SLC6A16

Summary

SLC6A16 (solute carrier family 6 member 16, HGNC:13622) is a protein-coding gene on chromosome 19q13.33, encoding Orphan sodium- and chloride-dependent neurotransmitter transporter NTT5 (Q9GZN6).

SLC6A16 shows structural characteristics of an Na(+)- and Cl(-)-dependent neurotransmitter transporter, including 12 transmembrane (TM) domains, intracellular N and C termini, and large extracellular loops containing multiple N-glycosylation sites.

Source: NCBI Gene 28968 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 124 total
• MANE Select transcript: NM_014037

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13622
Approved symbol	SLC6A16
Name	solute carrier family 6 member 16
Location	19q13.33
Locus type	gene with protein product
Status	Approved
Aliases	NTT5
Ensembl gene	ENSG00000063127
Ensembl biotype	protein_coding
OMIM	607972
Entrez	28968

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 6 protein_coding, 1 retained_intron

ENST00000335875, ENST00000454748, ENST00000594180, ENST00000594917, ENST00000597969, ENST00000598221, ENST00000598828

RefSeq mRNA: 1 — MANE Select: NM_014037 NM_014037

CCDS: CCDS42590

Canonical transcript exons

ENST00000335875 — 12 exons

Exon	Start	End
ENSE00000348942	49290605	49290767
ENSE00000719944	49309301	49309411
ENSE00000896072	49309651	49309826
ENSE00000896081	49308876	49309117
ENSE00001059028	49293223	49293382
ENSE00001116431	49310040	49310166
ENSE00001347055	49289638	49290392
ENSE00001406182	49310353	49310510
ENSE00001410954	49310933	49311411
ENSE00003020288	49325048	49325191
ENSE00003585183	49294367	49294553
ENSE00003643710	49293827	49294028

Expression profiles

Bgee: expression breadth ubiquitous, 183 present calls, max score 95.61.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.2368 / max 207.4991, expressed in 3 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
181995	0.1917	3
181994	0.0451	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	95.61	gold quality
right testis	UBERON:0004534	95.32	gold quality
adult organism	UBERON:0007023	93.61	gold quality
testis	UBERON:0000473	92.87	gold quality
sperm	CL:0000019	92.72	gold quality
male germ cell	CL:0000015	92.16	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.23	gold quality
right lobe of liver	UBERON:0001114	83.94	gold quality
tibial artery	UBERON:0007610	83.45	gold quality
popliteal artery	UBERON:0002250	83.44	gold quality
right coronary artery	UBERON:0001625	81.98	gold quality
body of pancreas	UBERON:0001150	81.10	gold quality
bronchial epithelial cell	CL:0002328	81.09	gold quality
right uterine tube	UBERON:0001302	80.69	gold quality
mucosa of stomach	UBERON:0001199	80.52	gold quality
left ovary	UBERON:0002119	80.38	gold quality
epithelium of bronchus	UBERON:0002031	79.68	gold quality
right ovary	UBERON:0002118	79.37	gold quality
aorta	UBERON:0000947	79.04	gold quality
left coronary artery	UBERON:0001626	78.61	gold quality
bronchus	UBERON:0002185	78.49	gold quality
coronary artery	UBERON:0001621	77.48	gold quality
left uterine tube	UBERON:0001303	76.86	gold quality
lower esophagus muscularis layer	UBERON:0035833	76.64	gold quality
lower esophagus	UBERON:0013473	76.60	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	76.27	gold quality
body of uterus	UBERON:0009853	75.86	gold quality
right lung	UBERON:0002167	75.68	gold quality
endocervix	UBERON:0000458	75.61	gold quality
ectocervix	UBERON:0012249	75.06	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.77
E-GEOD-100618	no	202.11

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

41 targeting SLC6A16, 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-3148	99.97	75.06	6478
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-6499-3P	99.90	66.38	1212
HSA-MIR-4302	99.89	67.94	1187
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-4499	99.62	67.29	1470
HSA-MIR-190A-5P	99.54	71.45	933
HSA-MIR-190B-5P	99.54	71.40	925
HSA-MIR-671-5P	99.52	67.11	1277
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-4519	99.48	66.10	859
HSA-MIR-3915	99.45	68.49	1905
HSA-MIR-6165	99.44	67.12	1389
HSA-MIR-4251	99.40	69.19	3363
HSA-MIR-4786-3P	99.36	68.35	1390
HSA-MIR-542-3P	99.34	67.58	1270
HSA-MIR-29A-5P	99.08	68.59	1813
HSA-MIR-511-5P	98.97	70.94	2268
HSA-MIR-4724-5P	98.87	67.75	1324
HSA-MIR-26B-3P	98.71	67.49	1102
HSA-MIR-6840-3P	98.68	65.95	1923
HSA-MIR-374B-3P	98.63	68.24	1360
HSA-MIR-323A-5P	98.59	65.13	651
HSA-MIR-4463	98.56	66.05	1071
HSA-MIR-7158-3P	98.46	66.45	728
HSA-MIR-4733-3P	98.35	65.20	994
HSA-MIR-4782-5P	98.35	69.33	1474

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Slc6a16	ENSMUSG00000094152
rattus_norvegicus	Slc6a16	ENSRNOG00000025220

Paralogs (19): SLC6A13 (ENSG00000010379), SLC6A7 (ENSG00000011083), SLC6A15 (ENSG00000072041), SLC6A2 (ENSG00000103546), SLC6A4 (ENSG00000108576), SLC6A12 (ENSG00000111181), SLC6A8 (ENSG00000130821), SLC6A6 (ENSG00000131389), SLC6A11 (ENSG00000132164), SLC6A3 (ENSG00000142319), SLC6A1 (ENSG00000157103), SLC6A20 (ENSG00000163817), SLC6A18 (ENSG00000164363), SLC6A5 (ENSG00000165970), SLC6A19 (ENSG00000174358), SLC6A9 (ENSG00000196517), SLC6A17 (ENSG00000197106), SLC6A14 (ENSG00000268104), (ENSG00000273554)

Protein

Protein identifiers

Orphan sodium- and chloride-dependent neurotransmitter transporter NTT5 — Q9GZN6 (reviewed: Q9GZN6)

Alternative names: Solute carrier family 6 member 16

All UniProt accessions (5): Q9GZN6, M0QYK3, M0QZL4, M0R1Y6, M0R2R5

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Membrane.

Tissue specificity. Highly expressed in peripheral tissues, particularly in testis, pancreas, and prostate.

Similarity. Belongs to the sodium:neurotransmitter symporter (SNF) (TC 2.A.22) family. SLC6A16 subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9GZN6-1	1	yes
Q9GZN6-2	2

RefSeq proteins (1): NP_054756* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000175	Na/ntran_symport	Family
IPR037272	SNS_sf	Homologous_superfamily

Pfam: PF00209

UniProt features (23 total): transmembrane region 12, topological domain 4, sequence variant 2, sequence conflict 2, chain 1, glycosylation site 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9GZN6-F1	80.51	0.58

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 (1): 229

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 79 (showing top): GOBP_SODIUM_ION_TRANSMEMBRANE_TRANSPORT, GOBP_NEUROTRANSMITTER_TRANSPORT, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_AMINO_ACID_TRANSPORT, GNF2_CCNA1, WINTER_HYPOXIA_METAGENE, MODULE_95, GOBP_TRANSMEMBRANE_TRANSPORT, GOBP_SODIUM_ION_TRANSPORT, GOMF_ACTIVE_TRANSMEMBRANE_TRANSPORTER_ACTIVITY, GOMF_SECONDARY_ACTIVE_TRANSMEMBRANE_TRANSPORTER_ACTIVITY, GOMF_SYMPORTER_ACTIVITY, GOMF_NEUROTRANSMITTER_TRANSMEMBRANE_TRANSPORTER_ACTIVITY, GOMF_TRANSPORTER_ACTIVITY, MODULE_163

GO Biological Process (4): neurotransmitter transport (GO:0006836), amino acid transport (GO:0006865), sodium ion transmembrane transport (GO:0035725), transmembrane transport (GO:0055085)

GO Molecular Function (4): neurotransmitter transmembrane transporter activity (GO:0005326), symporter activity (GO:0015293), transmembrane transporter activity (GO:0022857), metal ion binding (GO:0046872)

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	3
sodium ion transport	1
monoatomic cation transmembrane transport	1
cellular process	1
neurotransmitter transport	1
transmembrane transporter activity	1
secondary active transmembrane transporter activity	1
transporter activity	1
transmembrane transport	1
cation binding	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

416 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC6A16	SLC36A2	Q495M3	731
SLC6A16	TMEM253	P0C7T8	479
SLC6A16	NOXRED1	Q6NXP6	394
SLC6A16	METTL25	Q8N6Q8	390
SLC6A16	SLC35E4	Q6ICL7	380
SLC6A16	ANKRD30BL	A7E2S9	370
SLC6A16	TMEM50A	O95807	367
SLC6A16	SLC10A5	Q5PT55	336
SLC6A16	DPY19L4	Q7Z388	336
SLC6A16	SLC22A25	Q6T423	319
SLC6A16	ZNF254	O75437	307
SLC6A16	SLC35F6	Q8N357	306
SLC6A16	FAM162B	Q5T6X4	300
SLC6A16	TMEM9B	Q9NQ34	298
SLC6A16	ETFBKMT	Q8IXQ9	289

IntAct

3 interactions, top by confidence:

A	B	Type	Score
SLC6A13	SPTLC2	psi-mi:“MI:0914”(association)	0.350
SLC6A16	PSMD11	psi-mi:“MI:0914”(association)	0.350

BioGRID (77): SLC6A16 (Affinity Capture-MS), ASCC3 (Affinity Capture-MS), ATG13 (Affinity Capture-MS), BCAS2 (Affinity Capture-MS), BUB3 (Affinity Capture-MS), BYSL (Affinity Capture-MS), CALD1 (Affinity Capture-MS), CCPG1 (Affinity Capture-MS), CDKN2AIP (Affinity Capture-MS), CLPTM1 (Affinity Capture-MS), CYFIP2 (Affinity Capture-MS), DNAJB9 (Affinity Capture-MS), DNAJC16 (Affinity Capture-MS), DPYSL2 (Affinity Capture-MS), EIF2S1 (Affinity Capture-MS)

ESM2 similar proteins: A0A0G2K1Q8, A0AV02, A2A6C4, A5D7L5, A6QNW6, B1MTL0, B2RXE2, C1BKZ7, O18917, P04920, P0DX17, P13808, P16283, P23347, P23348, P35523, P35524, P48746, P48751, P58295, Q0P5V9, Q14940, Q15043, Q15477, Q3MJ16, Q504Y0, Q50L42, Q5FWH7, Q5RB85, Q5RD44, Q64347, Q6A4L1, Q6SJP2, Q761V0, Q8BXR1, Q8CJI3, Q8K0H7, Q8R420, Q8VI23, Q91WD2

Diamond homologs: A5PJX7, A7Y2W8, A7Y2X0, B3MRS1, B3NV41, B4GVM9, B4JMC1, B4L7U0, B4MEG2, B4NDL8, B4PZQ4, B4R4T6, G5EBN9, O18875, O35316, O35899, O55192, O88575, O88576, P23975, P23977, P23978, P27799, P27922, P28570, P28571, P28572, P28573, P30531, P31641, P31643, P31645, P31646, P31647, P31648, P31649, P31650, P31651, P31652, P31661

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	99
Likely benign	15
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2663 predictions. Top by Δscore:

Variant	Effect	Δscore
19:49293224:T:TA	donor_gain	1.0000
19:49293848:T:A	donor_gain	1.0000
19:49310030:T:TA	donor_gain	1.0000
19:49311058:CT:C	donor_gain	1.0000
19:49311058:CTCT:C	donor_gain	1.0000
19:49325046:AC:A	donor_gain	1.0000
19:49325047:CC:C	donor_gain	1.0000
19:49290393:C:CC	acceptor_gain	0.9900
19:49290571:C:CA	donor_gain	0.9900
19:49290604:CGGTG:C	donor_gain	0.9900
19:49293383:C:CC	acceptor_gain	0.9900
19:49294027:GCC:G	acceptor_loss	0.9900
19:49294029:CT:C	acceptor_loss	0.9900
19:49294030:T:G	acceptor_loss	0.9900
19:49309787:C:CT	acceptor_gain	0.9900
19:49309998:T:TA	donor_gain	0.9900
19:49310009:C:A	donor_gain	0.9900
19:49310076:C:CA	donor_gain	0.9900
19:49310375:C:CT	donor_gain	0.9900
19:49310400:T:TA	donor_gain	0.9900
19:49310435:CCAG:C	donor_gain	0.9900
19:49310507:CTGC:C	acceptor_gain	0.9900
19:49311018:A:AC	donor_gain	0.9900
19:49311019:G:C	donor_gain	0.9900
19:49311057:A:AC	donor_gain	0.9900
19:49311058:C:CC	donor_gain	0.9900
19:49311264:T:TA	donor_gain	0.9900
19:49325063:T:TA	donor_gain	0.9900
19:49325143:AGGCC:A	donor_gain	0.9900
19:49293267:G:GT	donor_gain	0.9800

AlphaMissense

4829 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:49310503:G:C	F141L	0.965
19:49310503:G:T	F141L	0.965
19:49310505:A:G	F141L	0.965
19:49309090:A:G	W339R	0.959
19:49309090:A:T	W339R	0.959
19:49294448:C:A	W445C	0.944
19:49294448:C:G	W445C	0.944
19:49310077:C:A	W221C	0.943
19:49310077:C:G	W221C	0.943
19:49310961:A:C	F129L	0.941
19:49310961:A:T	F129L	0.941
19:49310963:A:G	F129L	0.941
19:49290617:C:A	W643C	0.933
19:49290617:C:G	W643C	0.933
19:49294450:A:G	W445R	0.931
19:49294450:A:T	W445R	0.931
19:49309789:G:C	F246L	0.929
19:49309789:G:T	F246L	0.929
19:49309791:A:G	F246L	0.929
19:49310442:C:G	A162P	0.928
19:49308911:G:C	F398L	0.927
19:49308911:G:T	F398L	0.927
19:49308913:A:G	F398L	0.927
19:49310403:A:G	W175R	0.927
19:49310403:A:T	W175R	0.927
19:49294392:C:G	C464S	0.921
19:49294393:A:T	C464S	0.921
19:49310069:C:G	C224S	0.912
19:49310070:A:T	C224S	0.912
19:49310951:A:G	W133R	0.911

dbSNP variants (sampled 300 via entrez): RS1000045942 (19:49331368 G>A,T), RS1000065054 (19:49324608 T>C), RS1000234674 (19:49335668 A>C,G), RS1000285092 (19:49289551 A>G), RS1000305843 (19:49296350 A>G), RS1000362798 (19:49304699 A>G), RS1000419828 (19:49341816 T>C), RS1000439371 (19:49296640 G>A,C), RS1000457361 (19:49318932 C>T), RS1000487769 (19:49310659 C>T), RS1000554762 (19:49291376 A>G), RS1000653547 (19:49298643 G>T), RS1000663121 (19:49323222 A>T), RS1000683695 (19:49289899 T>C), RS1000798103 (19:49305398 C>T)

Disease associations

OMIM: gene MIM:607972 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST009597_143	Multiple sclerosis	3.000000e-18
GCST011096_16	Systemic lupus erythematosus	2.000000e-09
GCST90011866_22	Systemic lupus erythematosus	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 — Neutral amino acid transporter subfamily

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, increases methylation	6
Nickel	decreases expression	2
p-Chloromercuribenzoic Acid	increases expression, affects cotreatment	2
aristolochic acid I	increases expression	1
sodium arsenite	decreases expression	1
butyraldehyde	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment, increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression, decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Temozolomide	increases expression	1
Sunitinib	increases expression	1
Arsenic Trioxide	increases expression	1
Benzo(a)pyrene	decreases expression	1
Carbamazepine	increases expression	1
Copper	affects cotreatment, decreases expression	1
Diethylhexyl Phthalate	decreases expression	1
Phenobarbital	affects expression	1
Silicon Dioxide	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
1-Methyl-4-phenylpyridinium	increases expression	1
Cyclosporine	increases expression	1
Aflatoxin B1	decreases expression	1
Okadaic Acid	decreases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D4Q6	HCT116-SLC6A16-KO-c10	Cancer cell line	Male
CVCL_D4Q7	HCT116-SLC6A16-KO-c9	Cancer cell line	Male

Clinical trials (associated diseases)

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