PCYOX1

Summary

PCYOX1 (prenylcysteine oxidase 1, HGNC:20588) is a protein-coding gene on chromosome 2p13.3, encoding Prenylcysteine oxidase 1 (Q9UHG3). Prenylcysteine oxidase that cleaves the thioether bond of prenyl-L-cysteines, such as farnesylcysteine and geranylgeranylcysteine.

Prenylcysteine is released during the degradation of prenylated proteins. PCYOX1 catalyzes the degradation of prenylcysteine to yield free cysteines and a hydrophobic isoprenoid product (Tschantz et al., 1999 [PubMed 10585463]).

Source: NCBI Gene 51449 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 85 total
• MANE Select transcript: NM_016297

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20588
Approved symbol	PCYOX1
Name	prenylcysteine oxidase 1
Location	2p13.3
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0908, PCL1
Ensembl gene	ENSG00000116005
Ensembl biotype	protein_coding
OMIM	610995
Entrez	51449

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 9 protein_coding, 1 retained_intron

ENST00000264441, ENST00000414812, ENST00000422380, ENST00000433351, ENST00000451279, ENST00000480949, ENST00000884434, ENST00000923107, ENST00000955832, ENST00000955833

RefSeq mRNA: 1 — MANE Select: NM_016297 NM_016297

CCDS: CCDS1902

Canonical transcript exons

ENST00000433351 — 6 exons

Exon	Start	End
ENSE00000760030	70274959	70275170
ENSE00000963066	70258137	70258276
ENSE00001311728	70261212	70261386
ENSE00001640931	70276734	70281185
ENSE00003622619	70259360	70259566
ENSE00003786156	70275514	70275666

Expression profiles

Bgee: expression breadth ubiquitous, 284 present calls, max score 99.24.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 49.7477 / max 661.9916, expressed in 1812 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
20842	49.7477	1812

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
parotid gland	UBERON:0001831	99.24	gold quality
endothelial cell	CL:0000115	98.63	gold quality
parietal pleura	UBERON:0002400	98.35	gold quality
skin of hip	UBERON:0001554	97.88	gold quality
gingival epithelium	UBERON:0001949	97.71	gold quality
upper leg skin	UBERON:0004262	97.70	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	97.60	gold quality
gingiva	UBERON:0001828	97.56	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	97.30	gold quality
biceps brachii	UBERON:0001507	97.24	gold quality
Brodmann (1909) area 23	UBERON:0013554	97.21	gold quality
visceral pleura	UBERON:0002401	97.19	gold quality
seminal vesicle	UBERON:0000998	97.12	gold quality
mammalian vulva	UBERON:0000997	97.07	gold quality
mammary duct	UBERON:0001765	96.86	gold quality
renal medulla	UBERON:0000362	96.68	gold quality
esophagus squamous epithelium	UBERON:0006920	96.56	gold quality
synovial joint	UBERON:0002217	96.52	gold quality
caput epididymis	UBERON:0004358	96.42	gold quality
lower lobe of lung	UBERON:0008949	96.29	gold quality
heart right ventricle	UBERON:0002080	96.20	gold quality
middle temporal gyrus	UBERON:0002771	96.20	gold quality
germinal epithelium of ovary	UBERON:0001304	96.08	gold quality
pleura	UBERON:0000977	96.06	gold quality
urethra	UBERON:0000057	95.84	gold quality
corpus epididymis	UBERON:0004359	95.77	gold quality
pigmented layer of retina	UBERON:0001782	95.76	gold quality
retina	UBERON:0000966	95.73	gold quality
body of tongue	UBERON:0011876	95.44	gold quality
superficial temporal artery	UBERON:0001614	95.42	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	22.19
E-GEOD-130148	yes	7.87
E-MTAB-9543	no	2.41

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

139 targeting PCYOX1, 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-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-495-3P	99.96	72.81	4197
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-2110	99.96	66.68	1930
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-146A-5P	99.96	68.93	988
HSA-MIR-146B-5P	99.96	69.13	977
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-7153-5P	99.94	68.89	1006
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-3682-5P	99.93	67.97	1163
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-8063	99.91	69.76	3146

Literature-anchored findings (GeneRIF, showing 5)

• initial studies of the kinetic mechanism and stereospecificity of this unusual enzyme (PMID:12186880)
• Addition of the substrate farnesylcysteine to lipoprotein resulted in a time-dependent generation of H(2)O(2) which was stronger in very low density lipoprotein (VLDL) than in LDL or HDL, reflecting the greater protein content of PCL1 in VLDL. (PMID:19253276)
• Elevated prenylcysteine oxidase 1 (PCYOX1) activity could help to propagate the oxidative burden of low density lipoproteins (LDLs), thus making PCYOX1 a potential pharmacological target and a new biomarker in cardiovascular disease [Review]. (PMID:28930587)
• Prenylcysteine oxidase 1, an emerging player in atherosclerosis. (PMID:34548610)
• Prenylcysteine Oxidase 1 (PCYOX1), a New Player in Thrombosis. (PMID:35269975)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	pcyox1	ENSDARG00000103052
mus_musculus	Pcyox1	ENSMUSG00000029998
rattus_norvegicus	Pcyox1	ENSRNOG00000016704

Paralogs (1): PCYOX1L (ENSG00000145882)

Protein

Protein identifiers

Prenylcysteine oxidase 1 — Q9UHG3 (reviewed: Q9UHG3)

Alternative names: Prenylcysteine lyase

All UniProt accessions (6): B7Z8A2, C9JGT6, C9JM55, C9K055, Q9UHG3, F8W8W4

UniProt curated annotations — full annotation on UniProt →

Function. Prenylcysteine oxidase that cleaves the thioether bond of prenyl-L-cysteines, such as farnesylcysteine and geranylgeranylcysteine. Only active against free prenylcysteines and not prenylcysteine residues within prenylated proteins or peptides. Involved in the final step in the degradation of prenylated proteins, by degrading prenylcysteines after the protein has been degraded.

Subcellular location. Lysosome.

Tissue specificity. Widely expressed.

Similarity. Belongs to the prenylcysteine oxidase family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9UHG3-1	1	yes
Q9UHG3-2	2

RefSeq proteins (1): NP_057381* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR010795	Prenylcys_lyase	Domain
IPR017046	Prenylcysteine_Oxase1	Family
IPR036188	FAD/NAD-bd_sf	Homologous_superfamily

Pfam: PF07156, PF13450

Enzyme classification (BRENDA):

• EC 1.8.3.5 — prenylcysteine oxidase (BRENDA: 4 organisms, 9 substrates, 9 inhibitors, 5 Km, 1 kcat entries)

Substrate kinetics (BRENDA)

5 substrates with measured Km, best-characterized 5. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
FARNESYL-L-CYSTEINE	0.003	1
FARNESYLCYSTEINE	0.0007	1
GERANYLGERANYLCYSTEINE	0.0008	1
O2	0.05	1
S-(2E,6E)-FARNESYL-L-CYSTEINE	0.045	1

Catalyzed reactions (Rhea), 3 shown:

• S-(2E,6E)-farnesyl-L-cysteine + O2 + H2O = (2E,6E)-farnesal + L-cysteine + H2O2 (RHEA:30231)
• an S-polyprenyl-L-cysteine + O2 + H2O = a polyprenal + L-cysteine + H2O2 (RHEA:53892)
• [(2E,6E,10E)-geranylgeranyl]-L-cysteine + O2 + H2O = (2E,6E,10E)-geranylgeranial + L-cysteine + H2O2 (RHEA:70407)

UniProt features (10 total): glycosylation site 3, sequence variant 3, signal peptide 1, chain 1, splice variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UHG3-F1	91.61	0.81

Functional residue map

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

Glycosylation sites (3): 196, 323, 353

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 172 (showing top): GOBP_MODIFIED_AMINO_ACID_CATABOLIC_PROCESS, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GTGCCTT_MIR506, MODULE_239, ZHANG_BREAST_CANCER_PROGENITORS_UP, TGCCTTA_MIR124A, GOBP_MODIFIED_AMINO_ACID_METABOLIC_PROCESS, GOBP_PROTEIN_CATABOLIC_PROCESS, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_DN, GOBP_PROTEOLYSIS, FRASOR_TAMOXIFEN_RESPONSE_UP, GOCC_PROTEIN_LIPID_COMPLEX, WANG_SMARCE1_TARGETS_UP

GO Biological Process (2): prenylated protein catabolic process (GO:0030327), prenylcysteine catabolic process (GO:0030328)

GO Molecular Function (6): prenylcysteine oxidase activity (GO:0001735), FAD binding (GO:0071949), farnesylcysteine lyase activity (GO:0102149), protein binding (GO:0005515), oxidoreductase activity (GO:0016491), oxidoreductase activity, acting on a sulfur group of donors, oxygen as acceptor (GO:0016670)

GO Cellular Component (3): lysosome (GO:0005764), very-low-density lipoprotein particle (GO:0034361), extracellular exosome (GO:0070062)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
oxidoreductase activity, acting on a sulfur group of donors, oxygen as acceptor	2
modification-dependent protein catabolic process	1
modified amino acid catabolic process	1
flavin adenine dinucleotide binding	1
binding	1
catalytic activity	1
oxidoreductase activity, acting on a sulfur group of donors	1
lytic vacuole	1
triglyceride-rich plasma lipoprotein particle	1
extracellular vesicle	1

Protein interactions and networks

STRING

832 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PCYOX1	LAMP1	P11279	779
PCYOX1	PON1	P27169	568
PCYOX1	PON3	Q15166	561
PCYOX1	MVD	P53602	556
PCYOX1	PLAC8L1	A1L4L8	517
PCYOX1	ARB2A	Q8WUF8	517
PCYOX1	FNTB	P49356	484
PCYOX1	PYURF	Q96I23	471
PCYOX1	PHF24	Q9UPV7	470
PCYOX1	FOXRED2	Q8IWF2	450
PCYOX1	B4DL54	B4DL54	446
PCYOX1	ART4	Q93070	443
PCYOX1	RIMS4	Q9H426	442
PCYOX1	ZMPSTE24	O75844	438
PCYOX1	DCD	P58461	427

IntAct

113 interactions, top by confidence:

A	B	Type	Score
TRDN	TMEM223	psi-mi:“MI:0914”(association)	0.640
FBXO6	MAN2B1	psi-mi:“MI:0914”(association)	0.640
STX12	SNAP23	psi-mi:“MI:0914”(association)	0.640
UBE3B	CALM1	psi-mi:“MI:0914”(association)	0.620
HOXA1	PCYOX1	psi-mi:“MI:0915”(physical association)	0.560
ANTXR1	POTEF	psi-mi:“MI:0914”(association)	0.530
DLK1	TCAF2	psi-mi:“MI:0914”(association)	0.530
FDPS	ZMPSTE24	psi-mi:“MI:0914”(association)	0.530
BLVRA	DDHD2	psi-mi:“MI:0914”(association)	0.530
RHOBTB3	ARF5	psi-mi:“MI:0914”(association)	0.530
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
CD226	MEN1	psi-mi:“MI:0914”(association)	0.530
GPC3	CLGN	psi-mi:“MI:0914”(association)	0.530
ARF5	ARF4	psi-mi:“MI:0914”(association)	0.530
ANTXR1	WFS1	psi-mi:“MI:0914”(association)	0.530
LRRTM3	SGPL1	psi-mi:“MI:0914”(association)	0.530
GPC3	CANX	psi-mi:“MI:0914”(association)	0.530
RHOBTB3	ILVBL	psi-mi:“MI:0914”(association)	0.530
ENTPD4	PCYOX1	psi-mi:“MI:0915”(physical association)	0.500
GJB3	PCYOX1	psi-mi:“MI:0915”(physical association)	0.500
sseJ	AGPS	psi-mi:“MI:0914”(association)	0.460
KIF1C	PCYOX1	psi-mi:“MI:0915”(physical association)	0.400
UST	PCYOX1	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (127): PCYOX1 (Affinity Capture-MS), PCYOX1 (Affinity Capture-MS), PCYOX1 (Affinity Capture-MS), PCYOX1 (Affinity Capture-MS), PCYOX1 (Affinity Capture-MS), PCYOX1 (Affinity Capture-MS), PCYOX1 (Affinity Capture-MS), PCYOX1 (Affinity Capture-MS), PCYOX1 (Affinity Capture-MS), PCYOX1 (Affinity Capture-MS), PCYOX1 (Affinity Capture-MS), PCYOX1 (Affinity Capture-MS), PCYOX1 (Affinity Capture-MS), PCYOX1 (Affinity Capture-MS), PCYOX1 (Affinity Capture-MS)

ESM2 similar proteins: A0A0P0XM10, A0A2U8QPE6, A6MFL0, A8QL51, A8QL52, A8QL58, B0VXW0, B5AR80, B5U6Y8, G8XQX1, J7H670, O64411, P0C2D5, P0DO52, P19643, P21396, P21397, P21398, P23623, P27338, P49253, P54982, P56560, P57681, P58027, P58028, P81382, P81383, P86810, Q0J290, Q4JHE1, Q4JHE2, Q4JHE3, Q5NU32, Q5R748, Q5RE60, Q5RE98, Q64133, Q6NSN2, Q6PLK3

Diamond homologs: F1N2K1, P0A5A8, P35903, P57681, P9WMP0, P9WMP1, Q0P5H1, Q5R748, Q8C7K6, Q8NBM8, Q95KC9, Q99ML5, Q9CQF9, Q9UHG3, O32434, P56601, Q0J954, Q50008, Q5NAI7, Q7XR46

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 146 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
ERAD pathway	7	9.8×	8e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	70
Likely benign	5
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

899 predictions. Top by Δscore:

Variant	Effect	Δscore
2:70259355:CATA:C	acceptor_loss	1.0000
2:70259356:A:AG	acceptor_gain	1.0000
2:70259356:ATAGC:A	acceptor_gain	1.0000
2:70259357:T:G	acceptor_gain	1.0000
2:70259358:A:AG	acceptor_gain	1.0000
2:70259358:AGC:A	acceptor_gain	1.0000
2:70259359:G:GG	acceptor_gain	1.0000
2:70259359:GC:G	acceptor_gain	1.0000
2:70259359:GCG:G	acceptor_gain	1.0000
2:70259359:GCGA:G	acceptor_gain	1.0000
2:70259359:GCGAT:G	acceptor_gain	1.0000
2:70259507:C:T	donor_gain	1.0000
2:70259510:G:GT	donor_gain	1.0000
2:70259564:TGGG:T	donor_loss	1.0000
2:70259565:GG:G	donor_gain	1.0000
2:70259566:GG:G	donor_gain	1.0000
2:70259566:GGTA:G	donor_loss	1.0000
2:70259567:G:GA	donor_loss	1.0000
2:70259567:G:GG	donor_gain	1.0000
2:70259568:T:G	donor_loss	1.0000
2:70261208:GCA:G	acceptor_loss	1.0000
2:70261209:CAGGT:C	acceptor_loss	1.0000
2:70261210:A:C	acceptor_loss	1.0000
2:70261281:A:T	donor_gain	1.0000
2:70261383:TGAG:T	donor_loss	1.0000
2:70261385:AGGT:A	donor_loss	1.0000
2:70261386:GG:G	donor_loss	1.0000
2:70261387:G:GC	donor_loss	1.0000
2:70261388:T:A	donor_loss	1.0000
2:70274954:CAAA:C	acceptor_loss	1.0000

AlphaMissense

3311 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:70259535:T:A	N96K	0.994
2:70259535:T:G	N96K	0.994
2:70277277:A:T	E468V	0.994
2:70259360:C:A	A38E	0.991
2:70274990:T:C	F176L	0.991
2:70274992:C:A	F176L	0.991
2:70274992:C:G	F176L	0.991
2:70275577:T:A	V257D	0.991
2:70277267:A:C	S465R	0.990
2:70277269:T:A	S465R	0.990
2:70277269:T:G	S465R	0.990
2:70275589:T:C	L261P	0.989
2:70259405:T:C	L53P	0.987
2:70277276:G:A	E468K	0.987
2:70259384:G:A	G46D	0.985
2:70276806:T:A	V311D	0.985
2:70276922:G:T	G350W	0.985
2:70275569:T:A	N254K	0.984
2:70275569:T:G	N254K	0.984
2:70275170:G:A	G236R	0.982
2:70275170:G:C	G236R	0.982
2:70277313:T:C	L480P	0.982
2:70259381:G:A	G45D	0.981
2:70275589:T:A	L261H	0.981
2:70277302:C:A	N476K	0.981
2:70277302:C:G	N476K	0.981
2:70259537:T:C	L97P	0.980
2:70259369:G:A	G41E	0.979
2:70276922:G:A	G350R	0.979
2:70276922:G:C	G350R	0.979

dbSNP variants (sampled 300 via entrez): RS1000026098 (2:70271220 A>C), RS1000240214 (2:70272616 G>C), RS1000489724 (2:70279445 A>G), RS1000803526 (2:70279949 G>A), RS1000805865 (2:70267955 C>T), RS1000816802 (2:70278060 T>C), RS1000905992 (2:70261623 C>T), RS1001042051 (2:70262670 G>A,C), RS1001145588 (2:70278866 T>C), RS1001318688 (2:70273955 A>C), RS1001365335 (2:70270788 G>A,C,T), RS1001384862 (2:70271912 A>G), RS1001488723 (2:70266274 G>A,T), RS1001711543 (2:70266486 T>C), RS1001752604 (2:70272240 C>G,T)

Disease associations

OMIM: gene MIM:610995 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST002481_1	Acne (severe)	5.000000e-06
GCST006661_199	Male-pattern baldness	3.000000e-08
GCST007565_7	Morning person	4.000000e-14
GCST007576_26	Chronotype	4.000000e-14
GCST90013406_26	Liver enzyme levels (alkaline phosphatase)	9.000000e-16

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0008328	chronotype measurement
EFO:0004533	alkaline phosphatase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

60 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases expression, affects cotreatment, affects expression, decreases expression	5
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression, increases expression	3
Cyclosporine	decreases expression	3
Benzo(a)pyrene	affects methylation, increases methylation	2
Valproic Acid	affects expression, increases expression	2
Aflatoxin B1	affects expression, decreases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	decreases expression	1
bisphenol F	increases expression	1
2,4,6-tribromophenol	decreases expression	1
testosterone enanthate	affects expression	1
triphenyl phosphate	affects expression	1
decabromobiphenyl ether	decreases expression	1
trichostatin A	affects expression	1
afimoxifene	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	decreases expression	1
butyraldehyde	decreases expression	1
tetrabromobisphenol A	decreases expression	1
coumarin	increases phosphorylation	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluoro-n-nonanoic acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
bisphenol B	increases expression	1
abrine	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
bisphenol S	increases expression	1

Clinical trials (associated diseases)

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