PIPOX

Summary

PIPOX (pipecolic acid and sarcosine oxidase, HGNC:17804) is a protein-coding gene on chromosome 17q11.2, encoding Peroxisomal sarcosine oxidase (Q9P0Z9). Metabolizes sarcosine and L-pipecolic acid.

Enables L-pipecolate oxidase activity and sarcosine oxidase activity. Involved in L-lysine catabolic process to acetyl-CoA via L-pipecolate. Located in peroxisome.

Source: NCBI Gene 51268 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 62 total
• Druggable target: yes
• MANE Select transcript: NM_016518

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17804
Approved symbol	PIPOX
Name	pipecolic acid and sarcosine oxidase
Location	17q11.2
Locus type	gene with protein product
Status	Approved
Aliases	LPIPOX
Ensembl gene	ENSG00000179761
Ensembl biotype	protein_coding
OMIM	616713
Entrez	51268

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 7 protein_coding_CDS_not_defined, 6 protein_coding

ENST00000323372, ENST00000419875, ENST00000466889, ENST00000469082, ENST00000484308, ENST00000577182, ENST00000578748, ENST00000580241, ENST00000580383, ENST00000583215, ENST00000851649, ENST00000851650, ENST00000851651

RefSeq mRNA: 1 — MANE Select: NM_016518 NM_016518

CCDS: CCDS11248

Canonical transcript exons

ENST00000323372 — 8 exons

Exon	Start	End
ENSE00001284409	29043141	29043339
ENSE00001401855	29056175	29057216
ENSE00003474742	29044859	29045007
ENSE00003508966	29055813	29055888
ENSE00003532423	29055063	29055221
ENSE00003578874	29054545	29054691
ENSE00003588665	29052920	29053133
ENSE00003592251	29053413	29053595

Expression profiles

Bgee: expression breadth ubiquitous, 220 present calls, max score 98.47.

FANTOM5 (CAGE): breadth broad, TPM avg 2.9644 / max 486.6624, expressed in 351 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
160081	1.7522	226
160078	0.6640	141
160080	0.2684	112
160082	0.0986	27
160083	0.0634	16
160077	0.0514	26
208115	0.0433	22
160079	0.0231	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	98.47	gold quality
liver	UBERON:0002107	97.80	gold quality
nephron tubule	UBERON:0001231	97.37	gold quality
kidney epithelium	UBERON:0004819	97.30	gold quality
renal glomerulus	UBERON:0000074	97.03	gold quality
metanephric glomerulus	UBERON:0004736	96.61	gold quality
cranial nerve II	UBERON:0000941	94.08	gold quality
adult mammalian kidney	UBERON:0000082	91.91	gold quality
endothelial cell	CL:0000115	90.20	gold quality
kidney	UBERON:0002113	88.92	gold quality
adult organism	UBERON:0007023	87.45	gold quality
cortex of kidney	UBERON:0001225	86.30	gold quality
jejunal mucosa	UBERON:0000399	86.09	gold quality
medial globus pallidus	UBERON:0002477	84.54	gold quality
corpus epididymis	UBERON:0004359	83.70	gold quality
decidua	UBERON:0002450	82.87	gold quality
duodenum	UBERON:0002114	81.79	gold quality
metanephros	UBERON:0000081	81.53	gold quality
globus pallidus	UBERON:0001875	81.50	gold quality
pancreatic ductal cell	CL:0002079	81.00	gold quality
substantia nigra	UBERON:0002038	80.58	gold quality
putamen	UBERON:0001874	80.34	gold quality
hypothalamus	UBERON:0001898	79.64	gold quality
caudate nucleus	UBERON:0001873	79.45	gold quality
right uterine tube	UBERON:0001302	79.37	gold quality
midbrain	UBERON:0001891	79.35	gold quality
nucleus accumbens	UBERON:0001882	79.30	gold quality
islet of Langerhans	UBERON:0000006	78.09	gold quality
right frontal lobe	UBERON:0002810	77.76	gold quality
caput epididymis	UBERON:0004358	77.76	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-5061	yes	10.24
E-GEOD-83139	yes	9.45
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

41 targeting PIPOX, 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-150-5P	99.99	66.69	1976
HSA-MIR-371A-3P	99.99	66.77	91
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-4525	99.94	64.38	675
HSA-MIR-5010-5P	99.94	64.11	705
HSA-MIR-7978	99.86	66.90	856
HSA-MIR-4679	99.76	69.19	1229
HSA-MIR-548AU-3P	99.70	68.22	1373
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-298	99.63	67.56	1916
HSA-MIR-6132	99.60	65.83	1554
HSA-MIR-6836-5P	99.60	65.62	1538
HSA-MIR-7159-5P	99.53	72.12	2472
HSA-MIR-1275	99.47	67.90	2749
HSA-MIR-6722-3P	99.45	67.62	1919
HSA-MIR-4316	99.37	65.75	1360
HSA-MIR-504-3P	99.30	67.18	1745
HSA-MIR-7151-3P	99.04	69.72	2370
HSA-MIR-6506-5P	99.04	65.66	1386
HSA-MIR-1909-3P	99.03	66.56	1662
HSA-MIR-452-3P	99.01	66.25	1241
HSA-MIR-548Q	98.71	65.35	563
HSA-MIR-619-5P	98.57	64.97	1988
HSA-MIR-1910-3P	98.44	67.51	1695
HSA-MIR-4299	98.28	66.96	850
HSA-MIR-6511A-5P	98.13	67.47	1770
HSA-MIR-1914-5P	97.83	66.21	807
HSA-MIR-3921	97.81	67.45	1431
HSA-MIR-634	97.74	67.11	818
HSA-MIR-4329	97.68	66.26	1003

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	pipox	ENSDARG00000055591
mus_musculus	Pipox	ENSMUSG00000017453
rattus_norvegicus	Pipox	ENSRNOG00000008798
caenorhabditis_elegans		WBGENE00015783
caenorhabditis_elegans		WBGENE00015788

Protein

Protein identifiers

Peroxisomal sarcosine oxidase — Q9P0Z9 (reviewed: Q9P0Z9)

Alternative names: L-pipecolate oxidase, L-pipecolic acid oxidase

All UniProt accessions (3): Q9P0Z9, K7EJU8, K7EK30

UniProt curated annotations — full annotation on UniProt →

Function. Metabolizes sarcosine and L-pipecolic acid.

Subcellular location. Peroxisome.

Tissue specificity. Expressed in the liver and kidney.

Cofactor. Binds 1 FAD per subunit.

Similarity. Belongs to the MSOX/MTOX family.

RefSeq proteins (1): NP_057602* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006076	FAD-dep_OxRdtase	Domain
IPR036188	FAD/NAD-bd_sf	Homologous_superfamily
IPR045170	MTOX	Family

Pfam: PF01266

Enzyme classification (BRENDA):

• EC 1.5.3.7 — L-pipecolate oxidase (BRENDA: 9 organisms, 10 substrates, 11 inhibitors, 7 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

2 substrates with measured Km, best-characterized 2. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
L-PIPECOLIC ACID	0.74–6	5
L-PIPECOLATE	4.07	1

Catalyzed reactions (Rhea), 2 shown:

• L-pipecolate + O2 = L-1-piperideine-6-carboxylate + H2O2 + H(+) (RHEA:11992)
• sarcosine + O2 + H2O = formaldehyde + glycine + H2O2 (RHEA:13313)

UniProt features (9 total): sequence conflict 4, modified residue 2, chain 1, short sequence motif 1, binding site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9P0Z9-F1	94.63	0.92

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): 9–39

Post-translational modifications (2): 126, 319

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-71064	Lysine catabolism
R-HSA-9033241	Peroxisomal protein import
R-HSA-1430728	Metabolism
R-HSA-71291	Metabolism of amino acids and derivatives
R-HSA-9609507	Protein localization

MSigDB gene sets: 215 (showing top): GNF2_GSTM1, GOBP_ALPHA_AMINO_ACID_METABOLIC_PROCESS, GNF2_HPN, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, TGACCTY_ERR1_Q2, GOBP_ACETYL_COA_METABOLIC_PROCESS, LEE_LIVER_CANCER_CIPROFIBRATE_DN, chr17q11, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, CDP_01, NF1_Q6_01, GOBP_AMIDE_METABOLIC_PROCESS

GO Biological Process (2): obsolete lysine catabolic process (GO:0006554), obsolete L-lysine catabolic process to acetyl-CoA via L-pipecolate (GO:0033514)

GO Molecular Function (5): sarcosine oxidase activity (GO:0008115), L-pipecolate oxidase activity (GO:0050031), flavin adenine dinucleotide binding (GO:0050660), protein binding (GO:0005515), oxidoreductase activity (GO:0016491)

GO Cellular Component (3): peroxisome (GO:0005777), peroxisomal matrix (GO:0005782), cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Metabolism of amino acids and derivatives	1
Protein localization	1
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
oxidoreductase activity, acting on the CH-NH group of donors, oxygen as acceptor	2
nucleotide binding	1
anion binding	1
binding	1
catalytic activity	1
microbody	1
peroxisome	1
microbody lumen	1
cytoplasm	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1751 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PIPOX	SARDH	Q9UL12	653
PIPOX	DDO	Q99489	575
PIPOX	GNMT	Q14749	566
PIPOX	DCLRE1A	Q6PJP8	536
PIPOX	PAOX	Q6QHF9	506
PIPOX	AGXT	P21549	504
PIPOX	DAO	P14920	499
PIPOX	ALDH3A2	P51648	497
PIPOX	AASS	Q9UDR5	477
PIPOX	ACADVL	P49748	456
PIPOX	HAO2	Q9NYQ3	454
PIPOX	PRODH	O43272	453
PIPOX	HAO1	Q9UJM8	452
PIPOX	AGPS	O00116	433
PIPOX	ACTB	P02570	412

IntAct

8 interactions, top by confidence:

A	B	Type	Score
PIPOX	ZNF217	psi-mi:“MI:0914”(association)	0.530
PIPOX	POT1	psi-mi:“MI:0915”(physical association)	0.510
CARD8	HDAC3	psi-mi:“MI:0914”(association)	0.350
PIPOX	LALBA	psi-mi:“MI:0914”(association)	0.350
PIPOX	POT1	psi-mi:“MI:0915”(physical association)	0.000
ODF2L	PIPOX	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (27): ELP6 (Affinity Capture-MS), FKBP5 (Affinity Capture-MS), NAPG (Affinity Capture-MS), ELP4 (Affinity Capture-MS), ZNF217 (Affinity Capture-MS), ELP5 (Affinity Capture-MS), ELP4 (Affinity Capture-MS), ELP5 (Affinity Capture-MS), ZNF217 (Affinity Capture-MS), ELP6 (Affinity Capture-MS), NAPG (Affinity Capture-MS), FKBP5 (Affinity Capture-MS), PIPOX (Affinity Capture-MS), PIPOX (Affinity Capture-MS), ELP4 (Affinity Capture-MS)

ESM2 similar proteins: A2RU49, A3KCL7, A4FV42, A7MBI7, A7RDN6, D3ZDM7, D3ZLY0, O88587, O95671, P11172, P13439, P13676, P13798, P17256, P21964, P22734, P25409, P31228, P31754, P51175, P80227, Q03426, Q0V8R7, Q14CH1, Q29RU9, Q3TY86, Q4JIJ2, Q5E9T8, Q5H879, Q5R514, Q5U2W9, Q6GM82, Q86TI2, Q86WA6, Q8BGT5, Q8BVG4, Q8QZR5, Q8R164, Q8WXB1, Q922Z0

Diamond homologs: A1A9V4, A4TLT6, A7FH13, A7ZKG4, A7ZZ17, A8AI19, A9MH03, A9N5Q2, A9R633, B1IV43, B1JHH1, B1LIV1, B1X9H2, B2K770, B2TTL2, B4T2Z2, B4TET2, B4TSS2, B5F947, B5FL04, B5QY05, B5RBE0, B5YVS9, B6I9D6, B7LFZ3, B7LT77, B7M934, B7MIK0, B7MTJ0, B7NAT4, B7NL75, B7UP73, C4ZRZ9, P23342, P40854, P40859, P40873, P40874, P58523, P58524

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	54
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

4184 predictions. Top by Δscore:

Variant	Effect	Δscore
17:28956157:A:AC	donor_gain	1.0000
17:28956157:ACT:A	donor_gain	1.0000
17:28956158:C:CT	donor_gain	1.0000
17:28956158:CT:C	donor_gain	1.0000
17:28956158:CTC:C	donor_gain	1.0000
17:28956158:CTCCA:C	donor_gain	1.0000
17:28956262:C:CA	acceptor_loss	1.0000
17:28956262:C:CC	acceptor_gain	1.0000
17:28956346:TCAC:T	donor_loss	1.0000
17:28956348:A:AC	donor_gain	1.0000
17:28956348:AC:A	donor_gain	1.0000
17:28956349:C:CC	donor_gain	1.0000
17:28956349:CC:C	donor_gain	1.0000
17:28956349:CCT:C	donor_gain	1.0000
17:28956349:CCTG:C	donor_gain	1.0000
17:28956349:CCTGG:C	donor_gain	1.0000
17:28956463:GGCAA:G	acceptor_gain	1.0000
17:28956464:GCAA:G	acceptor_gain	1.0000
17:28956465:CAA:C	acceptor_gain	1.0000
17:28956465:CAAC:C	acceptor_gain	1.0000
17:28956466:AA:A	acceptor_gain	1.0000
17:28956468:C:CC	acceptor_gain	1.0000
17:28956713:ACTT:A	donor_loss	1.0000
17:28956715:TTA:T	donor_loss	1.0000
17:28956716:TA:T	donor_loss	1.0000
17:28956717:A:AC	donor_gain	1.0000
17:28956717:A:AT	donor_loss	1.0000
17:28956718:C:CC	donor_gain	1.0000
17:28956718:C:G	donor_loss	1.0000
17:28957243:C:CC	acceptor_gain	1.0000

AlphaMissense

2537 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:29056183:T:C	F351L	0.993
17:29056185:C:A	F351L	0.993
17:29056185:C:G	F351L	0.993
17:29044883:A:C	S47R	0.985
17:29044885:C:A	S47R	0.985
17:29044885:C:G	S47R	0.985
17:29044859:T:C	F39L	0.984
17:29044861:C:A	F39L	0.984
17:29044861:C:G	F39L	0.984
17:29044967:T:A	W75R	0.983
17:29044967:T:C	W75R	0.983
17:29055882:T:C	F346L	0.983
17:29055884:C:A	F346L	0.983
17:29055884:C:G	F346L	0.983
17:29056188:G:C	K352N	0.983
17:29056188:G:T	K352N	0.983
17:29043335:A:T	E37V	0.982
17:29044902:G:C	R53P	0.980
17:29054569:T:A	W229R	0.980
17:29054569:T:C	W229R	0.980
17:29055160:T:A	V302D	0.979
17:29055880:G:A	G345E	0.979
17:29055874:G:A	G343D	0.978
17:29055838:T:A	L331H	0.977
17:29056181:G:A	G350E	0.977
17:29044898:A:C	S52R	0.976
17:29044900:C:A	S52R	0.976
17:29044900:C:G	S52R	0.976
17:29044911:G:C	R56P	0.976
17:29044969:G:C	W75C	0.976

dbSNP variants (sampled 300 via entrez): RS1000057479 (17:29043642 C>T), RS1000193186 (17:29048212 T>C), RS1000430066 (17:29043278 A>C,G), RS1000517637 (17:29046643 A>G), RS1000584766 (17:29054819 G>A,C,T), RS1000589416 (17:29046271 C>T), RS1000831392 (17:29041752 A>AAAG), RS1001131497 (17:29048995 A>G), RS1001868908 (17:29044507 T>C), RS1001928036 (17:29049090 G>A), RS1001959193 (17:29049458 A>G), RS1002004498 (17:29042286 G>T), RS1002324897 (17:29046980 A>G), RS1002437689 (17:29046739 C>A), RS1002473309 (17:29042914 G>A)

Disease associations

OMIM: gene MIM:616713 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST006041_44	Major depressive disorder	4.000000e-06
GCST008163_46	Height	5.000000e-06
GCST012227_401	Hip circumference adjusted for BMI	1.000000e-08
GCST90093325_17	Language functional connectivity	5.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0008039	BMI-adjusted hip circumference
EFO:0007797	language measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2254 (SINGLE PROTEIN)

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, decreases expression, decreases methylation, affects cotreatment, increases expression	9
bisphenol A	affects expression, increases expression	3
Estradiol	decreases expression, increases expression	3
Cyclosporine	decreases expression	3
pipecolic acid	increases degradation, increases oxidation	2
entinostat	increases expression, affects cotreatment	2
belinostat	increases expression, affects cotreatment	2
Panobinostat	increases expression, affects cotreatment	2
Benzo(a)pyrene	decreases expression, increases methylation, affects methylation	2
Diethylhexyl Phthalate	decreases expression, increases expression	2
Phenylmercuric Acetate	decreases expression, affects cotreatment	2
Aflatoxin B1	affects expression, decreases expression	2
Genistein	increases expression	2
bisphenol F	affects cotreatment, decreases methylation	1
methylmercuric chloride	decreases expression, increases expression	1
methyleugenol	decreases expression	1
delta-1-piperidine-6-carboxylic acid	increases chemical synthesis	1
trichostatin A	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	decreases expression	1
perfluorooctanoic acid	decreases expression	1
periodate-oxidized adenosine	affects expression	1
vanadium pentoxide	increases expression	1
K 7174	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression, decreases expression	1
dorsomorphin	affects cotreatment, increases expression, decreases expression	1
Temozolomide	increases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Acetaminophen	decreases expression	1
Ethanol	decreases expression	1

ChEMBL screening assays

12 unique, capped per target: 12 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL700532	Binding	Kinetic parameter was evaluated for L-pipecolate oxidase in Frozen Rhesus monkey liver ith L-PA as substrate	Mechanism-based inactivation of l-pipecolate oxidase by a sulfur-containing substrate analog, 5-thia-l-pipecolic acid — Bioorg Med Chem Lett

Clinical trials (associated diseases)

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