SLC6A6

Summary

SLC6A6 (solute carrier family 6 member 6, HGNC:11052) is a protein-coding gene on chromosome 3p25.1, encoding Sodium- and chloride-dependent taurine transporter (P31641). Mediates sodium- and chloride-dependent transport of taurine.

This gene encodes a multi-pass membrane protein that is a member of a family of sodium and chloride-ion dependent transporters. The encoded protein transports taurine and beta-alanine. There is a pseudogene for this gene on chromosome 21. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 6533 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hypotaurinemic retinal degeneration and cardiomyopathy (Moderate, GenCC)
• GWAS associations: 5
• Clinical variants (ClinVar): 98 total — 1 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 16
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_003043

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11052
Approved symbol	SLC6A6
Name	solute carrier family 6 member 6
Location	3p25.1
Locus type	gene with protein product
Status	Approved
Aliases	TAUT
Ensembl gene	ENSG00000131389
Ensembl biotype	protein_coding
OMIM	186854
Entrez	6533

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 11 protein_coding, 4 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000452151, ENST00000452775, ENST00000610642, ENST00000613060, ENST00000613930, ENST00000615188, ENST00000618278, ENST00000621751, ENST00000622176, ENST00000622186, ENST00000622810, ENST00000649500, ENST00000855618, ENST00000923324, ENST00000923325, ENST00000923326, ENST00000923327, ENST00000951472

RefSeq mRNA: 3 — MANE Select: NM_003043 NM_001134367, NM_001134368, NM_003043

CCDS: CCDS33705, CCDS46765, CCDS77704

Canonical transcript exons

ENST00000622186 — 15 exons

Exon	Start	End
ENSE00001409707	14443624	14443863
ENSE00003693822	14481671	14481841
ENSE00003722485	14416412	14416453
ENSE00003736605	14466516	14466650
ENSE00003737932	14477205	14477342
ENSE00003747690	14447582	14447816
ENSE00003748729	14484867	14489349
ENSE00003748965	14472205	14472317
ENSE00003749300	14478466	14478568
ENSE00003752020	14479085	14479185
ENSE00003752981	14445717	14445851
ENSE00003753892	14457950	14458082
ENSE00003754219	14467853	14467956
ENSE00003754601	14468088	14468212
ENSE00003918833	14402606	14402847

Expression profiles

Bgee: expression breadth ubiquitous, 265 present calls, max score 98.24.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 84.2736 / max 2830.2012, expressed in 1819 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
35448	77.0770	1816
35449	4.8981	1354
35450	1.2864	654
35455	0.2886	111
35457	0.2808	98
35456	0.2003	85
35459	0.1589	71
35458	0.0835	50

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of paranasal sinus	UBERON:0005030	98.24	gold quality
palpebral conjunctiva	UBERON:0001812	97.76	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	97.50	gold quality
blood	UBERON:0000178	96.74	gold quality
visceral pleura	UBERON:0002401	96.31	gold quality
bronchial epithelial cell	CL:0002328	95.56	gold quality
nasal cavity mucosa	UBERON:0001826	95.27	gold quality
epithelium of nasopharynx	UBERON:0001951	95.01	gold quality
monocyte	CL:0000576	94.88	gold quality
mononuclear cell	CL:0000842	94.69	gold quality
leukocyte	CL:0000738	94.47	gold quality
skin of hip	UBERON:0001554	93.98	gold quality
germinal epithelium of ovary	UBERON:0001304	93.97	gold quality
left ovary	UBERON:0002119	93.69	gold quality
secondary oocyte	CL:0000655	93.48	gold quality
parietal pleura	UBERON:0002400	93.45	gold quality
adrenal cortex	UBERON:0001235	92.79	gold quality
ovary	UBERON:0000992	92.65	gold quality
left adrenal gland cortex	UBERON:0035825	92.64	gold quality
right lung	UBERON:0002167	92.63	gold quality
endometrium	UBERON:0001295	92.59	gold quality
pleura	UBERON:0000977	92.53	gold quality
right adrenal gland cortex	UBERON:0035827	92.46	gold quality
pigmented layer of retina	UBERON:0001782	92.35	gold quality
islet of Langerhans	UBERON:0000006	92.29	gold quality
left adrenal gland	UBERON:0001234	92.12	gold quality
upper leg skin	UBERON:0004262	92.12	gold quality
oocyte	CL:0000023	92.00	gold quality
trabecular bone tissue	UBERON:0002483	91.72	gold quality
adrenal gland	UBERON:0002369	91.59	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-GEOD-137537	yes	24.45
E-GEOD-81608	yes	19.05
E-ENAD-27	yes	10.27
E-GEOD-83139	yes	8.42
E-MTAB-5061	yes	5.86
E-MTAB-10137	yes	4.92
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): EGR1, HSF1, JUN, MEF2A, MYOD1, NFAT5, TP53, VDR, WT1

miRNA regulators (miRDB)

196 targeting SLC6A6, 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-5011-5P	100.00	83.46	5820
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-7152-3P	99.97	67.47	849
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-9-3P	99.96	70.88	2068

Literature-anchored findings (GeneRIF, showing 28)

• TNF-alpha-treated cells showed a higher mRNA level of the TAUT (taurine transporter) than did the control cells. (PMID:12062416)
• TauT is involved with p53 in renal development and apoptosis. (PMID:12163498)
• regulation by WT1 (PMID:12681485)
• nitric oxide plays an important role in downregulating microvillous plasma membrane taurine transporter activity in intrauterine growth restriction (PMID:15166008)
• The increased expression level of TAUT mRNA by hypertonicity was repressed by the specific Ca(2+)/CaM kinase II inhibitor. (PMID:15225620)
• TAUT activity in TNF-alpha-treated Caco-2 cells suggests that up-regulation was associated with an increase in the amount of TAUT. (PMID:15630186)
• reporter assay revealed that TNF-alpha-induced TAUT transcriptional activity through the NF-kappaB consensus-like sequence in the human TAUT promoter region (PMID:15907840)
• taurine cotransporter is regulated by oxidative stress and overexpression of aldose reductase and high glucose impair this response (PMID:16356117)
• Greater system beta activity in fetal platelets compared with T lymphocytes is the result of relatively greater TAUT mRNA and protein expression. (PMID:16956961)
• Report taurine transporter activity in fetal T lymphocytes in intrauterine growth restriction and with tumor necrosis factor-alpha treatment. (PMID:18703994)
• This study demonstrates the functional coexpression of TauT along with the PAT1 transporter (SLC36A1) at the apical membrane of the intestinal epithelium. (PMID:19074966)
• critical role in protecting against cisplatin-induced nephrotoxicity, possibly by attenuating a p53-dependent pathway (PMID:19423693)
• Glucose reduced taurine transporter (TauT) mRNA and protein in a dose-dependent manner. (PMID:19602579)
• TauT gene is overexpressed in peripheral blood mononuclear cells of type 2 diabetic patients. (PMID:21739148)
• Taurine transporter is a novel pathological marker for stressed motor neurons in amyotrophic lateral sclerosis. (PMID:23180277)
• Syncytiotrophoblast TauT activity is reduced in maternal obesity and pre-eclampsia compared to normal pregnancy. (PMID:23392873)
• Expression of TauT is differentially regulated by Vitamin D(3) and retinoic acid via formation of VDR and RXR complexes in the nuclei in a cell type-dependent manner. (PMID:23392891)
• Knockdown of TauT impairs kidney development, possibly through regulation of cell cycle-related genes. (PMID:23392892)
• Taurine transporter deficiency results in aberrant trophoblast turnover and fetal growth restriction. (PMID:23519128)
• Neurotransmitter transporters including SLC6A6 and SLC6A13 mediate the uptake of 5-aminolevulinic acid (ALA) and can play roles in the enhancement of ALA-induced accumulation of protoporphyrin in cancerous cells. (PMID:24842606)
• Immunocytochemistry and flow cytometry analyses revealed that these mAbs recognized the native form of the extracellular domain of SLC6A6 on the cell surface. (PMID:24866236)
• This is the first study to present information on the transcriptional regulation of taurine transporter gene and the localization of the taurine transporter protein in chondrocytic cells. (PMID:25501278)
• CNDP1 and CARNS are expressed in glomeruli and tubular cells; TauT is expressed in renal epithelial cells; CDNP1 may have a role in diabetic neuropathy (PMID:26206726)
• TauT gene expression is significantly upregulated in mononuclear leukocytes of type 1 diabetes patients and is related to HbA1c levels and inversely to plasma homocysteine. (PMID:26955642)
• Elevated SLC6A6 expression is associated with gastric cancer. (PMID:30767502)
• TAUT(SLC6A6) p.A78E still localized in the plasma membrane but is predicted to impact structural stabilization. (PMID:31345061)
• Protein kinases as regulators of osmolyte accumulation under stress conditions: An overview. (PMID:32114438)
• Significance of taurine transporter (TauT) in homeostasis and its layers of regulation (Review). (PMID:32705197)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	slc6a6a	ENSDARG00000012534
danio_rerio	slc6a6b	ENSDARG00000098438
mus_musculus	Slc6a6	ENSMUSG00000030096
rattus_norvegicus	Slc6a6	ENSRNOG00000009019

Paralogs (19): SLC6A13 (ENSG00000010379), SLC6A7 (ENSG00000011083), SLC6A16 (ENSG00000063127), SLC6A15 (ENSG00000072041), SLC6A2 (ENSG00000103546), SLC6A4 (ENSG00000108576), SLC6A12 (ENSG00000111181), SLC6A8 (ENSG00000130821), SLC6A11 (ENSG00000132164), SLC6A3 (ENSG00000142319), SLC6A1 (ENSG00000157103), SLC6A20 (ENSG00000163817), SLC6A18 (ENSG00000164363), SLC6A5 (ENSG00000165970), SLC6A19 (ENSG00000174358), SLC6A9 (ENSG00000196517), SLC6A17 (ENSG00000197106), SLC6A14 (ENSG00000268104), (ENSG00000273554)

Protein

Protein identifiers

Sodium- and chloride-dependent taurine transporter — P31641 (reviewed: P31641)

Alternative names: Solute carrier family 6 member 6, Taurine transporter

All UniProt accessions (7): A0A087WY96, A0A087WYN0, A0A087WYY8, A0A087WZ59, C9JPV1, P31641, H7C1B9

UniProt curated annotations — full annotation on UniProt →

Function. Mediates sodium- and chloride-dependent transport of taurine. Mediates transport of beta-alanine. Can also mediate transport of hypotaurine and gamma-aminobutyric acid (GABA).

Subcellular location. Cell membrane.

Tissue specificity. Expressed abundantly in placenta and skeletal muscle, at intermediate levels in heart, brain, lung, kidney and pancreas and at low levels in liver.

Post-translational modifications. Taurine transport activity is down-regulated upon Ser-322 phosphorylation.

Disease relevance. Hypotaurinemic retinal degeneration and cardiomyopathy (HTRDC) [MIM:145350] An autosomal recessive disorder characterized by low plasma taurine, childhood-onset progressive retinal degeneration, and cardiomyopathy. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Taurine transport activity is stimulated by thyrotropin. Taurine transport activity is inhibited by GABA, hypotaurine and beta-alanine. GABA transport activity is inhibited by taurine and beta-alanine. Taurine transport activity is inhibited by L-alanine, guanidinoethane sulfonate, homotaurine and phorbol 12-myristate 13-acetate. Taurine transport activity is stimulated by hypertonic stress.

Similarity. Belongs to the sodium:neurotransmitter symporter (SNF) (TC 2.A.22) family. SLC6A6 subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
P31641-1	1	yes
P31641-2	2

RefSeq proteins (3): NP_001127839, NP_001127840, NP_003034* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000175	Na/ntran_symport	Family
IPR002434	Na/ntran_symport_taurine	Family
IPR037272	SNS_sf	Homologous_superfamily

Pfam: PF00209

Catalyzed reactions (Rhea), 4 shown:

• 4-aminobutanoate(out) + chloride(out) + 2 Na(+)(out) = 4-aminobutanoate(in) + chloride(in) + 2 Na(+)(in) (RHEA:70687)
• taurine(out) + chloride(out) + 2 Na(+)(out) = taurine(in) + chloride(in) + 2 Na(+)(in) (RHEA:71223)
• hypotaurine(out) + chloride(out) + 2 Na(+)(out) = hypotaurine(in) + chloride(in) + 2 Na(+)(in) (RHEA:71243)
• beta-alanine(out) + chloride(out) + 2 Na(+)(out) = beta-alanine(in) + chloride(in) + 2 Na(+)(in) (RHEA:71247)

UniProt features (76 total): binding site 19, mutagenesis site 14, topological domain 13, transmembrane region 12, sequence variant 4, sequence conflict 4, glycosylation site 3, compositionally biased region 2, chain 1, region of interest 1, modified residue 1, disulfide bond 1, splice variant 1

Structure

Experimental structures (PDB)

45 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
9JD5	ELECTRON MICROSCOPY	2.58
9JCZ	ELECTRON MICROSCOPY	2.64
9L1C	ELECTRON MICROSCOPY	2.69
9K7B	ELECTRON MICROSCOPY	2.75
9L1A	ELECTRON MICROSCOPY	2.75
9J7O	ELECTRON MICROSCOPY	2.77
9J7M	ELECTRON MICROSCOPY	2.82
9L1E	ELECTRON MICROSCOPY	2.82
9JLN	ELECTRON MICROSCOPY	2.84
9KTX	ELECTRON MICROSCOPY	2.9
9L1B	ELECTRON MICROSCOPY	2.9
9K1I	ELECTRON MICROSCOPY	2.92
9K1V	ELECTRON MICROSCOPY	2.94
9K0O	ELECTRON MICROSCOPY	2.95
9KTV	ELECTRON MICROSCOPY	3
9JG4	ELECTRON MICROSCOPY	3.02
9JD9	ELECTRON MICROSCOPY	3.05
9JD6	ELECTRON MICROSCOPY	3.06
9K0C	ELECTRON MICROSCOPY	3.06
9K1X	ELECTRON MICROSCOPY	3.06
9KMK	ELECTRON MICROSCOPY	3.06
9KMJ	ELECTRON MICROSCOPY	3.1
9KML	ELECTRON MICROSCOPY	3.11
9K1H	ELECTRON MICROSCOPY	3.12
9J7N	ELECTRON MICROSCOPY	3.14
9JD3	ELECTRON MICROSCOPY	3.2
9JG5	ELECTRON MICROSCOPY	3.2
9KTS	ELECTRON MICROSCOPY	3.2
9KTU	ELECTRON MICROSCOPY	3.2
9K0N	ELECTRON MICROSCOPY	3.21

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P31641-F1	87.00	0.71

Antibody-complex structures (SAbDab): 14 — 9K0C, 9K0N, 9K0O, 9K1B, 9K1F, 9K1I, 9K1V, 9K1X, 9K1Z, 9K21, 9KMJ, 9KMK, 9KML, 9KMM

Functional residue map

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

Ligand- & substrate-binding residues (19): 56; 59; 60; 62; 62; 67; 83; 138; 138; 297; 300; 301 …

Post-translational modifications (1): 322

Disulfide bonds (1): 162–171

Glycosylation sites (3): 163, 179, 190

Mutagenesis-validated functional residues (14):

Position	Phenotype
57	reduces taurine transport.
58	reduces taurine transport.
62	reduces taurine transport.
63	reduces taurine transport.
138	reduces taurine transport.
300	reduces taurine transport.
301	reduces taurine transport.
308	reduces taurine transport.
333	reduces taurine transport.
337	reduces taurine transport.
402	reduces taurine transport.
405	reduces taurine transport; on its own and when associated with t-406.
406	reduces taurine transport.
406	reduces taurine transport; on its own and when associated with t-406.

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-352230	Amino acid transport across the plasma membrane
R-HSA-442660	SLC-mediated transport of neurotransmitters
R-HSA-382551	Transport of small molecules
R-HSA-425366
R-HSA-425393
R-HSA-425407	SLC-mediated transmembrane transport

MSigDB gene sets: 368 (showing top): AAGCAAT_MIR137, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_SODIUM_ION_TRANSMEMBRANE_TRANSPORT, MODULE_45, GOBP_NEUROTRANSMITTER_TRANSPORT, MODULE_16, GOBP_AMINO_ACID_TRANSMEMBRANE_TRANSPORT, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_CELL_CELL_SIGNALING, GOBP_ORGANIC_ACID_TRANSPORT, HOWLIN_PUBERTAL_MAMMARY_GLAND, GOBP_POSITIVE_REGULATION_OF_CELL_DIFFERENTIATION, INGRAM_SHH_TARGETS_UP, GOBP_AMINO_ACID_TRANSPORT, AAAGACA_MIR511

GO Biological Process (12): neurotransmitter transport (GO:0006836), amino acid transport (GO:0006865), taurine transmembrane transport (GO:0015734), alanine transport (GO:0032328), sodium ion transmembrane transport (GO:0035725), positive regulation of cell differentiation (GO:0045597), modulation of chemical synaptic transmission (GO:0050804), gamma-aminobutyric acid import (GO:0051939), amino acid import across plasma membrane (GO:0089718), import across plasma membrane (GO:0098739), transport across blood-brain barrier (GO:0150104), transmembrane transport (GO:0055085)

GO Molecular Function (10): amino acid:sodium symporter activity (GO:0005283), gamma-aminobutyric acid:sodium:chloride symporter activity (GO:0005332), taurine transmembrane transporter activity (GO:0005368), taurine:sodium symporter activity (GO:0005369), amino acid transmembrane transporter activity (GO:0015171), gamma-aminobutyric acid transmembrane transporter activity (GO:0015185), alanine transmembrane transporter activity (GO:0022858), symporter activity (GO:0015293), transmembrane transporter activity (GO:0022857), metal ion binding (GO:0046872)

GO Cellular Component (10): plasma membrane (GO:0005886), membrane (GO:0016020), basolateral plasma membrane (GO:0016323), apical plasma membrane (GO:0016324), dendrite (GO:0030425), microvillus membrane (GO:0031528), cell projection (GO:0042995), neuronal cell body (GO:0043025), postsynaptic membrane (GO:0045211), GABA-ergic synapse (GO:0098982)

Reactome top-level categories

Rollup of top-3 pathways:

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transport	3
nitrogen compound transport	2
gamma-aminobutyric acid transport	2
amino acid transmembrane transport	2
transmembrane transport	2
organic acid:sodium symporter activity	2
carboxylic acid transmembrane transporter activity	2
cellular anatomical structure	2
plasma membrane region	2
alkanesulfonate transmembrane transport	1
neutral amino acid transport	1
carboxylic acid transport	1
sodium ion transport	1
monoatomic cation transmembrane transport	1
cell differentiation	1
regulation of cell differentiation	1
positive regulation of cellular process	1
positive regulation of developmental process	1
chemical synaptic transmission	1
regulation of trans-synaptic signaling	1
acidic amino acid transport	1
import across plasma membrane	1
import into cell	1
vascular transport	1
cellular process	1
amino acid:monoatomic cation symporter activity	1
solute:sodium symporter activity	1
amino acid:sodium symporter activity	1
gamma-aminobutyric acid transmembrane transporter activity	1
secondary active monocarboxylate transmembrane transporter activity	1
sodium:chloride symporter activity	1
taurine transmembrane transport	1
sulfur compound transmembrane transporter activity	1
taurine transmembrane transporter activity	1
transmembrane transporter activity	1
amino acid transmembrane transporter activity	1
neutral L-amino acid transmembrane transporter activity	1
alanine transport	1
secondary active transmembrane transporter activity	1
transporter activity	1

Protein interactions and networks

STRING

1100 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC6A6	CSAD	Q9Y600	684
SLC6A6	NFAT5	O94916	622
SLC6A6	SLC5A3	P53794	599
SLC6A6	CDO1	P78513	581
SLC6A6	SLC38A2	Q96QD8	577
SLC6A6	CARNS1	A5YM72	576
SLC6A6	AKR1B1	P15121	571
SLC6A6	SLC36A1	Q7Z2H8	548
SLC6A6	GADL1	Q6ZQY3	533
SLC6A6	SLC15A1	P46059	491
SLC6A6	SLC15A2	Q16348	490
SLC6A6	SLC38A1	Q9H2H9	482
SLC6A6	WDR44	Q5JSH3	471
SLC6A6	ABCA8	O94911	461
SLC6A6	SLC1A1	P43005	459

IntAct

24 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
GPR21	TMEM120B	psi-mi:“MI:0914”(association)	0.530
ADGRG5	KLRG2	psi-mi:“MI:0914”(association)	0.530
NRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.480
SLC6A6	HSPA5	psi-mi:“MI:0915”(physical association)	0.400
PDZK1P1	ZBTB5	psi-mi:“MI:0914”(association)	0.350
LGALS9	PODXL	psi-mi:“MI:0914”(association)	0.350
NMUR2	TMEM63A	psi-mi:“MI:0914”(association)	0.350
	NBAS	psi-mi:“MI:0914”(association)	0.350
	SHTN1	psi-mi:“MI:0914”(association)	0.350
TNFRSF10C	SLC22A23	psi-mi:“MI:0914”(association)	0.350
OR6T1	PSMD11	psi-mi:“MI:0914”(association)	0.350
PDZK1	ZBTB5	psi-mi:“MI:0914”(association)	0.350
LGALS9	LGALS8	psi-mi:“MI:0914”(association)	0.350
SLC6A6	ELP1	psi-mi:“MI:0914”(association)	0.350
TMEM17	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
TMEM216	SNAP23	psi-mi:“MI:2364”(proximity)	0.270
KRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
KCNK3	ESYT2	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (69): SLC6A6 (Affinity Capture-MS), SLC6A6 (Proximity Label-MS), SLC6A6 (Proximity Label-MS), SLC6A6 (Affinity Capture-MS), SLC6A6 (Affinity Capture-MS), SLC6A6 (Affinity Capture-MS), SLC6A6 (Affinity Capture-MS), SLC6A6 (Affinity Capture-MS), SLC6A6 (Affinity Capture-MS), SLC6A6 (Proximity Label-MS), SLC6A6 (Proximity Label-MS), SLC6A6 (Proximity Label-MS), SLC6A6 (Affinity Capture-MS), SLC6A6 (Proximity Label-MS), SLC6A6 (Proximity Label-MS)

ESM2 similar proteins: A5PJX7, A7Y2W8, O18875, O35316, O35899, O55192, O88576, P23975, P23977, P23978, P27799, P28570, P28571, P28572, P28573, P30531, P31641, P31643, P31645, P31646, P31647, P31648, P31649, P31650, P31651, P31652, P31661, P48029, P48055, P48056, P48057, P48065, P48066, P51143, P51905, Q00589, Q01959, Q28039, Q2PG55, Q60857

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

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	3
Uncertain significance	65
Likely benign	6
Benign	2

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
3381774	NM_003043.6(SLC6A6):c.746C>T (p.Thr249Ile)	Pathogenic
870334	NM_003043.6(SLC6A6):c.1196G>T (p.Gly399Val)	Likely pathogenic
870335	NM_003043.6(SLC6A6):c.233C>A (p.Ala78Glu)	Likely pathogenic
974750	NC_000003.11:g.14406477_14509088dup	Likely pathogenic

SpliceAI

2580 predictions. Top by Δscore:

Variant	Effect	Δscore
3:14402737:G:GT	donor_gain	1.0000
3:14443622:A:AG	acceptor_gain	1.0000
3:14443623:G:GG	acceptor_gain	1.0000
3:14443623:GAAA:G	acceptor_gain	1.0000
3:14443859:TGGAG:T	donor_loss	1.0000
3:14443861:GAGGT:G	donor_loss	1.0000
3:14443862:AGGTG:A	donor_loss	1.0000
3:14443863:GGTGA:G	donor_loss	1.0000
3:14443864:G:T	donor_loss	1.0000
3:14443865:T:G	donor_loss	1.0000
3:14445751:T:TA	acceptor_gain	1.0000
3:14445752:G:A	acceptor_gain	1.0000
3:14445852:G:A	donor_loss	1.0000
3:14445853:T:A	donor_loss	1.0000
3:14445854:GAGTA:G	donor_loss	1.0000
3:14447813:GGGA:G	donor_gain	1.0000
3:14447814:GGA:G	donor_gain	1.0000
3:14447814:GGAG:G	donor_gain	1.0000
3:14447815:GA:G	donor_gain	1.0000
3:14447815:GAG:G	donor_gain	1.0000
3:14447817:G:GG	donor_gain	1.0000
3:14447841:G:GT	donor_gain	1.0000
3:14466646:CACAG:C	donor_loss	1.0000
3:14466647:ACAG:A	donor_loss	1.0000
3:14466648:CAGG:C	donor_loss	1.0000
3:14466649:AGGT:A	donor_loss	1.0000
3:14466650:GGTAC:G	donor_loss	1.0000
3:14466651:GTA:G	donor_loss	1.0000
3:14466652:T:A	donor_loss	1.0000
3:14477202:CAGT:C	acceptor_loss	1.0000

AlphaMissense

4063 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:14443764:T:A	W44R	1.000
3:14443764:T:C	W44R	1.000
3:14443766:G:C	W44C	1.000
3:14443766:G:T	W44C	1.000
3:14443823:C:A	N63K	1.000
3:14443823:C:G	N63K	1.000
3:14443827:T:A	W65R	1.000
3:14443827:T:C	W65R	1.000
3:14443833:T:C	F67L	1.000
3:14443835:C:A	F67L	1.000
3:14443835:C:G	F67L	1.000
3:14445722:T:C	F79L	1.000
3:14445724:T:A	F79L	1.000
3:14445724:T:G	F79L	1.000
3:14445792:G:A	G102D	1.000
3:14467856:T:A	W291R	1.000
3:14467856:T:C	W291R	1.000
3:14468149:T:C	F345L	1.000
3:14468151:T:A	F345L	1.000
3:14468151:T:G	F345L	1.000
3:14468161:G:C	G349R	1.000
3:14468170:G:C	A352P	1.000
3:14472214:T:C	L369P	1.000
3:14472219:T:C	F371L	1.000
3:14472221:C:A	F371L	1.000
3:14472221:C:G	F371L	1.000
3:14443756:G:T	R41M	0.999
3:14443757:G:C	R41S	0.999
3:14443757:G:T	R41S	0.999
3:14443782:T:C	F50L	0.999

dbSNP variants (sampled 300 via entrez): RS1000003700 (3:14486907 A>C,G), RS1000035329 (3:14416299 C>T), RS1000041706 (3:14412538 G>A), RS1000054048 (3:14448918 A>T), RS1000074873 (3:14415318 A>G), RS1000084450 (3:14459846 G>A,C), RS1000153587 (3:14458370 G>A), RS1000170101 (3:14475329 G>T), RS1000284910 (3:14475084 T>C,G), RS1000291990 (3:14460277 A>T), RS1000356905 (3:14442440 T>C), RS1000392125 (3:14481294 A>G), RS1000405339 (3:14448563 C>T), RS1000409311 (3:14442217 G>A), RS1000417189 (3:14406887 G>A)

Disease associations

OMIM: gene MIM:186854 | disease phenotypes: MIM:145350

GenCC curated gene-disease

Disease	Classification	Inheritance
hypotaurinemic retinal degeneration and cardiomyopathy	Moderate	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
hypotaurinemic retinal degeneration and cardiomyopathy	Limited	AR

Mondo (4): hypotaurinemic retinal degeneration and cardiomyopathy (MONDO:0007777), inherited retinal dystrophy (MONDO:0019118), retinal degeneration (MONDO:0004580), megacolon (MONDO:0001273)

Orphanet (1): OBSOLETE: Inherited retinal disorder (Orphanet:71862)

HPO phenotypes

16 total (17 of 16 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000639	Nystagmus
HP:0001634	Mitral valve prolapse
HP:0001644	Dilated cardiomyopathy
HP:0003577	Congenital onset
HP:0003593	Infantile onset
HP:0007401	Macular atrophy
HP:0007814	Retinal pigment epithelial mottling
HP:0007843	Attenuation of retinal blood vessels
HP:0007994	Peripheral visual field loss
HP:0008499	High hypermetropia
HP:0025169	Left ventricular systolic dysfunction
HP:0030329	Retinal thinning on OCT
HP:0030609	Photoreceptor layer loss on macular OCT
HP:0200070	Peripheral retinal atrophy
HP:0500182	Hypotaurinemia
HP:0000556	Retinal dystrophy

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST001692_3	Response to taxane treatment (docetaxel)	1.000000e-06
GCST007576_265	Chronotype	3.000000e-10
GCST008839_267	Height	9.000000e-08
GCST012099_14	Hypertrophic cardiomyopathy (sarcomere negative)	1.000000e-09
GCST012295_12	Schizophrenia, bipolar disorder or recurrent major depressive disorder x sex interaction	9.000000e-06

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0008328	chronotype measurement
EFO:0004952	disease recurrence
EFO:0008343	sex interaction measurement

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D008531	Megacolon	C06.405.469.158.701
D012162	Retinal Degeneration	C11.270.612; C11.768.585
D058499	Retinal Dystrophies	C11.768.585.658
C564157	Hypertaurinuric Cardiomyopathy (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5762 (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: 113,735 (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
CHEMBL239243	TAURINE	3	113,735

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: transporter — GABA transporter subfamily

ChEMBL bioactivities

3 potent at pChembl≥5 of 3 total, top 3 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.07	Kd	85.69	nM	CHEMBL5653589
7.07	ED50	85.69	nM	CHEMBL5653589
5.00	EC50	1e+04	nM	TAURINE

PubChem BioAssay actives

1 with measured affinity, of 65 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149432: Binding affinity to human SLC6A6 incubated for 45 mins by Kinobead based pull down assay	kd	0.0857	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Tetrachlorodibenzodioxin	affects cotreatment, increases expression, affects expression	5
bisphenol A	affects cotreatment, increases methylation, decreases expression, decreases methylation, increases expression	4
sodium arsenite	increases abundance, increases expression	4
Arsenic	affects methylation, increases abundance, increases expression, affects expression	4
Benzo(a)pyrene	affects methylation, increases expression, increases methylation	4
Estradiol	affects cotreatment, increases expression, affects expression, increases reaction	4
trichostatin A	affects cotreatment, increases expression	3
perfluorooctane sulfonic acid	decreases expression, increases expression	3
Air Pollutants	affects expression, increases expression, affects cotreatment, increases abundance, increases oxidation	3
Valproic Acid	increases methylation, increases expression	3
Cyclosporine	decreases expression, increases expression	3
Aflatoxin B1	affects expression, increases expression, increases methylation	3
Genistein	affects expression, increases expression	3
Cisplatin	affects cotreatment, increases expression, decreases expression	2
Ethinyl Estradiol	affects expression, decreases expression	2
Nickel	increases expression	2
Oxygen	increases expression	2
Ozone	affects cotreatment, increases oxidation, increases abundance, affects expression	2
Silicon Dioxide	increases expression	2
Tobacco Smoke Pollution	increases expression	2
Tretinoin	increases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression, increases expression	2
Cadmium Chloride	increases abundance, increases expression	2
aristolochic acid I	decreases expression	1
bisphenol F	affects cotreatment, increases methylation	1
chloroacetaldehyde	affects expression	1
methyleugenol	increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
glycidyl methacrylate	decreases expression	1

ChEMBL screening assays

5 unique, capped per target: 4 binding, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1016011	Binding	Inhibition of taurine transporter	Discovery of GlyT1 inhibitors with improved pharmacokinetic properties. — Bioorg Med Chem Lett
CHEMBL5209628	Functional	Substrate uptake by the Taurine Transporter (TauT, SLC6A6) as assessed by the fluorescent FLIPR membrane potential dye in HEK-293 JumpIN-SLC6A6 cells (PubChem AID: 1794824)	Membrane potential based assay for SLC6A6 using HEK-293 SLC6A6 OE cells

Cellosaurus cell lines

6 cell lines: 5 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D4QA	HCT116-SLC6A6-KO-c8	Cancer cell line	Male
CVCL_D4QB	HCT116-SLC6A6-KO-c9	Cancer cell line	Male
CVCL_D9S2	Ubigene HEK293 SLC6A6 KO	Transformed cell line	Female
CVCL_E1DE	Ubigene THP-1 SLC6A6 KO	Cancer cell line	Male
CVCL_TP04	HAP1 SLC6A6 (-) 1	Cancer cell line	Male
CVCL_XT33	HAP1 SLC6A6 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00716586	PHASE4	COMPLETED	Treatment of Cystoid Macular Edema in Patients With Retinal Degeneration
NCT04224207	PHASE3	COMPLETED	Management of Retinitis Pigmentosa by Mesenchymal Stem Cells by Wharton’s Jelly Derived Mesenchymal Stem Cells
NCT07082855	PHASE3	NOT_YET_RECRUITING	A Multicenter, Randomized, Double-Blind, Controlled Clinical Study of Minocycline for the Treatment of Retinitis Pigmentosa
NCT02157077	PHASE3	COMPLETED	Aflibercept After Ranibizumab in Exudative Age-related Macular Degeneration
NCT03954626	PHASE3	COMPLETED	Study to Collect Safety and ECG Data on Brolucizumab 6 mg Intravitreal Treatment in Patients With Wet AMD
NCT06305416	PHASE3	RECRUITING	A Efficacy and Safety Study of Ranibizumab 10mg/ml Injection (Incepta) in Patients With Diabetic Macular Edema
NCT03763227	PHASE2	COMPLETED	Intravitreal Ranibizumab (Lucentis®) in the Treatment of Non-leaking Macular Cysts in Retinal Dystrophy
NCT04068207	PHASE2	COMPLETED	Minocycline Treatment in Retinitis Pigmentosa
NCT04945772	PHASE2	COMPLETED	Efficacy and Safety of MCO-010 Optogenetic Therapy in Adults With Retinitis Pigmentosa [RESTORE]
NCT01399515	PHASE2	COMPLETED	Efficacy and Safety of Oral Valproic Acid for Retinitis Pigmentosa
NCT02348359	PHASE2	TERMINATED	X-82 to Treat Age-related Macular Degeneration
NCT04643886	PHASE2	TERMINATED	A Multiple Dose Study of Repeat Intravitreal Injections of GEM103 in Dry Age-related Macular Degeneration
NCT04684394	PHASE2	TERMINATED	A Multiple Dose Study of Repeat Intravitreal Injections of GEM103 in Neovascular Age-related Macular Degeneration
NCT06011798	PHASE2	COMPLETED	Assess the Efficacy and Safety of Repeat Intravitreal Injections of Foselutoclax (UBX1325) in Patients With DME (ASPIRE)
NCT07174687	PHASE2	RECRUITING	SGLT2 Inhibitors in Geographic Atrophy
NCT05902962	PHASE1	COMPLETED	SAD of IVT VP-001 in PRPF31 Mutation-Associated Retinal Dystrophy Subjects
NCT06319872	PHASE1	RECRUITING	The Effects of Disulfiram (Antabuse®) on Visual Acuity in Patients With Retinal Degeneration
NCT06455826	PHASE1	COMPLETED	MAD of IVT VP-001 in PRPF31 Mutation-Associated Retinal Dystrophy Subjects (Wallaby)
NCT00877032	PHASE1	COMPLETED	Safety And Tolerability Study Of RN6G In Patients With Dry, Age-Related Macular Degeneration
NCT01003691	PHASE1	COMPLETED	Safety And Tolerability Study Of RN6G In Subjects With Advanced Dry, Age-Related Macular Degeneration Including Geographic Atrophy
NCT01024998	PHASE1	COMPLETED	Safety and Tolerability Study of AAV2-sFLT01 in Patients With Neovascular Age-Related Macular Degeneration (AMD)
NCT02330978	PHASE1	COMPLETED	Intravitreal Mesenchymal Stem Cell Transplantation in Advanced Glaucoma.
NCT02543229	PHASE1	COMPLETED	Study Evaluating the Safety, Pharmacokinetics and Pharmacodynamics of OPT-302 With or Without Lucentis™ in Patients With Wet AMD
NCT03772938	PHASE1	UNKNOWN	Stem Cells Therapy in Degenerative Diseases of the Retina
NCT04246866	PHASE1	COMPLETED	First in Human Study to Evaluate the Safety and Tolerability of GEM103 in Geographic Atrophy Secondary to Dry Age Related Macular Degeneration
NCT04855045	PHASE2/PHASE3	UNKNOWN	An Open-label, Dose Escalation and Double-masked, Randomized, Controlled Trial Evaluating Safety and Tolerability of Sepofarsen in Children (<8 Years of Age) With LCA10 Caused by Mutations in the CEP290 Gene.
NCT03872479	PHASE1/PHASE2	UNKNOWN	Single Ascending Dose Study in Participants With LCA10
NCT04123626	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	A Study to Evaluate the Safety and Tolerability of QR-1123 in Subjects With Autosomal Dominant Retinitis Pigmentosa Due to the P23H Mutation in the RHO Gene
NCT04545736	PHASE1/PHASE2	RECRUITING	Oral Metformin for Treatment of ABCA4 Retinopathy
NCT06212297	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Fellow-eye Study (FE) of LX101 in Subjects With Inherited Retinal Dystrophy
NCT06852963	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	A Repeat-Dose, Open-Label, Two Arm Safety and Efficacy Study of Two Doses of VP-001 Administered Intravitreally in Participants With Confirmed PRPF31 Mutation-Associated Retinal Dystrophy, Including Participants Previously Treated With VP001
NCT07177196	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Personalized Antisense Oligonucleotide Therapy for a Single Participant With PRPH2 Mutation Associated With Retinal Dystrophy
NCT07063030	EARLY_PHASE1	RECRUITING	A Study of LX107 Gene Therapy in AIPL1-IRD Patients
NCT01546181	Not specified	COMPLETED	Retinal Imaging by Adaptive Optics in Healthy Eyes and During Retinal and General Diseases
NCT01876147	Not specified	COMPLETED	Visual and Functional Assessment in Low Vision Patients
NCT01920867	Not specified	UNKNOWN	Stem Cell Ophthalmology Treatment Study
NCT02014389	Not specified	RECRUITING	Evaluation of Objective Perimetry Using Chromatic Multifocal Pupillometer
NCT02983305	Not specified	COMPLETED	Optical Head-Mounted Display Technology for Low Vision Rehabilitation
NCT03592017	Not specified	COMPLETED	Performance of Long-wavelength Autofluorescence Imaging
NCT03662386	Not specified	TERMINATED	Prospective Analysis of Genotype-phenotype Correlations Observed in a Large Cohort of Patients With Hereditary Retinal Dystrophies - GEPHIRD