SLC29A4

Summary

SLC29A4 (solute carrier family 29 member 4, HGNC:23097) is a protein-coding gene on chromosome 7p22.1, encoding Equilibrative nucleoside transporter 4 (Q7RTT9). Electrogenic voltage-dependent transporter that mediates the transport of a variety of endogenous bioactive amines, cationic xenobiotics and drugs.

This gene encodes a member of the SLC29A/ENT transporter protein family. The encoded membrane protein catalyzes the reuptake of monoamines into presynaptic neurons, thus determining the intensity and duration of monoamine neural signaling. It has been shown to transport several compounds, including serotonin, dopamine, and the neurotoxin 1-methyl-4-phenylpyridinium. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 222962 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 174 total
• Druggable target: yes
• MANE Select transcript: NM_153247

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23097
Approved symbol	SLC29A4
Name	solute carrier family 29 member 4
Location	7p22.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ34923, ENT4
Ensembl gene	ENSG00000164638
Ensembl biotype	protein_coding
OMIM	609149
Entrez	222962

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 18 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000297195, ENST00000396872, ENST00000406453, ENST00000434816, ENST00000439491, ENST00000444741, ENST00000897308, ENST00000897309, ENST00000917413, ENST00000917414, ENST00000917415, ENST00000917416, ENST00000917417, ENST00000917418, ENST00000917419, ENST00000954421, ENST00000954422, ENST00000954423, ENST00000954424

RefSeq mRNA: 3 — MANE Select: NM_153247 NM_001040661, NM_001300847, NM_153247

CCDS: CCDS5340, CCDS75561

Canonical transcript exons

ENST00000396872 — 11 exons

Exon	Start	End
ENSE00001086235	5296936	5297198
ENSE00001086237	5291124	5291237
ENSE00001154543	5287809	5287985
ENSE00001181232	5294860	5294934
ENSE00001230227	5282943	5283082
ENSE00001721964	5298988	5299126
ENSE00001731214	5299240	5299427
ENSE00001745256	5290732	5290863
ENSE00001790484	5291693	5291821
ENSE00001951997	5302797	5306912
ENSE00003527486	5300422	5300662

Expression profiles

Bgee: expression breadth ubiquitous, 187 present calls, max score 97.38.

FANTOM5 (CAGE): breadth broad, TPM avg 1.0747 / max 33.4567, expressed in 539 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
77092	1.0747	539

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	97.38	gold quality
islet of Langerhans	UBERON:0000006	92.02	gold quality
cortical plate	UBERON:0005343	90.43	gold quality
hypothalamus	UBERON:0001898	89.68	gold quality
medial globus pallidus	UBERON:0002477	89.64	gold quality
ganglionic eminence	UBERON:0004023	89.34	gold quality
globus pallidus	UBERON:0001875	88.19	gold quality
anterior cingulate cortex	UBERON:0009835	86.74	gold quality
right frontal lobe	UBERON:0002810	86.14	gold quality
lateral globus pallidus	UBERON:0002476	85.03	gold quality
substantia nigra	UBERON:0002038	85.01	gold quality
midbrain	UBERON:0001891	84.36	gold quality
lateral nuclear group of thalamus	UBERON:0002736	84.32	gold quality
left ventricle myocardium	UBERON:0006566	84.00	gold quality
cardiac muscle of right atrium	UBERON:0003379	83.87	gold quality
pancreas	UBERON:0001264	83.74	gold quality
amygdala	UBERON:0001876	83.72	gold quality
adipose tissue	UBERON:0001013	83.25	gold quality
prefrontal cortex	UBERON:0000451	83.24	gold quality
neocortex	UBERON:0001950	83.01	gold quality
substantia nigra pars compacta	UBERON:0001965	82.49	gold quality
subcutaneous adipose tissue	UBERON:0002190	82.42	gold quality
frontal cortex	UBERON:0001870	82.20	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	82.06	gold quality
nucleus accumbens	UBERON:0001882	81.78	gold quality
cerebral cortex	UBERON:0000956	81.65	gold quality
adipose tissue of abdominal region	UBERON:0007808	81.63	gold quality
substantia nigra pars reticulata	UBERON:0001966	81.46	silver quality
omental fat pad	UBERON:0010414	81.45	gold quality
peritoneum	UBERON:0002358	81.44	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-GEOD-81547	yes	19.33
E-CURD-114	yes	12.44
E-ANND-3	yes	4.69

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): EWSR1, FOXC1, WT1

miRNA regulators (miRDB)

43 targeting SLC29A4, 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-4455	100.00	65.48	1587
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-6740-5P	100.00	65.64	932
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-3151-5P	99.86	63.83	1069
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-5004-5P	99.68	66.63	1294
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-1224-5P	99.48	65.59	803
HSA-MIR-3191-3P	99.45	63.94	356
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-5787	99.22	67.86	2628
HSA-MIR-491-5P	99.13	65.98	1468
HSA-MIR-887-5P	98.82	65.90	1347
HSA-MIR-4725-5P	98.67	65.42	628

Literature-anchored findings (GeneRIF, showing 16)

• may be a novel low affinity transporter for biogenic amines, might supplement the high affinity transporters in the brain (PMID:15448143)
• PMAT can function as a polyspecific organic cation transporter, which may play a role in organic cation transport in vivo. (PMID:16099839)
• ENT4, in addition to playing roles in cardiac serotonin transport, contributes to the regulation of extracellular adenosine concentrations, in particular under the acidotic conditions associated with ischemia. (PMID:16873718)
• our data suggest that PMAT is expressed on the apical membranes of renal epithelial cells and may use luminal proton gradient to drive organic cation reabsorption in the kidney. (PMID:17018840)
• Amino acid substitution at several sites results in loss of activity ane conformation. (PMID:17121826)
• PMAT, EMT, and OCT2 transporters are expressed in the endometrial stroma and can potentially regulate reuptake of monoamines in general and histamine in particular. (PMID:17393420)
• identification of ENT4 as a highly expressed transcript in desmoplastic small round cell tumor (DSRCT) may represent an attractive pathway for targeting chemotherapeutic drugs into DSRCT (PMID:18523561)
• The data suggest that PMAT is specifically expressed in podocytes and may play an important role in puromycin aminonucleoside-induced kidney injury. (PMID:19357181)
• The selectivity and kinetics of monoamine neurotransmitter transport by PMAT and OCT3 was determined. PMAT is expressed at much higher levels than hOCT3 in brain, whereas hOCT3 is selectively and highly expressed in adrenal gland and skeletal muscle. (PMID:20858707)
• Data show that ENT1, ENT2, ENT4 and CNT3 protein was detected on ovarian carcinoma cells in all effusions, with expression observed in 1-95% of tumor cells. (PMID:21822668)
• Transport kinetic analysis revealed that I89M mutant in PMAT protein had a 2.7-fold reduction in maximal transport velocity with no significant change in apparent binding affinity. (PMID:22562044)
• Cultured astroctye line 1321N1 and primary human astrocytes transport monoamines predominantly through PMAT. (PMID:24471494)
• In an adjusted logistic regression model, the G allele at rs3889348 (SLC29A4) was associated with metformin gastrointestinal intolerance. (PMID:30885951)
• Bidirectional transport of 2-chloroadenosine by equilibrative nucleoside transporter 4 (hENT4): Evidence for allosteric kinetics at acidic pH. (PMID:31537831)
• Clinically significant findings of high-risk mutations in human SLC29A4 gene associated with diabetes mellitus type 2 in Pakistani population. (PMID:34551672)
• PMAT variant rs3889348 is associated with metformin-induced gastrointestinal among Chinese Type 2 diabetes patients. (PMID:37458617)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	slc29a4a	ENSDARG00000059690
danio_rerio	slc29a4b	ENSDARG00000079873
mus_musculus	Slc29a4	ENSMUSG00000050822
rattus_norvegicus	Slc29a4	ENSRNOG00000001115
drosophila_melanogaster	Ent3	FBGN0036319

Paralogs (3): SLC29A1 (ENSG00000112759), SLC29A2 (ENSG00000174669), SLC29A3 (ENSG00000198246)

Protein

Protein identifiers

Equilibrative nucleoside transporter 4 — Q7RTT9 (reviewed: Q7RTT9)

Alternative names: Plasma membrane monoamine transporter, Solute carrier family 29 member 4

All UniProt accessions (3): C9IYM7, C9JZA2, Q7RTT9

UniProt curated annotations — full annotation on UniProt →

Function. Electrogenic voltage-dependent transporter that mediates the transport of a variety of endogenous bioactive amines, cationic xenobiotics and drugs. Utilizes the physiologic inside-negative membrane potential as a driving force to facilitate cellular uptake of organic cations. Functions as a Na(+)- and Cl(-)-independent bidirectional transporter. Substrate transport is pH-dependent and enhanced under acidic condition, which is most likely the result of allosteric changes in the transporter structure. Implicated in monoamine neurotransmitters uptake such as serotonin, dopamine, adrenaline/epinephrine, noradrenaline/norepinephrine, histamine and tyramine, thereby supporting a role in homeostatic regulation of aminergic neurotransmission in the central nervous system. Also responsible for the uptake of bioactive amines and drugs through the blood-cerebrospinal fluid (CSF) barrier, from the CSF into choroid plexus epithelial cells, thereby playing a significant role in the clearance of cationic neurotoxins, xenobiotics and metabolic waste in the brain. Involved in bidirectional transport of the purine nucleoside adenosine and plays a role in the regulation of extracellular adenosine concentrations in cardiac tissues, in particular during ischemia. May be involved in organic cation uptake from the tubular lumen into renal tubular cells, thereby contributing to organic cation reabsorption in the kidney. Also transports guanidine.

Subcellular location. Cell membrane. Apical cell membrane.

Tissue specificity. Mainly expressed in brain and skeletal muscle. In brain, expressed in cerebellum, cerebral cortex, medulla oblongata, occipital pole, frontal and temporal lobes putamen, spinal cord, substancia nigra, hippocampus, caudate nucleus, nucleus accumbens, pons and choroid plexus. Expressed in heart, in both cardiomyocytes and vascular endothelial cells. Also expressed in adrenal gland, small intestine, pancreas, kidney, liver, bone marrow, lymph node. Located in endometrial stroma, where the expression is high in the proliferative phase, decreases during the secretory phase, and is no longer detectable in the menstrual phase.

Post-translational modifications. N-glycosylated.

Activity regulation. Activated at acidic pH.

Domain organisation. Glu-206 is essential for cation selectivity and may function as the charge sensor for cationic substrates.

Miscellaneous. Does not interact with nucleosides, nucleobases or nucleotides, other than a moderate activity for adenosine. Mediates the uptake of neurotoxin 1-methyl-4-phenylpyridinium (MPP(+)).

Similarity. Belongs to the SLC29A/ENT transporter (TC 2.A.57) family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q7RTT9-1	1	yes
Q7RTT9-2	2

RefSeq proteins (3): NP_001035751, NP_001287776, NP_694979* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002259	Eqnu_transpt	Family
IPR036259	MFS_trans_sf	Homologous_superfamily

Pfam: PF01733

Catalyzed reactions (Rhea), 8 shown:

• dopamine(out) = dopamine(in) (RHEA:73863)
• serotonin(out) = serotonin(in) (RHEA:73867)
• (R)-noradrenaline(out) = (R)-noradrenaline(in) (RHEA:73871)
• (R)-adrenaline(out) = (R)-adrenaline(in) (RHEA:73875)
• histamine(out) = histamine(in) (RHEA:73879)
• guanidine(out) = guanidine(in) (RHEA:73883)
• tyramine(in) = tyramine(out) (RHEA:74783)
• adenosine(in) = adenosine(out) (RHEA:75343)

UniProt features (51 total): mutagenesis site 17, topological domain 11, transmembrane region 10, sequence conflict 5, sequence variant 3, chain 1, region of interest 1, site 1, glycosylation site 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7RTT9-F1	74.78	0.42

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): 206 (essential for cation selectivity)

Glycosylation sites (1): 523

Mutagenesis-validated functional residues (17):

Position	Phenotype
91	no significant change in dopamine, serotonin and mpp(+) uptake.
107	loss of dopamine, serotonin and mpp(+) uptake.
128	no significant change in dopamine, serotonin and mpp(+) uptake.
154	loss of dopamine, serotonin and mpp(+) uptake; increased uridine uptake.
163	loss of dopamine, serotonin and mpp(+) uptake.
206	loss of dopamine, serotonin and mpp(+) uptake; gain of uridine transport activity.
206	no change in dopamine, serotonin and mpp(+) uptake; no uridine uptake activity.
206	loss of dopamine, serotonin, adenosine and mpp(+) uptake; gain of uridine transport activity.
206	loss of dopamine, serotonin and mpp(+) uptake; no uridine uptake activity.
220	reduced dopamine, serotonin and mpp(+) uptake.
220	loss of dopamine, serotonin and mpp(+) uptake.
227	functional with slight increased dopamine, serotonin and mpp(+) uptake.
242	reduced dopamine, serotonin and mpp(+) uptake.
336	loss of dopamine, serotonin and mpp(+) uptake.
375	functional with increased dopamine, serotonin and mpp(+) uptake.
375	no change in adenosine uptake.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-83936	Transport of nucleosides and free purine and pyrimidine bases across the plasma membrane
R-HSA-382551	Transport of small molecules
R-HSA-425397	Transport of vitamins, nucleosides, and related molecules
R-HSA-425407	SLC-mediated transmembrane transport

MSigDB gene sets: 114 (showing top): GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_NEUROTRANSMITTER_UPTAKE, GCANCTGNY_MYOD_Q6, GOBP_NEUROTRANSMITTER_TRANSPORT, CAGCTG_AP4_Q5, chr7p22, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_ORGANIC_HYDROXY_COMPOUND_TRANSPORT, GOBP_CELLULAR_RESPONSE_TO_TOXIC_SUBSTANCE, GOMF_NUCLEOBASE_CONTAINING_COMPOUND_TRANSMEMBRANE_TRANSPORTER_ACTIVITY, GOBP_NUCLEOBASE_CONTAINING_COMPOUND_TRANSPORT, GOBP_DETOXIFICATION, LIAO_METASTASIS, GOCC_APICAL_PLASMA_MEMBRANE, GOBP_ORGANIC_CATION_TRANSPORT

GO Biological Process (23): histamine metabolic process (GO:0001692), neurotransmitter transport (GO:0006836), obsolete serotonin transport (GO:0006837), obsolete organic cation transport (GO:0015695), obsolete monoamine transport (GO:0015844), obsolete dopamine transport (GO:0015872), obsolete norepinephrine transport (GO:0015874), adenosine transport (GO:0032238), xenobiotic transport (GO:0042908), obsolete epinephrine transport (GO:0048241), histamine transport (GO:0051608), serotonin uptake (GO:0051610), histamine uptake (GO:0051615), norepinephrine uptake (GO:0051620), epinephrine uptake (GO:0051625), dopamine uptake (GO:0090494), monoatomic cation transmembrane transport (GO:0098655), export across plasma membrane (GO:0140115), transport across blood-brain barrier (GO:0150104), obsolete organic acid transmembrane transport (GO:1903825), cellular detoxification (GO:1990748), nucleoside transport (GO:0015858), nucleoside transmembrane transport (GO:1901642)

GO Molecular Function (10): neurotransmitter transmembrane transporter activity (GO:0005326), nucleoside transmembrane transporter activity (GO:0005337), obsolete organic acid transmembrane transporter activity (GO:0005342), monoatomic cation transmembrane transporter activity (GO:0008324), monoamine transmembrane transporter activity (GO:0008504), obsolete organic cation transmembrane transporter activity (GO:0015101), efflux transmembrane transporter activity (GO:0015562), toxin transmembrane transporter activity (GO:0019534), xenobiotic transmembrane transporter activity (GO:0042910), transmembrane transporter activity (GO:0022857)

GO Cellular Component (5): plasma membrane (GO:0005886), basolateral plasma membrane (GO:0016323), apical plasma membrane (GO:0016324), presynapse (GO:0098793), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Transport of vitamins, nucleosides, and related molecules	1
SLC-mediated transmembrane transport	1
Transport of small molecules	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transmembrane transporter activity	4
transport	3
nitrogen compound transport	2
catecholamine uptake	2
transmembrane transport	2
plasma membrane region	2
cellular anatomical structure	2
biogenic amine metabolic process	1
imidazole-containing compound metabolic process	1
nucleoside transport	1
organic hydroxy compound transport	1
neurotransmitter reuptake	1
neurotransmitter uptake	1
histamine transport	1
monoatomic cation transport	1
monoatomic ion transmembrane transport	1
export from cell	1
vascular transport	1
neurotransmitter transport	1
nucleobase-containing compound transmembrane transporter activity	1
carbohydrate derivative transmembrane transporter activity	1
nucleoside transmembrane transport	1
monoatomic ion transmembrane transporter activity	1
monoatomic cation transmembrane transport	1
active transmembrane transporter activity	1
xenobiotic transport	1
transporter activity	1
membrane	1
cell periphery	1
basal plasma membrane	1
apical part of cell	1
synapse	1

Protein interactions and networks

STRING

700 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC29A4	SLC18A2	Q05940	932
SLC29A4	SLC22A3	O75751	731
SLC29A4	SLC47A1	Q96FL8	729
SLC29A4	SLC47A2	Q86VL8	723
SLC29A4	SLC22A1	O15245	716
SLC29A4	SLC28A1	O00337	701
SLC29A4	SLC28A2	O43868	700
SLC29A4	SLC28A3	Q9HAS3	696
SLC29A4	SLC6A4	P31645	665
SLC29A4	SLC22A2	O15244	632
SLC29A4	SLC29A1	Q99808	605
SLC29A4	SLC22A4	Q9H015	596
SLC29A4	SLC6A2	P23975	514
SLC29A4	SLC6A3	Q01959	512
SLC29A4	SLC19A3	Q9BZV2	512

IntAct

3 interactions, top by confidence:

A	B	Type	Score
NS3	C15orf61	psi-mi:“MI:0914”(association)	0.350
TNFRSF10C	PLPP3	psi-mi:“MI:0914”(association)	0.350

BioGRID (12): SLC29A4 (Affinity Capture-RNA), SLC29A4 (Affinity Capture-MS), SLC29A4 (Affinity Capture-RNA), SLC29A4 (Co-fractionation), SLC29A4 (Co-fractionation), SLC29A4 (Co-fractionation), SLC29A4 (Co-fractionation), SLC29A4 (Co-fractionation), SLC29A4 (Co-fractionation), TMED10 (Co-fractionation), TMED9 (Co-fractionation), SLC29A4 (Affinity Capture-MS)

ESM2 similar proteins: A0A3Q2HW92, A6NDV4, A6NFX1, A6QLK4, B1AWJ5, F1NCD6, F1NJ67, F1PZV2, O35308, O35595, O70461, O95907, Q08DX7, Q0IHM1, Q0P5C0, Q0P5M9, Q13286, Q14728, Q29611, Q2YDU8, Q3T9M1, Q3U481, Q501I9, Q5R8G5, Q5R9A1, Q5U419, Q60HH0, Q61124, Q66H95, Q6NUT3, Q6UXD7, Q6ZMD2, Q7RTT9, Q8BFQ6, Q8CE47, Q8NA29, Q8R0G7, Q8R139, Q8TB61, Q8VCW4

Diamond homologs: A1L272, Q7RTT9, Q8R139

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
WT1	“up-regulates quantity by expression”	SLC29A4	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	137
Likely benign	16
Benign	11

Top pathogenic / likely-pathogenic (0)

SpliceAI

1993 predictions. Top by Δscore:

Variant	Effect	Δscore
7:5287802:A:AG	acceptor_gain	1.0000
7:5287803:A:G	acceptor_gain	1.0000
7:5287804:AGCAG:A	acceptor_gain	1.0000
7:5287805:GCA:G	acceptor_gain	1.0000
7:5287805:GCAGA:G	acceptor_gain	1.0000
7:5287808:G:GA	acceptor_gain	1.0000
7:5287981:TACTA:T	donor_gain	1.0000
7:5287985:AG:A	donor_loss	1.0000
7:5287986:G:GG	donor_gain	1.0000
7:5287987:T:G	donor_loss	1.0000
7:5287990:G:GG	donor_gain	1.0000
7:5290723:T:TA	acceptor_gain	1.0000
7:5290724:G:A	acceptor_gain	1.0000
7:5290728:TTA:T	acceptor_loss	1.0000
7:5290729:TA:T	acceptor_loss	1.0000
7:5290730:A:AC	acceptor_loss	1.0000
7:5290730:A:AG	acceptor_gain	1.0000
7:5290731:G:GT	acceptor_gain	1.0000
7:5290731:GC:G	acceptor_gain	1.0000
7:5290731:GCA:G	acceptor_gain	1.0000
7:5290731:GCAT:G	acceptor_gain	1.0000
7:5290731:GCATT:G	acceptor_gain	1.0000
7:5290733:ATTG:A	acceptor_gain	1.0000
7:5290864:G:GG	donor_gain	1.0000
7:5291112:G:A	acceptor_gain	1.0000
7:5291118:CTGCA:C	acceptor_loss	1.0000
7:5291119:T:TA	acceptor_gain	1.0000
7:5291119:TGCA:T	acceptor_loss	1.0000
7:5291121:CAGG:C	acceptor_loss	1.0000
7:5291122:A:AG	acceptor_gain	1.0000

AlphaMissense

3428 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:5294871:A:C	S186R	1.000
7:5294873:C:A	S186R	1.000
7:5294873:C:G	S186R	1.000
7:5300594:G:A	G461D	1.000
7:5300605:A:C	S465R	1.000
7:5300607:C:A	S465R	1.000
7:5300607:C:G	S465R	1.000
7:5290794:G:C	G78R	0.999
7:5290795:G:A	G78D	0.999
7:5290807:T:C	L82P	0.999
7:5290821:A:C	S87R	0.999
7:5290823:C:A	S87R	0.999
7:5290823:C:G	S87R	0.999
7:5291147:A:C	S109R	0.999
7:5291149:C:A	S109R	0.999
7:5291149:C:G	S109R	0.999
7:5291226:G:T	R135M	0.999
7:5294881:G:A	G189E	0.999
7:5294923:T:C	M203T	0.999
7:5294924:G:A	M203I	0.999
7:5294924:G:C	M203I	0.999
7:5294924:G:T	M203I	0.999
7:5294928:G:A	G205R	0.999
7:5294928:G:C	G205R	0.999
7:5294928:G:T	G205W	0.999
7:5294929:G:A	G205E	0.999
7:5294929:G:T	G205V	0.999
7:5296944:G:C	G210R	0.999
7:5299401:T:C	F395L	0.999
7:5299403:C:A	F395L	0.999

dbSNP variants (sampled 300 via entrez): RS1000014827 (7:5283534 A>C,G,T), RS1000054071 (7:5301990 C>A,T), RS1000186959 (7:5293641 G>C), RS1000463913 (7:5289895 T>G), RS1000522859 (7:5292780 C>G), RS1000554383 (7:5283415 C>T), RS1000589248 (7:5296757 G>A), RS1000660553 (7:5297440 A>G,T), RS1000717242 (7:5292990 C>T), RS1000730748 (7:5290095 C>T), RS1000871694 (7:5302285 A>G), RS1001196440 (7:5294482 A>G,T), RS1001247197 (7:5294335 A>G), RS1001267266 (7:5297937 A>C), RS1001387991 (7:5302100 C>G)

Disease associations

OMIM: gene MIM:609149 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): megacolon (MONDO:0001273)

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST010007_6	Weight gain in amisulpride-treated first-episode psychosis	4.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0005937	longitudinal BMI measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D008531	Megacolon	C06.405.469.158.701

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3509593 (SINGLE PROTEIN), CHEMBL6066081 (PROTEIN FAMILY)

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs3889348	SLC29A4		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: transporter — SLC29 family

Most potent curated ligand interactions (9 total), top 9:

Ligand	Action	Affinity	Parameter
decynium 22	Inhibition	7.0	pKi
rhodamine123	Inhibition	5.99	pKi
dipyridamole	Inhibition	5.9	pKi
verapamil	Inhibition	4.73	pKi
fluoxetine	Inhibition	4.64	pKi
quinidine	Inhibition	4.6	pKi
quinine	Inhibition	4.57	pKi
desipramine	Inhibition	4.49	pKi
cimetidine	Inhibition	3.3	pKi

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Cyclosporine	decreases expression, decreases methylation	3
Valproic Acid	affects expression, increases methylation	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
bisphenol A	affects expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
butyraldehyde	decreases expression	1
nickel sulfate	increases expression	1
pseudoisocyanine	decreases reaction, increases uptake	1
K 7174	decreases expression	1
ICG 001	increases expression	1
abrine	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
MT19c compound	decreases 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
Rosiglitazone	increases expression	1
Zoledronic Acid	decreases expression	1
Allergens	increases expression	1
Atrazine	increases expression	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Cisplatin	affects cotreatment, increases expression	1
Diazinon	increases methylation	1
Diethylhexyl Phthalate	decreases expression	1
Dopamine	increases uptake	1
Doxorubicin	decreases reaction, increases abundance	1
Epinephrine	increases uptake	1
Estradiol	affects cotreatment, increases expression	1
Histamine	increases uptake	1
Metformin	decreases reaction, increases abundance	1

ChEMBL screening assays

15 unique, capped per target: 13 admet, 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3531441	ADMET	Induction of human PMAT activity expressed in Xenopus laevis oocytes assessed as induction of inward current at 2.5 mM in NaCl buffer at pH 6 by two-microelectrode voltage-clamp method	Electrophysiological characterization of the polyspecific organic cation transporter plasma membrane monoamine transporter. — Drug Metab Dispos
CHEMBL4885543	Binding	Inhibition of Transporter, Adenosine at compound concentration of 10.0 uM in the Eurofins-Panlabs radioligand binding assay (Eurofins_assay_202020)	Profiling data from Eurofins-Panlabs

Cellosaurus cell lines

5 cell lines: 5 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D4L0	HCT116-SLC29A4-KO-c22	Cancer cell line	Male
CVCL_D4L1	HCT116-SLC29A4-KO-c9	Cancer cell line	Male
CVCL_TM78	HAP1 SLC29A4 (-) 1	Cancer cell line	Male
CVCL_TM79	HAP1 SLC29A4 (-) 2	Cancer cell line	Male
CVCL_TM80	HAP1 SLC29A4 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04340856	Not specified	COMPLETED	Retrospective, Uncontrolled Cohort Study on the Therapy of Chronic Megalon
NCT07470892	Not specified	NOT_YET_RECRUITING	Preoperative Fish Oil PN and Prognosis After Constipation Surgery