PCYOX1L

Summary

PCYOX1L (prenylcysteine oxidase 1 like, HGNC:28477) is a protein-coding gene on chromosome 5q32, encoding Prenylcysteine oxidase 1-like (Q8NBM8). Prenylcysteine oxidase that cleaves the thioether bond of prenyl-L-cysteines, such as farnesylcysteine and geranylgeranylcysteine.

Predicted to enable prenylcysteine oxidase activity. Predicted to be involved in prenylated protein catabolic process. Located in membrane.

Source: NCBI Gene 78991 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 78 total
• MANE Select transcript: NM_024028

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28477
Approved symbol	PCYOX1L
Name	prenylcysteine oxidase 1 like
Location	5q32
Locus type	gene with protein product
Status	Approved
Aliases	MGC3265
Ensembl gene	ENSG00000145882
Ensembl biotype	protein_coding
OMIM	621338
Entrez	78991

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 5 protein_coding, 3 nonsense_mediated_decay, 2 retained_intron

ENST00000274569, ENST00000503240, ENST00000505669, ENST00000507621, ENST00000510990, ENST00000511945, ENST00000514349, ENST00000885621, ENST00000885622, ENST00000955125

RefSeq mRNA: 3 — MANE Select: NM_024028 NM_001301054, NM_001301057, NM_024028

CCDS: CCDS4296

Canonical transcript exons

ENST00000274569 — 6 exons

Exon	Start	End
ENSE00001292406	149358046	149358156
ENSE00003481387	149364036	149364210
ENSE00003482941	149367360	149367500
ENSE00003541493	149367993	149369653
ENSE00003627698	149365942	149366153
ENSE00003644631	149362637	149362843

Expression profiles

Bgee: expression breadth ubiquitous, 265 present calls, max score 87.97.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 10.1847 / max 179.8601, expressed in 1736 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
59360	10.1847	1736

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
middle temporal gyrus	UBERON:0002771	87.97	gold quality
granulocyte	CL:0000094	87.27	gold quality
monocyte	CL:0000576	86.35	gold quality
mononuclear cell	CL:0000842	86.34	gold quality
leukocyte	CL:0000738	86.25	gold quality
cerebellar vermis	UBERON:0004720	86.10	gold quality
dorsal root ganglion	UBERON:0000044	85.82	gold quality
pons	UBERON:0000988	85.62	gold quality
Brodmann (1909) area 46	UBERON:0006483	85.23	gold quality
right hemisphere of cerebellum	UBERON:0014890	85.04	gold quality
trigeminal ganglion	UBERON:0001675	84.95	gold quality
cerebellar cortex	UBERON:0002129	84.81	gold quality
cerebellar hemisphere	UBERON:0002245	84.80	gold quality
prefrontal cortex	UBERON:0000451	84.55	gold quality
orbitofrontal cortex	UBERON:0004167	84.54	gold quality
superior vestibular nucleus	UBERON:0007227	84.48	gold quality
cerebellum	UBERON:0002037	84.33	gold quality
Brodmann (1909) area 9	UBERON:0013540	83.95	gold quality
frontal cortex	UBERON:0001870	83.63	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	83.46	gold quality
right uterine tube	UBERON:0001302	83.23	gold quality
substantia nigra pars compacta	UBERON:0001965	83.21	gold quality
neocortex	UBERON:0001950	83.07	gold quality
right frontal lobe	UBERON:0002810	82.97	gold quality
superior frontal gyrus	UBERON:0002661	82.79	gold quality
cervix squamous epithelium	UBERON:0006922	82.77	silver quality
parietal lobe	UBERON:0001872	82.67	gold quality
postcentral gyrus	UBERON:0002581	82.50	gold quality
cerebral cortex	UBERON:0000956	82.17	gold quality
blood	UBERON:0000178	82.15	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	3.33

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

53 targeting PCYOX1L, 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-6077	99.99	68.04	2299
HSA-MIR-3912-5P	99.95	66.11	925
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-4525	99.94	64.38	675
HSA-MIR-5010-5P	99.94	64.11	705
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-219A-5P	99.91	73.36	735
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-4782-3P	99.88	73.31	735
HSA-MIR-6766-3P	99.88	73.38	732
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-204-5P	99.79	71.62	2439
HSA-MIR-211-5P	99.79	71.65	2440
HSA-MIR-623	99.76	68.16	1170
HSA-MIR-7856-5P	99.75	69.99	2901
HSA-MIR-4502	99.65	66.99	1021
HSA-MIR-3679-3P	99.64	69.88	1599
HSA-MIR-4472	99.56	66.08	1478
HSA-MIR-4279	99.19	66.70	2437
HSA-MIR-4254	99.11	65.15	1315
HSA-MIR-320A-5P	98.88	66.75	1248
HSA-MIR-29B-1-5P	98.86	68.35	1364
HSA-MIR-5006-5P	98.79	66.92	1246
HSA-MIR-3611	98.76	68.76	1290
HSA-MIR-6868-3P	98.63	69.64	2259

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	pcyox1l	ENSDARG00000069003
danio_rerio		ENSDARG00000113268
mus_musculus	Pcyox1l	ENSMUSG00000024579
rattus_norvegicus	Pcyox1l	ENSRNOG00000019643

Paralogs (1): PCYOX1 (ENSG00000116005)

Protein

Protein identifiers

Prenylcysteine oxidase 1-like — Q8NBM8 (reviewed: Q8NBM8)

All UniProt accessions (3): D6R9J0, E7EVZ5, Q8NBM8

UniProt curated annotations — full annotation on UniProt →

Function. Prenylcysteine oxidase that cleaves the thioether bond of prenyl-L-cysteines, such as farnesylcysteine and geranylgeranylcysteine. Does not metabolize shorter prenyl chain compounds. Required in the mevalonate pathway to regulate prenylation and enhances the bactericidal activity of neutrophils. Promotes the assembly of the postsynaptic ion channel ASIC1a.

Subcellular location. Secreted.

Miscellaneous. The catalytic activity of PCYOX1L has been experimentally evaluated using ancestral sequence reconstruction. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Similarity. Belongs to the prenylcysteine oxidase family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8NBM8-1	1	yes
Q8NBM8-2	2

RefSeq proteins (3): NP_001287983, NP_001287986, NP_076933* (*=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

Catalyzed reactions (Rhea), 2 shown:

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

UniProt features (10 total): sequence variant 3, splice variant 2, sequence conflict 2, signal peptide 1, chain 1, glycosylation site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NBM8-F1	90.31	0.75

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 (1): 342

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-114608	Platelet degranulation

MSigDB gene sets: 130 (showing top): BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOCC_SECRETORY_GRANULE, REACTOME_PLATELET_ACTIVATION_SIGNALING_AND_AGGREGATION, AREB6_03, GOBP_MODIFIED_AMINO_ACID_CATABOLIC_PROCESS, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_LEUKOCYTE_MEDIATED_CYTOTOXICITY, GOBP_LEUKOCYTE_MEDIATED_IMMUNITY, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, TGCTGAY_UNKNOWN, GOBP_MYELOID_LEUKOCYTE_MEDIATED_IMMUNITY, AACTTT_UNKNOWN, GOBP_IMMUNE_EFFECTOR_PROCESS, GOBP_BIOLOGICAL_PROCESS_INVOLVED_IN_INTERACTION_WITH_SYMBIONT, GOBP_DEFENSE_RESPONSE_TO_BACTERIUM

GO Biological Process (3): prenylated protein catabolic process (GO:0030327), prenylcysteine catabolic process (GO:0030328), neutrophil-mediated killing of bacterium (GO:0070944)

GO Molecular Function (3): prenylcysteine oxidase activity (GO:0001735), oxidoreductase activity (GO:0016491), oxidoreductase activity, acting on a sulfur group of donors, oxygen as acceptor (GO:0016670)

GO Cellular Component (3): extracellular region (GO:0005576), membrane (GO:0016020), platelet alpha granule lumen (GO:0031093)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Response to elevated platelet cytosolic Ca2+	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
modification-dependent protein catabolic process	1
modified amino acid catabolic process	1
defense response to bacterium	1
neutrophil-mediated killing of symbiont cell	1
oxidoreductase activity, acting on a sulfur group of donors, oxygen as acceptor	1
catalytic activity	1
oxidoreductase activity, acting on a sulfur group of donors	1
platelet alpha granule	1
secretory granule lumen	1

Protein interactions and networks

STRING

726 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PCYOX1L	ZNF782	Q6ZMW2	457
PCYOX1L	AFAP1L1	Q8TED9	457
PCYOX1L	ARRDC3	Q96B67	428
PCYOX1L	ZDHHC24	Q6UX98	425
PCYOX1L	USP39	Q53GS9	424
PCYOX1L	ZNF248	Q8NDW4	410
PCYOX1L	EXD1	Q8NHP7	410
PCYOX1L	VPS13B	Q7Z7G8	404
PCYOX1L	CATSPERB	Q9H7T0	391
PCYOX1L	GXYLT1	Q4G148	389
PCYOX1L	PGAP2	Q9UHJ9	385
PCYOX1L	STARD9	Q9P2P6	381
PCYOX1L	ZNF462	Q96JM2	378
PCYOX1L	H2AJ	Q9BTM1	378
PCYOX1L	STON2	Q8WXE9	374

IntAct

35 interactions, top by confidence:

A	B	Type	Score
B3GNT3	PGRMC1	psi-mi:“MI:0914”(association)	0.670
FBXO6	MAN2B1	psi-mi:“MI:0914”(association)	0.640
CANX	PGRMC1	psi-mi:“MI:0914”(association)	0.570
CD1B	TOR1B	psi-mi:“MI:0914”(association)	0.530
IFNA21	IFIT3	psi-mi:“MI:0914”(association)	0.530
LACRT	PLXNA2	psi-mi:“MI:0914”(association)	0.530
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
CLGN	NPC1	psi-mi:“MI:0914”(association)	0.530
ITGA9	IGLL5	psi-mi:“MI:0914”(association)	0.350
LYZL2	MANBA	psi-mi:“MI:0914”(association)	0.350
CLU	TOR1A	psi-mi:“MI:0914”(association)	0.350
TEX101	NDUFA4	psi-mi:“MI:0914”(association)	0.350
CANX	HLA-A	psi-mi:“MI:0914”(association)	0.350
CLEC12B	GXYLT2	psi-mi:“MI:0914”(association)	0.350
APOA2	TMEM131L	psi-mi:“MI:0914”(association)	0.350
CCL3	KRBA1	psi-mi:“MI:0914”(association)	0.350
SCGB2A1	RAP1BL	psi-mi:“MI:0914”(association)	0.350
RLN1	RTL8C	psi-mi:“MI:0914”(association)	0.350
RLN2	AIP	psi-mi:“MI:0914”(association)	0.350
OR6T1	PSMD11	psi-mi:“MI:0914”(association)	0.350
PATE1	MANBA	psi-mi:“MI:0914”(association)	0.350
NMS	MANBA	psi-mi:“MI:0914”(association)	0.350
MANEA	AGRN	psi-mi:“MI:0914”(association)	0.350
LYZL2	ZZEF1	psi-mi:“MI:0914”(association)	0.350
DEFB106A	EMC8	psi-mi:“MI:0914”(association)	0.350

BioGRID (48): PCYOX1L (Affinity Capture-RNA), PCYOX1L (Affinity Capture-RNA), PCYOX1L (Affinity Capture-MS), PCYOX1L (Affinity Capture-MS), PCYOX1L (Affinity Capture-MS), PCYOX1L (Affinity Capture-MS), PCYOX1L (Affinity Capture-MS), PCYOX1L (Affinity Capture-MS), PCYOX1L (Affinity Capture-MS), PCYOX1L (Affinity Capture-MS), PCYOX1L (Affinity Capture-RNA), PCYOX1L (Affinity Capture-MS), PCYOX1L (Affinity Capture-MS), PCYOX1L (Affinity Capture-MS), PCYOX1L (Affinity Capture-RNA)

ESM2 similar proteins: A4IG53, A5PJK1, B1WC86, D2I2M6, F1N2K1, O95479, P58242, P70665, P82450, P98192, Q05AK6, Q08BG1, Q0P5H1, Q1JPD2, Q1LWG4, Q4V7R2, Q53F39, Q5R748, Q5RET5, Q5RFU0, Q5ZK82, Q61139, Q640M6, Q641Z7, Q658P3, Q6L5F5, Q6UX53, Q6ZT21, Q7G7C7, Q80XL7, Q8BMD6, Q8C7K6, Q8NBM8, Q8R2R1, Q8WTR4, Q92485, Q95KC9, Q99PR0, Q9D0Z3, Q9ES71

Diamond homologs: F1N2K1, P0A5A8, P35903, P57681, P9WMP0, P9WMP1, Q0P5H1, Q5R748, Q8C7K6, Q8NBM8, Q95KC9, Q99ML5, Q9CQF9, Q9UHG3

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 48 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	5	24.5×	3e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	68
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1144 predictions. Top by Δscore:

Variant	Effect	Δscore
5:149358167:G:GT	donor_gain	1.0000
5:149362616:A:AG	acceptor_gain	1.0000
5:149362617:C:G	acceptor_gain	1.0000
5:149362622:C:A	acceptor_gain	1.0000
5:149362623:G:A	acceptor_gain	1.0000
5:149362839:GCTGG:G	donor_gain	1.0000
5:149362841:TGGGT:T	donor_loss	1.0000
5:149362842:GG:G	donor_gain	1.0000
5:149362843:GG:G	donor_gain	1.0000
5:149362843:GGT:G	donor_loss	1.0000
5:149362844:G:GG	donor_gain	1.0000
5:149362844:GT:G	donor_loss	1.0000
5:149362845:T:G	donor_loss	1.0000
5:149364031:TGCA:T	acceptor_loss	1.0000
5:149364032:GCA:G	acceptor_loss	1.0000
5:149364034:AG:A	acceptor_gain	1.0000
5:149364034:AGG:A	acceptor_gain	1.0000
5:149364034:AGGG:A	acceptor_loss	1.0000
5:149364035:GG:G	acceptor_gain	1.0000
5:149364035:GGG:G	acceptor_gain	1.0000
5:149364035:GGGC:G	acceptor_gain	1.0000
5:149364035:GGGCT:G	acceptor_gain	1.0000
5:149364188:G:GT	donor_gain	1.0000
5:149366150:GCAG:G	donor_gain	1.0000
5:149366154:G:C	donor_loss	1.0000
5:149366155:T:G	donor_loss	1.0000
5:149367991:A:AG	acceptor_gain	1.0000
5:149367991:AGAG:A	acceptor_gain	1.0000
5:149367991:AGAGG:A	acceptor_gain	1.0000
5:149367992:G:GG	acceptor_gain	1.0000

AlphaMissense

3220 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:149365973:T:C	F168L	0.999
5:149365975:C:A	F168L	0.999
5:149365975:C:G	F168L	0.999
5:149368179:T:A	V337D	0.999
5:149368185:G:A	G339D	0.999
5:149368184:G:C	G339R	0.998
5:149368401:T:C	F411S	0.998
5:149367423:T:A	V249D	0.997
5:149368185:G:T	G339V	0.997
5:149368400:T:C	F411L	0.997
5:149368402:C:A	F411L	0.997
5:149368402:C:G	F411L	0.997
5:149368564:T:A	N465K	0.997
5:149368564:T:G	N465K	0.997
5:149368356:T:A	V396D	0.996
5:149364158:A:C	S140R	0.995
5:149364160:C:A	S140R	0.995
5:149364160:C:G	S140R	0.995
5:149368065:T:A	V299D	0.994
5:149368347:T:A	V393D	0.994
5:149368400:T:A	F411I	0.994
5:149368569:C:A	A467D	0.994
5:149362637:C:A	A30E	0.993
5:149362682:T:C	L45P	0.993
5:149365974:T:C	F168S	0.993
5:149368349:T:A	W394R	0.993
5:149368349:T:C	W394R	0.993
5:149368578:C:A	A470D	0.993
5:149366055:T:C	L195P	0.992
5:149368007:T:G	Y280D	0.992

dbSNP variants (sampled 300 via entrez): RS1000063328 (5:149360146 G>A), RS1000337746 (5:149357630 G>C), RS1000370434 (5:149357910 G>A), RS1000527359 (5:149364575 C>T), RS1000570611 (5:149363225 A>G), RS1000664845 (5:149358738 G>A), RS1000794434 (5:149360330 G>A), RS1000964716 (5:149364794 C>A,T), RS1001075729 (5:149366659 A>C,G), RS1001218259 (5:149356753 G>A), RS1001372454 (5:149356188 T>G), RS1001407439 (5:149366388 A>G), RS1001409965 (5:149362429 A>G,T), RS1001587389 (5:149356439 A>G), RS1002240203 (5:149366748 C>T)

Disease associations

OMIM: gene MIM:621338 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	4
trichostatin A	affects expression, increases expression	2
sodium arsenite	decreases expression, increases abundance	2
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, decreases expression	2
Benzo(a)pyrene	affects methylation, increases expression	2
Cadmium	increases abundance, increases expression	2
Cisplatin	affects cotreatment, increases expression	2
Tetrachlorodibenzodioxin	decreases expression	2
Tobacco Smoke Pollution	decreases expression	2
aristolochic acid I	increases expression	1
GSK-J4	decreases expression	1
2,4,6-tribromophenol	decreases expression	1
alpha phellandrene	decreases expression	1
alpha-pinene	increases oxidation, increases abundance, affects cotreatment	1
bisphenol A	decreases methylation, affects cotreatment	1
deoxynivalenol	decreases expression	1
decabromobiphenyl ether	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
tetrabromobisphenol A	decreases expression	1
methacrylaldehyde	increases abundance, affects cotreatment, increases oxidation	1
abrine	decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
jinfukang	increases expression, affects cotreatment	1
Sunitinib	increases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Arsenic	decreases expression, increases abundance	1
Carbamazepine	affects expression	1
Doxorubicin	decreases expression	1

Clinical trials (associated diseases)

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