SLCO2A1

Summary

SLCO2A1 (solute carrier organic anion transporter family member 2A1, HGNC:10955) is a protein-coding gene on chromosome 3q22.1-q22.2, encoding Solute carrier organic anion transporter family member 2A1 (Q92959). Mediates the transport of prostaglandins (PGs, mainly PGE2, PGE1, PGE3, PGF2alpha, PGD2, PGH2) and thromboxanes (thromboxane B2) across the cell membrane.

This gene encodes a prostaglandin transporter that is a member of the 12-membrane-spanning superfamily of transporters. The encoded protein may be involved in mediating the uptake and clearance of prostaglandins in numerous tissues.

Source: NCBI Gene 6578 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hypertrophic osteoarthropathy, primary, autosomal dominant (Definitive, GenCC) — +4 more curated relationships
• GWAS associations: 3
• Clinical variants (ClinVar): 381 total — 36 pathogenic, 27 likely-pathogenic (top 9% of genes corpus-wide)
• GTEx eGene: eQTL in 15 tissues, sQTL in 21 (q < 0.05)
• Phenotypes (HPO): 60
• ChEMBL bioactivity: 1 clinical-phase molecule tested; no curated mechanism-of-action drug
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.04 (unconstrained)
• MANE Select transcript: NM_005630

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10955
Approved symbol	SLCO2A1
Name	solute carrier organic anion transporter family member 2A1
Location	3q22.1-q22.2
Locus type	gene with protein product
Status	Approved
Aliases	PGT, OATP2A1
Ensembl gene	ENSG00000174640
Ensembl biotype	protein_coding
OMIM	601460
Entrez	6578

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 14 protein_coding, 4 nonsense_mediated_decay, 3 retained_intron, 2 protein_coding_CDS_not_defined

MANE Select: ENST00000310926

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 2: 1, TSL 3: 1, TSL 4: 1, TSL 5: 3

ENST00000310926, ENST00000462770, ENST00000464676, ENST00000477061, ENST00000478651, ENST00000478662, ENST00000481359, ENST00000493729, ENST00000860067, ENST00000860068, ENST00000860069, ENST00000860070, ENST00000860071, ENST00000860072, ENST00000860073, ENST00000860074, ENST00000860075, ENST00000988248, ENST00001029968, ENST00001108169, ENST00001108170, ENST00001116300, ENST00001144726

RefSeq mRNA: 1 — MANE Select: NM_005630 NM_005630

CCDS: CCDS3084

Canonical transcript exons

ENST00000310926 — 14 exons

Exon	Start	End
ENSE00001184806	133948893	133948971
ENSE00001184828	133932701	133934830
ENSE00001250528	134029707	134029925
ENSE00001305936	133951208	133951344
ENSE00003531773	133979481	133979618
ENSE00003541500	133945095	133945260
ENSE00003581552	133947256	133947445
ENSE00003599910	133973663	133973825
ENSE00003601676	133953663	133953761
ENSE00003617669	133954966	133955193
ENSE00003618950	133935774	133935897
ENSE00003622918	133948536	133948700
ENSE00003644863	133942605	133942768
ENSE00003657886	133938429	133938493

Expression profiles

Bgee: expression breadth ubiquitous, 252 present calls, max score 99.40.

FANTOM5 (CAGE): breadth broad, TPM avg 6.1463 / max 585.1530, expressed in 641 samples.

Highest expression (Bgee): lung, upper lobe of left lung, upper lobe of lung, lobe of thyroid gland, thyroid gland.

Genetic regulation across tissues (GTEx eQTL / sQTL)

SLCO2A1 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 15 tissues and its splicing (sQTL) in 21 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 36 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Thyroid	sqtl	7.1e-54	-1.08	3:133947365:C:T
Lung	sqtl	2.7e-53	-1.17	3:133947365:C:T
Nerve Tibial	eqtl	7.7e-12	+0.27	3:133952700:G:A
Esophagus Mucosa	sqtl	3.3e-10	+0.41	3:133936157:G:A
Colon Transverse	sqtl	7.3e-08	+0.50	3:133936157:G:A
Skin Sun Exposed Lower leg	sqtl	1.4e-07	+0.52	3:133936157:G:A
Nerve Tibial	sqtl	3.6e-07	+0.48	3:133936157:G:A
Esophagus Muscularis	sqtl	7.4e-07	+0.55	3:133947365:C:T
Adrenal Gland	sqtl	5.0e-06	-0.72	3:133947365:C:T
Adipose Visceral Omentum	sqtl	1.0e-05	-0.46	3:133936157:G:A
Skin Not Sun Exposed Suprapubic	sqtl	1.8e-05	+0.41	3:133936157:G:A
Prostate	sqtl	1.8e-05	-0.70	3:133948802:C:T
Adipose Subcutaneous	sqtl	8.5e-05	+0.39	3:133947365:C:T
Cells Cultured fibroblasts	eqtl	8.7e-05	+0.46	3:134123228:C:T
Heart Atrial Appendage	sqtl	1.1e-04	+0.49	3:133951229:T:C
Stomach	sqtl	3.0e-04	+0.54	3:133947365:C:T
Breast Mammary Tissue	sqtl	3.0e-04	+0.43	3:133947365:C:T
Esophagus Gastroesophageal Junction	sqtl	6.3e-04	+0.54	3:133947365:C:T
Pituitary	sqtl	3.0e-03	+0.59	3:133936157:G:A
Muscle Skeletal	eqtl	5.7e-03	-0.22	3:133978920:G:T

FANTOM5 promoters

5 alternative TSS:

Promoter ID	TPM avg	Samples expressed
44681	5.0564	561
44682	0.6154	267
44683	0.2787	135
44684	0.1410	70
44677	0.0549	23

Top tissues by expression

showing 100 of 289 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right lung	UBERON:0002167	99.40	gold quality
upper lobe of left lung	UBERON:0008952	97.97	gold quality
upper lobe of lung	UBERON:0008948	97.87	gold quality
right lobe of thyroid gland	UBERON:0001119	97.77	gold quality
left lobe of thyroid gland	UBERON:0001120	97.35	gold quality
thyroid gland	UBERON:0002046	96.91	gold quality
lower lobe of lung	UBERON:0008949	96.53	gold quality
seminal vesicle	UBERON:0000998	96.33	gold quality
lung	UBERON:0002048	94.85	gold quality
cardia of stomach	UBERON:0001162	94.10	gold quality
left uterine tube	UBERON:0001303	94.04	gold quality
mucosa of stomach	UBERON:0001199	93.42	gold quality
body of uterus	UBERON:0009853	93.28	gold quality
left adrenal gland cortex	UBERON:0035825	93.26	gold quality
adrenal cortex	UBERON:0001235	93.19	gold quality
left adrenal gland	UBERON:0001234	93.11	gold quality
decidua	UBERON:0002450	92.84	gold quality
tendon of biceps brachii	UBERON:0008188	92.73	gold quality
right adrenal gland	UBERON:0001233	92.55	gold quality
myometrium	UBERON:0001296	92.55	gold quality
right adrenal gland cortex	UBERON:0035827	92.46	gold quality
ectocervix	UBERON:0012249	91.96	gold quality
smooth muscle tissue	UBERON:0001135	91.81	gold quality
adrenal gland	UBERON:0002369	91.50	gold quality
right coronary artery	UBERON:0001625	91.07	gold quality
pylorus	UBERON:0001166	90.71	gold quality
left coronary artery	UBERON:0001626	90.47	gold quality
fundus of stomach	UBERON:0001160	90.34	gold quality
palpebral conjunctiva	UBERON:0001812	90.33	gold quality
gall bladder	UBERON:0002110	90.23	gold quality
coronary artery	UBERON:0001621	90.22	gold quality
minor salivary gland	UBERON:0001830	90.14	gold quality
prostate gland	UBERON:0002367	89.87	gold quality
endocervix	UBERON:0000458	89.86	gold quality
small intestine Peyer’s patch	UBERON:0003454	89.86	gold quality
right atrium auricular region	UBERON:0006631	89.79	gold quality
omental fat pad	UBERON:0010414	89.73	gold quality
peritoneum	UBERON:0002358	89.72	gold quality
visceral pleura	UBERON:0002401	89.63	gold quality
saliva-secreting gland	UBERON:0001044	89.60	gold quality
body of stomach	UBERON:0001161	89.39	gold quality
cardiac atrium	UBERON:0002081	89.37	gold quality
transverse colon	UBERON:0001157	89.34	gold quality
pericardium	UBERON:0002407	89.26	gold quality
mouth mucosa	UBERON:0003729	89.19	gold quality
parotid gland	UBERON:0001831	89.13	gold quality
placenta	UBERON:0001987	89.05	gold quality
adult mammalian kidney	UBERON:0000082	88.99	gold quality
tongue squamous epithelium	UBERON:0006919	88.86	silver quality
metanephros cortex	UBERON:0010533	88.84	gold quality
rectum	UBERON:0001052	88.72	gold quality
small intestine	UBERON:0002108	88.44	gold quality
mucosa of urinary bladder	UBERON:0001259	88.34	gold quality
mucosa of transverse colon	UBERON:0004991	88.21	gold quality
adipose tissue of abdominal region	UBERON:0007808	88.20	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	88.17	gold quality
metanephric glomerulus	UBERON:0004736	88.14	gold quality
pancreatic ductal cell	CL:0002079	88.13	silver quality
body of pancreas	UBERON:0001150	88.11	gold quality
urethra	UBERON:0000057	88.04	gold quality
uterine cervix	UBERON:0000002	87.92	gold quality
spleen	UBERON:0002106	87.92	gold quality
caecum	UBERON:0001153	87.71	gold quality
stomach	UBERON:0000945	87.65	gold quality
vagina	UBERON:0000996	87.55	gold quality
esophagus mucosa	UBERON:0002469	87.50	gold quality
lower esophagus muscularis layer	UBERON:0035833	87.50	gold quality
left ventricle myocardium	UBERON:0006566	87.43	gold quality
renal glomerulus	UBERON:0000074	87.41	gold quality
lower esophagus	UBERON:0013473	87.39	gold quality
esophagus	UBERON:0001043	87.37	gold quality
adenohypophysis	UBERON:0002196	87.26	gold quality
cortex of kidney	UBERON:0001225	86.68	gold quality
colon	UBERON:0001155	86.58	gold quality
metanephros	UBERON:0000081	86.54	gold quality
vermiform appendix	UBERON:0001154	86.53	gold quality
intestine	UBERON:0000160	86.44	gold quality
kidney	UBERON:0002113	86.42	gold quality
large intestine	UBERON:0000059	86.39	gold quality
apex of heart	UBERON:0002098	86.35	gold quality
heart	UBERON:0000948	86.24	gold quality
superficial temporal artery	UBERON:0001614	85.81	gold quality
skin of abdomen	UBERON:0001416	85.72	gold quality
heart left ventricle	UBERON:0002084	85.70	gold quality
cardiac ventricle	UBERON:0002082	85.54	gold quality
adult organism	UBERON:0007023	85.37	gold quality
gingival epithelium	UBERON:0001949	85.26	gold quality
gingiva	UBERON:0001828	85.14	gold quality
colonic mucosa	UBERON:0000317	85.13	gold quality
thoracic aorta	UBERON:0001515	85.08	gold quality
ascending aorta	UBERON:0001496	84.99	gold quality
muscle layer of sigmoid colon	UBERON:0035805	84.87	gold quality
sigmoid colon	UBERON:0001159	84.68	gold quality
tibial nerve	UBERON:0001323	84.41	gold quality
descending thoracic aorta	UBERON:0002345	84.39	gold quality
pituitary gland	UBERON:0000007	84.34	gold quality
colonic epithelium	UBERON:0000397	84.17	gold quality
epithelial cell of pancreas	CL:0000083	83.97	silver quality
duodenum	UBERON:0002114	83.93	gold quality
mucosa of sigmoid colon	UBERON:0004993	83.83	gold quality

Single-cell (SCXA)

Detected in 9 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-ANND-2	yes	713.61
E-GEOD-135922	yes	636.52
E-HCAD-11	yes	42.76
E-CURD-119	yes	40.43
E-HCAD-1	yes	39.28
E-MTAB-8410	yes	22.10
E-MTAB-6678	yes	6.33
E-MTAB-10137	no	515.82
E-ANND-3	no	0.00

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 74 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Seminal vesicle	tissue	79.9	high
Lung	tissue	43.4	low
Thyroid gland	tissue	41.4	not detected
Smooth muscle	tissue	31.3	not detected
Parathyroid gland	tissue	27.0	not detected
Placenta	tissue	22.0	medium
Urinary bladder	tissue	19.9	not detected
Vagina	tissue	19.8	not detected
Adrenal gland	tissue	18.9	not detected
Choroid plexus	tissue	18.3
Cervix	tissue	18.2	not detected
Fallopian tube	tissue	17.9	not detected
Gallbladder	tissue	17.6	low
Endometrium 1	tissue	17.1	not detected
Rectum	tissue	16.9	low
Pituitary gland	tissue	16.5
Kidney	tissue	16.2	high
Stomach 1	tissue	15.9	medium
Colon	tissue	15.8	low
Appendix	tissue	15.8	low
Pancreas	tissue	14.7	low
Adipose tissue	tissue	14.2	not detected
Spleen	tissue	13.8	not detected
Salivary gland	tissue	13.7	low
Prostate	tissue	12.2	not detected
Skin 1	tissue	10.1	not detected
Small intestine	tissue	10.1	not detected
Esophagus	tissue	9.7	not detected
Duodenum	tissue	9.7	not detected
Heart muscle	tissue	9.0	low
Tonsil	tissue	9.0	not detected
Lymph node	tissue	8.6	not detected
Thymus	tissue	7.8
Breast	tissue	6.0	not detected
Epididymis	tissue	5.8	not detected
Superior colliculi	tissue	5.8
Cerebral cortex	tissue	4.6	medium
Spinal cord	tissue	4.6
Occipital cortex	tissue	4.6
Insular cortex	tissue	3.9
Hypothalamus	tissue	3.7
Temporal cortex	tissue	3.7
Substantia nigra	tissue	3.6
Amygdala	tissue	3.5
Hippocampal formation	tissue	3.4
Retrosplenial and cingulate cortex	tissue	3.4
Septum	tissue	3.4
Prefrontal cortex	tissue	3.3
Motor cortex	tissue	3.3
Entorhinal cortex	tissue	3.3
Somatosensory cortex	tissue	3.3
Tongue	tissue	3.2
Putamen	tissue	3.2
Medulla oblongata	tissue	3.2
Thalamus	tissue	3.2
Pons	tissue	3.1
Retrosplenial cortex	tissue	3.1
Midbrain	tissue	3.0
Olfactory bulb	tissue	3.0
Basal ganglia	tissue	2.7	low

Brain sub-regions (HPA Brain Atlas): detected in 190; highest nTPM — Blood vessel (26.5), Dorsal spinal cord (4.6), Ventral spinal cord (4.5), Anterior thalamic nucleus, ventral (4.2), Anterior insular cortex, dorsal (4.0).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting SLCO2A1 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 88 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-6740-5P	100.00	65.64	932
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-6817-3P	99.79	68.35	2126
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-1200	99.71	70.42	1838
HSA-MIR-30B-3P	99.70	65.76	2325
HSA-MIR-3689A-3P	99.70	65.73	2306
HSA-MIR-3689B-3P	99.70	65.71	2311
HSA-MIR-3689C	99.70	65.71	2311
HSA-MIR-6779-5P	99.70	65.76	2363
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-5093	99.67	69.26	2291

Functional genomics

gnomAD constraint: pLI 1.6e-17, LOEUF 1.04, missense Z 1.11 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000310926 — one region, missense o/e 0.92.

Literature-anchored findings (GeneRIF, showing 40)

• Human endometrial stromal cells treated with a combination of cAMP and medroxyprogesterone acetate to induce decidualization showed an increase in protein and mRNA levels. (PMID:16339169)
• PGT level was significantly less in AD than in age-matched control brain homogenates. (PMID:18353443)
• The existing model to explain increased PGE(2) in colorectal neoplasia should be modified to include the novel mechanism of coordinated up- and down-regulation of genes involved in PGE(2) transport. (PMID:19138942)
• that PGT may play a role in transporting PGH(2) across cellular membranes. (PMID:20346915)
• expression in fetal membranesfound primarily in the choriodecidua (PMID:20357271)
• we found no indication for an association between SNPs in the prostaglandin F(2alpha) receptor gene or SLCO2A1 and IOP response to prostaglandin analogs in a population of European descent. (PMID:22060278)
• The findings confirmed that SLCO2A1 mutations inactivate prostaglandin E2 transport, and they indicated that mutations in SLCO2A1 are the pathogenic cause of primary hypertrophic osteoarthropathy. (PMID:22197487)
• Mutations in the prostaglandin transporter encoding gene SLCO2A1 cause primary hypertrophic osteoarthropathy and isolated digital clubbing. (PMID:22331663)
• Prostaglandin transporter mutations cause pachydermoperiostosis with myelofibrosis. (PMID:22553128)
• Mutations in the prostaglandin transporter SLCO2A1 cause primary hypertrophic osteoarthropathy with digital clubbing. (PMID:22696055)
• Report SLCO2A1 is a novel gene responsible for pachydermoperiostosis in Japanese patients. (PMID:22906430)
• genetic association study in population in China: Nine different SLCO2A1 mutations were identified in subjects with primary hypertrophic osteoarthropathy (PHO) in 7 previously undescribed families; different homozygous mutations of SLCO2A1 cause PHO. (PMID:23509104)
• Three novel mutations within the SLCO2A1 gene have been demonstrated to be associated with Chinese primary hypertrophic osteoarthropathy patients. (PMID:24153155)
• Identified two novel mutations in SLCO2A1. (PMID:24185079)
• Genetic variability in key genes in prostaglandin E2 pathway (COX-2, HPGD, ABCC4 and SLCO2A1) and their involvement in colorectal cancer development. (PMID:24694755)
• SLCO2A1 has a role in familial digital clubbing, colon neoplasia, and NSAID resistance (PMID:24838973)
• a novel nonsense mutation p.E141* of the SLCO2A1 gene is associated with pachydermoperiostosis (PMID:24929850)
• In this article we describe a novel mutation in the SLCO2A1 causing Pachydermoperiostosis in a Lebanese family (PMID:25059581)
• OATP2A1 also diminished the PGE2-mediated expression of interleukin-8 mRNA (IL-8) and hypoxia-inducible-factor 1alpha (HIF1alpha) protein in AGS-OATP2A1 cells. (PMID:25433165)
• Multiple drug resistance-associated protein 4 (MRP4), prostaglandin transporter (PGT), and 15-hydroxyprostaglandin dehydrogenase (15-PGDH) as determinants of PGE2 levels in cancer. (PMID:25433169)
• We herein report patients with pachydermoperiostosis (PDP)due to SLCO2A1 mutation in a Korean family. Similar to other East Asian populations, the SLCO2A1 gene may be a possible mutation spot of PDP in the Korean population. (PMID:25810087)
• SLCO2A1 and NOS3 are involved with prostaglandin reuptake/metabolism and nitric oxide production, respectively, and are consistently decreased in “non-Caucasian” fetal ductus arteriosus (PMID:26265282)
• overexpression of SLCO2A1 could induce and knockdown inhibit the invasion of lung cancer cells. expression levels of p-mTOR, p-AKT and p-S6 were up-regulated or down-regulated with the overexpression or knockdown of SLCO2A1. (PMID:26464663)
• findings indicate that loss-of-function mutations in the SLCO2A1 gene encoding a prostaglandin transporter cause the hereditary enteropathy CNSU (PMID:26539716)
• Data show that prostaglandin E3 (PGE3) uptake by prostaglandin transporter OATP2A1-expressing HEK293 cells (HEK/2A1) was the highest and followed by SLCO2B1 (HEK/1B1). (PMID:26692285)
• cytoplasmic OATP2A1 likely facilitates prostaglandin E2 loading into suitable intracellular compartment(s) for efficient exocytotic prostaglandin E2 release from colorectal cancer cells exposed to oxidative stress (PMID:26850138)
• Mutation analysis revealed a novel heterozygous mutation in the solute carrier organic anion transporter family member 2A1 gene at nucleotide 302 causing a substitution of the amino acid isoleucine to serine at codon 101 (p.IIe101Ser) in affected individuals. (PMID:27134495)
• An association was found between single nucleotide polymorphisms of the PTGFR and SLCO2A1 genes and the response to latanoprost in Han Chinese patients with glaucoma. These SNPs may be important determinants of differential response to latanoprost. (PMID:27336732)
• In Japanese patients with chronic nonspecific multiple ulcers of the small intestine, 2 of the 4 patients had mutation in the SLCO2A1 gene, became resistant to medical therapy, and underwent strictureplasty or ileal resection after long-term follow-up. (PMID:27467110)
• The findings reported here support causality of this SLCO2A1 mutation for autosomal recessive ICNC in this consanguineous Pakistani kindred. (PMID:27681482)
• A novel missense mutation c.101T > C in the SLCO2A1 gene causes pachydermoperiostosis of the complete type. (PMID:28602931)
• in individuals carrying the SLCO2A1 A396T variant, the combination of thiazide-specific effects on free water generation and the increase in collecting duct water permeability from reduced SLCO2A1 activity combine to produce thiazide-induced hyponatremia (PMID:28783044)
• The expression of SLCO2A1 was observed in one of four patients with chronic enteropathy associated with SLCO2A1 (CEAS) and in all 29 patients with Crohn’s Disease. The three with CEAS without SLCO2A1 expression had a homozygous splice-site mutation in SLCO2A1. The remaining one CEAS patient with positive expression of SLCO2A1 had compound heterozygous mutations. (PMID:30400730)
• A novel SLCO2A1 compound heterozygous mutation of p.I284V and p.C459R was identified in two PHO patients in a chinese family. (PMID:31004291)
• Chronic enteropathy associated with SLCO2A1 gene: A case report and literature review. (PMID:31196708)
• A novel mutation in the SLCO2A1 gene, encoding a prostaglandin transporter, induces chronic enteropathy. (PMID:33166338)
• [Clinical and genetic characteristics of patients with chronic enteropathy associated with SLCO2A1 gene]. (PMID:33397021)
• Differential Associations of SLCO Transporters with Prostate Cancer Aggressiveness between African Americans and European Americans. (PMID:33619025)
• Phenolsulfonphthalein as a surrogate substrate to assess altered function of the prostaglandin transporter SLCO2A1. (PMID:35299026)
• Clinical and Genetic Characteristics of Korean Patients Diagnosed with Chronic Enteropathy Associated with SLCO2A1 Gene: A KASID Multicenter Study. (PMID:35611666)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	slco2a1	ENSDARG00000061896
mus_musculus	Slco2a1	ENSMUSG00000032548
rattus_norvegicus	Slco2a1	ENSRNOG00000009005
caenorhabditis_elegans		WBGENE00009023

Paralogs (10): SLCO1A2 (ENSG00000084453), SLCO4A1 (ENSG00000101187), SLCO1B3 (ENSG00000111700), SLCO1B1 (ENSG00000134538), SLCO2B1 (ENSG00000137491), SLCO5A1 (ENSG00000137571), SLCO1C1 (ENSG00000139155), SLCO4C1 (ENSG00000173930), SLCO3A1 (ENSG00000176463), SLCO6A1 (ENSG00000205359)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1346021) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 8 distinct phenotype terms.

Mouse phenotype (MP)	Records
dilated heart left ventricle	1
dilated heart right ventricle	1
patent ductus arteriosus	1
abnormal cell physiology	1
abnormal urine homeostasis	1
abnormal prostaglandin level	1
postnatal lethality, complete penetrance	1
neonatal lethality, complete penetrance	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Pongo abelii	Q5RFF0	97.9%	Diamond
Bos taurus	Q8HYW2	97.2%	Diamond
Drosophila melanogaster	Q9VVH9	31.3%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
RYK	protein-coding	6259
C3orf36	ncRNA	80111
LINC02000	ncRNA	100507210
LINC02004	ncRNA	105374119
RAB6B	protein-coding	51560
SRPRB	protein-coding	58477
TF	protein-coding	7018

Protein

Protein identifiers

Solute carrier organic anion transporter family member 2A1 — Q92959 (reviewed: Q92959)

Alternative names: OATP2A1, PHOAR2, Prostaglandin transporter, Solute carrier family 21 member 2

All UniProt accessions (3): E7EU40, Q92959, F8W9W8

UniProt curated annotations — full annotation on UniProt →

Function. Mediates the transport of prostaglandins (PGs, mainly PGE2, PGE1, PGE3, PGF2alpha, PGD2, PGH2) and thromboxanes (thromboxane B2) across the cell membrane. PGs and thromboxanes play fundamental roles in diverse functions such as intraocular pressure, gastric acid secretion, renal salt and water transport, vascular tone, and fever. Plays a role in the clearance of PGs from the circulation through cellular uptake, which allows cytoplasmic oxidation and PG signal termination. PG uptake is dependent upon membrane potential and involves exchange of a monovalent anionic substrate (PGs exist physiologically as an anionic monovalent form) with a stoichiometry of 1:1 for divalent anions or of 1:2 for monovalent anions. Uses lactate, generated by glycolysis, as a counter-substrate to mediate PGE2 influx and efflux. Under nonglycolytic conditions, metabolites other than lactate might serve as counter-substrates. Although the mechanism is not clear, this transporter can function in bidirectional mode. When apically expressed in epithelial cells, it facilitates transcellular transport (also called vectorial release), extracting PG from the apical medium and facilitating transport across the cell toward the basolateral side, whereupon the PG exits the cell by simple diffusion. In the renal collecting duct, regulates renal Na+ balance by removing PGE2 from apical medium (PGE2 EP4 receptor is likely localized to the luminal/apical membrane and stimulates Na+ resorption) and transporting it toward the basolateral membrane (where PGE2 EP1 and EP3 receptors inhibit Na+ resorption). Plays a role in endometrium during decidualization, increasing uptake of PGs by decidual cells. Involved in critical events for ovulation. Regulates extracellular PGE2 concentration for follicular development in the ovaries. Expressed intracellularly, may contribute to vesicular uptake of newly synthesized intracellular PGs, thereby facilitating exocytotic secretion of PGs without being metabolized. Essential core component of the major type of large-conductance anion channel, Maxi-Cl, which plays essential roles in inorganic anion transport, cell volume regulation and release of ATP and glutamate not only in physiological processes but also in pathological processes. May contribute to regulate the transport of organic compounds in testis across the blood-testis-barrier.

Subcellular location. Cell membrane. Basal cell membrane. Cytoplasm. Lysosome.

Tissue specificity. Ubiquitous. Significant expression observed in lung, kidney, spleen, and heart. Expressed in the endometrium (at both mRNA and protein levels). Expressed in the ovaries (at mRNA and protein levels). In testis, primarily localized to the basal membrane of Sertoli cells and weakly expressed within the tubules.

Disease relevance. PHOAR2-enteropathy syndrome (PHOAR2E) [MIM:614441] An autosomal recessive disease characterized by primary hypertrophic osteoarthropathy and/or chronic non-specific ulcers of the small intestine. Affected individuals present with digital clubbing, periostosis, acroosteolysis, painful joint enlargement, and variable features of pachydermia that include thickened facial skin and a thickened scalp. Chronic ulcers of the small intestine result in abdominal pain and watery diarrhea, and are associated with chronic anemia. Other developmental anomalies include delayed closure of the cranial sutures and congenital heart disease. The disease is caused by variants affecting the gene represented in this entry. Hypertrophic osteoarthropathy, primary, autosomal dominant (PHOAD) [MIM:167100] A form of primary hypertrophic osteoarthropathy, a disease characterized by digital clubbing, periostosis, acroosteolysis, painful joint enlargement, and variable features of pachydermia that include thickened facial skin and a thickened scalp. PHOAD patients may also experience joint swelling and pain, and some have reported gastrointestinal symptoms, including watery diarrhea. Males are more commonly affected, and more severely affected, than females. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Chorionic gonadotropin stimulates expression in the ovaries.

Similarity. Belongs to the organo anion transporter (TC 2.A.60) family.

RefSeq proteins (1): NP_005621* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002350	Kazal_dom	Domain
IPR004156	OATP	Family
IPR020846	MFS_dom	Domain
IPR036058	Kazal_dom_sf	Homologous_superfamily
IPR036259	MFS_trans_sf	Homologous_superfamily

Pfam: PF03137, PF07648

Catalyzed reactions (Rhea)

• prostaglandin E2(out) = prostaglandin E2(in) (RHEA:50984)
• prostaglandin E3(out) + 2 (S)-lactate(in) = prostaglandin E3(in) + 2 (S)-lactate(out) (RHEA:74351)
• prostaglandin H2(out) + 2 (S)-lactate(in) = prostaglandin H2(in) + 2 (S)-lactate(out) (RHEA:74379)
• prostaglandin E2(out) + 2 (S)-lactate(in) = prostaglandin E2(in) + 2 (S)-lactate(out) (RHEA:74383)
• prostaglandin E1(out) + 2 (S)-lactate(in) = prostaglandin E1(in) + 2 (S)-lactate(out) (RHEA:74395)
• prostaglandin F2alpha(out) + 2 (S)-lactate(in) = prostaglandin F2alpha(in) + 2 (S)-lactate(out) (RHEA:74399)
• prostaglandin D2(out) + 2 (S)-lactate(in) = prostaglandin D2(in) + 2 (S)-lactate(out) (RHEA:74403)
• thromboxane B2(out) + 2 (S)-lactate(in) = thromboxane B2(in) + 2 (S)-lactate(out) (RHEA:74407)

UniProt features (115 total): helix 40, sequence variant 24, topological domain 13, transmembrane region 12, strand 11, turn 5, glycosylation site 3, disulfide bond 3, sequence conflict 2, chain 1, domain 1

Structure

Experimental structures (PDB)

8 structures by resolution:

PDB	Title	Method	Resolution (Å)
3MRR	Crystal Structure of MHC class I HLA-A2 molecule complexed with Human Prostaglandin …	X-RAY DIFFRACTION	1.6
8KGW	Molecular mechanism of prostaglandin transporter SLCO2A1	ELECTRON MICROSCOPY	2.96
9JV1	Cryo-EM structure of transporter2a1_PGE2	ELECTRON MICROSCOPY	3.1
8KGI	Molecular mechanism of prostaglandin transporter SLCO2A1	ELECTRON MICROSCOPY	3.2
8KGV	Molecular mechanism of prostaglandin transporter SLCO2A1	ELECTRON MICROSCOPY	3.2
9JUQ	Cryo-EM structure of transporter2a1	ELECTRON MICROSCOPY	3.2
9VH9	Molecular mechanism of prostaglandin transporter SLCO2A1	ELECTRON MICROSCOPY	3.4
9MGK	Human prostaglandin transporter(OATP2A1)	ELECTRON MICROSCOPY	4.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q92959-F1	82.27	0.48

Human Protein Atlas

Protein class: Metabolic proteins, Transporters, Electrochemical Potential-driven transporters, Predicted membrane proteins, Disease related genes, Potential drug targets, Human disease related genes

Protein evidence: Evidence at protein level

Antibody reliability (HPA): IH enhanced

Functional residue map

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

Disulfide bonds (3)

Type	Positions
Disulfide bond	444–474, 450–470, 459–494

Glycosylation sites (3)

Type	Positions
N-linked (glcnac…) asparagine	134, 478, 491

Function

Pathways and Gene Ontology

Reactome pathways

2 curated (TAS) of 8; 4 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

8 pathways:

ID	Pathway	Evidence
R-HSA-5619095	Defective SLCO2A1 causes primary, autosomal recessive hypertrophic osteoarthropathy 2 (PHOAR2) ⚕	curated
R-HSA-879518	Organic anion transport by SLCO transporters	curated
R-HSA-1643685	Disease ⚕	—
R-HSA-5619115	Disorders of transmembrane transporters ⚕	—
R-HSA-5619102	SLC transporter disorders ⚕	—
R-HSA-425407	SLC-mediated transmembrane transport	—
R-HSA-382551	Transport of small molecules	—
R-HSA-425397	Transport of vitamins, nucleosides, and related molecules	—

MSigDB gene sets: 294 (showing top): GSE45365_NK_CELL_VS_BCELL_UP, GOBP_SODIUM_INDEPENDENT_ORGANIC_ANION_TRANSPORT, BENPORATH_ES_WITH_H3K27ME3, TGACCTY_ERR1_Q2, SAENZ_DETOX_PATHWAY_AND_CARCINOGENESIS_DN, GOBP_ORGANIC_ACID_TRANSPORT, BROWNE_HCMV_INFECTION_48HR_DN, HOSHIDA_LIVER_CANCER_SUBCLASS_S3, ROZANOV_MMP14_TARGETS_UP, NF1_Q6_01, KYNG_DNA_DAMAGE_BY_GAMMA_RADIATION, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_UP, GOBP_ORGANIC_ANION_TRANSPORT, MORF_EPHA7, GOBP_MONOCARBOXYLIC_ACID_TRANSPORT

GO Biological Process (5): lipid transport (GO:0006869), prostaglandin transport (GO:0015732), sodium-independent organic anion transport (GO:0043252), monoatomic ion transport (GO:0006811), transmembrane transport (GO:0055085)

GO Molecular Function (5): lipid carrier activity (GO:0005319), prostaglandin transmembrane transporter activity (GO:0015132), protein binding (GO:0005515), secondary active transmembrane transporter activity (GO:0015291), transmembrane transporter activity (GO:0022857)

GO Cellular Component (6): lysosome (GO:0005764), plasma membrane (GO:0005886), basal plasma membrane (GO:0009925), membrane (GO:0016020), basolateral plasma membrane (GO:0016323), cytoplasm (GO:0005737)

Reactome top-level categories

6 top-level categories:

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

GO top-level categories

20 GO namespaces:

Category	Terms
transport	3
transmembrane transport	2
plasma membrane region	2
cellular anatomical structure	2
lipid localization	1
fatty acid transport	1
icosanoid transport	1
cellular process	1
molecular carrier activity	1
prostaglandin transport	1
icosanoid transmembrane transporter activity	1
binding	1
active transmembrane transporter activity	1
transporter activity	1
lytic vacuole	1
membrane	1
cell periphery	1
basal part of cell	1
basal plasma membrane	1
intracellular anatomical structure	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 1 of 16 annotations. The rest are phylogenetic / computational / electronic (IEA).

1 experimentally-supported GO terms:

GO term	NS	Evidence
basal plasma membrane	CC	direct assay

Protein interactions and networks

STRING

showing 15 of 722 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLCO2A1	HPGD	P15428	720
SLCO2A1	AMH	P03971	622
SLCO2A1	ABCC4	O15439	570
SLCO2A1	GNRH1	P01148	547
SLCO2A1	PTGER4	P35408	505
SLCO2A1	ITIH4	Q14624	496
SLCO2A1	PTGES	O14684	489
SLCO2A1	ABCB1	P08183	469
SLCO2A1	NR1I2	O75469	452
SLCO2A1	PTGER3	P43115	435
SLCO2A1	SLC41A2	Q96JW4	406
SLCO2A1	SLC22A8	Q8TCC7	389
SLCO2A1	PTGIS	Q16647	388
SLCO2A1	PTGFR	P43088	387
SLCO2A1	PTGER1	P34995	385

IntAct

Human interaction partners of SLCO2A1 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

2 partners by confidence:

Partner	Interaction type	MIscore	Records
GRB2	physical association	0.400	1
ATP5PD	association	0.350	1

BioGRID (6 interactions; top human partners by supporting records): ACBD3 (Affinity Capture-MS), ATP5D (Affinity Capture-MS), ATP5H (Affinity Capture-MS), PLD3 (Affinity Capture-MS), RDH14 (Affinity Capture-MS), TMX1 (Affinity Capture-MS)

Disease & clinical

Genetic variants

Variant evidence for SLCO2A1: 381 ClinVar records (63 pathogenic / likely pathogenic); 1 PharmGKB clinical annotation; 3 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	36
Likely pathogenic	27
Uncertain significance	127
Likely benign	122
Benign	33

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 63 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
225477	NM_005630.3(SLCO2A1):c.1807C>T (p.Arg603Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	6
225478	NM_005630.3(SLCO2A1):c.940+1G>A	Pathogenic	criteria provided, multiple submitters, no conflicts	6
4531214	NM_005630.3(SLCO2A1):c.941-1G>A	Pathogenic	criteria provided, multiple submitters, no conflicts	2
931465	NM_005630.3(SLCO2A1):c.290G>A (p.Arg97His)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	3
438675	NM_005630.3(SLCO2A1):c.664G>A (p.Gly222Arg)	Pathogenic	criteria provided, single submitter	5
37171	NM_005630.3(SLCO2A1):c.310G>T (p.Gly104Ter)	Pathogenic	criteria provided, single submitter	3
1174124	NM_005630.3(SLCO2A1):c.1660G>A (p.Gly554Arg)	Pathogenic	criteria provided, single submitter	3
30187	NM_005630.3(SLCO2A1):c.764G>A (p.Gly255Glu)	Pathogenic	criteria provided, single submitter	2
30188	NM_005630.3(SLCO2A1):c.1634del (p.Asn545fs)	Pathogenic	criteria provided, single submitter	2
37167	NM_005630.3(SLCO2A1):c.830dup (p.Phe278fs)	Pathogenic	criteria provided, single submitter	2
1483488	NM_005630.3(SLCO2A1):c.1106G>A (p.Gly369Asp)	Pathogenic	criteria provided, single submitter	2
1978090	NM_005630.3(SLCO2A1):c.1768del (p.Arg590fs)	Pathogenic	criteria provided, single submitter	2
2920737	NM_005630.3(SLCO2A1):c.440G>A (p.Trp147Ter)	Pathogenic	criteria provided, single submitter	2
620392	NM_005630.3(SLCO2A1):c.270C>G (p.Tyr90Ter)	Pathogenic	criteria provided, single submitter	1
1363789	NM_005630.3(SLCO2A1):c.1264_1265del (p.Thr422fs)	Pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore SLCO2A1’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 38 predictions of 1,669):

Position(s)	Effect	Δscore	Sites
3:133934831–133934832	acceptor_loss	1.0000	6
3:133935772–133935773	donor_loss	1.0000	5
3:133938427–133938428	donor_loss	1.0000	4
3:133942773	acceptor_gain	1.0000
3:133945266	acceptor_gain	1.0000
3:133953661–133953662	donor_loss	1.0000	5
3:133953762–133953763	acceptor_loss	1.0000	2
3:133973661–133973662	donor_loss	1.0000	5
3:133973826–133973827	acceptor_loss	1.0000	6
3:134029705–134029706	donor_loss	1.0000	3

AlphaMissense

1,511 missense substitutions predicted likely pathogenic (of 4,178 scored), across 397 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
D235	8	0.969	0.987
D577	8	0.962	0.987
D197	8	0.951	0.980
D196	8	0.949	0.973
F34	8	0.942	0.995
D250	8	0.906	0.976
F212	8	0.904	0.975
F278	8	0.904	0.972
F190	8	0.898	0.966
S89	8	0.866	0.997
F315	8	0.859	0.968
F551	8	0.835	0.947
H119	8	0.764	0.959
F348	7	0.991	0.999
C580	7	0.990	0.995
F63	7	0.987	0.997
W253	7	0.987	0.997
C420	7	0.986	0.994
C474	7	0.986	0.995
C459	7	0.985	0.995

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

5 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	7.38e-11
Liver Hepatocellular Carcinoma (validation)	favorable	0.000103
Liver Hepatocellular Carcinoma (TCGA)	favorable	0.000158
Kidney Renal Clear Cell Carcinoma (validation)	favorable	0.000194
Stomach Adenocarcinoma (TCGA)	unfavorable	0.000418

Disease associations

OMIM: gene MIM:601460 | disease phenotypes: MIM:167100, MIM:614441, MIM:259100

GenCC curated gene-disease

5 curated gene-disease records:

Disease	Classification	Inheritance	Records
hypertrophic osteoarthropathy, primary, autosomal dominant	Definitive	Autosomal dominant	2
hypertrophic osteoarthropathy, primary, autosomal recessive, 2	Definitive	Autosomal recessive	5
inflammatory bowel disease	Strong	Autosomal recessive
pachydermoperiostosis	Supportive	Autosomal recessive
chronic enteropathy associated with SLCO2A1 gene	Supportive	Autosomal recessive

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (4 panels, 4 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

4 panels:

Panel	Rating
Autosomal recessive primary hypertrophic osteoarthropathy	green
Paediatric disorders	green
Primary immunodeficiency or monogenic inflammatory bowel disease	green
Skeletal dysplasia	green

Mondo (6): hypertrophic osteoarthropathy, primary, autosomal dominant (MONDO:0008172), hypertrophic osteoarthropathy, primary, autosomal recessive, 2 (MONDO:0013756), primary hypertrophic osteoarthropathy (MONDO:0016620), (MONDO:0009799), chronic enteropathy associated with SLCO2A1 gene (MONDO:0018766), inflammatory bowel disease (MONDO:0005265)

Orphanet (2): Pachydermoperiostosis (Orphanet:2796), Primary hypertrophic osteoarthropathy (Orphanet:248095)

HPO phenotypes

60 phenotypes (HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000280	Coarse facial features
HP:0000508	Ptosis
HP:0000527	Long eyelashes
HP:0000771	Gynecomastia
HP:0000845	Elevated circulating growth hormone concentration
HP:0000939	Osteoporosis
HP:0000964	Eczematoid dermatitis
HP:0000969	Edema
HP:0000975	Hyperhidrosis
HP:0000982	Palmoplantar keratoderma
HP:0001051	Seborrheic dermatitis
HP:0001061	Acne
HP:0001072	Thickened skin
HP:0001217	Clubbing
HP:0001231	Abnormal fingernail morphology
HP:0001369	Arthritis
HP:0001376	Limitation of joint mobility
HP:0001386	Joint swelling
HP:0001744	Splenomegaly
HP:0001903	Anemia
HP:0002014	Diarrhea
HP:0002018	Nausea
HP:0002024	Malabsorption
HP:0002239	Gastrointestinal hemorrhage
HP:0002240	Hepatomegaly
HP:0002650	Scoliosis
HP:0002653	Bone pain
HP:0002705	High, narrow palate
HP:0002754	Osteomyelitis
HP:0002797	Osteolysis
HP:0002829	Arthralgia
HP:0002970	Genu varum
HP:0003073	Hypoalbuminemia
HP:0003103	Abnormal cortical bone morphology
HP:0003621	Juvenile onset
HP:0004398	Peptic ulcer
HP:0005208	Secretory diarrhea
HP:0005561	Abnormal bone marrow cell morphology
HP:0005930	Abnormal epiphysis morphology
HP:0006465	Periosteal thickening of long tubular bones
HP:0008069	Neoplasm of the skin
HP:0010541	Cutis gyrata of scalp
HP:0010720	Abnormal hair pattern
HP:0010829	Impaired temperature sensation
HP:0010885	Avascular necrosis
HP:0011362	Abnormal hair quantity
HP:0011462	Young adult onset
HP:0011974	Myelofibrosis
HP:0030314	Periostosis
HP:0030353	Decreased circulating insulin-like growth factor 1 concentration
HP:0030839	Knee pain
HP:0034049	Elevated urinary prostaglandin E2 level
HP:0100021	Cerebral palsy
HP:0100526	Neoplasm of the lung
HP:0100759	Clubbing of fingers
HP:0100760	Clubbing of toes
HP:0100774	Hyperostosis
HP:0200055	Small hand

GWAS associations

3 associations:

Study	Trait	p-value
GCST008839_479	Height	5e-16
GCST007552_19	Colorectal cancer	2e-12
GCST002337_119	Amyotrophic lateral sclerosis (sporadic)	6e-6

MeSH disease descriptors

2 disease descriptors:

Descriptor	Name	Tree numbers
D015212	Inflammatory Bowel Diseases	C06.405.205.731; C06.405.469.432
D010004	Osteoarthropathy, Primary Hypertrophic	C05.116.725; C05.550.648; C16.320.718

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2073703 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 3,213 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

1 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL815	DINOPROST	4	3,213

PharmGKB: 1 entry (CPIC guideline: no)

PharmGKB clinical annotations

1 annotations by evidence level (1 strongest → 4):

Variant	Association	Level	Drugs	Phenotypes
rs34550074	Toxicity	3	Thiazides;plain	Hypertension;Hyponatremia

PharmGKB variants

1 variants:

Variant	Genes	Level	Score	#Clin annots	Drugs
rs34550074	SLCO2A1	3	2.50	1	Thiazides;plain

PharmGKB variant annotations

Per-publication pharmacogenomic findings for this gene (significant associations).

1 published findings:

Variant	Drug(s)	Category	Finding	PMID
rs34550074	Thiazides, plain	Toxicity	Allele T is associated with increased likelihood of Hyponatremia when treated with Thiazides, plain in people with Hypertension as compared to allele C.	PMID:28783044

GtoPdb / IUPHAR curated pharmacology

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

Target class: transporter — SLCO family of organic anion transporting polypeptides

Most potent curated ligand interactions (2 total), top 2:

Ligand	Action	Affinity	Parameter
bromocresol green	Inhibition	5.44	pKi
bromsulphthalein	Inhibition	5.24	pKi

Binding affinities (BindingDB)

17 measured of 42 human assays (45 total across all organisms); most potent 17 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
NSC_5311503	KI	0.3 nM
NSC_3080928	KI	0.4 nM
CAS_41598-07-6	KI	1.7 nM
Prostaglandin D2	KI	38 nM
PGI2	KI	132 nM
AGN 191995	KI	228 nM
CAS_54751	KI	697 nM
(Z)-7-[(1R,3R,5S)-3,5-Dihydroxy-2-((E)-(S)-3-hydroxy-oct-1-enyl)-cyclopentyl]-hept-5-enoic acid	KI	861 nM
ILOPROST	KI	1040 nM
CAS_94079-80-8	KI	1340 nM
CAS_33458-93-4	KI	1420 nM
PGF2 Alpha, 1-isopropyl ester	KI	3200 nM
U46619	KI	3970 nM
AGN 191366	KI	8130 nM
CHEMBL1232918	KI	1.5e+07 nM
CHEMBL1089962	KI	5.1e+07 nM
CHEMBL2074701	KI	5.7e+07 nM

ChEMBL bioactivities

3 potent at pChembl≥5 of 3 total, top 3 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.64	Ki	23	nM	DINOPROST
7.42	Ki	38	nM	PROSTAGLANDIN D2
6.83	Ki	149	nM	LATANOPROST ACID

PubChem BioAssay actives

3 with measured affinity, of 18 total; 3 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
Dinoprost	679658: TP_TRANSPORTER: inhibition of PGE2 uptake in PGT-expressing HeLa cells	ki	0.0230	uM
(Z)-7-[(1R,2R,5S)-5-hydroxy-2-[(E,3S)-3-hydroxyoct-1-enyl]-3-oxocyclopentyl]hept-5-enoic acid	679658: TP_TRANSPORTER: inhibition of PGE2 uptake in PGT-expressing HeLa cells	ki	0.0380	uM
(Z)-7-[(1R,2R,3R,5S)-3,5-dihydroxy-2-[(3R)-3-hydroxy-5-phenylpentyl]cyclopentyl]hept-5-enoic acid	679659: TP_TRANSPORTER: inhibition of PGE1 uptake (PGE1: 0.0004 uM) in PGT-expressing HeLa cells	ki	0.1490	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases methylation, affects cotreatment, increases abundance, increases expression, decreases expression	5
Estradiol	increases expression, affects cotreatment, decreases expression, affects binding	4
bisphenol A	increases expression	3
Benzo(a)pyrene	affects methylation, increases expression	3
Aflatoxin B1	decreases methylation, increases expression, increases methylation	3
Arsenic	decreases expression, affects cotreatment, increases abundance	2
Diethylhexyl Phthalate	affects cotreatment, affects reaction, increases expression	2
Progesterone	affects cotreatment, decreases expression, affects expression, increases reaction	2
Tobacco Smoke Pollution	decreases expression	2
Genistein	increases expression	2
aristolochic acid I	decreases expression	1
bisphenol F	increases expression	1
Esketamine	decreases expression	1
bufotalin	decreases expression	1
diethyl phthalate	affects reaction, increases expression, affects cotreatment	1
lead acetate	decreases expression	1
diisononyl phthalate	affects cotreatment, affects reaction, increases expression	1
ethyl-p-hydroxybenzoate	increases expression	1
o,p’-DDT	increases expression	1
sulforaphane	decreases expression	1
perfluorooctanoic acid	increases expression	1
tobacco tar	decreases expression	1
manganese chloride	increases abundance, affects cotreatment, decreases expression	1
diisobutyl phthalate	affects reaction, increases expression, affects cotreatment	1
butylbenzyl phthalate	affects cotreatment, affects reaction, increases expression	1
cupric chloride	decreases expression	1
perfluorooctane sulfonic acid	increases expression	1
perfluoro-n-nonanoic acid	increases expression	1
lumiracoxib	decreases reaction, increases transport	1
bisphenol S	increases expression	1

ChEMBL screening assays

4 unique, capped per target: 4 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2075322	Functional	TP_TRANSPORTER: inhibition of PGE2 uptake in PGT-expressing HeLa cells	Cloning of mouse prostaglandin transporter PGT cDNA: species-specific substrate affinities. — *Am J Physiol*

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D4UQ	HuH7-SLCO2A1-KO-c2	Cancer cell line	Male
CVCL_D4UR	HuH7-SLCO2A1-KO-c3	Cancer cell line	Male

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

showing 60 of 301 trials:

NCT	Phase	Status	Title
NCT00167882	Phase 4	COMPLETED	The Influence of 5-Aminosalicylates on Thiopurine Metabolite Levels
NCT00205062	Phase 4	TERMINATED	Positron Emission Tomography (PET)-Computed Tomography (CT) in Inflammatory Bowel Disease (IBD)
NCT00567593	Phase 4	COMPLETED	Gene Regulation by Thiazolidinediones
NCT00746395	Phase 4	COMPLETED	Randomized, Placebo-controlled Trial of Lubiprostone as a Preparation for Capsule Endoscopy
NCT01034358	Phase 4	COMPLETED	Immune Response to the Human Papillomavirus Vaccine in Young Women With Inflammatory Bowel Disease
NCT01056913	Phase 4	COMPLETED	NITI CAR27 (ColonRing) Compression Anastomosis in Colorectal Surgery
NCT01067547	Phase 4	COMPLETED	A Trial of Iron Replacement in Patients With Iron Deficiency.
NCT01341808	Phase 4	COMPLETED	Immunogenicity of Hepatitis A Vaccine in Inflammatory Bowel Disease (IBD) Patients
NCT01908283	Phase 4	COMPLETED	Induction of Immunity Against Streptococcus Pneumoniae in Adults With Inflammatory Bowel Disease
NCT01934088	Phase 4	COMPLETED	Satisfaction With Nurse Administered Propofol Sedation vs. Midazolam With Fentanyl Sedation for Endoscopy
NCT02162862	Phase 4	COMPLETED	Treating Disrupted Sleep in Individuals With Inflammatory Bowel Disease
NCT02248337	Phase 4	COMPLETED	Low Volume Colon Preparation for IBD
NCT02281799	Phase 4	WITHDRAWN	Thiopurine Induced Pancreatitis in IBD Patients
NCT02392286	Phase 4	TERMINATED	Corticosteroid Dosage for Crohn’s Disease Flare
NCT02437591	Phase 4	COMPLETED	Study to Evaluate the Pharmacokinetics of Fidaxomicin in Inflammatory Bowel Disease (IBD) Subjects With Clostridium Difficile Infection (CDI)
NCT02453776	Phase 4	COMPLETED	Precision Dosing of Infliximab Versus Conventional Dosing of Infliximab
NCT02461758	Phase 4	COMPLETED	Trial of High Dose vs. Standard Dose Influenza Vaccine in Inflammatory Bowel Disease Patients
NCT02566889	Phase 4	TERMINATED	An Efficacy and Safety Study of Infliximab Dose Escalation in Pediatric Participants With Inflammatory Bowel Disease
NCT02774057	Phase 4	UNKNOWN	Trial of Captafer® vs. Oral Iron Sulfate in the Treatment of Iron Deficiency Anemia in Patients With IBD
NCT02806206	Phase 4	UNKNOWN	Prucalopride Prior to Small Bowel Capsule Endoscopy
NCT02946203	Phase 4	COMPLETED	Comparison of VoLumen and Breeza Oral Contrast Agents in Pediatric Patients
NCT02994836	Phase 4	COMPLETED	GIS-SUSANTI-TNF-2015 (Anti-TNF Discontinuation )
NCT03220841	Phase 4	UNKNOWN	Stricture Definition and Treatment (STRIDENT) Drug Therapy Study
NCT03351972	Phase 4	COMPLETED	Differences in Preparation for Small Bowel Capsule Endoscopy
NCT03466983	Phase 4	COMPLETED	A Trial Comparing the Incidence of Hypophosphatemia in Relation to Treatment With Iron Isomaltoside and Ferric Carboxymaltose in Subjects With Iron Deficiency Anaemia Due to Inflammatory Bowel Disease
NCT03591770	Phase 4	TERMINATED	Shingrix Vaccine in Patients With Moderate to Severe Ulcerative Colitis on Tofacitinib
NCT03629379	Phase 4	COMPLETED	Response to Ustekinumab for Anti-tnf Induced Psoriasiform Skin Lesions
NCT03723447	Phase 4	COMPLETED	Intraoperative TAP Block With Bupivacaine/Dexamethasone Against Liposomal Bupivacaine (Exparel®)
NCT03798691	Phase 4	COMPLETED	Immunogenicity of Herpes Zoster Subunit Vaccine in Inflammatory Bowel Disease Patients Treated With Vedolizumab
NCT03860012	Phase 4	UNKNOWN	Folic Acid in Pediatric Inflammatory Bowel Disease
NCT03885713	Phase 4	COMPLETED	Identification of Predictive Biomarkers for Response to Biologic Therapies and Tofacitinib in Inflammatory Bowel Disease
NCT03917303	Phase 4	RECRUITING	Control Crohn Safe Trial
NCT04045782	Phase 4	COMPLETED	Evaluation of the Safety and Effectiveness of Switching From Humira® to Imraldi® in Flanders
NCT04304950	Phase 4	COMPLETED	Chronotherapy in Inflammatory Bowel Disease
NCT04626947	Phase 4	TERMINATED	Prevention of Recurrent Clostridium Difficile Infection (CDI) in Patients With Inflammatory Bowel Disease (IBD).
NCT04646187	Phase 4	ENROLLING_BY_INVITATION	De-escalation of Anti-TNF Therapy in Inflammatory Bowel Disease
NCT04835506	Phase 4	ACTIVE_NOT_RECRUITING	Proactive Infliximab Optimization Using a Pharmacokinetic Dashboard Versus Standard of Care in Patients With Inflammatory Bowel Disease: The OPTIMIZE Trial
NCT04982172	Phase 4	COMPLETED	Model-informed Dose De-escalation of Infliximab in Patients With Inflammatory Bowel Diseases
NCT05180175	Phase 4	COMPLETED	The Nordic IBD Treatment Strategy Trial
NCT05280405	Phase 4	UNKNOWN	Early Proactive Therapeutic Drug Monitoring of Infliximab in Children: EPIC Study
NCT05340764	Phase 4	COMPLETED	Safety of Reduced Infliximab Infusion Time
NCT05439772	Phase 4	COMPLETED	Examining the Effect of Ondansetron on Bowel Prep Success
NCT05456932	Phase 4	UNKNOWN	Predicting Response to Iron Supplementation in Patients With Active Inflammatory Bowel Disease
NCT06055543	Phase 4	UNKNOWN	Impact of a New Plant-based High-energy Oral Nutritional Supplement on Nutritional Outcomes in Malnourished Patients
NCT06113913	Phase 4	RECRUITING	Subcutaneous Infliximab After A Previous Intravenous Dose Optimization
NCT06224270	Phase 4	WITHDRAWN	Study of Response to Zoster Vaccine in Adults with Inflammatory Bowel Disease Treated with Medications
NCT06346288	Phase 4	COMPLETED	A Study to Assess the Concentrations of Risankizumab in the Breast Milk of Adult Lactating Women With Inflammatory Bowel Disease
NCT06584162	Phase 4	RECRUITING	Subcutaneous Interval Lengthening of Vedolizumab for Economic Research
NCT06788340	Phase 4	NOT_YET_RECRUITING	MOdel-Informed Precision Dosing of Ustekinumab and VEdolizumab in Inflammatory Bowel Disease
NCT06794944	Phase 4	NOT_YET_RECRUITING	Use of Fidaxomicin Compared to Vancomycin for Decolonization of C. Difficile in Patients With Inflammatory Bowel Disease
NCT07161297	Phase 4	NOT_YET_RECRUITING	Remimazolam for Colonoscopy in IBD Patients
NCT07612267	Phase 4	RECRUITING	A Study to Measure Mirikizumab Levels in Breast Milk of Lactating Participants Receiving Mirikizumab Therapeutically for an Approved Indication
NCT07673497	Phase 4	COMPLETED	Can Vitamin D Replacement Correct Chronic Disease Anemia?
NCT07737665	Phase 4	RECRUITING	Efficacy of Melatonin Treatment on Sleep Quality Improvement in Inflammatory Bowel Disease Patients With Clinical Remission
NCT00175292	Phase 3	COMPLETED	A Randomized Controlled Trial of VSL#3 for the Prevention of Endoscopic Recurrence Following Surgery for Crohn’s Disease.
NCT00237653	Phase 3	TERMINATED	MICI-CMV:Valganciclovir in Recurrent Bouts of Cryptogenic Inflammatory Bowel Diseases With an Infection by Cytomegalovirus
NCT00321412	Phase 3	COMPLETED	Safety and Efficacy of AST-120 in Mild to Moderate Crohn’s Patients With Fistulas
NCT00408174	Phase 3	COMPLETED	Balsalazide Disodium vs. Mesalamine in Mildly to Moderately Active Ulcerative Colitis
NCT00486031	Phase 3	COMPLETED	Open-Label, Long-term Balsalziade Disodium Tablet Ulcerative Colitis Study
NCT00620126	Phase 3	COMPLETED	The Home Telemanagement (UC HAT) Trial for Patients With Ulcerative Colitis

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for SLCO2A1 across ~30M SureChEMBL compounds — explore on Sugi Predict.