SLC6A18

Summary

SLC6A18 (solute carrier family 6 member 18, HGNC:26441) is a protein-coding gene on chromosome 5p15.33, encoding Inactive sodium-dependent neutral amino acid transporter B(0)AT3 (Q96N87). Does not show neutral amino acid transporter activity.

The SLC6 family of proteins, which includes SLC6A18, act as specific transporters for neurotransmitters, amino acids, and osmolytes like betaine, taurine, and creatine. SLC6 proteins are sodium cotransporters that derive the energy for solute transport from the electrochemical gradient for sodium ions (Hoglund et al., 2005 [PubMed 16125675]).

Source: NCBI Gene 348932 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 159 total
• Phenotypes (HPO): 6
• Dosage sensitivity (ClinGen): haploinsufficiency dosage sensitivity unlikely, triplosensitivity no evidence
• MANE Select transcript: NM_182632

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26441
Approved symbol	SLC6A18
Name	solute carrier family 6 member 18
Location	5p15.33
Locus type	gene with protein product
Status	Approved
Aliases	FLJ31236, Xtrp2
Ensembl gene	ENSG00000164363
Ensembl biotype	protein_coding
OMIM	610300
Entrez	348932

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 1 protein_coding, 1 retained_intron

ENST00000324642, ENST00000513607

RefSeq mRNA: 1 — MANE Select: NM_182632 NM_182632

CCDS: CCDS3860

Canonical transcript exons

ENST00000324642 — 12 exons

Exon	Start	End
ENSE00001166846	1240531	1240659
ENSE00001227480	1244608	1244767
ENSE00001227500	1242707	1242863
ENSE00001227582	1245848	1246189
ENSE00001227591	1225381	1225637
ENSE00001261718	1239450	1239562
ENSE00001303550	1235481	1235662
ENSE00001303627	1244214	1244373
ENSE00001315813	1237950	1238060
ENSE00001325112	1232751	1232888
ENSE00001325194	1243555	1243759
ENSE00003541226	1232219	1232359

Expression profiles

Bgee: expression breadth broad, 16 present calls, max score 80.28.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0034 / max 5.0930, expressed in 1 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
55546	0.0034	1

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
upper arm skin	UBERON:0004263	80.28	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	70.78	gold quality
kidney epithelium	UBERON:0004819	69.60	gold quality
buccal mucosa cell	CL:0002336	68.94	gold quality
left ventricle myocardium	UBERON:0006566	66.49	gold quality
cardiac muscle of right atrium	UBERON:0003379	65.38	gold quality
adult mammalian kidney	UBERON:0000082	65.05	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	62.83	gold quality
pancreatic ductal cell	CL:0002079	62.23	silver quality
kidney	UBERON:0002113	62.12	gold quality
cerebellar vermis	UBERON:0004720	61.88	gold quality
biceps brachii	UBERON:0001507	59.76	gold quality
tibialis anterior	UBERON:0001385	59.39	silver quality
adult organism	UBERON:0007023	58.95	gold quality
ileal mucosa	UBERON:0000331	58.84	silver quality
decidua	UBERON:0002450	58.84	gold quality
heart right ventricle	UBERON:0002080	58.67	gold quality
gingival epithelium	UBERON:0001949	58.06	gold quality
cartilage tissue	UBERON:0002418	57.98	gold quality
esophagus squamous epithelium	UBERON:0006920	57.81	gold quality
secondary oocyte	CL:0000655	57.25	gold quality
quadriceps femoris	UBERON:0001377	57.23	gold quality
gingiva	UBERON:0001828	57.03	gold quality
postcentral gyrus	UBERON:0002581	56.82	gold quality
amniotic fluid	UBERON:0000173	56.64	gold quality
parotid gland	UBERON:0001831	56.61	gold quality
deltoid	UBERON:0001476	56.44	gold quality
oocyte	CL:0000023	56.33	gold quality
myocardium	UBERON:0002349	56.26	gold quality
vastus lateralis	UBERON:0001379	56.17	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.79

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

3 targeting SLC6A18, 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-7978	99.86	66.90	856
HSA-MIR-1972	97.67	67.38	1172
HSA-MIR-7108-3P	94.37	64.79	183

Functional genomics

ClinGen dosage: haploinsufficiency 40 (dosage sensitivity unlikely), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 3)

• variable number of tandem repeats in SLC6A18 are not associated with hypertension. (PMID:18554081)
• These results suggest that SLC6A18 or neighboring genes are associated with increased susceptibility to myocardial infarction. (PMID:21420947)
• Mutations in SLC6A18 gene is associated with stress fracture. (PMID:25023003)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	slc6a18	ENSDARG00000068387
mus_musculus	Slc6a18	ENSMUSG00000021612
rattus_norvegicus	Slc6a18	ENSRNOG00000016253

Paralogs (19): SLC6A13 (ENSG00000010379), SLC6A7 (ENSG00000011083), SLC6A16 (ENSG00000063127), SLC6A15 (ENSG00000072041), SLC6A2 (ENSG00000103546), SLC6A4 (ENSG00000108576), SLC6A12 (ENSG00000111181), SLC6A8 (ENSG00000130821), SLC6A6 (ENSG00000131389), SLC6A11 (ENSG00000132164), SLC6A3 (ENSG00000142319), SLC6A1 (ENSG00000157103), SLC6A20 (ENSG00000163817), SLC6A5 (ENSG00000165970), SLC6A19 (ENSG00000174358), SLC6A9 (ENSG00000196517), SLC6A17 (ENSG00000197106), SLC6A14 (ENSG00000268104), (ENSG00000273554)

Protein

Protein identifiers

Inactive sodium-dependent neutral amino acid transporter B(0)AT3 — Q96N87 (reviewed: Q96N87)

Alternative names: Sodium- and chloride-dependent transporter XTRP2, Solute carrier family 6 member 18, System B(0) neutral amino acid transporter AT3

All UniProt accessions (1): Q96N87

UniProt curated annotations — full annotation on UniProt →

Function. Does not show neutral amino acid transporter activity.

Subcellular location. Membrane.

Tissue specificity. Abundantly expressed in kidney, but not in intestine.

Disease relevance. Genetic variations in SLC6A18 might contribute to the disease phentotype in some individuals with iminoglycinuria or hyperglycinuria, that carry variants in SLC36A2, SLC6A19 or SLC6A20.

Polymorphism. Genetic variation in SLC6A18 is not a significant predictor for elevated systolic or diastolic blood pressure and is not associated with hypertension in the Japanese population.

Similarity. Belongs to the sodium:neurotransmitter symporter (SNF) (TC 2.A.22) family. SLC6A18 subfamily.

RefSeq proteins (1): NP_872438* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000175	Na/ntran_symport	Family
IPR002438	Neutral_aa_SLC6	Family
IPR037272	SNS_sf	Homologous_superfamily
IPR042701	B0AT3_SLC6sbd	Domain

Pfam: PF00209

UniProt features (37 total): topological domain 13, transmembrane region 12, sequence variant 6, glycosylation site 4, chain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96N87-F1	90.62	0.81

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 (4): 144, 168, 174, 354

Function

Pathways and Gene Ontology

Reactome pathways

11 pathways

ID	Pathway
R-HSA-352230	Amino acid transport across the plasma membrane
R-HSA-442660	SLC-mediated transport of neurotransmitters
R-HSA-5619079
R-HSA-5659729
R-HSA-1643685	Disease
R-HSA-382551	Transport of small molecules
R-HSA-425366
R-HSA-425393
R-HSA-425407	SLC-mediated transmembrane transport
R-HSA-5619102	SLC transporter disorders
R-HSA-5619115	Disorders of transmembrane transporters

MSigDB gene sets: 78 (showing top): GOBP_SODIUM_ION_TRANSMEMBRANE_TRANSPORT, GOBP_NEUROTRANSMITTER_TRANSPORT, GOBP_AMINO_ACID_TRANSMEMBRANE_TRANSPORT, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_AMINO_ACID_TRANSPORT, NIKOLSKY_BREAST_CANCER_5P15_AMPLICON, GOCC_APICAL_PLASMA_MEMBRANE, GOBP_RENAL_ABSORPTION, ACEVEDO_METHYLATED_IN_LIVER_CANCER_DN, GOBP_TRANSMEMBRANE_TRANSPORT, GOBP_SODIUM_ION_TRANSPORT, GOBP_RENAL_SYSTEM_PROCESS, GOCC_CELL_PROJECTION_MEMBRANE, GOCC_APICAL_PART_OF_CELL, GOCC_CLUSTER_OF_ACTIN_BASED_CELL_PROJECTIONS

GO Biological Process (5): neurotransmitter transport (GO:0006836), amino acid transport (GO:0006865), sodium ion transmembrane transport (GO:0035725), renal amino acid absorption (GO:1990297), amino acid transmembrane transport (GO:0003333)

GO Molecular Function (3): amino acid transmembrane transporter activity (GO:0015171), symporter activity (GO:0015293), transmembrane transporter activity (GO:0022857)

GO Cellular Component (4): plasma membrane (GO:0005886), apical plasma membrane (GO:0016324), brush border membrane (GO:0031526), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
SLC-mediated transport of amino acids	1
SLC-mediated transmembrane transport	1
Transport of small molecules	1
Disorders of transmembrane transporters	1
Disease	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transport	2
transmembrane transport	2
sodium ion transport	1
monoatomic cation transmembrane transport	1
renal absorption	1
amino acid transport	1
amino acid transmembrane transport	1
transmembrane transporter activity	1
secondary active transmembrane transporter activity	1
transporter activity	1
membrane	1
cell periphery	1
apical part of cell	1
plasma membrane region	1
brush border	1
apical plasma membrane	1
cell projection membrane	1
cellular anatomical structure	1

Protein interactions and networks

STRING

780 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC6A18	SLC36A2	Q495M3	957
SLC6A18	CLPTM1L	Q96KA5	690
SLC6A18	XYLT2	Q9H1B5	497
SLC6A18	CLTRN	Q9HBJ8	485
SLC6A18	OR4X2	Q8NGF9	483
SLC6A18	SLC36A3	Q495N2	461
SLC6A18	CLPTM1	O96005	405
SLC6A18	LRRC55	Q6ZSA7	397
SLC6A18	TERT	O14746	394
SLC6A18	OR4K5	Q8NGD3	392
SLC6A18	TTC16	Q8NEE8	392
SLC6A18	C3orf22	Q8N5N4	391
SLC6A18	GEMIN8	Q9NWZ8	379
SLC6A18	SLC5A2	P31639	376
SLC6A18	ZDHHC11	Q9H8X9	375

IntAct

3 interactions, top by confidence:

A	B	Type	Score
SLC5A7	FUT4	psi-mi:“MI:0914”(association)	0.350
SLC6A18	CLGN	psi-mi:“MI:0914”(association)	0.350

BioGRID (6): SLC6A18 (Affinity Capture-MS), SLC6A18 (Affinity Capture-MS), CLGN (Affinity Capture-MS), SORD (Affinity Capture-MS), THEM6 (Affinity Capture-MS), UGGT1 (Affinity Capture-MS)

ESM2 similar proteins: A5PJX7, B0JZG0, B4GVM9, C5MK33, D3INW7, E9PXX9, O00337, O18875, O43868, O55192, O62667, O88575, O88627, P02730, P04919, P15575, P23562, P23975, P23977, P28570, P28571, P28573, P31661, P48029, P48055, P48065, P51905, P97689, Q01959, Q13336, Q29GB8, Q2PG55, Q5QF96, Q61327, Q62674, Q62773, Q64093, Q6IFT6, Q6PGE7, Q8VBW1

Diamond homologs: A5PJX7, A7Y2W8, A7Y2X0, B3MRS1, B3NV41, B4GVM9, B4JMC1, B4L7U0, B4MEG2, B4NDL8, B4PZQ4, B4R4T6, G5EBN9, O18875, O35316, O35899, O45813, O55192, O76689, O88575, O88576, P23975, P23977, P23978, P27799, P27922, P28570, P28571, P28572, P28573, P30531, P31641, P31643, P31645, P31646, P31647, P31648, P31649, P31650, P31651

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	119
Likely benign	20
Benign	14

Top pathogenic / likely-pathogenic (0)

SpliceAI

2207 predictions. Top by Δscore:

Variant	Effect	Δscore
5:1232238:C:G	acceptor_gain	1.0000
5:1232351:GTGGA:G	donor_gain	1.0000
5:1232354:GA:G	donor_gain	1.0000
5:1232355:AGTAG:A	donor_loss	1.0000
5:1232356:G:GG	donor_gain	1.0000
5:1232358:AGGTA:A	donor_loss	1.0000
5:1232360:G:GA	donor_loss	1.0000
5:1232361:T:G	donor_loss	1.0000
5:1232749:A:AG	acceptor_gain	1.0000
5:1232749:AG:A	acceptor_gain	1.0000
5:1232750:G:GG	acceptor_gain	1.0000
5:1232750:GG:G	acceptor_gain	1.0000
5:1232750:GGGCT:G	acceptor_gain	1.0000
5:1232889:G:C	donor_loss	1.0000
5:1235659:G:T	donor_gain	1.0000
5:1240656:ACAG:A	donor_loss	1.0000
5:1240659:GGTGA:G	donor_loss	1.0000
5:1240660:G:GC	donor_loss	1.0000
5:1242705:A:AG	acceptor_gain	1.0000
5:1242706:G:GG	acceptor_gain	1.0000
5:1242706:GAAAC:G	acceptor_gain	1.0000
5:1242846:G:GT	donor_gain	1.0000
5:1242858:GA:G	donor_gain	1.0000
5:1242859:A:G	donor_gain	1.0000
5:1242859:ATAAG:A	donor_loss	1.0000
5:1242863:GGTAC:G	donor_loss	1.0000
5:1243553:A:AG	acceptor_gain	1.0000
5:1243554:G:GG	acceptor_gain	1.0000
5:1243554:GA:G	acceptor_gain	1.0000
5:1243554:GAGT:G	acceptor_gain	1.0000

AlphaMissense

4086 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:1232326:T:A	W90R	0.959
5:1232326:T:C	W90R	0.959
5:1232328:G:C	W90C	0.917
5:1232328:G:T	W90C	0.917
5:1232314:A:C	S86R	0.913
5:1232316:C:A	S86R	0.913
5:1232316:C:G	S86R	0.913
5:1235612:T:A	W191R	0.913
5:1235612:T:C	W191R	0.913
5:1232783:A:C	S112R	0.886
5:1232785:C:A	S112R	0.886
5:1232785:C:G	S112R	0.886
5:1232336:T:A	I93N	0.880
5:1235522:T:C	F161L	0.872
5:1235524:C:A	F161L	0.872
5:1235524:C:G	F161L	0.872
5:1232224:T:C	F56L	0.868
5:1232226:C:A	F56L	0.868
5:1232226:C:G	F56L	0.868
5:1244252:T:C	F459L	0.866
5:1244254:C:A	F459L	0.866
5:1244254:C:G	F459L	0.866
5:1232359:G:T	G101W	0.851
5:1232359:G:A	G101R	0.850
5:1232359:G:C	G101R	0.850
5:1232327:G:C	W90S	0.849
5:1240607:T:C	F308L	0.847
5:1240609:C:A	F308L	0.847
5:1240609:C:G	F308L	0.847
5:1225607:T:C	F44L	0.842

dbSNP variants (sampled 300 via entrez): RS1000023003 (5:1238954 G>A), RS1000040210 (5:1232439 G>A,C,T), RS1000097700 (5:1237710 C>T), RS1000286069 (5:1227620 A>G), RS1000391177 (5:1225954 A>G), RS1000444941 (5:1225732 T>A), RS1000458372 (5:1238814 G>A), RS1000678424 (5:1223907 C>T), RS1000708887 (5:1226781 C>T), RS1000761659 (5:1226666 T>C), RS1000782456 (5:1230759 G>A), RS1000784630 (5:1243430 C>A,T), RS1000807243 (5:1246020 G>A,T), RS1000899104 (5:1223550 A>G), RS1000921862 (5:1243546 G>T)

Disease associations

OMIM: gene MIM:610300 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

6 total (6 of 6 shown, HPO-id order):

HPO	Term
HP:0002154	Hyperglycinemia
HP:0003080	Hydroxyprolinuria
HP:0003108	Hyperglycinuria
HP:0003137	Prolinuria
HP:0003260	Hydroxyprolinemia
HP:0008358	Hyperprolinemia

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST002553_8	Pancreatic cancer	1.000000e-13
GCST008225_3	Renal cell carcinoma	6.000000e-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 — Neutral amino acid transporter subfamily

CTD chemical–gene interactions

12 total (human), top 12 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases methylation, increases methylation, increases mutagenesis	2
bisphenol A	decreases methylation	1
terbufos	increases methylation	1
aflatoxin B2	decreases methylation	1
3-iodothyronamine	affects uptake	1
abrine	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Fonofos	increases methylation	1
Lead	affects methylation	1
Parathion	increases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Valproic Acid	increases methylation	1

Clinical trials (associated diseases)

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