SLC18A1

Summary

SLC18A1 (solute carrier family 18 member A1, HGNC:10934) is a protein-coding gene on chromosome 8p21.3, encoding Chromaffin granule amine transporter (P54219). Electrogenic antiporter that exchanges one cationic monoamine with two intravesicular protons across the membrane of secretory and synaptic vesicles.

The vesicular monoamine transporter acts to accumulate cytosolic monoamines into vesicles, using the proton gradient maintained across the vesicular membrane. Its proper function is essential to the correct activity of the monoaminergic systems that have been implicated in several human neuropsychiatric disorders. The transporter is a site of action of important drugs, including reserpine and tetrabenazine (Peter et al., 1993 [PubMed 7905859]). See also SLC18A2 (MIM 193001).

Source: NCBI Gene 6570 — RefSeq curated summary.

At a glance

• GWAS associations: 31
• Clinical variants (ClinVar): 174 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_003053

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10934
Approved symbol	SLC18A1
Name	solute carrier family 18 member A1
Location	8p21.3
Locus type	gene with protein product
Status	Approved
Aliases	CGAT
Ensembl gene	ENSG00000036565
Ensembl biotype	protein_coding
OMIM	193002
Entrez	6570

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 9 protein_coding, 1 nonsense_mediated_decay, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000265808, ENST00000276373, ENST00000381608, ENST00000437980, ENST00000440926, ENST00000517776, ENST00000519026, ENST00000519171, ENST00000522513, ENST00000524272, ENST00000898947, ENST00000898948

RefSeq mRNA: 4 — MANE Select: NM_003053 NM_001135691, NM_001142324, NM_001142325, NM_003053

CCDS: CCDS47814, CCDS47815, CCDS6013

Canonical transcript exons

ENST00000276373 — 16 exons

Exon	Start	End
ENSE00000683447	20150666	20150744
ENSE00000683456	20178435	20178493
ENSE00000683458	20179121	20179484
ENSE00001234866	20165047	20165107
ENSE00001364284	20180841	20181087
ENSE00001799030	20164869	20164964
ENSE00001952947	20144855	20145876
ENSE00003545986	20148007	20148070
ENSE00003556793	20173036	20173128
ENSE00003581935	20147603	20147722
ENSE00003663588	20149676	20149727
ENSE00003664653	20174361	20174444
ENSE00003669795	20171405	20171494
ENSE00003680396	20147258	20147391
ENSE00003790085	20171103	20171146
ENSE00003847911	20183063	20183136

Expression profiles

Bgee: expression breadth broad, 79 present calls, max score 78.75.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.3083 / max 218.1221, expressed in 69 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
92150	0.1708	46
92149	0.1376	39

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
diaphragm	UBERON:0001103	78.75	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.68	gold quality
buccal mucosa cell	CL:0002336	78.50	silver quality
rectum	UBERON:0001052	72.12	gold quality
olfactory bulb	UBERON:0002264	66.75	gold quality
monocyte	CL:0000576	65.71	gold quality
leukocyte	CL:0000738	65.68	gold quality
mononuclear cell	CL:0000842	65.56	gold quality
granulocyte	CL:0000094	65.04	gold quality
cervix squamous epithelium	UBERON:0006922	63.06	gold quality
type B pancreatic cell	CL:0000169	62.62	gold quality
mucosa of sigmoid colon	UBERON:0004993	62.61	silver quality
mucosa of urinary bladder	UBERON:0001259	61.89	gold quality
adrenal tissue	UBERON:0018303	60.96	gold quality
right adrenal gland	UBERON:0001233	58.24	gold quality
mucosa of transverse colon	UBERON:0004991	57.66	gold quality
small intestine Peyer’s patch	UBERON:0003454	57.61	gold quality
vermiform appendix	UBERON:0001154	56.63	gold quality
colonic mucosa	UBERON:0000317	56.58	gold quality
small intestine	UBERON:0002108	56.48	gold quality
adrenal gland	UBERON:0002369	55.95	gold quality
vena cava	UBERON:0004087	55.85	gold quality
ileal mucosa	UBERON:0000331	54.89	silver quality
caecum	UBERON:0001153	54.24	gold quality
epithelium of nasopharynx	UBERON:0001951	54.22	gold quality
cervix epithelium	UBERON:0004801	52.88	gold quality
transverse colon	UBERON:0001157	52.43	gold quality
substantia nigra	UBERON:0002038	52.03	gold quality
duodenum	UBERON:0002114	51.94	gold quality
tibialis anterior	UBERON:0001385	51.92	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.91

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

52 targeting SLC18A1, 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-3646	100.00	73.56	5283
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-7152-3P	99.97	67.47	849
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-4766-5P	99.75	69.23	2662
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-4530	99.69	66.47	1509
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-646	99.68	67.84	1645
HSA-MIR-12124	99.68	69.17	2700
HSA-MIR-298	99.63	67.56	1916
HSA-MIR-4743-3P	99.62	68.12	2095
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-4649-3P	99.56	66.90	1783
HSA-MIR-3153	99.55	67.59	2337
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-4672	99.50	71.58	2893
HSA-MIR-766-3P	99.47	65.24	1811
HSA-MIR-766-5P	99.47	67.91	2225
HSA-MIR-3915	99.45	68.49	1905

Literature-anchored findings (GeneRIF, showing 24)

• Human bronchial arterial smooth muscle cells express OCT-1 and extraneuronal monoamine transporter(EMT). EMT is the predominant plasma membrane transporter for norepinephrine uptake. (PMID:12807698)
• Greater expression of VMAT 1 in von Hippel-Lindau syndrome than multiple endocrine neoplasia type 2. Expression of VMAT 2 did not differ significantly. (PMID:16189177)
• VMAT1Delta15 is not localized in large, dense core vesicles as the native form but in the endoplasmic reticulum. While VMAT1 can take up serotonin, VMAT1Delta15 cannot, indicating different functions for the two forms of VMAT1. (PMID:16326835)
• Expression analysis confirmed that VMAT1 is expressed in human brain at the mRNA and protein level. Results suggest that variations in the VMAT1 gene may confer susceptibility to Bipolar Disorder in patients of European descent. (PMID:16936705)
• Our findings support the hypothesis that anxiety-related personality traits are associated with variation in the VMAT1/SLC18A1 gene. (PMID:18249496)
• Polymorphism in VMAT1 gene on chromosome 8p is associated with schizophrenia. (PMID:18451639)
• we found a significant down-regulation of the gene coding for the vesicular monoamine transporter (VMAT1)in enteroendocrine cells infected with Chlamydia trachomatis (PMID:21883697)
• Deletion of amino acids 307-338 in hVMAT1 isoform-b abolishes transport activity, and a 136-Thr partially reduces activity of isoform-a. (PMID:23090274)
• The data of this study showed that VMAT1 polymorphisms influence monoamine signaling, the functional response of emotional brain circuits and risk for psychopathology. (PMID:23337945)
• SLC18A1 gene polymorphisms are associated with the risk of paranoid schizophrenia in Russians and Tatars. (PMID:25842846)
• VMAT1 and VMAT2 are expressed in the majority of neuroblastomas (PMID:26338179)
• VMAT1 rs1390938/Thr136Ile is associated with mood, personality, and alcohol use in the general population. Subjects homozygous for the “hyperfunction” allele (AA; Ile/Ile) appear to be more resilient to these disorders. (PMID:26861143)
• Genetic variants in VMAT1 contribute to the severity of alcohol withdrawal in patients of European descent. (PMID:26876819)
• results contribute to the evidence indicating an association between the VMAT1 gene and structural brain alterations in depression. (PMID:28408293)
• rs2270641 SNP was associated with ASD risk only in over-dominant model. AA genotype of the rs1390938 was protective against ASD under dominant and recessive models. (PMID:28476685)
• The germline deletions at SLC18A1 contributed to the development of CRC. (PMID:28968818)
• Vmat1 polymorphisms are not associated with suicidal behavior. (PMID:29536333)
• Polymorphisms within the SLC18A gene are associated with asthenozoospermia through sperm count and motility. (PMID:29602729)
• SLC18A1 as one potential pleiotropic gene overlapped between Mood disorders and Cardiometabolic diseases. Genetic variation in SLC18A1 made statistically significant contributions to Body Mass Index. (PMID:29998543)
• SLC18A1 might complement other biomarkers currently under study in relation to programmed cell death protein 1/programmed cell death protein ligand 1 inhibition (PMID:30194079)
• SLC18A1 variants correlated with Anger and Vigor scores, only among males. (PMID:30656852)
• SV2 was highly expressed in neuroblastoma (NB) and can thus be useful marker in NB diagnostics. VMAT1 and VMAT2 were also expressed in NB but similar to syn less reliable as tumor markers. (PMID:31317476)
• Finding suggests that monoamine uptake by VMAT1 initially declined in early human evolution (from 130Glu/136Asn to 130Gly/136Thr) but increased along with the emergence of the 130Gly/136Ile variant around the time of the out of Africa dispersal of modern humans. (PMID:31791232)
• Sclerosing Paragangliomas: Correlations of Histological Features with Patients’ Genotype and Vesicular Monoamine Transporter Expression. (PMID:35524772)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	SLC18A1	ENSDARG00000078157
mus_musculus	Slc18a1	ENSMUSG00000036330
rattus_norvegicus	Slc18a1	ENSRNOG00000011992
drosophila_melanogaster	Vmat	FBGN0260964
caenorhabditis_elegans		WBGENE00000295
caenorhabditis_elegans		WBGENE00012280
caenorhabditis_elegans		WBGENE00013996

Paralogs (3): SLC18B1 (ENSG00000146409), SLC18A2 (ENSG00000165646), SLC18A3 (ENSG00000187714)

Protein

Protein identifiers

Chromaffin granule amine transporter — P54219 (reviewed: P54219)

Alternative names: Solute carrier family 18 member 1, Vesicular amine transporter 1

All UniProt accessions (3): E5RK12, P54219, Q96GL6

UniProt curated annotations — full annotation on UniProt →

Function. Electrogenic antiporter that exchanges one cationic monoamine with two intravesicular protons across the membrane of secretory and synaptic vesicles. Uses the electrochemical proton gradient established by the V-type proton-pump ATPase to accumulate high concentrations of monoamines inside the vesicles prior to their release via exocytosis. Transports catecholamines and indolamines with higher affinity for serotonin. Regulates the transvesicular monoaminergic gradient that determines the quantal size. Mediates presynaptic monoaminergic vesicle transport in the amygdala and prefrontal brain regions related with emotion processing in response to environmental stimuli. Unable to uptake serotonin.

Subcellular location. Cytoplasmic vesicle. Secretory vesicle membrane. Secretory vesicle. Synaptic vesicle membrane Cytoplasmic vesicle. Secretory vesicle membrane Endoplasmic reticulum membrane.

Tissue specificity. Expressed primarily in neuroendocrine tissues. Highly expressed in chromaffin cells of the adrenal medulla (at protein level). Detected in peripheral sympathetic ganglia (at protein level). Found in some paracrine cells in stomach and duodenum (at protein level). Expressed in substantia nigra. Expressed in gastrointestinal tract. Expressed in gastrointestinal tract.

Activity regulation. Strongly inhibited by reserpine. Also inhibited to a lesser extent by ketanserin and fenfluramine. Not significantly inhibited by tetrabenazine.

Similarity. Belongs to the major facilitator superfamily. Vesicular transporter family.

Isoforms (3)

UniProt ID	Names	Canonical?
P54219-1	1	yes
P54219-2	2, VMAT1delta15
P54219-3	3

RefSeq proteins (4): NP_001129163, NP_001135796, NP_001135797, NP_003044* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001958	Tet-R_TetA/multi-R_MdtG-like	Family
IPR011701	MFS	Family
IPR020846	MFS_dom	Domain
IPR036259	MFS_trans_sf	Homologous_superfamily
IPR050930	MFS_Vesicular_Transporter	Family

Pfam: PF07690

Catalyzed reactions (Rhea), 3 shown:

• dopamine(in) + 2 H(+)(out) = dopamine(out) + 2 H(+)(in) (RHEA:73739)
• serotonin(in) + 2 H(+)(out) = serotonin(out) + 2 H(+)(in) (RHEA:73743)
• (R)-noradrenaline(in) + 2 H(+)(out) = (R)-noradrenaline(out) + 2 H(+)(in) (RHEA:73747)

UniProt features (68 total): helix 19, sequence variant 15, topological domain 13, transmembrane region 12, glycosylation site 3, splice variant 2, chain 1, region of interest 1, compositionally biased region 1, turn 1

Structure

Experimental structures (PDB)

8 structures.

PDB	Method	Resolution (Å)
8TGN	ELECTRON MICROSCOPY	3.3
8TGI	ELECTRON MICROSCOPY	3.4
8TGL	ELECTRON MICROSCOPY	3.4
8TGH	ELECTRON MICROSCOPY	3.5
8TGJ	ELECTRON MICROSCOPY	3.5
8TGM	ELECTRON MICROSCOPY	3.5
8TGG	ELECTRON MICROSCOPY	3.6
8TGK	ELECTRON MICROSCOPY	3.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P54219-F1	76.89	0.50

Functional residue map

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

Glycosylation sites (3): 58, 87, 104

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-442660	SLC-mediated transport of neurotransmitters

MSigDB gene sets: 472 (showing top): RNGTGGGC_UNKNOWN, AP1_01, REACTOME_INNATE_IMMUNE_SYSTEM, YAGI_AML_WITH_INV_16_TRANSLOCATION, TGCGCANK_UNKNOWN, MORF_MSH3, GOBP_NEUROTRANSMITTER_UPTAKE, KAAB_FAILED_HEART_ATRIUM_DN, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GOCC_SECRETORY_GRANULE, ENK_UV_RESPONSE_KERATINOCYTE_UP, AREB6_03, KAAB_HEART_ATRIUM_VS_VENTRICLE_UP, GOZGIT_ESR1_TARGETS_DN, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP

GO Biological Process (12): aminergic neurotransmitter loading into synaptic vesicle (GO:0015842), obsolete monoamine transport (GO:0015844), obsolete dopamine transport (GO:0015872), serotonin uptake (GO:0051610), norepinephrine uptake (GO:0051620), dopamine uptake (GO:0090494), neurotransmitter transport (GO:0006836), obsolete serotonin transport (GO:0006837), xenobiotic transport (GO:0042908), establishment of localization in cell (GO:0051649), transmembrane transport (GO:0055085), proton transmembrane transport (GO:1902600)

GO Molecular Function (6): serotonin:sodium:chloride symporter activity (GO:0005335), monoamine transmembrane transporter activity (GO:0008504), monoamine:proton antiporter activity (GO:0015311), xenobiotic transmembrane transporter activity (GO:0042910), protein binding (GO:0005515), transmembrane transporter activity (GO:0022857)

GO Cellular Component (11): endoplasmic reticulum membrane (GO:0005789), secretory granule membrane (GO:0030667), synaptic vesicle membrane (GO:0030672), terminal bouton (GO:0043195), clathrin-sculpted monoamine transport vesicle membrane (GO:0070083), presynapse (GO:0098793), endoplasmic reticulum (GO:0005783), membrane (GO:0016020), transport vesicle membrane (GO:0030658), cytoplasmic vesicle (GO:0031410), synapse (GO:0045202)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
SLC-mediated transmembrane transport	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transport	3
catecholamine uptake	2
monoamine transmembrane transporter activity	2
cytoplasmic vesicle membrane	2
bounding membrane of organelle	2
cellular anatomical structure	2
cytoplasm	2
amine transport	1
neurotransmitter loading into synaptic vesicle	1
organic hydroxy compound transport	1
nitrogen compound transport	1
neurotransmitter reuptake	1
establishment of localization	1
cellular localization	1
cellular process	1
monoatomic cation transmembrane transport	1
sodium:chloride symporter activity	1
serotonin uptake	1
active transmembrane transporter activity	1
proton transmembrane transporter activity	1
antiporter activity	1
transmembrane transporter activity	1
xenobiotic transport	1
binding	1
transporter activity	1
transmembrane transport	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
secretory granule	1
synaptic vesicle	1
exocytic vesicle membrane	1
axon terminus	1
presynapse	1
transport vesicle membrane	1
clathrin-coated vesicle membrane	1
clathrin-sculpted monoamine transport vesicle	1
synapse	1
endomembrane system	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

940 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC18A1	SLC17A1	Q14916	802
SLC18A1	SLC16A1	P53985	777
SLC18A1	TPH1	P17752	609
SLC18A1	SLC6A2	P23975	603
SLC18A1	SLC6A4	P31645	572
SLC18A1	DBH	P09172	542
SLC18A1	SLC6A3	Q01959	540
SLC18A1	SLC32A1	Q9H598	518
SLC18A1	HTR1D	P28221	514
SLC18A1	DDC	P20711	512
SLC18A1	MAOA	P21397	506
SLC18A1	TH	P07101	491
SLC18A1	MAOB	P27338	475
SLC18A1	GNAQ	P50148	466
SLC18A1	SLC17A9	Q9BYT1	457

IntAct

10 interactions, top by confidence:

A	B	Type	Score
SLC18A1	RAB38	psi-mi:“MI:0915”(physical association)	0.400
SLC18A1	LIMK2	psi-mi:“MI:0914”(association)	0.350
SYNGAP1	POTEF	psi-mi:“MI:0914”(association)	0.350
CACNA1C	SNRPGP15	psi-mi:“MI:0914”(association)	0.350
SYNGAP1	IGLON5	psi-mi:“MI:0914”(association)	0.350
SLC18A1	UBXN8	psi-mi:“MI:0914”(association)	0.350
SLC18A1	USP1	psi-mi:“MI:0914”(association)	0.350
SLC18A1	CLGN	psi-mi:“MI:0914”(association)	0.350
YWHAG	RPSA2	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (196): NDUFA3 (Affinity Capture-MS), ALDH3B2 (Affinity Capture-MS), APOB (Affinity Capture-MS), SDC2 (Affinity Capture-MS), OCLN (Affinity Capture-MS), MICU1 (Affinity Capture-MS), EMC7 (Affinity Capture-MS), EMC2 (Affinity Capture-MS), MTX3 (Affinity Capture-MS), PXMP2 (Affinity Capture-MS), EMC10 (Affinity Capture-MS), TMEM205 (Affinity Capture-MS), SFXN5 (Affinity Capture-MS), EMC8 (Affinity Capture-MS), ZMPSTE24 (Affinity Capture-MS)

ESM2 similar proteins: A0A2K2BF92, A2SWM2, B0JZE1, B8AF63, E2RFJ3, F1NCD6, O80605, P53988, P54219, P57057, Q01818, Q08DX7, Q0IHM1, Q17QZ3, Q1JP63, Q2XWK0, Q2YDU8, Q3TIT8, Q58CV5, Q5F3N0, Q5M7K3, Q5R5T8, Q5TF39, Q5U3U7, Q5ZIT9, Q640L2, Q6DEJ6, Q6YK44, Q7SY29, Q7ZU13, Q8AVC3, Q8BFT9, Q8BH31, Q8K078, Q8N4V2, Q8NA29, Q8NCC5, Q8NHS3, Q8R070, Q8R090

Diamond homologs: A0A166Z003, A0A455ZIM5, O35304, O74852, P51564, P54219, Q08C75, Q16572, Q62666, O17444, P39886, P81721, Q01827, Q05940, Q27963, Q8BRU6, Q91498, Q91514, P34711, P59845, P9WJY4, P9WJY5, Q01818, Q8R090, P32369, P33449, P39843, P9WG90, P9WG91, Q28487, G4MWA9, P0A0J4, P0A0J5, P0A0J6, P0A0J7, P42670, Q07282, Q5HHX4, Q6GBD5, Q6GIU7

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
reserpine	“down-regulates activity”	SLC18A1	“chemical inhibition”
ketanserin	“down-regulates activity”	SLC18A1	“chemical inhibition”

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	154
Likely benign	5
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

4830 predictions. Top by Δscore:

Variant	Effect	Δscore
17:43012176:CAGGC:C	acceptor_loss	1.0000
17:43012177:A:AG	acceptor_gain	1.0000
17:43012177:AG:A	acceptor_gain	1.0000
17:43012178:G:GA	acceptor_gain	1.0000
17:43012178:GG:G	acceptor_gain	1.0000
17:43012178:GGC:G	acceptor_gain	1.0000
17:43012178:GGCC:G	acceptor_gain	1.0000
17:43012274:CAAG:C	donor_loss	1.0000
17:43012275:AAG:A	donor_loss	1.0000
17:43012278:G:GG	donor_gain	1.0000
17:43012278:GT:G	donor_loss	1.0000
17:43012279:T:G	donor_loss	1.0000
17:43013192:AAGGT:A	donor_loss	1.0000
17:43013193:AGGT:A	donor_loss	1.0000
17:43013194:GGTA:G	donor_loss	1.0000
17:43013196:T:G	donor_loss	1.0000
17:43013261:A:AG	acceptor_gain	1.0000
17:43013262:C:G	acceptor_gain	1.0000
17:43013265:A:AG	acceptor_gain	1.0000
17:43013265:AGT:A	acceptor_gain	1.0000
17:43013265:AGTG:A	acceptor_gain	1.0000
17:43013266:G:GA	acceptor_gain	1.0000
17:43013266:GT:G	acceptor_gain	1.0000
17:43013266:GTG:G	acceptor_gain	1.0000
17:43013266:GTGG:G	acceptor_gain	1.0000
17:43013266:GTGGC:G	acceptor_gain	1.0000
17:43013267:T:TA	acceptor_gain	1.0000
17:43013590:A:T	donor_gain	1.0000
17:43013594:G:GT	donor_gain	1.0000
17:43013608:G:GT	donor_gain	1.0000

AlphaMissense

3419 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:20173065:G:T	A232D	0.987
8:20147683:A:G	L417P	0.983
8:20178464:C:T	G173D	0.983
8:20149685:G:C	S379R	0.982
8:20149685:G:T	S379R	0.982
8:20149687:T:G	S379R	0.982
8:20174384:C:T	G203E	0.982
8:20174391:C:G	G201R	0.981
8:20150722:A:C	S346R	0.980
8:20150722:A:T	S346R	0.980
8:20150724:T:G	S346R	0.980
8:20171439:G:C	F260L	0.979
8:20171439:G:T	F260L	0.979
8:20171441:A:G	F260L	0.979
8:20171475:A:C	S248R	0.978
8:20171475:A:T	S248R	0.978
8:20171477:T:G	S248R	0.978
8:20173056:C:T	G235D	0.977
8:20178465:C:G	G173R	0.976
8:20147351:A:C	F457L	0.975
8:20147351:A:T	F457L	0.975
8:20147353:A:G	F457L	0.975
8:20147722:C:T	G404D	0.974
8:20174402:C:G	R197P	0.974
8:20173085:T:A	R225S	0.973
8:20173085:T:G	R225S	0.973
8:20174385:C:G	G203R	0.973
8:20174385:C:T	G203R	0.973
8:20148007:C:G	G404R	0.972
8:20174382:A:G	S204P	0.972

dbSNP variants (sampled 300 via entrez): RS1000011153 (8:20162299 C>A,G), RS1000133095 (8:20171699 T>C), RS1000208853 (8:20173768 C>A,T), RS1000224941 (8:20160184 T>A), RS1000283638 (8:20165358 C>T), RS1000323163 (8:20169557 T>G), RS1000436421 (8:20175872 T>C), RS1000437263 (8:20154819 C>T), RS1000447766 (8:20165569 C>G), RS1000493390 (8:20150410 G>A,T), RS1000565461 (8:20161447 G>A,T), RS1000718462 (8:20153861 C>T), RS1000736198 (8:20156568 G>A), RS1000770717 (8:20153993 C>A), RS1000856320 (8:20171793 C>T)

Disease associations

OMIM: gene MIM:193002 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

31 associations (top):

Study	Trait	p-value
GCST000137_1	Triglycerides	5.000000e-12
GCST000551_3	Major depressive disorder (broad)	7.000000e-07
GCST001905_5	Hypertriglyceridemia	4.000000e-11
GCST002468_8	Triglycerides	7.000000e-09
GCST003615_3	Persistent hepatitis B virus infection	3.000000e-12
GCST005194_158	Coronary artery disease	6.000000e-07
GCST007096_59	Pulse pressure	3.000000e-06
GCST007099_17	Systolic blood pressure	8.000000e-09
GCST007738_10	Metabolic syndrome	5.000000e-13
GCST007738_11	Metabolic syndrome	5.000000e-14
GCST007738_12	Metabolic syndrome	8.000000e-22
GCST007738_13	Metabolic syndrome	1.000000e-18
GCST007738_14	Metabolic syndrome	3.000000e-17
GCST007738_5	Metabolic syndrome	9.000000e-22
GCST007738_6	Metabolic syndrome	9.000000e-21
GCST007738_7	Metabolic syndrome	8.000000e-15
GCST007738_8	Metabolic syndrome	2.000000e-16
GCST007738_9	Metabolic syndrome	6.000000e-15
GCST009602_40	Metabolic syndrome	1.000000e-24
GCST010060_10	Cholesterol	3.000000e-18
GCST010060_11	Cholesterol	2.000000e-16
GCST010241_99	Apolipoprotein A1 levels	1.000000e-12
GCST010242_484	HDL cholesterol levels	9.000000e-31
GCST010244_244	Triglyceride levels	5.000000e-26
GCST010244_267	Triglyceride levels	5.000000e-17
GCST010396_278	Gut microbiota (bacterial taxa, hurdle binary method)	7.000000e-06
GCST011742_18	Triglyceride levels in HIV infection	2.000000e-08
GCST011742_4	Triglyceride levels in HIV infection	2.000000e-06
GCST012071_9	Response to selenium supplementation (change in plasma selenium concentration)	8.000000e-06
GCST90002398_275	Neutrophil count	2.000000e-10

EFO canonical traits (9, from GWAS)

EFO ID	Trait name
EFO:0004530	triglyceride measurement
EFO:0005763	pulse pressure measurement
EFO:0006335	systolic blood pressure
EFO:0000195	metabolic syndrome
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004614	apolipoprotein A 1 measurement
EFO:0007874	gut microbiome measurement
EFO:0600021	response to dietary selenium supplementation
EFO:0004833	neutrophil count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1838 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 330,645 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL772	RESERPINE	4	330,645

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: transporter — SLC18 family of vesicular amine transporters

Most potent curated ligand interactions (3 total), top 3:

Ligand	Action	Affinity	Parameter
reserpine	Inhibition	7.45	pKi
ketanserin	Inhibition	5.8	pKi
tetrabenazine	Inhibition	4.7	pKi

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.30	IC50	50	nM	RESERPINE
5.70	EC50	2000	nM	CHEMBL5209629

CTD chemical–gene interactions

20 total (human), top 20 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
1-Methyl-4-phenylpyridinium	decreases reaction, increases uptake, affects expression, affects reaction	2
propionaldehyde	decreases expression	1
phenethylamine	decreases reaction, increases uptake	1
beta-methylcholine	affects expression	1
CGP 52608	affects binding, increases reaction	1
U 0126	affects expression, affects reaction	1
naphthol AS-E phosphate	decreases expression	1
(+)-JQ1 compound	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Benzo(a)pyrene	increases methylation, affects methylation	1
Dopamine	decreases reaction, increases uptake	1
Endosulfan	decreases expression	1
Histamine	decreases reaction, increases uptake	1
Norepinephrine	decreases reaction, increases uptake	1
Plant Extracts	affects cotreatment, decreases expression	1
Reserpine	decreases reaction, increases uptake	1
Serotonin	decreases reaction, increases uptake	1
Tetrabenazine	decreases reaction, increases uptake	1
Tretinoin	increases expression	1
Permethrin	increases expression	1

ChEMBL screening assays

2 unique, capped per target: 1 functional, 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5209601	Functional	Substrate uptake and inhibition of the chromaffin granule amine transporter (VAT1, VMAT1, SLC18A1) as assessed by uptake of a fluorescent substrate (FFN206) in HEK-293 JumpIN-SLC18A1 cells (PubChem AID: 1794818)	FFN206 based assay for SLC18A1 using HEK-293 SLC18A1 OE cells
CHEMBL868808	Binding	Binding affinity to VMAT1	Synthesis and in vivo validation of [O-methyl-11C]2-{4-[4-(7-methoxynaphthalen-1-yl)piperazin- 1-yl]butyl}-4-methyl-2H-[1,2,4]triazine-3,5-dione: a novel 5-HT1A receptor agonist positron emission tomography ligand. — J Med Chem

Clinical trials (associated diseases)

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