SLC22A24

Summary

SLC22A24 (solute carrier family 22 member 24, HGNC:28542) is a protein-coding gene on chromosome 11q12.3, encoding Steroid transmembrane transporter SLC22A24 (Q8N4F4). Renal transmembrane organic anion/dicarboxylate exchanger that participates in the reabsorption of conjugated steroids including estradiol-17beta-D-glucuronide (or 17beta-estradiol 17-O-(beta-D-glucuronate)), androstanediol glucuronide (or 5alpha-androstane-3alpha,17beta-diol 3-….

SLC22A24 belongs to a large family of transmembrane proteins that function as uniporters, symporters, and antiporters to transport organic ions across cell membranes (Jacobsson et al., 2007 [PubMed 17714910]).

Source: NCBI Gene 283238 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 116 total
• MANE Select transcript: NM_001136506

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28542
Approved symbol	SLC22A24
Name	solute carrier family 22 member 24
Location	11q12.3
Locus type	gene with protein product
Status	Approved
Aliases	MGC34821, NET46
Ensembl gene	ENSG00000197658
Ensembl biotype	protein_coding
OMIM	611698
Entrez	283238

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000326192, ENST00000417740, ENST00000612278, ENST00000908490

RefSeq mRNA: 2 — MANE Select: NM_001136506 NM_001136506, NM_173586

CCDS: CCDS73308, CCDS76422

Canonical transcript exons

ENST00000612278 — 10 exons

Exon	Start	End
ENSE00001268514	63119181	63119335
ENSE00001268522	63134665	63134768
ENSE00001406356	63143378	63144221
ENSE00001641529	63081558	63081666
ENSE00001668235	63104175	63104298
ENSE00001675867	63095991	63096106
ENSE00001686642	63083243	63083457
ENSE00001709199	63080920	63081123
ENSE00001768566	63118912	63119080
ENSE00003723012	63079940	63080000

Expression profiles

Bgee: expression breadth broad, 11 present calls, max score 72.54.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	72.54	gold quality
adult mammalian kidney	UBERON:0000082	55.77	gold quality
upper leg skin	UBERON:0004262	52.38	silver quality
kidney	UBERON:0002113	51.98	gold quality
right lobe of liver	UBERON:0001114	50.43	gold quality
cortex of kidney	UBERON:0001225	47.20	gold quality
liver	UBERON:0002107	46.84	silver quality
metanephros cortex	UBERON:0010533	46.02	gold quality
metanephros	UBERON:0000081	44.26	gold quality
renal medulla	UBERON:0000362	43.40	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	43.37	gold quality
nipple	UBERON:0002030	43.35	gold quality
secondary oocyte	CL:0000655	42.57	gold quality
layer of synovial tissue	UBERON:0007616	42.11	gold quality
oviduct epithelium	UBERON:0004804	41.58	gold quality
middle temporal gyrus	UBERON:0002771	41.45	gold quality
vastus lateralis	UBERON:0001379	41.41	gold quality
quadriceps femoris	UBERON:0001377	41.37	gold quality
superficial temporal artery	UBERON:0001614	41.33	gold quality
primary visual cortex	UBERON:0002436	41.11	gold quality
palpebral conjunctiva	UBERON:0001812	41.10	gold quality
ventral tegmental area	UBERON:0002691	41.02	gold quality
mucosa of paranasal sinus	UBERON:0005030	40.98	gold quality
occipital lobe	UBERON:0002021	40.76	gold quality
amniotic fluid	UBERON:0000173	40.69	gold quality
jejunal mucosa	UBERON:0000399	40.59	gold quality
biceps brachii	UBERON:0001507	40.57	gold quality
epithelium of nasopharynx	UBERON:0001951	40.45	gold quality
myocardium	UBERON:0002349	40.45	gold quality
gingival epithelium	UBERON:0001949	40.43	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.60

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): HNF1A

miRNA regulators (miRDB)

16 targeting SLC22A24, 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-5692A	100.00	74.40	6850
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-577	99.78	69.13	2479
HSA-MIR-136-5P	99.50	67.26	1153
HSA-MIR-6074	98.89	69.64	2187
HSA-MIR-935	98.82	69.36	1072
HSA-MIR-6731-3P	98.61	67.86	749
HSA-MIR-3668	98.52	68.76	951
HSA-MIR-6884-3P	98.05	65.32	750
HSA-MIR-3977	98.00	68.17	1500
HSA-MIR-4286	97.20	64.37	1587
HSA-MIR-3935	96.33	66.79	797
HSA-MIR-3943	95.87	64.57	523
HSA-MIR-503-3P	92.89	66.09	537

Literature-anchored findings (GeneRIF, showing 1)

• Functional genomic studies reveal a previously uncharacterized protein involved in steroid homeostasis, opening up new possibilities for SLC22A24 as a pharmacological target for regulating steroid levels. (PMID:31553721)

Cross-species orthologs

52 orthologs

Organism	Symbol	Gene ID
danio_rerio	slc22a4	ENSDARG00000005335
danio_rerio	oatx	ENSDARG00000019713
danio_rerio	si:dkey-166k12.1	ENSDARG00000054690
danio_rerio	slc22a15	ENSDARG00000055445
danio_rerio	si:dkey-119m7.4	ENSDARG00000071049
danio_rerio	slc22a21	ENSDARG00000094112
danio_rerio	si:dkey-119m7.8	ENSDARG00000096654
danio_rerio	slc22a5	ENSDARG00000101021
drosophila_melanogaster	Orct	FBGN0019952
drosophila_melanogaster	CG15221	FBGN0030331
drosophila_melanogaster	Balat	FBGN0033778
drosophila_melanogaster	CG4630	FBGN0033809
drosophila_melanogaster	CG5592	FBGN0035645
drosophila_melanogaster	CG10486	FBGN0035647
drosophila_melanogaster	SLC22A	FBGN0037140
drosophila_melanogaster	CG7458	FBGN0037144
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), SLC22A5 (ENSG00000197375), SLC22A12 (ENSG00000197891), SLC22A6 (ENSG00000197901), SLC22A31 (ENSG00000259803)

Protein

Protein identifiers

Steroid transmembrane transporter SLC22A24 — Q8N4F4 (reviewed: Q8N4F4)

Alternative names: Solute carrier family 22 member 24

All UniProt accessions (1): Q8N4F4

UniProt curated annotations — full annotation on UniProt →

Function. Renal transmembrane organic anion/dicarboxylate exchanger that participates in the reabsorption of conjugated steroids including estradiol-17beta-D-glucuronide (or 17beta-estradiol 17-O-(beta-D-glucuronate)), androstanediol glucuronide (or 5alpha-androstane-3alpha,17beta-diol 3-O-(beta-D-glucuronate)), and estrone 3-sulfate, as well as bile acids taurocholate and glycocholate, driven by an outward gradient of dicarboxylates such as glutarate or succinate. Similar uptake function as Isoform 1. Lack of transporter activity.

Subcellular location. Cell membrane Cell membrane.

Tissue specificity. Localized to the kidney. Highly specific expression pattern in the nephron, localized to segment 3 of the proximal tubule. Localized to the kidney. Highly specific expression pattern in the nephron, localized to segment 3 of the proximal tubule.

Activity regulation. Transport is chloride sensitive and transtimulated by glutaric acid. Transport is inhibited by anionic compounds from different chemical classes.

Polymorphism. Presence of two potential AG acceptor sites at the splice junction between exons 9 and 10, thus resulting in two different splice variants.

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?
Q8N4F4-2	1	yes
Q8N4F4-1	3
Q8N4F4-3	2

RefSeq proteins (2): NP_001129978, NP_775857 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005828	MFS_sugar_transport-like	Family
IPR020846	MFS_dom	Domain
IPR036259	MFS_trans_sf	Homologous_superfamily

Pfam: PF00083

Catalyzed reactions (Rhea), 7 shown:

• estrone 3-sulfate(out) + glutarate(in) = estrone 3-sulfate(in) + glutarate(out) (RHEA:72151)
• 17beta-estradiol 17-O-(beta-D-glucuronate)(out) + glutarate(in) = 17beta-estradiol 17-O-(beta-D-glucuronate)(in) + glutarate(out) (RHEA:72155)
• taurocholate(out) + glutarate(in) = taurocholate(in) + glutarate(out) (RHEA:72159)
• 5alpha-androstane-3alpha,17beta-diol 3-O-(beta-D-glucuronate)(out) + glutarate(in) = 5alpha-androstane-3alpha,17beta-diol 3-O-(beta-D-glucuronate)(in) + glutarate(out) (RHEA:72175)
• glycocholate(out) + glutarate(in) = glycocholate(in) + glutarate(out) (RHEA:72351)
• dehydroepiandrosterone 3-sulfate(out) + glutarate(in) = dehydroepiandrosterone 3-sulfate(in) + glutarate(out) (RHEA:72355)
• glutarate(in) + succinate(out) = glutarate(out) + succinate(in) (RHEA:72359)

UniProt features (19 total): transmembrane region 12, splice variant 3, sequence conflict 2, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N4F4-F1	87.62	0.60

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 51 (showing top): MORF_RAGE, MORF_FLT1, MORF_ESR1, GOBP_ORGANIC_HYDROXY_COMPOUND_TRANSPORT, MORF_FANCG, GOBP_ORGANIC_ANION_TRANSPORT, GOBP_LIPID_METABOLIC_PROCESS, MORF_PML, GOBP_STEROL_TRANSPORT, MORF_IKBKG, GOBP_LIPID_LOCALIZATION, MORF_MT4, GOBP_TRANSMEMBRANE_TRANSPORT, GOBP_STEROID_METABOLIC_PROCESS, MORF_MYC

GO Biological Process (7): monoatomic ion transport (GO:0006811), steroid metabolic process (GO:0008202), obsolete organic anion transport (GO:0015711), sterol transmembrane transport (GO:0035382), lipid metabolic process (GO:0006629), lipid transport (GO:0006869), transmembrane transport (GO:0055085)

GO Molecular Function (1): transmembrane transporter activity (GO:0022857)

GO Cellular Component (2): plasma membrane (GO:0005886), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transport	3
transmembrane transport	2
lipid metabolic process	1
sterol transport	1
primary metabolic process	1
lipid localization	1
cellular process	1
transporter activity	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

496 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC22A24	FAM187B	Q17R55	649
SLC22A24	OR5AR1	Q8NGP9	641
SLC22A24	OR7G3	Q8NG95	626
SLC22A24	MAGEB16	A2A368	573
SLC22A24	OR2L8	Q8NGY9	540
SLC22A24	CBY2	Q8NA61	528
SLC22A24	ABCA10	Q8WWZ4	501
SLC22A24	ZNF80	P51504	489
SLC22A24	SLC67A1	Q96BI1	487
SLC22A24	SLC35G4	P0C7Q5	480
SLC22A24	EFCAB13	Q8IY85	478
SLC22A24	CCHCR1	Q8TD31	468
SLC22A24	OR10X1	Q8NGY0	434
SLC22A24	SLC22A14	Q9Y267	423
SLC22A24	SLC35G3	Q8N808	420

IntAct

4 interactions, top by confidence:

A	B	Type	Score
SLC22A24		psi-mi:“MI:0915”(physical association)	0.370
EWSR1	SLC22A24	psi-mi:“MI:0915”(physical association)	0.370
SLC22A24	ADCY3	psi-mi:“MI:0914”(association)	0.350

BioGRID (13): SLC22A24 (Two-hybrid), ADCY3 (Affinity Capture-MS), CYP4X1 (Affinity Capture-MS), FASTKD3 (Affinity Capture-MS), FBXO21 (Affinity Capture-MS), GDE1 (Affinity Capture-MS), CPSF3L (Affinity Capture-MS), INTS6 (Affinity Capture-MS), MICU2 (Affinity Capture-MS), C1orf27 (Affinity Capture-MS), SLC25A16 (Affinity Capture-MS), WLS (Affinity Capture-MS), ZC3H14 (Affinity Capture-MS)

ESM2 similar proteins: A0A3Q2IDB4, A0A8B7HA97, A4ZYQ5, A6NK97, G1SZD9, O35956, O57379, O88909, P22732, P23945, P43427, Q0IHM1, Q2KIV1, Q3ZAV1, Q4U2R8, Q4W8A2, Q4W8A3, Q5R9C4, Q5RC45, Q5RCH6, Q5RET7, Q63ZE4, Q66J52, Q6DFR1, Q6NUB3, Q6NYN7, Q6PXP3, Q6T423, Q70BM6, Q76M72, Q76M99, Q80UJ1, Q863Y9, Q864Z3, Q8CFZ5, Q8HY24, Q8IVM8, Q8MK48, Q8N4F4, Q8R0S9

Diamond homologs: A0A3Q2IDB4, A0A8B7HA97, A6NK97, A6QLW8, B2GV36, G1SZD9, O34691, O35956, O57379, O75751, O88446, O88909, Q1RPP5, Q28ES4, Q2KIV1, Q3YAW7, Q3ZAV1, Q4U2R8, Q4W8A2, Q4W8A3, Q5R540, Q5R9C4, Q5RC45, Q5RCH6, Q5RLM2, Q63ZE4, Q66J52, Q66J54, Q6A4L0, Q6NYN7, Q6T423, Q70BM6, Q76M72, Q76M99, Q80UJ1, Q864Z3, Q8CFZ5, Q8HY24, Q8IVM8, Q8MK48

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	108
Likely benign	7
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1721 predictions. Top by Δscore:

Variant	Effect	Δscore
11:63096111:A:T	acceptor_gain	1.0000
11:63096114:A:T	acceptor_gain	1.0000
11:63096116:C:CT	acceptor_gain	1.0000
11:63096117:A:T	acceptor_gain	1.0000
11:63143376:A:AC	donor_gain	1.0000
11:63081130:G:GC	acceptor_gain	0.9900
11:63096110:C:CT	acceptor_gain	0.9900
11:63096113:C:CT	acceptor_gain	0.9900
11:63104143:A:C	donor_gain	0.9900
11:63104165:T:A	donor_gain	0.9900
11:63119179:A:AC	donor_gain	0.9900
11:63119180:C:CC	donor_gain	0.9900
11:63143362:A:AC	donor_gain	0.9900
11:63143363:C:CC	donor_gain	0.9900
11:63081125:T:C	acceptor_gain	0.9800
11:63084312:T:TA	donor_gain	0.9800
11:63095984:AACTT:A	donor_loss	0.9800
11:63095985:ACTT:A	donor_loss	0.9800
11:63095986:CTT:C	donor_loss	0.9800
11:63095987:TTAC:T	donor_loss	0.9800
11:63095988:TACC:T	donor_loss	0.9800
11:63095989:A:AA	donor_loss	0.9800
11:63095989:A:AC	donor_gain	0.9800
11:63095990:C:CC	donor_gain	0.9800
11:63096103:CAAG:C	acceptor_gain	0.9800
11:63143376:AT:A	donor_gain	0.9800
11:63143376:ATCT:A	donor_gain	0.9800
11:63081025:CAGGG:C	acceptor_gain	0.9700
11:63095983:GAACT:G	donor_loss	0.9700
11:63096105:AG:A	acceptor_gain	0.9700

AlphaMissense

3601 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:63119016:A:C	S242R	0.969
11:63119016:A:T	S242R	0.969
11:63119018:T:G	S242R	0.969
11:63143634:C:G	C49S	0.968
11:63143635:A:T	C49S	0.968
11:63143507:A:C	F91L	0.967
11:63143507:A:T	F91L	0.967
11:63143509:A:G	F91L	0.967
11:63143732:G:C	F16L	0.966
11:63143732:G:T	F16L	0.966
11:63143734:A:G	F16L	0.966
11:63119072:A:G	W224R	0.963
11:63119072:A:T	W224R	0.963
11:63104233:A:G	L299P	0.962
11:63143771:A:C	F3L	0.961
11:63143771:A:T	F3L	0.961
11:63143773:A:G	F3L	0.961
11:63083304:G:C	S408R	0.957
11:63083304:G:T	S408R	0.957
11:63083306:T:G	S408R	0.957
11:63081123:C:A	R465S	0.955
11:63081123:C:G	R465S	0.955
11:63081576:A:G	L459P	0.955
11:63143433:C:G	C116S	0.955
11:63143434:A:T	C116S	0.955
11:63119327:C:G	R172P	0.952
11:63081620:A:C	S444R	0.950
11:63081620:A:T	S444R	0.950
11:63081622:T:G	S444R	0.950
11:63081570:G:T	P461H	0.947

dbSNP variants (sampled 300 via entrez): RS1000036229 (11:63122294 C>A), RS1000069082 (11:63131385 C>T), RS1000113970 (11:63099015 A>T), RS1000153748 (11:63136294 C>T), RS1000160257 (11:63108775 G>T), RS1000198731 (11:63099764 G>C), RS1000268782 (11:63136489 G>A,T), RS1000276218 (11:63099325 C>T), RS1000283002 (11:63083166 C>A), RS1000304958 (11:63095073 T>C), RS1000331355 (11:63088234 C>T), RS1000408610 (11:63122470 G>A), RS1000448237 (11:63118569 T>C), RS1000575442 (11:63142139 T>C), RS1000584601 (11:63103215 A>G,T)

Disease associations

OMIM: gene MIM:611698 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST002438_11	Conotruncal heart defects	1.000000e-06
GCST010512_7	Serum uric acid levels	1.000000e-08
GCST012020_434	Serum metabolite levels	5.000000e-39

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0005939	parental genotype effect measurement
EFO:0004761	uric acid measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

1 total (human), top 1 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases methylation	1

Clinical trials (associated diseases)

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