SLC22A5

Summary

SLC22A5 (solute carrier family 22 member 5, HGNC:10969) is a protein-coding gene on chromosome 5q31.1, encoding Organic cation/carnitine transporter 2 (O76082). Sodium-ion dependent, high affinity carnitine transporter.

Polyspecific organic cation transporters in the liver, kidney, intestine, and other organs are critical for elimination of many endogenous small organic cations as well as a wide array of drugs and environmental toxins. The encoded protein is a plasma integral membrane protein which functions both as an organic cation transporter and as a sodium-dependent high affinity carnitine transporter. The encoded protein is involved in the active cellular uptake of carnitine. Mutations in this gene are the cause of systemic primary carnitine deficiency (CDSP), an autosomal recessive disorder manifested early in life by hypoketotic hypoglycemia and acute metabolic decompensation, and later in life by skeletal myopathy or cardiomyopathy. Alternative splicing of this gene results in multiple transcript variants.

Source: NCBI Gene 6584 — RefSeq curated summary.

At a glance

• Gene–disease (curated): systemic primary carnitine deficiency disease (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 53
• Clinical variants (ClinVar): 1,359 total — 113 pathogenic, 102 likely-pathogenic
• Phenotypes (HPO): 42
• Druggable target: yes
• MANE Select transcript: NM_003060

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10969
Approved symbol	SLC22A5
Name	solute carrier family 22 member 5
Location	5q31.1
Locus type	gene with protein product
Status	Approved
Aliases	OCTN2, SCD
Ensembl gene	ENSG00000197375
Ensembl biotype	protein_coding
OMIM	603377
Entrez	6584

Gene structure

Transcript identifiers

Ensembl transcripts: 34 — 18 protein_coding, 8 retained_intron, 7 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000245407, ENST00000415928, ENST00000435065, ENST00000437841, ENST00000447841, ENST00000448810, ENST00000461013, ENST00000475308, ENST00000479605, ENST00000685543, ENST00000686757, ENST00000686868, ENST00000687740, ENST00000688151, ENST00000689271, ENST00000690900, ENST00000692212, ENST00000692355, ENST00000692413, ENST00000692825, ENST00000693308, ENST00000693763, ENST00000893296, ENST00000893297, ENST00000893298, ENST00000893299, ENST00000893300, ENST00000893301, ENST00000893302, ENST00000938827, ENST00000938828, ENST00000938829, ENST00000953171, ENST00000953172

RefSeq mRNA: 2 — MANE Select: NM_003060 NM_001308122, NM_003060

CCDS: CCDS4154, CCDS78058

Canonical transcript exons

ENST00000245407 — 10 exons

Exon	Start	End
ENSE00000899303	132384147	132384301
ENSE00001871907	132394185	132395612
ENSE00001944466	132369710	132370365
ENSE00002492882	132378378	132378481
ENSE00003481454	132388921	132389021
ENSE00003523773	132390690	132390904
ENSE00003599559	132393676	132393811
ENSE00003614873	132392433	132392615
ENSE00003680577	132385328	132385499
ENSE00003787991	132387025	132387151

Expression profiles

Bgee: expression breadth ubiquitous, 235 present calls, max score 95.46.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.1597 / max 248.2672, expressed in 1523 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
58441	3.4249	1302
58443	1.1336	511
58442	0.9795	534
58445	0.9662	527
58444	0.6090	244
58440	0.0464	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
gastrocnemius	UBERON:0001388	95.46	gold quality
mucosa of transverse colon	UBERON:0004991	95.13	gold quality
muscle of leg	UBERON:0001383	93.45	gold quality
ileal mucosa	UBERON:0000331	92.84	gold quality
jejunal mucosa	UBERON:0000399	92.76	gold quality
hindlimb stylopod muscle	UBERON:0004252	91.69	gold quality
metanephros cortex	UBERON:0010533	91.22	gold quality
right uterine tube	UBERON:0001302	90.61	gold quality
adult mammalian kidney	UBERON:0000082	90.15	gold quality
right hemisphere of cerebellum	UBERON:0014890	89.95	gold quality
cerebellar hemisphere	UBERON:0002245	89.91	gold quality
apex of heart	UBERON:0002098	89.75	gold quality
cerebellar cortex	UBERON:0002129	89.71	gold quality
tibialis anterior	UBERON:0001385	89.48	gold quality
rectum	UBERON:0001052	88.50	gold quality
nephron tubule	UBERON:0001231	88.41	gold quality
transverse colon	UBERON:0001157	88.20	gold quality
cerebellum	UBERON:0002037	87.54	gold quality
kidney	UBERON:0002113	87.29	gold quality
small intestine Peyer’s patch	UBERON:0003454	87.28	gold quality
duodenum	UBERON:0002114	87.20	gold quality
heart left ventricle	UBERON:0002084	87.16	gold quality
body of pancreas	UBERON:0001150	87.01	gold quality
muscle organ	UBERON:0001630	87.00	gold quality
cortex of kidney	UBERON:0001225	86.98	gold quality
pancreatic ductal cell	CL:0002079	86.66	gold quality
cardiac ventricle	UBERON:0002082	86.61	gold quality
small intestine	UBERON:0002108	86.55	gold quality
adenohypophysis	UBERON:0002196	86.31	gold quality
islet of Langerhans	UBERON:0000006	85.84	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.41

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CEBPB, ESR1, HIF1A, HSF1, MYOG, NR4A2, PPARA, PPARG

miRNA regulators (miRDB)

80 targeting SLC22A5, 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-4481	100.00	66.42	1669
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-3617-3P	99.98	67.86	918
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-1229-3P	99.97	66.49	906
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-552-5P	99.93	68.56	1583
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-1271-5P	99.91	71.99	1972
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-629-3P	99.85	67.99	1875
HSA-MIR-4766-5P	99.75	69.23	2662
HSA-MIR-199A-3P	99.75	70.48	929
HSA-MIR-199B-3P	99.75	70.48	929

Literature-anchored findings (GeneRIF, showing 40)

• has functional sites for carnitine and Na(+) and carnitine-binding site is involved, in part, in the recognition of organic cations (PMID:12183691)
• novel missense mutations in the OCTN2 gene (1340A >G and 83G>T) were found in two Saudi patients with sytemic carnitine deficiency (PMID:12408185)
• Demonstration that l-carnitine uptake in differentiated Caco-2 cells is primarily mediated by OCTN2, located on the brush border membrane (PMID:12684216)
• downregulated in elderly persons and in myelodysplastic syndrome patients; reduction was more than 85% compared to younger adults (PMID:12802501)
• multiple domains of the OCTN2 transporter are required for carnitine transport (PMID:14506273)
• tyrosine residues are involved in coupling the sodium electrochemical gradient to transmembrane solute transfer in the sodium-dependent co-transporter OCTN2 (PMID:14665638)
• a G–>C transversion in trhe promoter of SLC22A5 is associated with Crohn disease (PMID:15107849)
• The reported properties of OCTN2 resemble those observed for l-carnitine uptake in placental brush border vesicles, suggesting that OCTN2 may mediate most maternofetal carnitine transport in humans. (PMID:15238359)
• truncating R254X mutation in the OCTN2 gene found in a Saudi Arabian kindred suggesting that it may be a recurrent mutation or a very ancient founder mutation (PMID:15303004)
• OCTN2 is localized in the apical membrane of syncytiotrophoblasts, suggesting a major role in the uptake of carnitine during fetal development. (PMID:15486076)
• homozygous deletion of 17081C of the SLC22A5 gene that results in a frameshift at R282D and leads ultimately to a premature stop codon (V295X) in the OCTN2 carnitine transporter in children with cardiomyopathy and decreased plasma carnitine (PMID:15487009)
• Carnitine transport by OCTN2 requires functional linkage between transmembrane domains (TMD) 1-7 and TMD11. (PMID:15499185)
• Double transfection of OCTN2 with PDZK1 stimulated the uptake by OCTN2 of its endogenous substrate carnitine. (PMID:15523054)
• 2 functionally relevant polymorphisms in the SLC22A4 / 22A5 genes at the IBD5 locus that alter gene/protein function and are associated with increased risk for Crohn’s disease. (PMID:15685536)
• 8 new mutations were found: V153fsX193, W275X, R289X, 1267del+3_+23, M1I, T232M, T468R. (PMID:15714519)
• The 1672C>T SLC22A4 and -207G>C SLC22A5 polymorphisms are genetic markers of susceptibility/protection haplotypes for Crohn’s disease. (PMID:16333318)
• the 1672T variant of the OCTN1 gene and the -207C variant of the OCTN2 gene represent risk factors for Crohn disease in the Greek population (PMID:16437728)
• OCTN2 is expressed in the human heart and can be modulated by drug administration. Moreover, OCTN2 can contribute to the cardiac uptake of cardiovascular drugs (PMID:16490820)
• none of the 4 haplotypes present in the SLC22A4/SLC22A5 region in 5q31 showed significant association with rheumatoid arthritis in our Spanish cohort (PMID:16652416)
• A recent report identified polymorphisms in SLC22A4 (OCTN1) and SLC22A5 (OCTN2) as being responsible for the IBD5 association inflammatory bowel disease). (PMID:16773684)
• Association of type 1 diabetes of single nucleotide polymorphism mapping to SLC22A5 gene. (PMID:16796743)
• This study suggests that although loss-of-function mutations in OCTN2 are likely to be rare, common variants of OCTN2 found in healthy populations may contribute to variation in the disposition of carnitine and some clinically used drugs. (PMID:16931768)
• The frequency of the NOD2/CARD15 susceptibility variants in the Hungarian pediatric CD population is high. SLC22A4 and SLC22A5 mutation screening do not confirm the assumption that the carriage of these genotypes means an obligatory susceptibility to CD. (PMID:17006998)
• The observed kinetics, immunohistolocalization, and inhibition studies indicate that the high-affinity uptake of carnitine in the Caki-1 cell line is most likely mediated by OCTN2 (PMID:17274673)
• The IBD5 locus is associated with CD in the Swedish population. The strongest association is with the marker SNP IGR2096a_1, lying p-telomeric to SLC22A4 and SLC22A5. The effect of the TC haplotype was not an independent determinant in this population. (PMID:17340776)
• SLC22A5 -207C allele occurred in 48.8% of the patients with UC and 51.4% of the controls. (PMID:17387389)
• Detection of mutations by tandem mass spectrometry in Carnitine transporter deficiency. (PMID:17417720)
• polymorphisms associated with pediatric onset of Crohn’s disease (PMID:17451203)
• Report patient with OCTN2 mutations/deficiency and N-acetylglutamate synthase deficiency. (PMID:17703373)
• Hypoxia resulted in significant reductions in OCTN2-mediated carnitine uptake in BeWo cells, a model of human trophoblast (PMID:17725851)
• There was no evidence for epistasis between the IL23R gene and the Crohn’s disease susceptibility genes CARD15 and SLC22A4/5. (PMID:17786191)
• Contributions of phosphorylation to regulation of OCTN2 uptake of carnitine are minimal in BeWo cells. (PMID:17977516)
• OCTN2-mediated competence and sporulation factor transport serves as an example of a host-bacterial interaction that allows the host to monitor and respond to changes in the behavior or composition of colonic flora. (PMID:18005709)
• The CG haplotype comprising C allele of the -446C > T and G alleles of the -368T > G in SLC22A5 seemed to be a predictor of steroid resistance in Japanese patients with Crohn’s disease. (PMID:18274826)
• Mutation in SLC22A5 is unlikely to be an important cause of cardiomyopathy in humans. (PMID:18337137)
• OCTN1 and OCTN2 mRNA expression was detected in HCLE and HCjE cells of rabbits and humans. OCTN1 and OCTN2 were predominately localized in the apical membranes of the cells. (PMID:18641280)
• transports L-carnitine, which is a essential co-factor in the metabolism of lipids and consequently in the production of cellular energy, to cell membrane surfaces. (review) (PMID:18646596)
• Determine OCTN1/2 and CARD15 gene polymorphisms in Chinese patients with inflammatory bowel disease. (PMID:18756601)
• Role of Na+/L-carnitine transporter (OCTN2) in renal handling of pivaloylcarnitine and valproylcarnitine formed during pivalic acid-containing prodrugs and valproic acid treatment. (PMID:18762717)
• Protein expression and function of OCTN2 in BeWo cells can be regulated by forskolin treatment. (PMID:19091402)

Cross-species orthologs

50 orthologs

Organism	Symbol	Gene ID
danio_rerio	slc22a4	ENSDARG00000005335
danio_rerio	oatx	ENSDARG00000019713
danio_rerio	si:dkey-166k12.1	ENSDARG00000054690
danio_rerio	si:dkey-119m7.4	ENSDARG00000071049
danio_rerio	si:dkey-119m7.8	ENSDARG00000096654
mus_musculus	Slc22a5	ENSMUSG00000018900
mus_musculus	Slc22a21	ENSMUSG00000063652
rattus_norvegicus	Slc22a5	ENSRNOG00000008432
rattus_norvegicus	Slc22a21	ENSRNOG00000069239
drosophila_melanogaster	Orct	FBGN0019952
drosophila_melanogaster	CG15221	FBGN0030331
drosophila_melanogaster	Balat	FBGN0033778
drosophila_melanogaster	CG5592	FBGN0035645
drosophila_melanogaster	CG10486	FBGN0035647
drosophila_melanogaster	CG14691	FBGN0037829
drosophila_melanogaster	CG14855	FBGN0038260
drosophila_melanogaster	CG14856	FBGN0038261
drosophila_melanogaster	CG14857	FBGN0038262
drosophila_melanogaster	CG12783	FBGN0038448
drosophila_melanogaster	CG7333	FBGN0038715
drosophila_melanogaster	CG7342	FBGN0038716
drosophila_melanogaster	CG17751	FBGN0038717
drosophila_melanogaster	CG17752	FBGN0038718
drosophila_melanogaster	CG16727	FBGN0038719
drosophila_melanogaster	CG6231	FBGN0038720
drosophila_melanogaster	CG4465	FBGN0038750
drosophila_melanogaster	CG4462	FBGN0038752
drosophila_melanogaster	CG4459	FBGN0038753
drosophila_melanogaster	CG6356	FBGN0039178
drosophila_melanogaster	CG3690	FBGN0040350
drosophila_melanogaster	CG31103	FBGN0051103
drosophila_melanogaster	CG31106	FBGN0051106
drosophila_melanogaster	CG31272	FBGN0051272
drosophila_melanogaster	CG33233	FBGN0053233
drosophila_melanogaster	CG33234	FBGN0053234
drosophila_melanogaster	Orct2	FBGN0086365
drosophila_melanogaster	CG42269	FBGN0259164
drosophila_melanogaster	CG44098	FBGN0264907
caenorhabditis_elegans		WBGENE00003837
caenorhabditis_elegans	oct-1	WBGENE00003842
caenorhabditis_elegans		WBGENE00003843
caenorhabditis_elegans		WBGENE00006220
caenorhabditis_elegans		WBGENE00008110
caenorhabditis_elegans		WBGENE00011456
caenorhabditis_elegans		WBGENE00014127
caenorhabditis_elegans		WBGENE00015088
caenorhabditis_elegans		WBGENE00017751
caenorhabditis_elegans		WBGENE00019408
caenorhabditis_elegans		WBGENE00020701
caenorhabditis_elegans		WBGENE00044455

Paralogs (22): SLC22A16 (ENSG00000004809), SLC22A17 (ENSG00000092096), SLC22A2 (ENSG00000112499), SLC22A7 (ENSG00000137204), SLC22A23 (ENSG00000137266), SLC22A14 (ENSG00000144671), SLC22A3 (ENSG00000146477), SLC22A8 (ENSG00000149452), SLC22A9 (ENSG00000149742), SVOPL (ENSG00000157703), SLC22A15 (ENSG00000163393), SVOP (ENSG00000166111), SLC22A11 (ENSG00000168065), SLC22A13 (ENSG00000172940), SLC22A1 (ENSG00000175003), SLC22A10 (ENSG00000184999), SLC22A25 (ENSG00000196600), SLC22A4 (ENSG00000197208), SLC22A24 (ENSG00000197658), SLC22A12 (ENSG00000197891), SLC22A6 (ENSG00000197901), SLC22A31 (ENSG00000259803)

Protein

Protein identifiers

Organic cation/carnitine transporter 2 — O76082 (reviewed: O76082)

Alternative names: High-affinity sodium-dependent carnitine cotransporter, Solute carrier family 22 member 5

All UniProt accessions (12): A0A8I5KTN6, A0A8I5KUR7, A0A8I5KUV4, A0A8I5KW68, A0A8I5KXW0, A0A8I5KYG6, A0A8I5QL37, O76082, F8WCC9, H7BZC0, H7BZF0, H7C1R8

UniProt curated annotations — full annotation on UniProt →

Function. Sodium-ion dependent, high affinity carnitine transporter. Involved in the active cellular uptake of carnitine. Transports one sodium ion with one molecule of carnitine. Also transports organic cations such as tetraethylammonium (TEA) without the involvement of sodium. Relative uptake activity ratio of carnitine to TEA is 11.3. In intestinal epithelia, transports the quorum-sensing pentapeptide CSF (competence and sporulation factor) from B.subtilis which induces cytoprotective heat shock proteins contributing to intestinal homeostasis. May also contribute to regulate the transport of organic compounds in testis across the blood-testis-barrier. Retained in the ER, unable to perform carnitine uptake.

Subunit / interactions. Interacts with PDZK1.

Subcellular location. Cell membrane. Apical cell membrane. Basal cell membrane Endoplasmic reticulum.

Tissue specificity. Strongly expressed in kidney, skeletal muscle, heart and placenta. Primarily expressed by surface epithelial cells of the colon (at protein level). Expressed in CD68 macrophage and CD43 T-cells but not in CD20 B-cells. In testis, localized to Sertoli cell basal membranes, peritubular myoid cells and Leydig cells.

Post-translational modifications. Glycosylated. Glycosylation affects the expression levels. Not glycosylated.

Disease relevance. Systemic primary carnitine deficiency (CDSP) [MIM:212140] Autosomal recessive disorder of fatty acid oxidation caused by defective carnitine transport. Present early in life with hypoketotic hypoglycemia and acute metabolic decompensation, or later in life with skeletal myopathy or cardiomyopathy. The disease is caused by variants affecting the gene represented in this entry. Expression in colon is increased in Crohn’s disease and human ulcerative colitis (at protein level).

Activity regulation. Inhibited by emetine, quinidine and verapamil. The IC(50) of emetine is 4.2 uM. Not inhibited by valproic acid. Transport of (R)-carnitine is stimulated by cholesterol in the plasma membrane.

Induction. Intestinal expression is induced by IFNG.

Similarity. Belongs to the major facilitator (TC 2.A.1) superfamily. Organic cation transporter (TC 2.A.1.19) family.

Isoforms (3)

UniProt ID	Names	Canonical?
O76082-1	1	yes
O76082-2	2
O76082-3	3, OCTN2VT

RefSeq proteins (2): NP_001295051, NP_003051* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004749	Orgcat_transp/SVOP	Family
IPR005828	MFS_sugar_transport-like	Family
IPR005829	Sugar_transporter_CS	Conserved_site
IPR020846	MFS_dom	Domain
IPR036259	MFS_trans_sf	Homologous_superfamily
IPR045915	S22A4/5	Family

Pfam: PF00083

Catalyzed reactions (Rhea), 10 shown:

• (R)-carnitine(out) + Na(+)(out) = (R)-carnitine(in) + Na(+)(in) (RHEA:72091)
• (S)-carnitine(out) + Na(+)(out) = (S)-carnitine(in) + Na(+)(in) (RHEA:72095)
• O-acetyl-(R)-carnitine(out) + Na(+)(out) = O-acetyl-(R)-carnitine(in) + Na(+)(in) (RHEA:72099)
• O-propanoyl-(R)-carnitine(out) + Na(+)(out) = O-propanoyl-(R)-carnitine(in) + Na(+)(in) (RHEA:72103)
• an O-acyl-(R)-carnitine(out) + Na(+)(out) = an O-acyl-(R)-carnitine(in) + Na(+)(in) (RHEA:72107)
• L-glutamyl-L-arginyl-glycyl-L-methionyl-L-threonine(out) + Na(+)(out) = L-glutamyl-L-arginyl-glycyl-L-methionyl-L-threonine(in) + Na(+)(in) (RHEA:72111)
• glycine betaine(out) + Na(+)(out) = glycine betaine(in) + Na(+)(in) (RHEA:72115)
• glycine betaine(out) + (R)-carnitine(in) = glycine betaine(in) + (R)-carnitine(out) (RHEA:72119)
• O-butanoyl-(R)-carnitine(out) + Na(+)(out) = O-butanoyl-(R)-carnitine(in) + Na(+)(in) (RHEA:72123)
• N,N-dimethylglycine(out) + Na(+)(out) = N,N-dimethylglycine(in) + Na(+)(in) (RHEA:76591)

UniProt features (149 total): sequence variant 111, topological domain 12, transmembrane region 12, glycosylation site 3, splice variant 3, mutagenesis site 2, modified residue 2, chain 1, sequence conflict 1, region of interest 1, binding site 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
9PDQ	ELECTRON MICROSCOPY	2.72
9PMD	ELECTRON MICROSCOPY	2.99
9PFB	ELECTRON MICROSCOPY	3.06

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O76082-F1	86.45	0.58

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): 218–225

Post-translational modifications (2): 486, 550

Glycosylation sites (3): 57, 64, 91

Mutagenesis-validated functional residues (2):

Position	Phenotype
91	reduces expression to 50%. no effect on carnitine transporter activity.
352	loss of both carnitine and organic cation transport functionalities. no effect on protein expression.

Function

Pathways and Gene Ontology

Reactome pathways

13 pathways

ID	Pathway
R-HSA-200425	Carnitine shuttle
R-HSA-549127	SLC-mediated transport of organic cations
R-HSA-5619053	Defective SLC22A5 causes systemic primary carnitine deficiency (CDSP)
R-HSA-1430728	Metabolism
R-HSA-1643685	Disease
R-HSA-382551	Transport of small molecules
R-HSA-425366
R-HSA-425407	SLC-mediated transmembrane transport
R-HSA-549132
R-HSA-556833	Metabolism of lipids
R-HSA-5619102	SLC transporter disorders
R-HSA-5619115	Disorders of transmembrane transporters
R-HSA-8978868	Fatty acid metabolism

MSigDB gene sets: 759 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_UP, GOBP_DIGESTION, FARMER_BREAST_CANCER_CLUSTER_7, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, MODULE_169, GOBP_CIRCULATORY_SYSTEM_PROCESS, MODULE_255, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_PAIRED_DONORS_WITH_INCORPORATION_OR_REDUCTION_OF_MOLECULAR_OXYGEN, GOBP_RESPONSE_TO_PEPTIDE, YAO_HOXA10_TARGETS_VIA_PROGESTERONE_UP, TTTGTAG_MIR520D, GOBP_MODIFIED_AMINO_ACID_TRANSPORT, STEARMAN_LUNG_CANCER_EARLY_VS_LATE_DN, MENSE_HYPOXIA_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN

GO Biological Process (16): sodium ion transport (GO:0006814), response to symbiotic bacterium (GO:0009609), quaternary ammonium group transport (GO:0015697), carnitine transport (GO:0015879), response to type II interferon (GO:0034341), response to tumor necrosis factor (GO:0034612), positive regulation of intestinal epithelial structure maintenance (GO:0060731), sodium-dependent organic cation transport (GO:0070715), transport across blood-brain barrier (GO:0150104), (R)-carnitine transport (GO:1900749), (R)-carnitine transmembrane transport (GO:1902270), carnitine transmembrane transport (GO:1902603), xenobiotic detoxification by transmembrane export across the plasma membrane (GO:1990961), monoatomic ion transport (GO:0006811), xenobiotic transport (GO:0042908), transmembrane transport (GO:0055085)

GO Molecular Function (12): ATP binding (GO:0005524), obsolete organic cation transmembrane transporter activity (GO:0015101), amino-acid betaine transmembrane transporter activity (GO:0015199), carnitine transmembrane transporter activity (GO:0015226), symporter activity (GO:0015293), quaternary ammonium group transmembrane transporter activity (GO:0015651), PDZ domain binding (GO:0030165), xenobiotic transmembrane transporter activity (GO:0042910), (R)-carnitine transmembrane transporter activity (GO:1901235), nucleotide binding (GO:0000166), protein binding (GO:0005515), transmembrane transporter activity (GO:0022857)

GO Cellular Component (9): cytoplasm (GO:0005737), endoplasmic reticulum (GO:0005783), cytosol (GO:0005829), plasma membrane (GO:0005886), basal plasma membrane (GO:0009925), apical plasma membrane (GO:0016324), brush border membrane (GO:0031526), extracellular exosome (GO:0070062), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-8 pathways:

Category	Pathways
Fatty acid metabolism	1
SLC-mediated transmembrane transport	1
SLC transporter disorders	1
Transport of small molecules	1
Metabolism	1
Disorders of transmembrane transporters	1
Disease	1
Metabolism of lipids	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transmembrane transport	3
transport	3
cellular anatomical structure	3
amino-acid betaine transport	2
response to cytokine	2
carnitine transport	2
carnitine transmembrane transport	2
quaternary ammonium group transmembrane transporter activity	2
modified amino acid transmembrane transporter activity	2
transmembrane transporter activity	2
cytoplasm	2
plasma membrane region	2
metal ion transport	1
response to symbiont	1
response to bacterium	1
nitrogen compound transport	1
innate immune response	1
positive regulation of digestive system process	1
intestinal epithelial structure maintenance	1
regulation of intestinal epithelial structure maintenance	1
vascular transport	1
(R)-carnitine transport	1
xenobiotic export from cell	1
detoxification	1
export across plasma membrane	1
cellular process	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
secondary active transmembrane transporter activity	1
quaternary ammonium group transport	1
protein domain specific binding	1
xenobiotic transport	1
carnitine transmembrane transporter activity	1
(R)-carnitine transmembrane transport	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
transporter activity	1
intracellular anatomical structure	1
endomembrane system	1

Protein interactions and networks

STRING

1332 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC22A5	NOD2	Q9HC29	739
SLC22A5	SLC47A1	Q96FL8	686
SLC22A5	SLC47A2	Q86VL8	679
SLC22A5	SLC15A1	P46059	672
SLC22A5	P4HA2	O15460	665
SLC22A5	SLC25A20	O43772	656
SLC22A5	SLC15A2	Q16348	654
SLC22A5	SLCO4C1	Q6ZQN7	649
SLC22A5	NHERF4	Q86UT5	640
SLC22A5	SLCO2B1	O94956	611
SLC22A5	SLCO1A2	P46721	603
SLC22A5	SLCO3A1	Q9UIG8	592
SLC22A5	ABCG2	Q9UNQ0	590
SLC22A5	SLCO4A1	Q96BD0	587
SLC22A5	CPT2	P23786	584

IntAct

38 interactions, top by confidence:

A	B	Type	Score
SLC22A5	HMGCS1	psi-mi:“MI:0915”(physical association)	0.560
SLC22A5	MTUS2	psi-mi:“MI:0915”(physical association)	0.560
SLC22A5	NOTCH2NLC	psi-mi:“MI:0915”(physical association)	0.560
SLC22A5	KRT27	psi-mi:“MI:0915”(physical association)	0.560
KRTAP6-3	SLC22A5	psi-mi:“MI:0915”(physical association)	0.560
KRT34	SLC22A5	psi-mi:“MI:0915”(physical association)	0.560
	SLC22A5	psi-mi:“MI:0915”(physical association)	0.560
CXCR4	TMEM120B	psi-mi:“MI:0914”(association)	0.530
YIPF3	TMEM120B	psi-mi:“MI:0914”(association)	0.530
SLC22A9	GPR89A	psi-mi:“MI:0914”(association)	0.530
SLC22A5	CLGN	psi-mi:“MI:0914”(association)	0.530
NEK4	E2F8	psi-mi:“MI:0914”(association)	0.350
YIPF3	TMEM223	psi-mi:“MI:0914”(association)	0.350
PDZK1P1	ZBTB5	psi-mi:“MI:0914”(association)	0.350
SLC22A9	GPR89A	psi-mi:“MI:0914”(association)	0.350
	DENND11	psi-mi:“MI:0914”(association)	0.350
KLRC4	RAP1BL	psi-mi:“MI:0914”(association)	0.350
SLC22A4	RTL8C	psi-mi:“MI:0914”(association)	0.350
PDZK1	ZBTB5	psi-mi:“MI:0914”(association)	0.350
YIPF3	GPR89A	psi-mi:“MI:0914”(association)	0.350
SLC22A5	GPR89B	psi-mi:“MI:0914”(association)	0.350
RHBG	PEDS1	psi-mi:“MI:0914”(association)	0.350
SLC22A4	TMEM131L	psi-mi:“MI:0914”(association)	0.350
SLC22A5	TMEM131L	psi-mi:“MI:0914”(association)	0.350
SLC22A5	Slc22a5	psi-mi:“MI:0403”(colocalization)	0.270
SLC22A5	MTUS2	psi-mi:“MI:0915”(physical association)	0.000
SLC22A5	NOTCH2NLC	psi-mi:“MI:0915”(physical association)	0.000
SLC22A5	KRT27	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (122): SLC22A5 (Affinity Capture-MS), SLC22A5 (Affinity Capture-MS), SLC22A5 (Affinity Capture-MS), HMGCS1 (Affinity Capture-MS), SLC22A5 (Two-hybrid), SLC22A5 (Two-hybrid), SLC22A5 (Two-hybrid), SLC22A5 (Two-hybrid), KRTAP6-3 (Two-hybrid), NOTCH2NL (Two-hybrid), NBPF19 (Two-hybrid), SLC22A5 (Affinity Capture-MS), SLC22A5 (Proximity Label-MS), SLC22A5 (Proximity Label-MS), SLC22A5 (Affinity Capture-MS)

ESM2 similar proteins: A6NK97, A6QLW8, A7MBE0, A9CB25, B2GV36, O02713, O08966, O15245, O35956, O57379, O70594, O75751, O76082, O77504, O88446, O88909, Q1RPP5, Q3YAW7, Q4U2R8, Q4W8A2, Q4W8A3, Q5R540, Q5R5H7, Q5R9C4, Q5RCH6, Q5RLM2, Q63089, Q6A4L0, Q6DFR1, Q6NUB3, Q6NYN7, Q70BM6, Q80UJ1, Q863T6, Q864Z3, Q8HY24, Q8MJI6, Q8MK48, Q8TCC7, Q8VC69

Diamond homologs: A0A3Q2IDB4, A0A8B7HA97, A6NK97, A6QLW8, A7MBE0, A9CB25, B2GV36, G1SZD9, J9VLA6, O02713, O08966, O15244, O15245, O35956, O57379, O70577, O70594, O75751, O76082, O77504, O88446, O88909, Q1RPP5, Q28ES4, Q2KIV1, Q3YAW7, Q3ZAV1, Q4U2R8, Q4W8A2, Q4W8A3, Q504N2, Q5R540, Q5R5H7, Q5R9C4, Q5RC45, Q5RCH6, Q5RLM2, Q63089, Q63ZE4, Q66J52

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

1359 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	113
Likely pathogenic	102
Uncertain significance	445
Likely benign	463
Benign	38

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1042938	NM_003060.4(SLC22A5):c.113C>A (p.Ser38Tyr)	Pathogenic
1068602	NC_000005.9:g.(?131713846)(131714183_?)del	Pathogenic
1068603	NC_000005.9:g.(?131719829)(131728317_?)del	Pathogenic
1068932	NM_003060.4(SLC22A5):c.37G>T (p.Glu13Ter)	Pathogenic
1070131	NM_003060.4(SLC22A5):c.587_588del (p.Phe196fs)	Pathogenic
1072441	NM_003060.4(SLC22A5):c.1347C>A (p.Tyr449Ter)	Pathogenic
1074182	NM_003060.4(SLC22A5):c.479C>A (p.Ser160Ter)	Pathogenic
1398476	NM_003060.4(SLC22A5):c.860_861del (p.Gln287fs)	Pathogenic
1417216	NM_003060.4(SLC22A5):c.328C>T (p.Gln110Ter)	Pathogenic
1419604	NM_003060.4(SLC22A5):c.1446C>G (p.Tyr482Ter)	Pathogenic
1426461	NM_003060.4(SLC22A5):c.976C>T (p.Gln326Ter)	Pathogenic
1430105	NM_003060.4(SLC22A5):c.69_71del (p.Phe23del)	Pathogenic
1432590	NM_003060.4(SLC22A5):c.835G>T (p.Glu279Ter)	Pathogenic
1452650	NM_003060.4(SLC22A5):c.1289del (p.Val430fs)	Pathogenic
1453057	NM_003060.4(SLC22A5):c.449del (p.Phe150fs)	Pathogenic
1453608	NM_003060.4(SLC22A5):c.494_497del (p.Asp165fs)	Pathogenic
1455669	NC_000005.9:g.(?131713846)(131720003_?)del	Pathogenic
1458137	NC_000005.9:g.(?131722697)(131724733_?)del	Pathogenic
1458534	NM_003060.4(SLC22A5):c.92C>T (p.Pro31Leu)	Pathogenic
1459138	NM_003060.4(SLC22A5):c.902C>A (p.Ala301Asp)	Pathogenic
1686642	NM_003060.4(SLC22A5):c.420G>A (p.Trp140Ter)	Pathogenic
1984056	NM_003060.4(SLC22A5):c.104_153delinsATGGTATGTCAGTCGTGTTCCTGGCGGGGACCCCGGAGCACCGCTGTCGA (p.Thr35_Ala44delinsAsnGlyMetSerValValPheLeuAlaGly)	Pathogenic
2002392	NM_003060.4(SLC22A5):c.1264_1265dup (p.Asp423fs)	Pathogenic
2021354	NM_003060.4(SLC22A5):c.428del (p.Pro143fs)	Pathogenic
2043699	NM_003060.4(SLC22A5):c.1392_1409del (p.Val465_Ser470del)	Pathogenic
2048266	NM_003060.4(SLC22A5):c.1409C>A (p.Ser470Tyr)	Pathogenic
2075336	NM_003060.4(SLC22A5):c.1586+2T>G	Pathogenic
2120259	NM_003060.4(SLC22A5):c.1090del (p.Asp364fs)	Pathogenic
2136331	NM_003060.4(SLC22A5):c.350G>A (p.Trp117Ter)	Pathogenic
2136332	NM_003060.4(SLC22A5):c.497+1G>T	Pathogenic

SpliceAI

2171 predictions. Top by Δscore:

Variant	Effect	Δscore
5:132370336:G:GT	donor_gain	1.0000
5:132384141:TCCCA:T	acceptor_loss	1.0000
5:132384142:CCCA:C	acceptor_loss	1.0000
5:132384143:CCA:C	acceptor_loss	1.0000
5:132384145:A:AC	acceptor_loss	1.0000
5:132384146:GGTTT:G	acceptor_gain	1.0000
5:132384231:GAT:G	donor_gain	1.0000
5:132384322:T:G	donor_gain	1.0000
5:132385497:GTG:G	donor_gain	1.0000
5:132387147:GTGAG:G	donor_gain	1.0000
5:132387148:TGAGG:T	donor_loss	1.0000
5:132387150:AGG:A	donor_loss	1.0000
5:132387152:G:A	donor_loss	1.0000
5:132387152:G:GG	donor_gain	1.0000
5:132387153:T:G	donor_loss	1.0000
5:132388899:A:AG	acceptor_gain	1.0000
5:132388900:C:G	acceptor_gain	1.0000
5:132388903:AT:A	acceptor_gain	1.0000
5:132388903:ATGAT:A	acceptor_gain	1.0000
5:132388904:T:G	acceptor_gain	1.0000
5:132388910:T:A	acceptor_gain	1.0000
5:132388916:T:A	acceptor_gain	1.0000
5:132388918:CAGT:C	acceptor_loss	1.0000
5:132388919:A:AG	acceptor_gain	1.0000
5:132388919:AGTTA:A	acceptor_loss	1.0000
5:132388920:G:GT	acceptor_gain	1.0000
5:132388920:GT:G	acceptor_gain	1.0000
5:132388920:GTT:G	acceptor_gain	1.0000
5:132389019:GTG:G	donor_gain	1.0000
5:132389020:TGGTA:T	donor_loss	1.0000

AlphaMissense

3624 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:132385443:G:C	W256C	0.997
5:132385443:G:T	W256C	0.997
5:132392585:A:C	S474R	0.996
5:132392587:C:A	S474R	0.996
5:132392587:C:G	S474R	0.996
5:132393711:G:A	G496R	0.996
5:132393711:G:C	G496R	0.996
5:132370120:T:A	C50S	0.995
5:132370121:G:C	C50S	0.995
5:132387051:T:C	L284P	0.995
5:132392541:G:C	R459T	0.995
5:132392542:A:C	R459S	0.995
5:132392542:A:T	R459S	0.995
5:132392582:G:C	G473R	0.995
5:132370093:T:C	F41L	0.994
5:132370095:C:A	F41L	0.994
5:132370095:C:G	F41L	0.994
5:132378450:G:C	G156R	0.994
5:132385400:G:A	G242D	0.994
5:132385441:T:A	W256R	0.994
5:132385441:T:C	W256R	0.994
5:132392577:G:C	R471P	0.994
5:132370309:T:A	C113S	0.993
5:132370310:G:C	C113S	0.993
5:132384260:G:A	G204D	0.993
5:132384301:G:A	G218R	0.993
5:132384301:G:C	G218R	0.993
5:132392541:G:T	R459I	0.993
5:132392549:G:C	G462R	0.993
5:132392550:G:A	G462D	0.993

dbSNP variants (sampled 300 via entrez): RS1000028052 (5:132386091 T>A), RS1000300318 (5:132378430 T>C), RS1000318884 (5:132386264 G>A,C), RS1000399781 (5:132371609 C>T), RS1000624303 (5:132385012 G>C), RS1000631059 (5:132378058 T>A,G), RS1000745273 (5:132372888 C>G,T), RS1000902101 (5:132377935 T>C), RS1001231079 (5:132379761 G>A), RS1001347922 (5:132373552 C>T), RS1001401676 (5:132373109 A>G), RS1001529129 (5:132380666 C>G,T), RS1001631155 (5:132386534 C>T), RS1001703424 (5:132380092 A>T), RS1001915887 (5:132368781 T>C)

Disease associations

OMIM: gene MIM:603377 | disease phenotypes: MIM:212140, MIM:115200, MIM:617143

GenCC curated gene-disease

Disease	Classification	Inheritance
systemic primary carnitine deficiency disease	Definitive	Autosomal recessive
adrenoleukodystrophy	Limited	Autosomal recessive
short QT syndrome	Disputed Evidence	Autosomal recessive

ClinGen Gene-Disease Validity (2)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
systemic primary carnitine deficiency disease	Definitive	AR
short QT syndrome	Disputed	AR

Mondo (6): systemic primary carnitine deficiency disease (MONDO:0008919), congenital nervous system disorder (MONDO:0002320), dilated cardiomyopathy 1A (MONDO:0007269), congenital myasthenic syndrome 20 (MONDO:0014939), short QT syndrome (MONDO:0000453), adrenoleukodystrophy (MONDO:0018544)

Orphanet (2): Systemic primary carnitine deficiency (Orphanet:158), Familial dilated cardiomyopathy with conduction defect due to LMNA mutation (Orphanet:300751)

HPO phenotypes

42 total (30 of 42 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000467	Neck muscle weakness
HP:0001252	Hypotonia
HP:0001254	Lethargy
HP:0001259	Coma
HP:0001262	Excessive daytime somnolence
HP:0001263	Global developmental delay
HP:0001289	Confusion
HP:0001290	Generalized hypotonia
HP:0001298	Encephalopathy
HP:0001324	Muscle weakness
HP:0001414	Microvesicular hepatic steatosis
HP:0001508	Failure to thrive
HP:0001635	Congestive heart failure
HP:0001638	Cardiomyopathy
HP:0001639	Hypertrophic cardiomyopathy
HP:0001640	Cardiomegaly
HP:0001653	Mitral regurgitation
HP:0001706	Endocardial fibroelastosis
HP:0001944	Dehydration
HP:0001946	Ketosis
HP:0001987	Hyperammonemia
HP:0001988	Recurrent hypoglycemia
HP:0002013	Vomiting
HP:0002014	Diarrhea
HP:0002098	Respiratory distress
HP:0002240	Hepatomegaly
HP:0002312	Clumsiness
HP:0002910	Elevated circulating hepatic transaminase concentration
HP:0003198	Myopathy

GWAS associations

53 associations (top):

Study	Trait	p-value
GCST000368_1	Fibrinogen	1.000000e-06
GCST000368_5	Fibrinogen	1.000000e-12
GCST000804_9	Asthma	2.000000e-07
GCST000817_96	Height	7.000000e-16
GCST000879_15	Crohn’s disease	1.000000e-20
GCST001217_17	Metabolic traits	3.000000e-57
GCST001725_83	Inflammatory bowel disease	1.000000e-52
GCST001838_1	Palmitic acid (16:0) levels	2.000000e-07
GCST001841_4	Palmitoleic acid (16:1n-7) levels	6.000000e-09
GCST002449_3	Plasma omega-6 polyunsaturated fatty acid levels (arachidonic acid)	4.000000e-06
GCST004131_32	Inflammatory bowel disease	4.000000e-27
GCST004132_10	Crohn’s disease	6.000000e-36
GCST004133_36	Ulcerative colitis	2.000000e-06
GCST004342_1	Vaccenic acid (18:1n-7) levels	6.000000e-17
GCST004342_3	Vaccenic acid (18:1n-7) levels	2.000000e-16
GCST004618_31	White blood cell count (basophil)	2.000000e-09
GCST004863_105	Mosquito bite size	3.000000e-20
GCST006249_8	Serum metabolite levels	9.000000e-15
GCST006249_92	Serum metabolite levels	2.000000e-11
GCST006862_23	Asthma	2.000000e-11
GCST006976_55	Macular thickness	2.000000e-10
GCST007268_20	Diastolic blood pressure	6.000000e-09
GCST007564_20	Asthma or allergic disease (pleiotropy)	5.000000e-10
GCST007993_12	Asthma (adult onset)	3.000000e-13
GCST007995_19	Asthma (childhood onset)	9.000000e-11
GCST008916_106	Asthma	2.000000e-25
GCST009150_9	Low density lipoprotein cholesterol levels	1.000000e-12
GCST009391_708	Metabolite levels	4.000000e-07
GCST009798_69	Asthma	1.000000e-26
GCST010204_60	Low density lipoprotein cholesterol levels	7.000000e-09

EFO canonical traits (14, from GWAS)

EFO ID	Trait name
EFO:0004725	metabolite measurement
EFO:0005680	omega-6 polyunsaturated fatty acid measurement
EFO:0007974	vaccenic acid measurement
EFO:0005090	basophil count
EFO:0008378	mosquito bite reaction size measurement
EFO:0006336	diastolic blood pressure
EFO:1002011	adult onset asthma
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0010358	lysophosphatidylcholine 16:1 measurement
EFO:0006501	carotid plaque build
EFO:0004346	neuroimaging measurement
EFO:0007986	reticulocyte count
EFO:0005091	monocyte count
EFO:0004736	aspartate aminotransferase measurement

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D000326	Adrenoleukodystrophy	C10.228.140.163.100.084; C10.228.140.163.100.362.250; C10.228.140.695.625.250; C10.314.400.250; C10.597.606.360.455.124; C16.320.322.500.124; C16.320.400.525.124; C16.320.565.189.084; C16.320.565.189.362.250; C16.320.565.663.100; C18.452.132.100.084; C18.452.132.100.362.250; C18.452.648.189.084; C18.452.648.189.362.250; C18.452.648.663.100; C19.053.500.270
C580439	Short Qt Syndrome (supp.)
C536778	Systemic carnitine deficiency (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2073693 (SINGLE PROTEIN)

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

PharmGKB clinical annotations

3 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs2631367	Efficacy	3	imatinib	Gastrointestinal Stromal Tumors
rs2631372	Efficacy	3	imatinib	Gastrointestinal Stromal Tumors
rs274558	Toxicity	3	imatinib	Gastrointestinal Stromal Tumors

PharmGKB variants

4 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2631367	SLC22A5	3	2.75	1	imatinib
rs2631372	SLC22A5	3	2.25	1	imatinib
rs2631370	SLC22A5		0.00	0
rs274558	SLC22A5	3	3.00	1	imatinib

GtoPdb / IUPHAR curated pharmacology

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

Target class: transporter — Organic zwitterions/cation transporters (OCTN)

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Carnitine	affects binding, increases abundance, affects cotreatment, increases expression, affects reaction (+5 more)	12
Doxorubicin	decreases reaction, increases abundance, affects cotreatment, increases expression, decreases expression	4
Estradiol	increases expression	3
pivaloylcarnitine	increases uptake, decreases reaction, increases transport, affects binding	2
Cisplatin	affects cotreatment, decreases expression	2
Metformin	decreases reaction, increases abundance	2
aristolochic acid I	increases expression	1
talinolol	decreases reaction, increases uptake	1
tetrahydropalmatine	decreases reaction, increases import	1
beta-lapachone	increases expression	1
mono-(2-ethylhexyl)phthalate	increases expression	1
afimoxifene	decreases reaction, increases expression	1
enilconazole	decreases expression	1
sodium arsenite	decreases expression	1
valproylcarnitine	increases uptake	1
3-(2,2,2-trimethylhydrazine)propionate	increases uptake	1
di-n-butylphosphoric acid	affects expression	1
grepafloxacin	affects reaction, increases uptake	1
ziprasidone	decreases reaction, increases uptake	1
CGP 52608	affects binding, increases reaction	1
Grape Seed Proanthocyanidins	affects cotreatment, increases expression	1
jinfukang	affects cotreatment, decreases expression	1
Atorvastatin	decreases reaction, increases uptake	1
Quetiapine Fumarate	decreases reaction, increases uptake	1
Oxaliplatin	increases import, increases response to substance, decreases reaction	1
Olanzapine	decreases reaction, increases uptake	1
Rosiglitazone	increases expression	1
Temozolomide	affects response to substance	1
Decitabine	increases expression	1
Sunitinib	decreases expression	1

ChEMBL screening assays

97 unique, capped per target: 79 functional, 18 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2076256	Functional	TP_TRANSPORTER: uptake in OCTN2-expressing HEK293 cells	Na(+)-dependent carnitine transport by organic cation transporter (OCTN2): its pharmacological and toxicological relevance. — J Pharmacol Exp Ther
CHEMBL3531368	ADMET	Inhibition of OCTN2 (unknown origin) expressed in HEK293 cells assessed as reduction of [3H]carnitine substrate uptake at 100 uM by liquid scintillation counting	Evaluation and prediction of potential drug-drug interactions of linagliptin using in vitro cell culture methods. — Drug Metab Dispos

Cellosaurus cell lines

8 cell lines: 4 cancer cell line, 3 finite cell line, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_0J44	GM10665	Finite cell line	Male
CVCL_B2FM	Abcam HeLa SLC22A5 KO	Cancer cell line	Female
CVCL_D4J3	HCT116-SLC22A5-KO-c4	Cancer cell line	Male
CVCL_D4J4	HCT116-SLC22A5-KO-c5	Cancer cell line	Male
CVCL_F1QL	HyCyte HK-2 KO-hSLC22A5	Transformed cell line	Male
CVCL_N153	GM10666	Finite cell line	Female
CVCL_N154	GM10667	Finite cell line	Male
CVCL_TM00	HAP1 SLC22A5 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01904396	PHASE4	UNKNOWN	Identification of Carnitine-Responsive Cardiomyopathy
NCT05003648	PHASE4	ACTIVE_NOT_RECRUITING	Treating Leg Symptoms in Women With X-linked Adrenoleukodystrophy
NCT00007020	PHASE3	COMPLETED	Compassionate Treatment of Patients With Inborn Errors of Bile Acid Metabolism With Cholic Acid
NCT00545597	PHASE3	TERMINATED	A Phase III Trial of Lorenzo’s Oil in Adrenomyeloneuropathy
NCT00004418	PHASE2	TERMINATED	Effect of Glycerol Trierucate on Clinical Course of Adrenoleukodystrophy
NCT00383448	PHASE2	COMPLETED	HSCT for High Risk Inherited Inborn Errors
NCT01043640	PHASE2	COMPLETED	Allogeneic Bone Marrow Transplant for Inherited Metabolic Disorders
NCT03864523	PHASE2	COMPLETED	Effect of Pioglitazone Administered to Patients With Adrenomyeloneuropathy
NCT05200104	PHASE2	WITHDRAWN	Study to Assess PXL065 in Subjects With Adrenomyeloneuropathy (AMN) Form of X-linked Adrenoleukodystrophy (X-ALD or ALD)
NCT01586455	PHASE1	COMPLETED	Human Placental-Derived Stem Cell Transplantation
NCT01787578	PHASE1	WITHDRAWN	Safety and Pharmacodynamic Study of Sobetirome in X-Linked Adrenoleukodystrophy (X-ALD)
NCT02254863	PHASE1	RECRUITING	UCB Transplant of Inherited Metabolic Diseases With Administration of Intrathecal UCB Derived Oligodendrocyte-Like Cells
NCT02595489	PHASE1	COMPLETED	A Pilot Study of Vitamin D in Boys With X-linked Adrenoleukodystrophy
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT07201714	EARLY_PHASE1	RECRUITING	Oral Carnitine in Heart Failure Patients
NCT00187733	Not specified	COMPLETED	Influence of OCTN2 Variants on Carnitine Status and Plasma Triglycerides
NCT02635269	Not specified	UNKNOWN	Fat and Sugar Metabolism During Exercise in Patients With Metabolic Myopathy
NCT05910151	Not specified	UNKNOWN	Selective Screening of Children for Hereditary Metabolic Diseases by Tandem Mass Spectrometry in Kazakhstan
NCT06546137	Not specified	RECRUITING	National Network for Cardiovascular Genomics: Advancing Cardiovascular Healthcare for Hereditary Diseases in Brazil’s Unified Health System Through a Multicenter Registry
NCT00176904	PHASE2/PHASE3	COMPLETED	Stem Cell Transplant for Inborn Errors of Metabolism
NCT02961803	PHASE2/PHASE3	COMPLETED	MD1003-AMN MD1003 in Adrenomyeloneuropathy
NCT03231878	PHASE2/PHASE3	COMPLETED	A Clinical Study to Evaluate the Efficacy and Safety of MIN-102 (IMP) in Male AMN Patients.
NCT04303416	PHASE2/PHASE3	COMPLETED	Plasma Exchange With Albumin in AMN Patients
NCT01372228	PHASE1/PHASE2	TERMINATED	Phase I/II Pilot Study of Mixed Chimerism to Treat Inherited Metabolic Disorders
NCT02559830	PHASE1/PHASE2	UNKNOWN	Autologous Hematopoietic Stem Cell Gene Therapy for Metachromatic Leukodystrophy and Adrenoleukodystrophy
NCT03196765	PHASE1/PHASE2	WITHDRAWN	Safety, Pharmacokinetics and Pharmacodynamics of NV1205 in Pediatric Male Subjects With Adrenoleukodystrophy
NCT03513328	PHASE1/PHASE2	COMPLETED	Conditioning Regimen for Allogeneic Hematopoietic Stem-Cell Transplantation
NCT05394064	PHASE1/PHASE2	TERMINATED	A Study to Evaluate Administration of SBT101 Gene Therapy in Adult Patients With Adrenomyeloneuropathy (AMN)
NCT00004442	Not specified	TERMINATED	Study of Bile Acids in Patients With Peroxisomal Disorders
NCT00004450	Not specified	COMPLETED	Randomized Study of Beta Interferon and Thalidomide in Patients With Adrenoleukodystrophy
NCT00005900	Not specified	UNKNOWN	Study of Pulmonary Complications in Pediatric Patients With Storage Disorders Undergoing Allogeneic Hematopoietic Stem Cell Transplantation
NCT00278044	Not specified	UNKNOWN	Clinical Study and Gene Mutation Analysis of Adrenoleukodystrophy in Taiwanese Children
NCT01165060	Not specified	COMPLETED	The Effect of Bezafibrate on the Level of Very Long Chain Fatty Acids (VLCFA) in X-linked Adrenoleukodystrophy (X-ALD)
NCT01594853	Not specified	COMPLETED	Exercise Study of Function and Pathology for Women With X-linked Adrenoleukodystrophy
NCT02204904	Not specified	TERMINATED	Observational Study to Evaluate Allogeneic HSCT Outcomes for Cerebral Adrenoleukodystrophy (CALD)
NCT02233257	Not specified	NO_LONGER_AVAILABLE	Expanded Access for Lorenzo’s Oil (GTO/GTE) in Adrenoleukodystrophy
NCT02698579	Not specified	ACTIVE_NOT_RECRUITING	Long-term Follow-up of Participants With Cerebral Adrenoleukodystrophy Who Were Treated With Lenti-D Drug Product
NCT02699190	Not specified	COMPLETED	LeukoSEQ: Whole Genome Sequencing as a First-Line Diagnostic Tool for Leukodystrophies
NCT02948062	Not specified	WITHDRAWN	Early Diagnosis Of Childhood Cerebral ALD
NCT02952482	Not specified	COMPLETED	Newborn Screening for Adrenoleukodystrophy