrogen atom from C-4 (or possibly C-3) initiating desaturation pathway, followed by sequential abstraction of a hydrogen atom or proton-coupled electron transfer. CYP27C1 appears to be localized to skin. (PMID:28701464)
• Cytochrome P450 27C1 Level Dictates Lung Cancer Tumorigenicity and Sensitivity towards Multiple Anticancer Agents and Its Potential Interplay with the IGF-1R/Akt/p53 Signaling Pathway. (PMID:35887201)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
danio_rerio	cyp27c1	ENSDARG00000092660
drosophila_melanogaster	sad	FBGN0003312

Paralogs (3): CYP24A1 (ENSG00000019186), CYP27B1 (ENSG00000111012), CYP27A1 (ENSG00000135929)

Protein

Protein identifiers

Cytochrome P450 27C1 — Q4G0S4 (reviewed: Q4G0S4)

Alternative names: All-trans retinol 3,4-desaturase

All UniProt accessions (2): A0A7N4I3A3, Q4G0S4

UniProt curated annotations — full annotation on UniProt →

Function. A cytochrome P450 monooxygenase that catalyzes the 3,4 desaturation of all-trans-retinol (also called vitamin A1) to all-trans-3,4-didehydroretinol (also called vitamin A2) in the skin. Desaturates with lower efficiency all-trans retinal and all-trans retinoic acid. Forms minor amounts of 3-hydroxy and 4-hydroxy all-trans-retinol derivatives. Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate and reducing the second into a water molecule. Two electrons are provided by NADPH via a two-protein mitochondrial transfer system comprising flavoprotein FDXR (adrenodoxin/ferredoxin reductase) and nonheme iron-sulfur protein FDX1 or FDX2 (adrenodoxin/ferredoxin).

Subcellular location. Mitochondrion membrane.

Tissue specificity. Widely expressed, with highest levels in the liver, kidney and pancreas. Expressed in the skin (at protein level).

Pathway. Cofactor metabolism; retinol metabolism.

Similarity. Belongs to the cytochrome P450 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q4G0S4-2	2	yes
Q4G0S4-1	1

RefSeq proteins (3): NP_001001665, NP_001354430, NP_001354431* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001128	Cyt_P450	Family
IPR002401	Cyt_P450_E_grp-I	Family
IPR017972	Cyt_P450_CS	Conserved_site
IPR036396	Cyt_P450_sf	Homologous_superfamily
IPR050479	CYP11_CYP27_families	Family

Pfam: PF00067

Enzyme classification (BRENDA):

• EC 1.14.19.53 — all-trans-retinol 3,4-desaturase (BRENDA: 2 organisms, 10 substrates, 4 inhibitors, 11 Km, 11 kcat entries)

Substrate kinetics (BRENDA)

8 substrates with measured Km, best-characterized 8. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ALL-TRANS-RETINOL	0.0002–0.0011	3
ALL-TRANS-RETINOIC ACID	—	2
ALL-TRANS-RETINAL	0.0003	1
ALL-TRANS-RETINALDEHYDE	0.0001	1
ALL-TRANS-RETINALDEHYDE FROM CELLULAR RETINOL-BI	0.0001	1
ALL-TRANS-RETINOIC ACID FROM CELLULAR RETINOIC A	0.0003	1
ALL-TRANS-RETINOIC ACID FROM CELLULAR RETINOIC A	0.0001	1
ALL-TRANS-RETINOL FROM CELLULAR RETINOL-BINDING	0.0001	1

Catalyzed reactions (Rhea), 3 shown:

• all-trans-retinol + 2 reduced [adrenodoxin] + O2 + 2 H(+) = all-trans-3,4-didehydroretinol + 2 oxidized [adrenodoxin] + 2 H2O (RHEA:50292)
• all-trans-retinol + 2 reduced [adrenodoxin] + O2 + 2 H(+) = all-trans-4-hydroxyretinol + 2 oxidized [adrenodoxin] + H2O (RHEA:50300)
• all-trans-retinol + 2 reduced [adrenodoxin] + O2 + 2 H(+) = all-trans-3-hydroxyretinol + 2 oxidized [adrenodoxin] + H2O (RHEA:65520)

UniProt features (8 total): transit peptide 1, chain 1, region of interest 1, compositionally biased region 1, binding site 1, splice variant 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q4G0S4-F1	86.39	0.71

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 (1): 488 (axial binding residue)

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 64 (showing top): GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_DN, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_PAIRED_DONORS_WITH_INCORPORATION_OR_REDUCTION_OF_MOLECULAR_OXYGEN, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_RETINOL_METABOLIC_PROCESS, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GOCC_MITOCHONDRIAL_ENVELOPE, GOBP_RETINAL_METABOLIC_PROCESS, GOBP_RETINOIC_ACID_METABOLIC_PROCESS, GOBP_LIPID_METABOLIC_PROCESS, GOBP_ORGANIC_ACID_METABOLIC_PROCESS, GOBP_ALDEHYDE_METABOLIC_PROCESS, DOUGLAS_BMI1_TARGETS_UP, chr2q14, GOBP_ISOPRENOID_METABOLIC_PROCESS, GOBP_PRIMARY_ALCOHOL_METABOLIC_PROCESS

GO Biological Process (5): retinol metabolic process (GO:0042572), retinoic acid metabolic process (GO:0042573), retinal metabolic process (GO:0042574), alcohol metabolic process (GO:0006066), lipid metabolic process (GO:0006629)

GO Molecular Function (14): retinoic acid binding (GO:0001972), monooxygenase activity (GO:0004497), 11-cis retinal binding (GO:0005502), all-trans retinal binding (GO:0005503), iron ion binding (GO:0005506), heme binding (GO:0020037), all-trans retinol 3,4-desaturase activity (GO:0061896), all-trans retinal 3,4-desaturase activity (GO:0061897), all-trans retinoic acid 3,4-desaturase activity (GO:0061898), 11-cis-retinal 3,4-desaturase activity (GO:0061899), all-trans-retinol binding (GO:1904768), oxidoreductase activity (GO:0016491), oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen (GO:0016705), metal ion binding (GO:0046872)

GO Cellular Component (3): mitochondrion (GO:0005739), mitochondrial membrane (GO:0031966), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen	4
retinoid metabolic process	3
hormone metabolic process	2
olefinic compound metabolic process	2
oxidoreductase activity	2
retinal binding	2
primary alcohol metabolic process	1
monocarboxylic acid metabolic process	1
aldehyde metabolic process	1
small molecule metabolic process	1
primary metabolic process	1
retinoid binding	1
monocarboxylic acid binding	1
transition metal ion binding	1
tetrapyrrole binding	1
retinol binding	1
catalytic activity	1
cation binding	1
cytoplasm	1
intracellular membrane-bounded organelle	1
mitochondrion	1
mitochondrial envelope	1
organelle membrane	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1048 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CYP27C1	FDX1	P10109	717
CYP27C1	OR6C68	A6NDL8	572
CYP27C1	OR6C4	Q8NGE1	481
CYP27C1	VN1R1	Q9GZP7	437
CYP27C1	OR2AP1	Q8NGE2	433
CYP27C1	CYB5RL	Q6IPT4	425
CYP27C1	OR10P1	Q8NGE3	417
CYP27C1	CYB5R4	Q7L1T6	417
CYP27C1	CYB5R2	Q6BCY4	410
CYP27C1	CYB5R1	Q9UHQ9	410
CYP27C1	CYB5B	O43169	405
CYP27C1	SAYSD1	Q9NPB0	400
CYP27C1	CYB5R3	P00387	397
CYP27C1	C1QTNF9B	B2RNN3	393
CYP27C1	CYP20A1	Q6UW02	356

IntAct

6 interactions, top by confidence:

A	B	Type	Score
CYP27C1	MTNR1A	psi-mi:“MI:0915”(physical association)	0.370
ADAM32	GPR89A	psi-mi:“MI:0914”(association)	0.350
RAMP2	GXYLT2	psi-mi:“MI:0914”(association)	0.350
SLC1A3	DDX11L8	psi-mi:“MI:0914”(association)	0.350
SLC39A12	ESYT2	psi-mi:“MI:0914”(association)	0.350

BioGRID (9): CYP27C1 (Affinity Capture-MS), CYP27C1 (Two-hybrid), CYP27C1 (Affinity Capture-MS), CYP27C1 (Affinity Capture-MS), CYP27C1 (Positive Genetic), CYP27C1 (Affinity Capture-MS), CYP27C1 (Affinity Capture-MS), CYP27C1 (Affinity Capture-MS), CYP27C1 (Affinity Capture-MS)

ESM2 similar proteins: A0A1I9Q5Z0, A0A481NR20, A8WGA0, E1BHJ4, G3V7X8, O18635, O23051, O44220, O73853, P05093, P0DOX0, P11715, P48416, P82712, Q07973, Q09128, Q09660, Q2XVA1, Q4G0S4, Q64441, Q6JD68, Q6WG30, Q7KR10, Q811W2, Q8HYM9, Q8HYN0, Q8HYN1, Q8W4T9, Q91Z85, Q92045, Q92113, Q940V4, Q95328, Q9EPT4, Q9GLD2, Q9GMC8, Q9LUC5, Q9NGX9, Q9NR63, Q9SHG5

Diamond homologs: A0A0A2J1Z6, A0A0C3HJL3, A0A0G4P2K0, A0A100IM63, A0A101MN42, A0A1B4XBH1, A0A1L9WUV2, A0A397HSG2, A0A3G9HRC2, A0A3Q9FEJ4, A0A3S9NM20, A0A411KZZ4, A0A455R5H4, A0A8K1AW54, A1DN29, A2QLV1, A2Y8E0, A7VMU4, B1B557, B2RML6, B8MV61, B8NHD9, B8NWW3, B8QHP5, C8V0D4, D4AY62, D7PI20, E9FCP5, F1SY49, F1SY74, F1SY83, G0KYB2, G5EJN7, G7XMT1, G9MLG2, I7ZK32, L8AXV5, M2YJD1, O00061, O08336

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	59
Likely benign	3
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1386 predictions. Top by Δscore:

Variant	Effect	Δscore
2:127187388:C:CC	acceptor_gain	1.0000
2:127193308:C:CT	acceptor_gain	1.0000
2:127193309:A:T	acceptor_gain	1.0000
2:127193787:A:AC	donor_gain	1.0000
2:127193788:C:CC	donor_gain	1.0000
2:127193788:CG:C	donor_gain	1.0000
2:127201120:A:AC	donor_gain	1.0000
2:127201121:C:CC	donor_gain	1.0000
2:127203374:T:A	donor_gain	1.0000
2:127193088:CCCTA:C	donor_loss	0.9900
2:127193089:CCTA:C	donor_loss	0.9900
2:127193090:CTA:C	donor_loss	0.9900
2:127193091:TAC:T	donor_loss	0.9900
2:127193093:CCT:C	donor_loss	0.9900
2:127193293:TGGGT:T	acceptor_gain	0.9900
2:127193294:GGGTC:G	acceptor_gain	0.9900
2:127193297:TCTG:T	acceptor_loss	0.9900
2:127193297:TCTGA:T	acceptor_gain	0.9900
2:127193298:C:CC	acceptor_gain	0.9900
2:127193298:CT:C	acceptor_gain	0.9900
2:127193298:CTGAG:C	acceptor_loss	0.9900
2:127193313:A:C	acceptor_gain	0.9900
2:127193317:C:CT	acceptor_gain	0.9900
2:127193318:A:T	acceptor_gain	0.9900
2:127195361:G:T	donor_gain	0.9900
2:127195499:CGT:C	acceptor_gain	0.9900
2:127201121:CTGAA:C	donor_gain	0.9900
2:127203366:CCTCA:C	donor_loss	0.9900
2:127203367:CTCA:C	donor_loss	0.9900
2:127203368:TCA:T	donor_loss	0.9900

AlphaMissense

3467 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000002630 (2:127189174 C>A,G,T), RS1000110424 (2:127195567 T>C), RS1000190095 (2:127213026 G>A), RS1000242334 (2:127212738 T>A), RS1000472323 (2:127192011 T>A,C), RS1000516700 (2:127204286 G>A,C), RS1000572324 (2:127191802 TCA>T), RS1000623902 (2:127186450 TG>T), RS1000947514 (2:127210185 C>A,T), RS1001004722 (2:127187975 T>C), RS1001056849 (2:127187732 T>A), RS1001118508 (2:127202886 C>G,T), RS1001174507 (2:127219165 T>A,C), RS1001193738 (2:127221111 G>A), RS1001212616 (2:127205370 C>A,G,T)

Disease associations

OMIM: gene MIM:620605 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST000747_6	Self-rated health	2.000000e-06
GCST002686_3	Protein C levels	4.000000e-09
GCST006119_10	Protein C levels	7.000000e-24

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004778	self rated health
EFO:0004633	protein C measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — CYP24, CYP26 and CYP27 families

CTD chemical–gene interactions

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression, increases methylation	6
Benzo(a)pyrene	affects methylation, increases expression	3
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
aristolochic acid I	increases expression	1
methylmercuric chloride	decreases expression	1
bisphenol A	affects cotreatment, decreases methylation	1
sodium arsenite	affects expression	1
butyraldehyde	decreases expression	1
benzo(e)pyrene	increases methylation	1
potassium chromate(VI)	decreases expression	1
fipronil	affects cotreatment, decreases expression	1
entinostat	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	decreases expression, affects cotreatment	1
(+)-JQ1 compound	decreases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Vorinostat	decreases expression	1
Carbamazepine	affects expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
DEET	decreases expression, affects cotreatment	1
Estradiol	affects cotreatment, increases expression	1
Methapyrilene	increases methylation	1
Rotenone	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Cadmium Chloride	increases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.