SLC10A4

Summary

SLC10A4 (solute carrier family 10 member 4, HGNC:22980) is a protein-coding gene on chromosome 4p11, encoding Putative sodium/bile acid cotransporter 4 (Q96EP9). No significant bile acid transporter activity could be measured despite its similarity to bile acid:sodium symporters.

Predicted to enable bile acid:sodium symporter activity. Predicted to be involved in bile acid and bile salt transport and regulation of neurotransmitter loading into synaptic vesicle. Predicted to act upstream of or within adult behavior and response to xenobiotic stimulus. Predicted to be located in plasma membrane. Predicted to be active in several cellular components, including dopaminergic synapse; serotonergic synapse; and synaptic vesicle membrane.

Source: NCBI Gene 201780 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 64 total
• MANE Select transcript: NM_152679

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:22980
Approved symbol	SLC10A4
Name	solute carrier family 10 member 4
Location	4p11
Locus type	gene with protein product
Status	Approved
Aliases	MGC29802
Ensembl gene	ENSG00000145248
Ensembl biotype	protein_coding
OMIM	618563
Entrez	201780

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 1 protein_coding, 1 retained_intron

ENST00000273861, ENST00000652393

RefSeq mRNA: 1 — MANE Select: NM_152679 NM_152679

CCDS: CCDS3482

Canonical transcript exons

ENST00000273861 — 3 exons

Exon	Start	End
ENSE00000969590	48484932	48485142
ENSE00001136251	48488427	48489526
ENSE00001136258	48483343	48484151

Expression profiles

Bgee: expression breadth ubiquitous, 156 present calls, max score 95.91.

FANTOM5 (CAGE): breadth broad, TPM avg 1.0729 / max 331.8912, expressed in 284 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
47577	0.7986	231
47581	0.0639	28
47578	0.0466	13
47579	0.0405	10
47574	0.0322	11
47582	0.0292	13
47576	0.0240	13
47575	0.0190	6
47580	0.0190	9

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
substantia nigra pars reticulata	UBERON:0001966	95.91	gold quality
substantia nigra pars compacta	UBERON:0001965	92.65	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.57	gold quality
substantia nigra	UBERON:0002038	81.78	gold quality
midbrain	UBERON:0001891	78.66	gold quality
pituitary gland	UBERON:0000007	74.73	gold quality
superior vestibular nucleus	UBERON:0007227	74.69	gold quality
adenohypophysis	UBERON:0002196	73.63	gold quality
endothelial cell	CL:0000115	71.70	gold quality
prefrontal cortex	UBERON:0000451	71.50	gold quality
hypothalamus	UBERON:0001898	70.87	gold quality
putamen	UBERON:0001874	68.28	gold quality
ganglionic eminence	UBERON:0004023	68.16	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	68.10	gold quality
caudate nucleus	UBERON:0001873	67.61	gold quality
anterior cingulate cortex	UBERON:0009835	66.96	gold quality
Brodmann (1909) area 9	UBERON:0013540	66.93	gold quality
parotid gland	UBERON:0001831	66.03	silver quality
frontal cortex	UBERON:0001870	66.02	gold quality
neocortex	UBERON:0001950	65.81	gold quality
right frontal lobe	UBERON:0002810	65.14	gold quality
ascending aorta	UBERON:0001496	64.57	gold quality
forebrain	UBERON:0001890	64.11	gold quality
nucleus accumbens	UBERON:0001882	64.09	gold quality
thoracic aorta	UBERON:0001515	64.05	gold quality
brain	UBERON:0000955	63.02	gold quality
cerebral cortex	UBERON:0000956	62.96	gold quality
sperm	CL:0000019	62.73	silver quality
primary visual cortex	UBERON:0002436	62.70	gold quality
Brodmann (1909) area 46	UBERON:0006483	62.52	silver quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-HCAD-25	yes	8.39
E-ANND-3	no	2.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): EGR1, ESR1, SP1, STAT5B, TP53, WT1

miRNA regulators (miRDB)

52 targeting SLC10A4, 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-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-8067	99.86	69.59	2260
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-576-5P	99.84	70.46	2582
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-323A-3P	99.79	70.30	1739
HSA-MIR-26A-5P	99.78	73.52	2303
HSA-MIR-26B-5P	99.78	73.51	2305
HSA-MIR-132-3P	99.73	70.56	1424
HSA-MIR-212-3P	99.73	70.65	1424
HSA-MIR-4465	99.71	72.56	2096
HSA-MIR-497-3P	99.61	69.71	1990

Literature-anchored findings (GeneRIF, showing 4)

• Northern analysis revealed that SLC10A4 mRNA is ubiquitously expressed in human tissues with the highest levels of mRNA expression in brain, placenta, and liver. (PMID:17106928)
• The extracellular N-terminus of SLC10A4 was predicted to be relatively longer at the amino acid level than those of SLC10A1, SLC10A2 and SLC10A6. We examined the relationship between the N-terminus and transport activity of SLC10A4. (PMID:23589386)
• Depletion of SLC10A4 is observed in the brain with increased severity of Alzheimer’s disease-related neuronal degeneration. (PMID:23948907)
• SLC10A4 failed to show transport activity for a series of neurotransmitters and neuromodulators, indicating that SLC10A4 does not seem to represent a typical neurotransmitter transporter such as DAT, SERT, CHT1 or VMAT2 (PMID:26084360)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	slc10a4	ENSDARG00000009131
mus_musculus	Slc10a4-ps	ENSMUSG00000060204
rattus_norvegicus	Slc10a4	ENSRNOG00000026091

Paralogs (5): SLC10A1 (ENSG00000100652), SLC10A2 (ENSG00000125255), SLC10A3 (ENSG00000126903), SLC10A6 (ENSG00000145283), SLC10A5 (ENSG00000253598)

Protein

Protein identifiers

Putative sodium/bile acid cotransporter 4 — Q96EP9 (reviewed: Q96EP9)

Alternative names: Na(+)/bile acid cotransporter 4, Solute carrier family 10 member 4

All UniProt accessions (1): Q96EP9

UniProt curated annotations — full annotation on UniProt →

Function. No significant bile acid transporter activity could be measured despite its similarity to bile acid:sodium symporters.

Subcellular location. Cell membrane.

Tissue specificity. Highly expressed in brain and small intestine, and moderately expressed in colon, heart, prostate, and testis. Very low levels were detected in kidney, liver, ovary, placenta, spleen, and thymus.

Post-translational modifications. Activated following N-terminal proteolytic cleavage by thrombin and/or proteases.

Similarity. Belongs to the bile acid:sodium symporter (BASS) (TC 2.A.28) family.

RefSeq proteins (1): NP_689892* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002657	BilAc:Na_symport/Acr3	Family
IPR004710	Bilac:Na_transpt	Family
IPR038770	Na+/solute_symporter_sf	Homologous_superfamily

Pfam: PF01758

UniProt features (24 total): topological domain 8, transmembrane region 7, glycosylation site 5, chain 1, region of interest 1, compositionally biased region 1, site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96EP9-F1	71.42	0.43

Functional residue map

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

Catalytic / active sites (1): 87–88 (cleavage; by thrombin)

Glycosylation sites (5): 6, 18, 24, 181, 195

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 69 (showing top): BENPORATH_ES_WITH_H3K27ME3, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_ORGANIC_ACID_TRANSPORT, GOBP_ORGANIC_HYDROXY_COMPOUND_TRANSPORT, GOBP_ORGANIC_ANION_TRANSPORT, GOBP_BILE_ACID_AND_BILE_SALT_TRANSPORT, chr4p11, GOBP_MONOCARBOXYLIC_ACID_TRANSPORT, GOBP_LIPID_LOCALIZATION, GOBP_TRANSMEMBRANE_TRANSPORT, GOBP_SODIUM_ION_TRANSPORT, GOMF_LIPID_TRANSPORTER_ACTIVITY, GOMF_METAL_ION_TRANSMEMBRANE_TRANSPORTER_ACTIVITY, GOMF_MONOATOMIC_CATION_TRANSMEMBRANE_TRANSPORTER_ACTIVITY, GOMF_ACTIVE_TRANSMEMBRANE_TRANSPORTER_ACTIVITY

GO Biological Process (4): bile acid and bile salt transport (GO:0015721), monoatomic ion transport (GO:0006811), sodium ion transport (GO:0006814), transmembrane transport (GO:0055085)

GO Molecular Function (3): bile acid:sodium symporter activity (GO:0008508), protein binding (GO:0005515), symporter activity (GO:0015293)

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	2
lipid transport	1
monocarboxylic acid transport	1
organic hydroxy compound transport	1
metal ion transport	1
cellular process	1
organic acid:sodium symporter activity	1
bile acid transmembrane transporter activity	1
secondary active monocarboxylate transmembrane transporter activity	1
binding	1
secondary active transmembrane transporter activity	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

692 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC10A4	SLC10A7	Q0GE19	690
SLC10A4	SLAIN2	Q9P270	539
SLC10A4	SLC5A7	Q9GZV3	534
SLC10A4	SLC18A2	Q05940	519
SLC10A4	SLC18A3	Q16572	501
SLC10A4	SLC6A4	P31645	499
SLC10A4	TMEM169	Q96HH4	492
SLC10A4	SLC18B1	Q6NT16	486
SLC10A4	NDNF	Q8TB73	443
SLC10A4	NFXL1	Q6ZNB6	433
SLC10A4	NTS	P30990	386
SLC10A4	NIPAL1	Q6NVV3	384
SLC10A4	NYAP2	Q9P242	383
SLC10A4	DCUN1D4	Q92564	382
SLC10A4	FRYL	O94915	381

IntAct

18 interactions, top by confidence:

A	B	Type	Score
TMEM218	SLC10A4	psi-mi:“MI:0915”(physical association)	0.560
COL4A5	SLC10A4	psi-mi:“MI:0915”(physical association)	0.560
VMA12	SLC10A4	psi-mi:“MI:0915”(physical association)	0.560
SLC10A4	SLC35A4	psi-mi:“MI:0915”(physical association)	0.560
SLC10A4	DNAJC30	psi-mi:“MI:0915”(physical association)	0.560
	TSPO	psi-mi:“MI:0914”(association)	0.350
SLC10A4	ILVBL	psi-mi:“MI:0914”(association)	0.350
SLC35A4	SLC10A4	psi-mi:“MI:0915”(physical association)	0.000
DNAJC30	SLC10A4	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (33): TMEM218 (Two-hybrid), SLC35A4 (Two-hybrid), DNAJC30 (Two-hybrid), COL4A5 (Two-hybrid), TMEM199 (Two-hybrid), SLC10A4 (Co-fractionation), SLC10A4 (Co-fractionation), AP2M1 (Affinity Capture-MS), EMC3 (Affinity Capture-MS), EMC4 (Affinity Capture-MS), EMP3 (Affinity Capture-MS), ENPEP (Affinity Capture-MS), EPHA7 (Affinity Capture-MS), EXPH5 (Affinity Capture-MS), GBA2 (Affinity Capture-MS)

ESM2 similar proteins: A0AV02, A2AWR3, A2VCW5, A4QN56, A6QP84, B2RXV4, D4A7H1, F7B113, G8XYX6, O08705, O70324, P09131, P19634, P21129, P23791, P26431, P26434, P26435, P36021, P48761, P48762, P97751, Q0V8N6, Q14973, Q28036, Q3KNW5, Q3UEZ8, Q4JLT5, Q5PT54, Q5PT56, Q5R9A7, Q61165, Q70EX6, Q71RS6, Q7Z3F1, Q8BFW9, Q8BLV3, Q8BUE1, Q8BZ00, Q8C261

Diamond homologs: A6QP84, O08705, P09131, P26435, P70172, Q12908, Q14973, Q28727, Q3KNW5, Q3UEZ8, Q4JLT5, Q5PT55, Q5PT56, Q60414, Q62633, Q70EX6, Q7XVB3, Q96EP9, Q9CXB2, P21129, Q0V8N6, Q93YR2, B8BDK4, F4JPW1, Q5PT54, Q650U0, Q8VYY4, Q1EBV7, Q5VRB2, O34524, Q6K739, Q8RXE8, Q8ZKL0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	63
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

215 predictions. Top by Δscore:

Variant	Effect	Δscore
4:48484148:TCAGG:T	donor_loss	1.0000
4:48484150:AGGT:A	donor_loss	1.0000
4:48484152:G:GA	donor_loss	1.0000
4:48484926:CTGCA:C	acceptor_loss	1.0000
4:48484927:TGCA:T	acceptor_loss	1.0000
4:48484928:GCAGC:G	acceptor_loss	1.0000
4:48484929:CAGC:C	acceptor_loss	1.0000
4:48484930:A:AC	acceptor_loss	1.0000
4:48484930:A:AG	acceptor_gain	1.0000
4:48484931:G:GA	acceptor_gain	1.0000
4:48484931:GC:G	acceptor_gain	1.0000
4:48484931:GCA:G	acceptor_gain	1.0000
4:48484931:GCAT:G	acceptor_gain	1.0000
4:48484931:GCATC:G	acceptor_gain	1.0000
4:48485139:GAAG:G	donor_gain	1.0000
4:48485140:AAGGT:A	donor_loss	1.0000
4:48485142:GGTAA:G	donor_loss	1.0000
4:48485143:G:GG	donor_gain	1.0000
4:48485143:GTAAG:G	donor_loss	1.0000
4:48485144:T:A	donor_loss	1.0000
4:48484153:T:G	donor_loss	0.9900
4:48484927:T:A	acceptor_gain	0.9900
4:48485140:AAG:A	donor_gain	0.9900
4:48484152:G:GG	donor_gain	0.9800
4:48484915:C:G	acceptor_gain	0.9800
4:48484961:T:TA	acceptor_gain	0.9800
4:48485141:AG:A	donor_gain	0.9800
4:48485142:GG:G	donor_gain	0.9800
4:48484916:A:AG	acceptor_gain	0.9700
4:48485138:TGAAG:T	donor_gain	0.9700

AlphaMissense

2822 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:48485093:G:A	G251D	0.999
4:48488645:T:A	N340K	0.999
4:48488645:T:G	N340K	0.999
4:48485081:C:A	P247H	0.998
4:48485081:C:G	P247R	0.998
4:48485092:G:C	G251R	0.998
4:48483916:G:C	G119R	0.997
4:48483922:G:C	G121R	0.997
4:48483923:G:A	G121D	0.997
4:48483901:T:C	C114R	0.996
4:48483917:G:A	G119D	0.996
4:48483925:T:C	C122R	0.996
4:48484109:C:A	S183Y	0.996
4:48484109:C:T	S183F	0.996
4:48485105:G:C	R255P	0.996
4:48485126:C:A	A262D	0.996
4:48488657:T:G	C344W	0.996
4:48484092:T:G	C177W	0.995
4:48484136:G:A	G192D	0.995
4:48483927:C:G	C122W	0.994
4:48484000:T:C	F147L	0.994
4:48484002:C:A	F147L	0.994
4:48484002:C:G	F147L	0.994
4:48484090:T:C	C177R	0.994
4:48485078:T:A	I246K	0.994
4:48485093:G:T	G251V	0.994
4:48488548:C:G	P308R	0.994
4:48488644:A:T	N340I	0.994
4:48488655:T:C	C344R	0.994
4:48488713:T:G	F363C	0.994

dbSNP variants (sampled 300 via entrez): RS1001396672 (4:48484177 A>G), RS1001468558 (4:48484441 G>A,T), RS1003524575 (4:48489985 G>GT), RS1003741661 (4:48483045 A>G), RS1005146291 (4:48485497 A>C), RS1005637390 (4:48489583 A>G,T), RS1006043323 (4:48489943 C>T), RS1006155467 (4:48483824 C>A,G,T), RS1007148187 (4:48489035 G>C), RS1007542513 (4:48483383 G>A,T), RS1007549480 (4:48489420 A>C), RS1007612941 (4:48483499 G>A,C,T), RS1008145440 (4:48487564 G>A), RS1008545012 (4:48481596 T>G), RS1009769644 (4:48483489 C>A)

Disease associations

OMIM: gene MIM:618563 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST001729_12	Crohn’s disease	2.000000e-08
GCST008103_79	Bipolar disorder	1.000000e-06

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 — SLC10 family of sodium-bile acid co-transporters

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases methylation, affects cotreatment, increases expression	8
mercuric bromide	increases expression, affects cotreatment	2
entinostat	increases expression, affects cotreatment	2
Benzo(a)pyrene	increases methylation, increases mutagenesis	2
Tretinoin	increases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, increases expression	2
fluorene-9-bisphenol	decreases expression	1
methylmercuric chloride	increases expression	1
trichostatin A	increases expression	1
sodium arsenite	decreases expression	1
cobaltous chloride	decreases expression	1
nickel sulfate	decreases expression	1
beta-methylcholine	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	decreases expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
NSC 689534	affects binding, decreases expression	1
(+)-JQ1 compound	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Arsenic	affects methylation	1
Copper	affects binding, decreases expression	1
Folic Acid	increases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Rotenone	decreases expression	1
Triclosan	decreases expression	1
Aflatoxin B1	decreases methylation	1
Particulate Matter	increases expression	1

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D4CH	HCT116-SLC10A4-KO-c2	Cancer cell line	Male
CVCL_D4CI	HCT116-SLC10A4-KO-c8	Cancer cell line	Male
CVCL_TL42	HAP1 SLC10A4 (-) 1	Cancer cell line	Male
CVCL_XS84	HAP1 SLC10A4 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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