SLC67A1

Summary

SLC67A1 (solute carrier family 67 member 1, HGNC:10964) is a protein-coding gene on chromosome 11p15.4, encoding Solute carrier family 67 member A1 (Q96BI1). May act as a transporter of organic cations based on a proton efflux antiport mechanism.

This gene is one of several tumor-suppressing subtransferable fragments located in the imprinted gene domain of 11p15.5, an important tumor-suppressor gene region. Alterations in this region have been associated with the Beckwith-Wiedemann syndrome, Wilms tumor, rhabdomyosarcoma, adrenocortical carcinoma, and lung, ovarian, and breast cancer. This gene is imprinted, with preferential expression from the maternal allele. Mutations in this gene have been found in Wilms’ tumor and lung cancer. This protein may act as a transporter of organic cations, and have a role in the transport of chloroquine and quinidine-related compounds in kidney. Several alternatively spliced transcript variants encoding different isoforms have been described.

Source: NCBI Gene 5002 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 91 total — 3 pathogenic
• Phenotypes (HPO): 8
• Druggable target: yes
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
• MANE Select transcript: NM_002555

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10964
Approved symbol	SLC67A1
Name	solute carrier family 67 member 1
Location	11p15.4
Locus type	gene with protein product
Status	Approved
Aliases	BWR1A, TSSC5, ITM
Ensembl gene	ENSG00000110628
Ensembl biotype	protein_coding
OMIM	602631
Entrez	5002

Gene structure

Transcript identifiers

Ensembl transcripts: 44 — 36 protein_coding, 4 protein_coding_CDS_not_defined, 4 retained_intron

ENST00000347936, ENST00000380574, ENST00000441077, ENST00000449603, ENST00000449793, ENST00000463571, ENST00000467719, ENST00000485423, ENST00000492567, ENST00000495518, ENST00000498209, ENST00000498244, ENST00000649076, ENST00000888491, ENST00000888492, ENST00000888493, ENST00000888494, ENST00000888495, ENST00000888496, ENST00000888497, ENST00000888498, ENST00000888499, ENST00000888500, ENST00000888501, ENST00000888502, ENST00000888503, ENST00000888504, ENST00000888505, ENST00000888506, ENST00000888507, ENST00000888508, ENST00000888509, ENST00000888510, ENST00000925567, ENST00000925568, ENST00000925569, ENST00000948726, ENST00000948727, ENST00000948728, ENST00000948729, ENST00000948730, ENST00000948731, ENST00000948732, ENST00000948733

RefSeq mRNA: 4 — MANE Select: NM_002555 NM_001315501, NM_001315502, NM_002555, NM_183233

CCDS: CCDS7740, CCDS81542

Canonical transcript exons

ENST00000610526 — 0 exons

Expression profiles

Bgee: expression breadth ubiquitous, 132 present calls, max score 98.73.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 17.3988 / max 255.9662, expressed in 1779 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
112713	15.2266	1770
112716	0.7545	106
112710	0.4561	153
112711	0.3337	167
112715	0.2593	136
112712	0.2065	65
112714	0.1474	90
112709	0.0147	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of transverse colon	UBERON:0004991	98.73	gold quality
duodenum	UBERON:0002114	97.79	gold quality
right lobe of liver	UBERON:0001114	97.18	gold quality
metanephros cortex	UBERON:0010533	95.66	gold quality
small intestine Peyer’s patch	UBERON:0003454	94.76	gold quality
liver	UBERON:0002107	94.55	gold quality
transverse colon	UBERON:0001157	94.34	gold quality
lower esophagus mucosa	UBERON:0035834	94.32	gold quality
cortex of kidney	UBERON:0001225	94.09	gold quality
small intestine	UBERON:0002108	93.92	gold quality
adult mammalian kidney	UBERON:0000082	93.85	gold quality
right atrium auricular region	UBERON:0006631	93.45	gold quality
blood	UBERON:0000178	93.16	gold quality
left testis	UBERON:0004533	92.36	gold quality
right testis	UBERON:0004534	92.22	gold quality
stromal cell of endometrium	CL:0002255	91.42	gold quality
granulocyte	CL:0000094	91.38	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	90.84	gold quality
right uterine tube	UBERON:0001302	90.77	gold quality
skin of abdomen	UBERON:0001416	90.72	gold quality
testis	UBERON:0000473	90.58	gold quality
zone of skin	UBERON:0000014	90.39	gold quality
skin of leg	UBERON:0001511	90.37	gold quality
left lobe of thyroid gland	UBERON:0001120	90.20	gold quality
spleen	UBERON:0002106	90.20	gold quality
gall bladder	UBERON:0002110	90.13	gold quality
apex of heart	UBERON:0002098	89.89	gold quality
right lobe of thyroid gland	UBERON:0001119	89.79	gold quality
thyroid gland	UBERON:0002046	89.78	gold quality
body of stomach	UBERON:0001161	89.68	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	11.44

Regulation

Is transcription factor: no

Functional genomics

ClinGen dosage: haploinsufficiency 0 (no evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 18)

• involved in the drug resistance mechanism of tumors (PMID:11925925)
• UbcH6-RING105 may define a novel ubiquitin-proteasome pathway that targets TSSC5 in mammalian cells (PMID:16314844)
• study reports the imprinting status of SLC22A18AS in breast tissue and breast cancer, and shows that gain of imprinting affects both the sense, and antisense transcripts at this locus (PMID:16624517)
• Mutational analysis of the two Sp1 sites suggested their requirement for the promoter activityof SLC22A18. (PMID:18996451)
• recent demonstration that the promoter of this gene is positively regulated by Sp1 (PMID:18996451)
• Low expression of SLC22A18 was associated with tumor progression, recurrence and poor survival after breast surgery (PMID:21144813)
• SLC22A18 downregulation via promoter methylation is associated with the development and progression of glioma. (PMID:21936894)
• SLC22A18 functions as a tumor suppressor in glioma and represents a candidate biomarker for long-term survival in this disease. (PMID:22153794)
• The expression level of SLC22A18 in non-small cell lung cancer was significantly higher than that in normal tissue. (PMID:22237119)
• SLC22A18 protein expression predicted a significantly shorter overall survival in 51 patients receiving TMZ therapy, whereas no differences in overall survival were observed in 35 patients without TMZ therapy (PMID:23514245)
• Upregulated expression of SLC22A18 enhanced the radiosensitivity of glioma U251 cells. (PMID:24481489)
• microRNA-137 functions as a tumor suppressor in human non-small cell lung cancer by targeting SLC22A18 (PMID:25498886)
• Establish SLC22A18 as a tumor suppressor in colon epithelial cells and propose that SLC22A18 is potentially a marker of diagnostic and prognostic values. (PMID:26196590)
• Data provide evidence that SLC22A18 and/or CDKN1C are tumor modifier genes involved in the tumorigenesis of SDHD-mutated paraganglioma. (PMID:27402879)
• These results suggest that SLC22A18 may act as a tumor suppressor by regulating the expression levels of cell growth-related proteins, and vinca alkaloids might show therapeutic efficacy against low-SLC22A18-expressing breast cancer. (PMID:30145211)
• suppression of SLC22A18 decreased the supply of intracellular free fatty acids from triglyceride-rich lipid droplets by impairing the lysosomal/autophagy degradation pathway and reduced the invasive activity of HepG2 cells by decreasing IGFBP-1 expression (PMID:30635741)
• The effect of genetic variants of SLC22A18 on proliferation, migration, and invasion of colon cancer cells. (PMID:38366023)
• SLC22A18 gene is imprinted, with preferential expression from the maternal allele. (PMID:9751628)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	slc22a18	ENSDARG00000052271
mus_musculus	Slc22a18	ENSMUSG00000000154
rattus_norvegicus	Slc22a18	ENSRNOG00000020562
caenorhabditis_elegans		WBGENE00008273

Protein

Protein identifiers

Solute carrier family 67 member A1 — Q96BI1 (reviewed: Q96BI1)

Alternative names: Beckwith-Wiedemann syndrome chromosomal region 1 candidate gene A protein, Efflux transporter-like protein, Imprinted multi-membrane-spanning polyspecific transporter-related protein 1, Organic cation transporter-like protein 2, Solute carrier family 22 member 1-like, Solute carrier family 22 member 18, Tumor-suppressing STF cDNA 5 protein, Tumor-suppressing subchromosomal transferable fragment candidate gene 5 protein, p45-Beckwith-Wiedemann region 1 A

All UniProt accessions (3): Q96BI1, E9PMN7, E9PRM7

UniProt curated annotations — full annotation on UniProt →

Function. May act as a transporter of organic cations based on a proton efflux antiport mechanism. May play a role in the transport of chloroquine and quinidine-related compounds in kidney. Plays a role in the regulation of lipid metabolism.

Subunit / interactions. Interacts with RNF167.

Subcellular location. Apical cell membrane.

Tissue specificity. Expressed at high levels in adult and fetal kidney and liver, and adult colon. Expressed in fetal renal proximal tubules (at protein level). Expressed at lower levels in heart, brain and lung.

Disease relevance. Lung cancer (LNCR) [MIM:211980] A common malignancy affecting tissues of the lung. The most common form of lung cancer is non-small cell lung cancer (NSCLC) that can be divided into 3 major histologic subtypes: squamous cell carcinoma, adenocarcinoma, and large cell lung cancer. NSCLC is often diagnosed at an advanced stage and has a poor prognosis. The gene represented in this entry may be involved in disease pathogenesis. Rhabdomyosarcoma, embryonal, 1 (RMSE1) [MIM:268210] A form of rhabdomyosarcoma, a highly malignant tumor of striated muscle derived from primitive mesenchymal cells and exhibiting differentiation along rhabdomyoblastic lines. Rhabdomyosarcoma is one of the most frequently occurring soft tissue sarcomas and the most common in children. It occurs in four forms: alveolar, pleomorphic, embryonal and botryoidal rhabdomyosarcomas. The disease may be caused by variants affecting the gene represented in this entry.

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

RefSeq proteins (4): NP_001302430, NP_001302431, NP_002546, NP_899056 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001958	Tet-R_TetA/multi-R_MdtG-like	Family
IPR011701	MFS	Family
IPR020846	MFS_dom	Domain
IPR036259	MFS_trans_sf	Homologous_superfamily

Pfam: PF07690

UniProt features (24 total): transmembrane region 10, sequence conflict 7, sequence variant 6, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96BI1-F1	86.91	0.69

Function

Pathways and Gene Ontology

Reactome pathways

9 pathways

ID	Pathway
R-HSA-549127	SLC-mediated transport of organic cations
R-HSA-5619066	Defective SLC22A18 causes lung cancer (LNCR) and embryonal rhabdomyosarcoma 1 (RMSE1)
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-5619102	SLC transporter disorders
R-HSA-5619115	Disorders of transmembrane transporters

MSigDB gene sets: 161 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_DN, AP1_01, KAAB_HEART_ATRIUM_VS_VENTRICLE_UP, GAUSSMANN_MLL_AF4_FUSION_TARGETS_A_DN, BROWNE_HCMV_INFECTION_48HR_DN, FONTAINE_PAPILLARY_THYROID_CARCINOMA_UP, ONKEN_UVEAL_MELANOMA_UP, MODULE_99, GOBP_DETOXIFICATION, HNF4_01, GOTZMANN_EPITHELIAL_TO_MESENCHYMAL_TRANSITION_DN, TGANTCA_AP1_C, SANSOM_APC_TARGETS_DN, GOCC_APICAL_PLASMA_MEMBRANE, AFFAR_YY1_TARGETS_DN

GO Biological Process (4): obsolete organic cation transport (GO:0015695), xenobiotic transport (GO:0042908), xenobiotic detoxification by transmembrane export across the plasma membrane (GO:1990961), transmembrane transport (GO:0055085)

GO Molecular Function (4): ubiquitin protein ligase binding (GO:0031625), xenobiotic transmembrane transporter activity (GO:0042910), protein binding (GO:0005515), transmembrane transporter activity (GO:0022857)

GO Cellular Component (5): nuclear envelope (GO:0005635), cytoplasm (GO:0005737), plasma membrane (GO:0005886), membrane (GO:0016020), apical plasma membrane (GO:0016324)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
SLC-mediated transmembrane transport	1
SLC transporter disorders	1
Transport of small molecules	1
Disorders of transmembrane transporters	1
Disease	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transport	2
cellular anatomical structure	2
xenobiotic export from cell	1
detoxification	1
export across plasma membrane	1
cellular process	1
ubiquitin-like protein ligase binding	1
transmembrane transporter activity	1
xenobiotic transport	1
binding	1
transporter activity	1
transmembrane transport	1
nucleus	1
endomembrane system	1
organelle envelope	1
intracellular anatomical structure	1
membrane	1
cell periphery	1
apical part of cell	1
plasma membrane region	1

Protein interactions and networks

STRING

1148 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC67A1	PHLDA2	Q53GA4	952
SLC67A1	SLC67A1-AS	Q8N1D0	901
SLC67A1	CDKN1C	P49918	890
SLC67A1	KCNQ1	P51787	867
SLC67A1	TSSC4	Q9Y5U2	831
SLC67A1	RNF167	Q9H6Y7	828
SLC67A1	ASCL2	Q99929	791
SLC67A1	IGF2	P01344	789
SLC67A1	OSBPL5	Q9H0X9	711
SLC67A1	NAP1L4	Q99733	671
SLC67A1	SLC22A31	A6NKX4	671
SLC67A1	TSPAN32	Q96QS1	669
SLC67A1	SLC22A23	A1A5C7	649
SLC67A1	SNRPN	P14648	638
SLC67A1	IGF2R	P11717	633

IntAct

57 interactions, top by confidence:

A	B	Type	Score
GYPA	TCAF2	psi-mi:“MI:0914”(association)	0.640
VSIG1	TTI1	psi-mi:“MI:0914”(association)	0.640
SLC67A1	NKX3-1	psi-mi:“MI:0915”(physical association)	0.560
HSD17B11	SLC67A1	psi-mi:“MI:0915”(physical association)	0.560
SLC67A1	TLCD4	psi-mi:“MI:0915”(physical association)	0.560
SLC67A1	TMX2	psi-mi:“MI:0915”(physical association)	0.560
MME	TMEM223	psi-mi:“MI:0914”(association)	0.530
SLC7A1	TMEM223	psi-mi:“MI:0914”(association)	0.530
SLC39A5	TMEM223	psi-mi:“MI:0914”(association)	0.530
C3AR1	TMEM120B	psi-mi:“MI:0914”(association)	0.530
POMK	TMEM120B	psi-mi:“MI:0914”(association)	0.530
HAVCR2	TCAF2	psi-mi:“MI:0914”(association)	0.530
LAMP3	METTL15	psi-mi:“MI:0914”(association)	0.530
SPACA1	GOLIM4	psi-mi:“MI:0914”(association)	0.530
CHST10	B4GAT1	psi-mi:“MI:0914”(association)	0.530
ITM2A	NDUFB5	psi-mi:“MI:0914”(association)	0.530
AMIGO3	CANX	psi-mi:“MI:0914”(association)	0.530
HLA-DPA1	TYW5	psi-mi:“MI:0914”(association)	0.530
MRAP2	GOLIM4	psi-mi:“MI:0914”(association)	0.530
CA14	EXOC5	psi-mi:“MI:0914”(association)	0.530
TNFSF8	LGALS8	psi-mi:“MI:0914”(association)	0.530
SLC67A1	ECI2	psi-mi:“MI:0915”(physical association)	0.400
		psi-mi:“MI:0914”(association)	0.350
	ESYT2	psi-mi:“MI:0914”(association)	0.350
E5	ESYT2	psi-mi:“MI:0914”(association)	0.350
	HAX1	psi-mi:“MI:0914”(association)	0.350
HLA-DPA1	GXYLT2	psi-mi:“MI:0914”(association)	0.350
SLC39A4	TMEM120B	psi-mi:“MI:0914”(association)	0.350
CLEC2D	TMEM120B	psi-mi:“MI:0914”(association)	0.350

BioGRID (101): SLC22A18 (Affinity Capture-MS), SLC22A18 (Affinity Capture-MS), SLC22A18 (Affinity Capture-MS), SLC22A18 (Affinity Capture-MS), SLC22A18 (Affinity Capture-MS), SLC22A18 (Affinity Capture-MS), SLC22A18 (Affinity Capture-MS), SLC22A18 (Affinity Capture-MS), SLC22A18 (Affinity Capture-MS), SLC22A18 (Affinity Capture-MS), SLC22A18 (Affinity Capture-MS), SLC22A18 (Affinity Capture-MS), SLC22A18 (Affinity Capture-MS), SLC22A18 (Affinity Capture-MS), SLC22A18 (Affinity Capture-MS)

ESM2 similar proteins: A0A3Q2HW92, A6NDV4, A6NFX1, D2HKB0, D3ZVU9, F1NCD6, F1NJ67, F1PZV2, O09014, Q0IHM1, Q0P5M9, Q14728, Q14CX5, Q3T9M1, Q3U481, Q3UGX3, Q58CT4, Q58CV5, Q5JZQ7, Q5VTY9, Q66H95, Q6AY78, Q6NUT3, Q6PDE8, Q6UXD7, Q6W5G4, Q6ZMD2, Q7RTT9, Q80T22, Q8BFQ6, Q8CE47, Q8IVW8, Q8N697, Q8NA29, Q8R139, Q8TED4, Q8VCW4, Q8VCY8, Q8WUG5, Q91VM4

Diamond homologs: P9WEL1, Q96BI1, Q6AY78, Q78KK3

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
RNF167	“down-regulates quantity by destabilization”	SLC22A18	polyubiquitination

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	0
Uncertain significance	50
Likely benign	10
Benign	8

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
59748	GRCh38/hg38 11p15.5-15.4(chr11:218365-3377077)x3	Pathogenic
6976	NM_002555.6(SLC22A18):c.864_865ins[NC_000011.10:g.2919738_2919848]	Pathogenic
6978	NM_002555.6(SLC22A18):c.698C>T (p.Ser233Phe)	Pathogenic

SpliceAI

2188 predictions. Top by Δscore:

Variant	Effect	Δscore
11:2909576:A:AG	acceptor_gain	1.0000
11:2909577:G:GG	acceptor_gain	1.0000
11:2909577:GCC:G	acceptor_gain	1.0000
11:2909709:GG:G	donor_gain	1.0000
11:2909710:GG:G	donor_gain	1.0000
11:2909711:G:GG	donor_gain	1.0000
11:2917986:A:AG	acceptor_gain	1.0000
11:2917987:G:GG	acceptor_gain	1.0000
11:2917987:GGC:G	acceptor_gain	1.0000
11:2918094:AG:A	donor_gain	1.0000
11:2918095:GG:G	donor_gain	1.0000
11:2918096:G:GG	donor_gain	1.0000
11:2919299:C:CA	acceptor_gain	1.0000
11:2919300:G:A	acceptor_gain	1.0000
11:2919301:GCTCA:G	acceptor_loss	1.0000
11:2919302:CTCAG:C	acceptor_loss	1.0000
11:2919303:TCAG:T	acceptor_loss	1.0000
11:2919305:A:AG	acceptor_gain	1.0000
11:2919305:AGGGC:A	acceptor_loss	1.0000
11:2919306:G:GA	acceptor_loss	1.0000
11:2919306:G:GG	acceptor_gain	1.0000
11:2919340:T:TA	acceptor_gain	1.0000
11:2919405:ATGGT:A	donor_loss	1.0000
11:2919407:GGT:G	donor_loss	1.0000
11:2922100:A:AG	acceptor_gain	1.0000
11:2922101:G:GG	acceptor_gain	1.0000
11:2922470:T:TA	acceptor_gain	1.0000
11:2922553:ACAGG:A	donor_loss	1.0000
11:2922555:AGG:A	donor_loss	1.0000
11:2922556:GGTG:G	donor_loss	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000233303 (11:2911235 A>T), RS1000438831 (11:2905479 C>T), RS1000586990 (11:2921778 A>C), RS1000647394 (11:2910996 G>A,C), RS1000672542 (11:2899721 G>A,T), RS1000741140 (11:2904547 G>A), RS1000774163 (11:2924081 TG>T,TGG), RS1000842260 (11:2918986 G>A), RS1000983308 (11:2924265 G>A), RS1001093583 (11:2914277 C>T), RS1001438116 (11:2915142 C>T), RS1001517434 (11:2904951 G>A), RS1001525279 (11:2919197 C>A,T), RS1001572678 (11:2900451 G>A), RS1001632991 (11:2904953 A>G)

Disease associations

OMIM: gene MIM:602631 | disease phenotypes:

GenCC curated gene-disease

Mondo (3): lung adenocarcinoma (MONDO:0005061), breast adenocarcinoma (MONDO:0004988), lung carcinoma (MONDO:0005138)

Orphanet (1): NON RARE IN EUROPE: Adenocarcinoma of the lung (Orphanet:415268)

HPO phenotypes

8 total (8 of 8 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0001442	Typified by somatic mosaicism
HP:0003002	Breast carcinoma
HP:0006519	Alveolar cell carcinoma
HP:0006743	Embryonal rhabdomyosarcoma
HP:0030078	Lung adenocarcinoma
HP:0030358	Non-small cell lung carcinoma

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST000386_2	Bilirubin levels	1.000000e-07
GCST000769_7	Calcium levels	5.000000e-06
GCST005980_1	Total bilirubin levels	5.000000e-11
GCST009151_8	High density lipoprotein cholesterol levels	6.000000e-14
GCST010241_13	Apolipoprotein A1 levels	2.000000e-18
GCST010242_36	HDL cholesterol levels	1.000000e-15
GCST010725_20	Malaria	4.000000e-69
GCST010725_33	Malaria	2.000000e-67
GCST010725_51	Malaria	1.000000e-55

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004570	bilirubin measurement
EFO:0004838	calcium measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004614	apolipoprotein A 1 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066435 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: transporter — Orphan or poorly characterized SLC22 family members

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, increases expression	6
Valproic Acid	increases methylation, affects expression, increases expression	4
Cyclosporine	increases expression, affects expression	3
bisphenol A	decreases methylation, increases expression	2
Air Pollutants	affects expression, increases abundance, increases expression	2
Cisplatin	increases expression, affects expression, affects cotreatment	2
Smoke	decreases expression, increases abundance, increases expression	2
Tretinoin	decreases expression, increases expression	2
Aflatoxin B1	decreases expression, increases methylation	2
bisphenol F	affects cotreatment, decreases methylation	1
triphenyl phosphate	affects expression	1
quercitrin	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
benzo(e)pyrene	decreases methylation	1
aflatoxin B2	increases methylation	1
cupric chloride	decreases expression	1
4-phenylbutyric acid	increases expression	1
CGP 52608	affects binding, increases reaction	1
monomethylarsonous acid	decreases expression	1
K 7174	increases expression	1
jinfukang	affects cotreatment, increases expression	1
prothioconazole	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Decitabine	affects expression	1
Sunitinib	increases expression	1
Arsenic Trioxide	decreases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Acetaminophen	decreases expression	1
Arsenic	affects methylation	1
Vehicle Emissions	decreases expression, increases abundance	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652446	Binding	Binding affinity to human SLC22A18 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D4VE	LS180-SLC22A18-KO-c3	Cancer cell line	Female
CVCL_D4VF	LS180-SLC22A18-KO-c5	Cancer cell line	Female
CVCL_TL97	HAP1 SLC22A18 (-) 1	Cancer cell line	Male
CVCL_TL98	HAP1 SLC22A18 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02399566	PHASE4	UNKNOWN	Clinical Trial of Erlotinib and Pemetrexed for Maintenance Treatment in Lung Adenocarcinoma
NCT02804646	PHASE4	UNKNOWN	Endostar Durative Transfusion Combined With Chemotherapy in the Treatment of Advanced Lung Adenocarcinoma
NCT05183828	PHASE4	RECRUITING	Effect of HSD3B1 (1245C) Gene Mutation on Treatment of Stage I-III Breast Cancer
NCT00158041	PHASE4	COMPLETED	Subcutaneous Amifostine Safety Study
NCT00277160	PHASE4	COMPLETED	A Study of Primary Prophylaxis With Neulasta (Pegfilgrastim) Versus Secondary Prophylaxis After Chemotherapy in Elderly Subjects (>/= 65 Years Old) With Cancer
NCT00365508	PHASE4	COMPLETED	Counseling and Nicotine Replacement Therapy in Helping Adult Smokers Quit Smoking
NCT00440960	PHASE4	COMPLETED	Anesthesia in Flexible Bronchoscopy for Lung Cancer Diagnostic
NCT00492843	PHASE4	TERMINATED	Loading Dose or Standard Dose of Intravenous Ibandronate in Treating Patients With Lung Cancer and Skeletal Metastasis
NCT00666978	PHASE4	COMPLETED	Health Education Counseling With or Without Bupropion in Helping African Americans Stop Smoking
NCT00675168	PHASE4	UNKNOWN	Positron Emission Tomography (PET)/Computed Tomography (CT) and Roentgen in Lung Cancer: Evaluation of Patients in General Practice
NCT00712647	PHASE4	COMPLETED	Carotene and Retinol Efficacy Trial
NCT00747773	PHASE4	COMPLETED	Cryospray Ablation of Surgical Resection Specimens To Determine Safety And Histological Effect In The Lung
NCT01060137	PHASE4	COMPLETED	Fentanyl Matrix in Lung Cancer Pain
NCT01381627	PHASE4	UNKNOWN	Safety Evaluation of Dexmedetomidine for EBUS-TBNA
NCT01741506	PHASE4	COMPLETED	Coagulation Profile in Patients Undergoing Video Assisted Thorascopic Surgery (VATS) for Lung Cancer
NCT02246023	PHASE4	COMPLETED	Fractionated Versus Target-controlled Propofol Administration in Bronchoscopy
NCT02275702	PHASE4	COMPLETED	Randomized Study of Preoperative Dexamethasone for Quality of Recovery in VATS Lung Resection Patients
NCT02346318	PHASE4	UNKNOWN	The Randomized Controlled Clinical Trial of Kushen Injection
NCT02476526	PHASE4	COMPLETED	Safety of Low Dose IV Contrast CT Scanning in Chronic Kidney Disease
NCT02490059	PHASE4	COMPLETED	Ultrathin Bronchoscopy for Solitary Pulmonary Nodules
NCT02504801	PHASE4	UNKNOWN	Efficacy of Nebulized Pulmicort Respules in Primary Lung Cancer Patients With COPD
NCT02869789	PHASE4	COMPLETED	An Investigational Immuno-therapy Study for Safety of Nivolumab in Combination With Ipilimumab to Treat Advanced Cancers
NCT03302221	PHASE4	WITHDRAWN	Regional Haemodynamic Changes in Radial Artery Assessment With Continuous Pulsed-wave Doppler Ultrasound
NCT03313544	PHASE4	UNKNOWN	Evolution of the Heart Function When Monitoring Immunotherapies Anti-cancerous Inhibiting PD-1
NCT03394222	PHASE4	COMPLETED	Effect of Preoperative Budesonide Inhalation on Arterial Blood Oxygenation and Intrapulmonary Shunt During OLV
NCT03570645	PHASE4	COMPLETED	Comparison of the Duration of Ropivacaine Combined With Dexmedetomidine or Dexamethasone on Paravertebral Block
NCT00002852	PHASE3	COMPLETED	Surgery With or Without Chemotherapy in Treating Patients With Stage I Non-small Cell Lung Cancer
NCT00005838	PHASE3	COMPLETED	Combination Chemotherapy Plus Radiation Therapy With or Without AE-941 in Treating Patients With Stage III Non-small Cell Lung Cancer That Cannot Be Removed By Surgery
NCT00020709	PHASE3	COMPLETED	Combination Chemotherapy and Radiation Therapy With or Without Gefitinib in Treating Patients With Stage III Non-Small Cell Lung Cancer That Cannot Be Removed By Surgery
NCT00049543	PHASE3	COMPLETED	Gefitinib in Treating Patients With Stage IB, II, or IIIA Non-small Cell Lung Cancer That Was Completely Removed by Surgery
NCT00946712	PHASE3	TERMINATED	S0819: Carboplatin and Paclitaxel With or Without Bevacizumab and/or Cetuximab in Treating Patients With Stage IV or Recurrent Non-Small Cell Lung Cancer
NCT01798485	PHASE3	TERMINATED	A Phase 3 Study of Ganetespib in Combination With Docetaxel Versus Docetaxel Alone in Patients With Advanced NSCLC
NCT02011997	PHASE3	UNKNOWN	Comparison of cVATS Segmentectomy Versus Lobectomy for Lung Adenocarcinoma in Situ and With Microinvasion
NCT03391869	PHASE3	ACTIVE_NOT_RECRUITING	Nivolumab and Ipilimumab With or Without Local Consolidation Therapy in Treating Patients With Stage IV Non-Small Cell Lung Cancer
NCT03676192	PHASE3	COMPLETED	To Compare Efficacy and Safety of CT-P16 and European Union-Approved Avastin as First-Line Treatment for Metastatic or Recurrent Non-Squamous Non-Small Cell Lung Cancer
NCT04339218	PHASE3	RECRUITING	Cryoablation in Combination (or Not) With Pembrolizumab and Pemetrexed-carboplatin in 1st-line Treatment for Patients With Metastatic Lung Adenocarcinoma
NCT05204758	PHASE3	COMPLETED	Prophylactic TCM for Mitigation of EGFR-TKI Related Dermatological Adverse Effect
NCT05717803	PHASE3	RECRUITING	Segmentectomy for Ground Glass-dominant Invasive Lung Cancer (ECTOP-1012)
NCT05943795	PHASE3	ACTIVE_NOT_RECRUITING	A Clinical Study of SI-B001 Combined With Docetaxel in the Treatment of Non-small Cell Lung Adenocarcinoma and Lung Squamous Cell Carcinoma
NCT06031181	PHASE3	RECRUITING	Sublobar Resection for Adenocarcinoma in Situ/Minimally Invasive Adenocarcinoma Diagnosed by Intraoperative Frozen Section (ECTOP-1019)