SLC18B1

Summary

SLC18B1 (solute carrier family 18 member B1, HGNC:21573) is a protein-coding gene on chromosome 6q23.2, encoding MFS-type transporter SLC18B1 (Q6NT16). Proton-coupled polyamine antiporter involved in the translocation of polyamines from cytosol into secretory vesicles prior to their release via exocytosis.

This gene encodes a protein, which has high sequence similarity to rat, xenopus and zebrafish proteins. The protein function is unknown.

Source: NCBI Gene 116843 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 102 total
• MANE Select transcript: NM_052831

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21573
Approved symbol	SLC18B1
Name	solute carrier family 18 member B1
Location	6q23.2
Locus type	gene with protein product
Status	Approved
Aliases	dJ55C23.6
Ensembl gene	ENSG00000146409
Ensembl biotype	protein_coding
OMIM	613361
Entrez	116843

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 9 protein_coding, 2 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay

ENST00000275227, ENST00000367918, ENST00000460518, ENST00000647932, ENST00000650136, ENST00000650278, ENST00000650298, ENST00000870975, ENST00000870976, ENST00000870977, ENST00000870978, ENST00000930283, ENST00000954660

RefSeq mRNA: 1 — MANE Select: NM_052831 NM_052831

CCDS: CCDS5163

Canonical transcript exons

ENST00000275227 — 14 exons

Exon	Start	End
ENSE00000975708	132783933	132784089
ENSE00001125452	132779268	132779404
ENSE00001125521	132787434	132787581
ENSE00001825455	132798414	132798637
ENSE00001862569	132769370	132770336
ENSE00002859296	132771036	132771129
ENSE00002872880	132770890	132770939
ENSE00002895142	132772993	132773088
ENSE00002909724	132774222	132774313
ENSE00002930452	132772132	132772206
ENSE00003574083	132789764	132789837
ENSE00003574870	132790177	132790272
ENSE00003614511	132796982	132797121
ENSE00003666480	132776328	132776429

Expression profiles

Bgee: expression breadth ubiquitous, 252 present calls, max score 95.97.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 5.8171 / max 233.0770, expressed in 1348 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
75627	5.5065	1342
75626	0.1780	101
75624	0.0968	52
75625	0.0358	13

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
epithelial cell of pancreas	CL:0000083	95.97	gold quality
germinal epithelium of ovary	UBERON:0001304	93.34	gold quality
nasal cavity epithelium	UBERON:0005384	91.57	gold quality
amygdala	UBERON:0001876	91.10	gold quality
esophagus squamous epithelium	UBERON:0006920	91.06	gold quality
bronchial epithelial cell	CL:0002328	90.84	gold quality
gingival epithelium	UBERON:0001949	90.76	gold quality
bronchus	UBERON:0002185	90.32	gold quality
caudate nucleus	UBERON:0001873	90.13	gold quality
palpebral conjunctiva	UBERON:0001812	89.86	gold quality
anterior cingulate cortex	UBERON:0009835	89.80	gold quality
ileal mucosa	UBERON:0000331	89.79	gold quality
oviduct epithelium	UBERON:0004804	89.67	gold quality
nasal cavity mucosa	UBERON:0001826	89.65	gold quality
parietal pleura	UBERON:0002400	89.57	gold quality
Brodmann (1909) area 23	UBERON:0013554	89.20	gold quality
gingiva	UBERON:0001828	89.15	gold quality
primary visual cortex	UBERON:0002436	89.15	gold quality
temporal lobe	UBERON:0001871	89.14	gold quality
lateral globus pallidus	UBERON:0002476	88.92	gold quality
putamen	UBERON:0001874	88.87	gold quality
Ammon’s horn	UBERON:0001954	88.87	gold quality
Brodmann (1909) area 9	UBERON:0013540	88.79	gold quality
mucosa of paranasal sinus	UBERON:0005030	88.75	gold quality
placenta	UBERON:0001987	88.61	gold quality
occipital lobe	UBERON:0002021	88.61	gold quality
nucleus accumbens	UBERON:0001882	88.55	gold quality
substantia nigra	UBERON:0002038	88.43	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	88.23	gold quality
right frontal lobe	UBERON:0002810	88.08	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-36552	yes	49.83
E-ANND-3	yes	5.48
E-GEOD-124858	no	32.29

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

60 targeting SLC18B1, 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-3924	100.00	72.09	2394
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-651-3P	99.94	73.48	5177
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-548D-3P	99.87	70.67	4362
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-5003-3P	99.85	69.29	2517
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-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	slc18b1	ENSDARG00000044047
mus_musculus	Slc18b1	ENSMUSG00000037455
rattus_norvegicus	Slc18b1	ENSRNOG00000016371
caenorhabditis_elegans		WBGENE00018860

Paralogs (3): SLC18A1 (ENSG00000036565), SLC18A2 (ENSG00000165646), SLC18A3 (ENSG00000187714)

Protein

Protein identifiers

MFS-type transporter SLC18B1 — Q6NT16 (reviewed: Q6NT16)

Alternative names: Solute carrier family 18 member B1, Vesicular polyamine transporter

All UniProt accessions (5): Q6NT16, A0A3B3ISL3, A0A3B3IT67, A0A3B3ITL9, A0A3B3IU67

UniProt curated annotations — full annotation on UniProt →

Function. Proton-coupled polyamine antiporter involved in the translocation of polyamines from cytosol into secretory vesicles prior to their release via exocytosis. Uses the electrochemical proton gradient generated by a V-type proton-pumping ATPase to couple the efflux of protons with the uptake of a polyamine molecule. Facilitates vesicular storage of spermine and spermidine in astrocytes with an impact on glutamatergic neuronal transmission and memory formation. Upon antigen stimulation, regulates polyamine accumulation and release in mast cell secretory granules, which in turn potentiates mast cell degranulation and histamine secretion.

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

Tissue specificity. Expressed in various tissues including lung, placenta, adrenal gland, liver, testis, and brain.

Similarity. Belongs to the major facilitator superfamily.

RefSeq proteins (1): NP_439896* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
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:

• spermine(in) + n H(+)(out) = spermine(out) + n H(+)(in) (RHEA:74263)
• spermidine(in) + n H(+)(out) = spermidine(out) + n H(+)(in) (RHEA:74267)
• serotonin(in) + n H(+)(out) = serotonin(out) + n H(+)(in) (RHEA:74295)

UniProt features (35 total): topological domain 13, transmembrane region 12, modified residue 3, sequence variant 3, chain 1, region of interest 1, compositionally biased region 1, sequence conflict 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
9D7V	ELECTRON MICROSCOPY	3.3
9D7W	ELECTRON MICROSCOPY	3.3
9D7X	ELECTRON MICROSCOPY	3.4
9D7U	ELECTRON MICROSCOPY	3.97

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6NT16-F1	84.89	0.50

Antibody-complex structures (SAbDab): 4 — 9D7U, 9D7V, 9D7W, 9D7X

Functional residue map

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

Post-translational modifications (3): 1, 21, 438

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 116 (showing top): GCM_MAP4K4, GOBP_NEUROTRANSMITTER_UPTAKE, GOCC_SECRETORY_GRANULE, GOBP_NEUROTRANSMITTER_TRANSPORT, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_ORGANIC_HYDROXY_COMPOUND_TRANSPORT, KOYAMA_SEMA3B_TARGETS_UP, GOZGIT_ESR1_TARGETS_UP, GOMF_PROTON_TRANSMEMBRANE_TRANSPORTER_ACTIVITY, TURASHVILI_BREAST_DUCTAL_CARCINOMA_VS_DUCTAL_NORMAL_DN, GOBP_ORGANIC_CATION_TRANSPORT, TAKEDA_TARGETS_OF_NUP98_HOXA9_FUSION_16D_DN, GOBP_IMPORT_INTO_CELL, GOBP_TRANSMEMBRANE_TRANSPORT, GOBP_MONOAMINE_TRANSPORT

GO Biological Process (6): spermine transport (GO:0000296), spermidine transport (GO:0015848), serotonin uptake (GO:0051610), transmembrane transport (GO:0055085), polyamine transmembrane transport (GO:1902047), proton transmembrane transport (GO:1902600)

GO Molecular Function (3): monoamine:proton antiporter activity (GO:0015311), polyamine:proton antiporter activity (GO:0015312), transmembrane transporter activity (GO:0022857)

GO Cellular Component (6): secretory granule membrane (GO:0030667), synaptic vesicle membrane (GO:0030672), membrane (GO:0016020), transport vesicle membrane (GO:0030658), cytoplasmic vesicle (GO:0031410), synapse (GO:0045202)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
polyamine transport	3
transmembrane transport	2
proton transmembrane transporter activity	2
antiporter activity	2
cytoplasmic vesicle membrane	2
bounding membrane of organelle	2
organic hydroxy compound transport	1
nitrogen compound transport	1
neurotransmitter reuptake	1
transport	1
cellular process	1
monoatomic cation transmembrane transport	1
monoamine transmembrane transporter activity	1
polyamine transmembrane transporter activity	1
transporter activity	1
secretory granule	1
synaptic vesicle	1
exocytic vesicle membrane	1
cellular anatomical structure	1
transport vesicle	1
cytoplasm	1
intracellular vesicle	1
cell junction	1

Protein interactions and networks

STRING

416 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC18B1	SLC17A1	Q14916	859
SLC18B1	SLC16A1	P53985	831
SLC18B1	ATP13A3	Q9H7F0	533
SLC18B1	SLC3A2	P08195	527
SLC18B1	SLC17A5	Q9NRA2	510
SLC18B1	SLC10A4	Q96EP9	486
SLC18B1	SLC22A23	A1A5C7	448
SLC18B1	SLC22A1	O15245	448
SLC18B1	DMRTA2	Q96SC8	444
SLC18B1	PANX2	Q96RD6	443
SLC18B1	MOXD1	Q6UVY6	439
SLC18B1	PANX1	Q96RD7	434
SLC18B1	ZNF584	Q8IVC4	433
SLC18B1	SLC17A9	Q9BYT1	429
SLC18B1	CNBD1	Q8NA66	422

IntAct

7 interactions, top by confidence:

A	B	Type	Score
SLC18B1	F2RL1	psi-mi:“MI:0915”(physical association)	0.370
	DENND11	psi-mi:“MI:0914”(association)	0.350
LAMP1	DST	psi-mi:“MI:0914”(association)	0.350
LAMTOR2	SCAMP3	psi-mi:“MI:0914”(association)	0.350
SLC18B1	BACH1	psi-mi:“MI:0914”(association)	0.350
SLC18B1	AP3D1	psi-mi:“MI:0914”(association)	0.350

BioGRID (37): SLC18B1 (Affinity Capture-MS), SLC18B1 (Proximity Label-MS), SLC18B1 (Two-hybrid), SLC18B1 (Affinity Capture-MS), SLC18B1 (Affinity Capture-MS), USP10 (Affinity Capture-MS), LAMP1 (Affinity Capture-MS), BACH1 (Affinity Capture-MS), LAMTOR5 (Affinity Capture-MS), SLC18B1 (Co-fractionation), SLC18B1 (Co-fractionation), SLC18B1 (Co-fractionation), SLC18B1 (Co-fractionation), SLC18B1 (Co-fractionation), SLC18B1 (Co-fractionation)

ESM2 similar proteins: A1L1W9, A1L272, A2SWM2, A8WGF7, D3Z5L6, D4A9K4, F4IKF6, G5E8K6, G8XYX6, O15374, O35440, O70324, O70451, O70594, P30638, P36021, P53985, P53986, P53987, P53988, P57057, P58355, Q00910, Q03064, Q0VA82, Q3MHW6, Q3U9N9, Q569T7, Q5M7K3, Q5U3U7, Q5XGK0, Q63344, Q640L2, Q6DCX5, Q6GPQ3, Q6NMN6, Q6NT16, Q6NUB3, Q7ZWG6, Q8AVC3

Diamond homologs: D3Z5L6, D4A9K4, Q6NT16, A0A0H3JTK0, A8GCZ5, O34546, P0A0J4, P0A0J5, P0A0J6, P0A0J7, Q58955, Q5HHX4, Q6GBD5, Q6GIU7

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	69
Likely benign	10
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2464 predictions. Top by Δscore:

Variant	Effect	Δscore
6:132770337:CT:C	acceptor_loss	1.0000
6:132771030:A:AC	donor_gain	1.0000
6:132771031:C:CC	donor_gain	1.0000
6:132771032:T:TC	donor_loss	1.0000
6:132771033:C:CC	donor_loss	1.0000
6:132771034:A:AC	donor_gain	1.0000
6:132771035:C:CA	donor_loss	1.0000
6:132771035:C:CC	donor_gain	1.0000
6:132771035:CA:C	donor_gain	1.0000
6:132771035:CACTT:C	donor_gain	1.0000
6:132771041:T:C	donor_gain	1.0000
6:132771127:GCA:G	acceptor_gain	1.0000
6:132771127:GCACT:G	acceptor_loss	1.0000
6:132771128:CA:C	acceptor_gain	1.0000
6:132771128:CAC:C	acceptor_gain	1.0000
6:132771129:ACTAA:A	acceptor_loss	1.0000
6:132771130:C:CC	acceptor_gain	1.0000
6:132771131:T:C	acceptor_loss	1.0000
6:132772183:AATC:A	donor_gain	1.0000
6:132772948:CTA:C	donor_gain	1.0000
6:132772991:A:AC	donor_gain	1.0000
6:132772992:C:CC	donor_gain	1.0000
6:132773085:CTGA:C	acceptor_gain	1.0000
6:132773086:TGA:T	acceptor_gain	1.0000
6:132773089:C:CC	acceptor_gain	1.0000
6:132773099:G:C	acceptor_gain	1.0000
6:132773099:G:GC	acceptor_gain	1.0000
6:132773100:T:C	acceptor_gain	1.0000
6:132773102:T:C	acceptor_gain	1.0000
6:132773102:T:TC	acceptor_gain	1.0000

AlphaMissense

2933 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:132787458:A:C	F159L	0.993
6:132787458:A:T	F159L	0.993
6:132787460:A:G	F159L	0.993
6:132787506:G:C	S143R	0.992
6:132787506:G:T	S143R	0.992
6:132787508:T:G	S143R	0.992
6:132771119:C:G	G391R	0.991
6:132771119:C:T	G391R	0.991
6:132783987:C:G	G202R	0.991
6:132783987:C:T	G202R	0.991
6:132784050:C:G	G181R	0.991
6:132787486:G:T	A150E	0.991
6:132787536:A:C	C133W	0.991
6:132790272:C:G	A62P	0.991
6:132771056:C:G	G412R	0.990
6:132787538:A:G	C133R	0.990
6:132787548:A:C	F129L	0.990
6:132787548:A:T	F129L	0.990
6:132787550:A:G	F129L	0.990
6:132790271:G:T	A62D	0.989
6:132772132:C:T	G387D	0.988
6:132783997:A:C	F198L	0.988
6:132783997:A:T	F198L	0.988
6:132783999:A:G	F198L	0.988
6:132784062:C:G	G177R	0.988
6:132784062:C:T	G177R	0.988
6:132789764:C:T	G118D	0.988
6:132783986:C:T	G202E	0.987
6:132787514:C:G	A141P	0.987
6:132784037:C:T	G185D	0.986

dbSNP variants (sampled 300 via entrez): RS1000030837 (6:132772619 C>T), RS1000035342 (6:132770180 C>T), RS1000071098 (6:132775861 T>C), RS1000132326 (6:132781823 G>C), RS1000249995 (6:132781524 C>T), RS1000256153 (6:132786827 G>A,C,T), RS1000411015 (6:132792339 G>A,C), RS1000484837 (6:132792513 T>C), RS1000633077 (6:132771302 A>G), RS1000696622 (6:132787078 T>C), RS1000972582 (6:132774608 A>C,T), RS1001024323 (6:132787699 C>A,T), RS1001291931 (6:132785749 C>A), RS1001381143 (6:132797004 A>T), RS1001389956 (6:132797295 C>G,T)

Disease associations

OMIM: gene MIM:613361 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

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 — SLC18 family of vesicular amine transporters

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases expression	7
trichostatin A	affects cotreatment, increases expression	3
entinostat	affects cotreatment, increases expression	2
Vorinostat	affects cotreatment, increases expression	2
Panobinostat	affects cotreatment, increases expression	2
Acetaminophen	decreases expression	2
Tetrachlorodibenzodioxin	decreases expression	2
Cyclosporine	decreases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	decreases expression	1
FR900359	increases phosphorylation	1
methylmercuric chloride	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	decreases expression	1
nickel sulfate	increases expression	1
AM 251	decreases 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
dorsomorphin	affects cotreatment, increases expression	1
(+)-JQ1 compound	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Calcitriol	decreases expression, affects cotreatment	1
Dimethyl Sulfoxide	increases expression	1
Hydrogen Peroxide	affects expression	1
Ivermectin	decreases expression	1
Methyl Methanesulfonate	decreases expression	1
Paraquat	increases expression	1
Quercetin	decreases expression	1
Testosterone	affects cotreatment, decreases expression	1
Thimerosal	decreases 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_D4IF	HCT116-SLC18B1-KO-c3	Cancer cell line	Male
CVCL_D4IG	HCT116-SLC18B1-KO-c4	Cancer cell line	Male
CVCL_TL76	HAP1 SLC18B1 (-) 1	Cancer cell line	Male
CVCL_XS90	HAP1 SLC18B1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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