SLC12A6

Summary

SLC12A6 (solute carrier family 12 member 6, HGNC:10914) is a protein-coding gene on chromosome 15q14, encoding Solute carrier family 12 member 6 (Q9UHW9). Mediates electroneutral potassium-chloride cotransport when activated by cell swelling.

This gene is a member of the K-Cl cotransporter (KCC) family. K-Cl cotransporters are integral membrane proteins that lower intracellular chloride concentrations below the electrochemical equilibrium potential. The proteins encoded by this gene are activated by cell swelling induced by hypotonic conditions. Alternate splicing results in multiple transcript variants encoding different isoforms. Mutations in this gene are associated with agenesis of the corpus callosum with peripheral neuropathy.

Source: NCBI Gene 9990 — RefSeq curated summary.

At a glance

• Gene–disease (curated): agenesis of the corpus callosum with peripheral neuropathy (Definitive, GenCC) — +1 more curated relationship
• GWAS associations: 1
• Clinical variants (ClinVar): 1,700 total — 63 pathogenic, 134 likely-pathogenic
• Phenotypes (HPO): 87
• MANE Select transcript: NM_001365088

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10914
Approved symbol	SLC12A6
Name	solute carrier family 12 member 6
Location	15q14
Locus type	gene with protein product
Status	Approved
Aliases	KCC3A, KCC3B
Ensembl gene	ENSG00000140199
Ensembl biotype	protein_coding
OMIM	604878
Entrez	9990

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 13 protein_coding, 5 retained_intron, 3 nonsense_mediated_decay

ENST00000290209, ENST00000354181, ENST00000397702, ENST00000397707, ENST00000458406, ENST00000558589, ENST00000558667, ENST00000558950, ENST00000559076, ENST00000559236, ENST00000559441, ENST00000559484, ENST00000559523, ENST00000559664, ENST00000560023, ENST00000560164, ENST00000560611, ENST00000561080, ENST00000561120, ENST00000675289, ENST00000676379

RefSeq mRNA: 7 — MANE Select: NM_001365088 NM_001042494, NM_001042495, NM_001042496, NM_001042497, NM_001365088, NM_005135, NM_133647

CCDS: CCDS10036, CCDS42010, CCDS42011, CCDS42012, CCDS58352

Canonical transcript exons

ENST00000354181 — 26 exons

Exon	Start	End
ENSE00000941691	34245693	34245867
ENSE00000941696	34240661	34240829
ENSE00001108072	34241233	34241337
ENSE00001108074	34250298	34250355
ENSE00001108076	34250631	34250729
ENSE00001108094	34245285	34245403
ENSE00001210112	34250899	34251057
ENSE00001210114	34252170	34252384
ENSE00001210118	34254348	34254589
ENSE00001210139	34257642	34257788
ENSE00001687897	34255262	34255392
ENSE00001785086	34256229	34256283
ENSE00002555136	34336410	34336752
ENSE00002562432	34337332	34337781
ENSE00003491565	34236708	34236815
ENSE00003508990	34242102	34242221
ENSE00003511251	34235181	34235314
ENSE00003522341	34238232	34238401
ENSE00003567507	34258813	34258944
ENSE00003571045	34238965	34239160
ENSE00003575026	34275345	34275389
ENSE00003635769	34243974	34244072
ENSE00003643579	34236015	34236199
ENSE00003660657	34237419	34237550
ENSE00003680466	34260926	34261020
ENSE00003894853	34229784	34233972

Expression profiles

Bgee: expression breadth ubiquitous, 274 present calls, max score 95.06.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 19.9371 / max 1519.8923, expressed in 1769 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
149231	6.2641	1446
149246	5.3492	1593
149242	2.0321	538
149243	1.7073	268
149241	1.5676	305
149247	1.4535	679
149236	0.8352	177
149239	0.4219	81
149240	0.2223	53
149237	0.0838	39

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
esophagus squamous epithelium	UBERON:0006920	95.06	gold quality
blood	UBERON:0000178	94.27	gold quality
secondary oocyte	CL:0000655	93.55	gold quality
trabecular bone tissue	UBERON:0002483	93.24	gold quality
sperm	CL:0000019	92.90	gold quality
pharyngeal mucosa	UBERON:0000355	92.42	gold quality
monocyte	CL:0000576	92.11	gold quality
oral cavity	UBERON:0000167	92.07	gold quality
gingiva	UBERON:0001828	92.02	gold quality
pons	UBERON:0000988	91.90	gold quality
gingival epithelium	UBERON:0001949	91.85	gold quality
mononuclear cell	CL:0000842	91.60	gold quality
leukocyte	CL:0000738	91.56	gold quality
body of tongue	UBERON:0011876	91.54	gold quality
lower esophagus mucosa	UBERON:0035834	91.49	gold quality
upper leg skin	UBERON:0004262	91.37	gold quality
superior surface of tongue	UBERON:0007371	91.20	gold quality
jejunal mucosa	UBERON:0000399	91.14	gold quality
bone element	UBERON:0001474	90.93	gold quality
adult organism	UBERON:0007023	90.88	gold quality
amniotic fluid	UBERON:0000173	90.87	gold quality
bone marrow	UBERON:0002371	90.82	gold quality
inferior vagus X ganglion	UBERON:0005363	90.79	gold quality
epithelium of esophagus	UBERON:0001976	90.70	gold quality
tendon of biceps brachii	UBERON:0008188	90.66	gold quality
visceral pleura	UBERON:0002401	90.64	gold quality
superior vestibular nucleus	UBERON:0007227	90.62	gold quality
subthalamic nucleus	UBERON:0001906	90.54	gold quality
lower lobe of lung	UBERON:0008949	90.38	gold quality
esophagus mucosa	UBERON:0002469	90.36	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.05

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

166 targeting SLC12A6, 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-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-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4713-3P	100.00	65.92	505
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-146A-5P	99.96	68.93	988
HSA-MIR-146B-5P	99.96	69.13	977
HSA-MIR-6778-3P	99.96	67.29	2693

Literature-anchored findings (GeneRIF, showing 28)

• human osteoblasts express functional K-Cl cotransporters in their cell membrane that seem to be able to induce the indirect activation of volume-sensitive Cl- channels by KCl through an increase in the intracellular ions, water influx and cell swelling. (PMID:12637262)
• all of the CCCs examined (NKCC1, NKCC2, KCC1, KCC3, and KCC4) can promote NH4(+) translocation, presumably through binding of the ion at the K(+) site (PMID:12657561)
• KCC activation by IGF-1 plays an important role in IGF-1 signaling to promote growth and spread of gynecological cancers. (PMID:15262997)
• Not only truncating but also missense mutations of the KCC3 gene are associated with Andermann syndrome. (PMID:16606917)
• Among patients with early-stage node-negative breast cancer, disease-free survival (DFS) and overall survival (OS) curves were significantly different based on IGF-1 and KCC expression. (PMID:17133354)
• KCC3 mutations in exon 22 constitute a recurrent mutation site for hereditary motor and sensory neuropathy with agenesis of the corpus callosum (HMSN/ACC), regardless of ethnic origin. (PMID:17893295)
• KCC3 down-regulates E-cadherin/beta-catenin complex formation by inhibiting transcription of E-cadherin gene and accelerating proteosome-dependent degradation of beta-catenin protein (PMID:18006853)
• study provides evidence that the upstream SLC12A6 G/A promoter SNP is functional not only by changing the DNA primary structure but also by influencing the allelic epigenotype and consequently by influencing the chromatin organization (PMID:18536702)
• Using a yeast 2-hybrid it was discovered that the C-terminal domain of KCC3, that is lost in most hereditary motor and sensory neuropathy with agenesis of the corpus callosum-causing mutations, directly interacts with brain-specific creatine kinase. (PMID:18566107)
• Study identified two sites in KCC3 that are rapidly dephosphorylated in hypotonic conditions in cultured cells and human red blood cells in parallel with increased transport activity. (PMID:19665974)
• mutations of the KCC3 gene may result in non-syndromic childhood onset of demyelinating hereditary motor and sensory neuropathy (PMID:20020398)
• The Wnk3 protein isoforms have a similar effect on SLC12 cotransporters. NKCC1/2 and NCC were inhibited, even in hypertonicity, while KCCs were activated, even in isotonic conditions. (PMID:21613606)
• mis-trafficking of mutant protein is an important pathophysiological feature of HMSN/ACC causative KCC3 mutations. (PMID:21628467)
• KCC3 is the dominant isoform in erythrocytes, with variable expression of KCC1 and KCC4 that could result in modulation of KCC activity (PMID:21733850)
• Neuropathic features of hereditary motor and sensory neuropathy/agenesis of corpus callosum in transgenic mouse lines are predominantly due to a neuronal KCC3 deficit, while the auditory impairment is due to loss of non-neuronal KCC3 expression. (PMID:22423107)
• serine residue 96 of human KCC3 is a third site that has to be dephosphorylated for full activation of the cotransporter during hypotonicity. (PMID:24043619)
• SLC12A6 has been shown to be causative in Andermann Syndrome. (PMID:24341143)
• SPAK may promote KCC3-mediated cervix tumor aggressiveness via the NF-kappaB/p38 MAPK/MMP2 axis. (PMID:24655550)
• These results suggest that the expression of KCC3 in ESCC may affect cellular invasion and be related to a worse prognosis in patients with ESCC. (PMID:25110711)
• Neurodegenerative deficits in hereditary motor and sensory neuropathy associated with agenesis of the corpus callosum are primarily caused by an axonopathy superimposed upon abnormal development, affecting peripheral but also central nervous system axons, all ultimately because of a genetic defect in the axonal cotransporter KCC3. (PMID:27230413)
• These results suggest that the function of the peripheral nervous system depends on finely tuned, kinase-regulated KCC3 activity and implicate abnormal cell volume homeostasis as a previously unreported mechanism of axonal degeneration. (PMID:27485015)
• we present the first Mexican patients with hereditary motor and sensory neuropathy with agenesis of the corpus callosum and a novel heterozygous frameshift variant, c.2097du p or p.(Trp700Leufs*19) of the SLC12A6 gene (PMID:30038111)
• AS may also occur in the Roma population with a new mutation being found: frameshift mutation c.2604delT in the exon 20 of the SLC12A6 gene. Roma patients with probable AS should be primarily tested for this mutation. (PMID:30868738)
• SLC12A ion transporter mutations in sporadic and familial human congenital hydrocephalus. (PMID:31393094)
• De novo variants in SLC12A6 cause sporadic early-onset progressive sensorimotor neuropathy. (PMID:31439721)
• ZnR/GPR39 controls cell migration by orchestrating recruitment of KCC3 into protrusions, re-organization of actin and activation of MMP. (PMID:33465674)
• Novel heterozygous variants of SLC12A6 in Japanese families with Charcot-Marie-Tooth disease. (PMID:35733399)
• Late-onset sensory-motor axonal neuropathy, a novel SLC12A6-related phenotype. (PMID:36542484)

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
danio_rerio	slc12a6	ENSDARG00000105485
mus_musculus	Slc12a6	ENSMUSG00000027130
rattus_norvegicus	Slc12a6	ENSRNOG00000005196
drosophila_melanogaster	CG10413	FBGN0032689
drosophila_melanogaster	Ncc69	FBGN0036279
drosophila_melanogaster	kcc	FBGN0261794
caenorhabditis_elegans		WBGENE00012543
caenorhabditis_elegans		WBGENE00019205
caenorhabditis_elegans		WBGENE00020207

Paralogs (8): SLC12A2 (ENSG00000064651), SLC12A3 (ENSG00000070915), SLC12A1 (ENSG00000074803), SLC12A7 (ENSG00000113504), SLC12A4 (ENSG00000124067), SLC12A5 (ENSG00000124140), SLC12A9 (ENSG00000146828), SLC12A8 (ENSG00000221955)

Protein

Protein identifiers

Solute carrier family 12 member 6 — Q9UHW9 (reviewed: Q9UHW9)

Alternative names: Electroneutral potassium-chloride cotransporter 3, K-Cl cotransporter 3

All UniProt accessions (8): Q9UHW9, A0A6Q8PH21, B3KXX3, H0YKE6, H0YKJ2, H0YKL8, H0YKQ8, H0YMQ9

UniProt curated annotations — full annotation on UniProt →

Function. Mediates electroneutral potassium-chloride cotransport when activated by cell swelling. May contribute to cell volume homeostasis in single cells. Mediates electroneutral potassium-chloride cotransport when activated by cell swelling. May contribute to cell volume homeostasis in single cells. Mediates electroneutral potassium-chloride cotransport when activated by cell swelling. May contribute to cell volume homeostasis in single cells. Mediates electroneutral potassium-chloride cotransport when activated by cell swelling. May contribute to cell volume homeostasis in single cells. Mediates electroneutral potassium-chloride cotransport when activated by cell swelling. May contribute to cell volume homeostasis in single cells. Mediates electroneutral potassium-chloride cotransport when activated by cell swelling. May contribute to cell volume homeostasis in single cells.

Subunit / interactions. Homodimer; adopts a domain-swap conformation at the scissor helices connecting the transmembrane domain and C-terminal domain. Heterodimer with K-Cl cotransporter SLC12A5. Interacts (via C-terminus) with CKB; the interaction may be required for potassium-chloride cotransport activity.

Subcellular location. Cell membrane. Basolateral cell membrane.

Tissue specificity. Expressed in brain (at protein level). Highly expressed in heart, brain and kidney. Detected at lower levels in skeletal muscle, placenta, lung and pancreas. Detected in umbilical vein endothelial cells. More abundant in kidney. Testis specific.

Post-translational modifications. Phosphorylated, phosphorylation regulates transporter activity. Phosphorylated at Thr-991 and Thr-1048 by OXSR1/OSR1 and STK39/SPAK downstream of WNK kinases (WNK1, WNK2, WNK3 or WNK4), inhibiting the potassium-chloride cotransport activity. N-glycosylated.

Disease relevance. Agenesis of the corpus callosum, with peripheral neuropathy (ACCPN) [MIM:218000] A disease that is characterized by severe progressive sensorimotor neuropathy, intellectual disability, dysmorphic features and complete or partial agenesis of the corpus callosum. The disease is caused by variants affecting the gene represented in this entry. Charcot-Marie-Tooth disease, axonal, type 2II (CMT2II) [MIM:620068] A dominant axonal form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Neuropathies of the CMT2 group are characterized by signs of axonal degeneration in the absence of obvious myelin alterations, normal or slightly reduced nerve conduction velocities, and progressive distal muscle weakness and atrophy. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Inhibited following phosphorylation by OXSR1/OSR1 and STK39/SPAK: phosphorylation takes place downstream of WNK kinases (WNK1, WNK2, WNK3 or WNK4) in response to hyperosmotic stress and subsequent cell shrinkage. Activated by N-ethylmaleimide (NEM). Inhibited by DIOA, bumetanide and furosemide.

Domain organisation. N-terminal loop binds to the intracellular vestibule of the transporter, arresting the transporter in an inhibited state.

Induction. Up-regulated by VEGF. Down-regulated by TNF.

Miscellaneous. Produced by alternative promoter usage. Does not differ in the osmotic set point of swelling activation but, activation is more rapid. Does not differ in the osmotic set point of swelling activation but, activation is more rapid.

Similarity. Belongs to the SLC12A transporter family. K/Cl co-transporter subfamily.

Isoforms (6)

UniProt ID	Names	Canonical?
Q9UHW9-1	1, KCC3a	yes
Q9UHW9-2	2, KCC3b
Q9UHW9-3	3, KCC3a-X2M
Q9UHW9-4	4, KCC3a-S3
Q9UHW9-5	5, KCC3a-S, KCC3a-S1, KCC3a-S2
Q9UHW9-6	6, KCC3b-X2M

RefSeq proteins (7): NP_001035959, NP_001035960, NP_001035961, NP_001035962, NP_001352017, NP_005126, NP_598408 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000076	KCL_cotranspt	Family
IPR004841	AA-permease/SLC12A_dom	Domain
IPR004842	SLC12A_fam	Family
IPR018491	SLC12_C	Domain

Pfam: PF00324, PF03522

Catalyzed reactions (Rhea), 1 shown:

• K(+)(in) + chloride(in) = K(+)(out) + chloride(out) (RHEA:72427)

UniProt features (181 total): helix 41, strand 35, turn 17, transmembrane region 12, modified residue 12, sequence variant 12, mutagenesis site 12, binding site 11, topological domain 10, splice variant 5, region of interest 4, glycosylation site 4, compositionally biased region 2, disulfide bond 2, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

8 structures.

PDB	Method	Resolution (Å)
6M22	ELECTRON MICROSCOPY	2.7
6M1Y	ELECTRON MICROSCOPY	3.2
7AIN	ELECTRON MICROSCOPY	3.2
7AIO	ELECTRON MICROSCOPY	3.31
7D90	ELECTRON MICROSCOPY	3.6
7NGB	ELECTRON MICROSCOPY	3.64
6Y5R	ELECTRON MICROSCOPY	3.76
6Y5V	ELECTRON MICROSCOPY	4.08

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UHW9-F1	79.80	0.54

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 (11): 147; 148; 151; 443; 443; 444; 444; 446; 447; 448; 603

Post-translational modifications (12): 32, 120, 148, 736, 778, 981, 991, 1023, 1029, 1032, 1048, 1121

Disulfide bonds (2): 375–390, 410–420

Glycosylation sites (4): 379, 398, 411, 428

Mutagenesis-validated functional residues (12):

Position	Phenotype
96	increases rb(+) uptake; when associated with d-991 and d-991.
96	decreases rb(+) uptake; when associated with d-991 and d-1048.
505	decrease in cl(-) efflux.
586	decrease in cl(-) efflux.
668	increases transporter activity.
715	no effect on transporter activity.
746	slightly reduces transporter activity.
991	decreased phosphorylation by wnk kinases, leading to increased potassium-chloride cotransport activity. increases rb(+)
991	decreases rb(+) uptake; when associated with d-96 and d-1048.
1032	does not affect potassium-chloride cotransport activity.
1048	decreased phosphorylation by wnk kinases, leading to increased potassium-chloride cotransport activity. increases rb(+)
1048	decreases rb(+) uptake; when associated with d-96 and d-991.

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-426117	Cation-coupled Chloride cotransporters
R-HSA-5619039	Defective SLC12A6 causes agenesis of the corpus callosum, with peripheral neuropathy (ACCPN)
R-HSA-1643685	Disease
R-HSA-382551	Transport of small molecules
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: 434 (showing top): GOBP_POTASSIUM_ION_TRANSPORT, GOZGIT_ESR1_TARGETS_DN, GOBP_CELLULAR_RESPONSE_TO_CARBOHYDRATE_STIMULUS, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GAUSSMANN_MLL_AF4_FUSION_TARGETS_C_UP, GOBP_POTASSIUM_ION_HOMEOSTASIS, GOBP_INORGANIC_ANION_TRANSPORT, chr15q14, RACCACAR_AML_Q6, FOXO4_01, GGGTGGRR_PAX4_03, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, ACEVEDO_LIVER_CANCER_WITH_H3K27ME3_UP, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_CELL_CELL_SIGNALING

GO Biological Process (14): angiogenesis (GO:0001525), monoatomic ion transport (GO:0006811), cell volume homeostasis (GO:0006884), chemical synaptic transmission (GO:0007268), chloride ion homeostasis (GO:0055064), potassium ion homeostasis (GO:0055075), cellular response to glucose stimulus (GO:0071333), cellular hypotonic response (GO:0071476), cellular hypotonic salinity response (GO:0071477), potassium ion transmembrane transport (GO:0071805), chloride transmembrane transport (GO:1902476), potassium ion import across plasma membrane (GO:1990573), potassium ion transport (GO:0006813), transmembrane transport (GO:0055085)

GO Molecular Function (8): potassium ion transmembrane transporter activity (GO:0015079), potassium:chloride symporter activity (GO:0015379), protein kinase binding (GO:0019901), metal ion binding (GO:0046872), protein binding (GO:0005515), symporter activity (GO:0015293), chloride:monoatomic cation symporter activity (GO:0015377), transmembrane transporter activity (GO:0022857)

GO Cellular Component (5): plasma membrane (GO:0005886), membrane (GO:0016020), basolateral plasma membrane (GO:0016323), axon (GO:0030424), synapse (GO:0045202)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
SLC-mediated transport of inorganic anions	1
SLC transporter disorders	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
inorganic ion homeostasis	2
potassium ion transmembrane transport	2
blood vessel morphogenesis	1
anatomical structure formation involved in morphogenesis	1
regulation of cell size	1
cellular homeostasis	1
anterograde trans-synaptic signaling	1
monoatomic anion homeostasis	1
monoatomic cation homeostasis	1
intracellular glucose homeostasis	1
response to glucose	1
cellular response to hexose stimulus	1
hypotonic response	1
cellular response to osmotic stress	1
hypotonic salinity response	1
cellular response to salt stress	1
cellular hypotonic response	1
potassium ion transport	1
monoatomic cation transmembrane transport	1
chloride transport	1
monoatomic anion transmembrane transport	1
inorganic cation import across plasma membrane	1
metal ion transport	1
cellular process	1
metal ion transmembrane transporter activity	1
potassium ion transmembrane transporter activity	1
chloride:monoatomic cation symporter activity	1
kinase binding	1
cation binding	1
binding	1
secondary active transmembrane transporter activity	1
chloride transmembrane transporter activity	1
monoatomic anion:monoatomic cation symporter activity	1
transporter activity	1
transmembrane transport	1
membrane	1
cell periphery	1
cellular anatomical structure	1
basal plasma membrane	1

Protein interactions and networks

STRING

1174 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC12A6	STK39	Q9UEW8	885
SLC12A6	OXSR1	O95747	720
SLC12A6	SPG11	Q96JI7	685
SLC12A6	WNK3	Q9BYP7	658
SLC12A6	STK24	Q9Y6E0	633
SLC12A6	WNK1	P54963	625
SLC12A6	ZNF618	Q5T7W0	564
SLC12A6	SEMA6D	Q8NFY4	547
SLC12A6	WNK4	Q96J92	531
SLC12A6	VAV2	P52735	471
SLC12A6	PGK1	P00558	470
SLC12A6	WNK2	Q9Y3S1	460
SLC12A6	SLC26A1	Q9H2B4	454
SLC12A6	SPG7	Q9UQ90	441
SLC12A6	SPG21	Q9NZD8	437

IntAct

87 interactions, top by confidence:

A	B	Type	Score
ENTREP1	WWP2	psi-mi:“MI:0914”(association)	0.850
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
PDGFRB	PIK3R2	psi-mi:“MI:0914”(association)	0.610
SLC12A6	STK39	psi-mi:“MI:0915”(physical association)	0.560
SLC12A6	CKB	psi-mi:“MI:0915”(physical association)	0.530
SLC12A6	CKB	psi-mi:“MI:0403”(colocalization)	0.530
GPR21	TMEM120B	psi-mi:“MI:0914”(association)	0.530
ZNRF4	UPK3BL1	psi-mi:“MI:0914”(association)	0.530
LGALS1	PODXL	psi-mi:“MI:0914”(association)	0.530
LGALS3	PODXL	psi-mi:“MI:0914”(association)	0.530
SLC12A4	CLGN	psi-mi:“MI:0914”(association)	0.530
CLGN	NPC1	psi-mi:“MI:0914”(association)	0.530
PTGIR	TMEM63A	psi-mi:“MI:0914”(association)	0.530
NRN1	SLC1A1	psi-mi:“MI:0914”(association)	0.530
TMEM9	ESYT2	psi-mi:“MI:0914”(association)	0.530
RAB6B	RAB6A	psi-mi:“MI:0914”(association)	0.530
SLC12A4	JAGN1	psi-mi:“MI:0914”(association)	0.530
RAB6B	SBF1	psi-mi:“MI:0914”(association)	0.530
SLC12A4	LGALS3	psi-mi:“MI:0914”(association)	0.530
SLC12A6	RPL30	psi-mi:“MI:0915”(physical association)	0.400
SLC12A6	H1-2	psi-mi:“MI:0915”(physical association)	0.400
SLC12A6	Ckb	psi-mi:“MI:0915”(physical association)	0.400
OR2A2	SLC12A6	psi-mi:“MI:0915”(physical association)	0.400
SLC12A6	SLC25A35	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (202): SLC12A6 (Affinity Capture-MS), SLC12A6 (Affinity Capture-MS), SLC12A6 (Affinity Capture-MS), SLC12A6 (Affinity Capture-MS), SLC12A6 (Affinity Capture-MS), SLC12A6 (Proximity Label-MS), SLC12A6 (Affinity Capture-MS), SLC12A6 (Affinity Capture-MS), SLC12A6 (Affinity Capture-MS), SLC12A6 (Affinity Capture-MS), SLC12A6 (Affinity Capture-MS), SLC12A6 (Affinity Capture-MS), SLC12A6 (Affinity Capture-MS), SLC12A6 (Affinity Capture-MS), SLC12A6 (Affinity Capture-MS)

ESM2 similar proteins: A0A078H868, A0AAS4, A0JP80, A6X919, D4AD75, O70536, O77760, O77761, P23913, P35610, P53439, P56079, Q14739, Q20696, Q20735, Q28677, Q2PZI1, Q4JM44, Q4R763, Q5R7H4, Q5RK27, Q60457, Q61263, Q63632, Q63633, Q657W3, Q6AX73, Q6Z0E2, Q7T3T4, Q7TSX5, Q86VZ5, Q8IWX5, Q8NHU3, Q8VCQ6, Q91V14, Q924N4, Q965Q4, Q9D4B1, Q9FJB4, Q9H2X9

Diamond homologs: A0A0G2KTI4, A2BFP5, O60146, P38329, P55018, P59158, Q0VGW6, Q66HR0, Q924N4, Q99MR3, Q9BXP2, Q9UHW9, Q09573, Q28677, Q2UVJ5, Q5RK27, Q63632, Q63633, Q6Z0E2, Q7YRU6, Q91V14, Q9H2X9, Q9JIS8, Q9UP95, Q9WVL3, Q9Y666, Q657W3, A0AV02, Q8VI23

SIGNOR signaling

8 interactions.

A	Effect	B	Mechanism
WNK1	down-regulates	SLC12A6	phosphorylation
WNK3	“down-regulates activity”	SLC12A6	phosphorylation
SLC12A6	“down-regulates quantity”	chloride	relocalization
STK39	“down-regulates activity”	SLC12A6	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 109 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
chloride transmembrane transport	6	15.2×	2e-03
transmembrane transport	6	10.8×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

1700 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	63
Likely pathogenic	134
Uncertain significance	559
Likely benign	763
Benign	95

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1029941	NM_001365088.1(SLC12A6):c.1151C>G (p.Ser384Ter)	Pathogenic
1073089	NC_000015.9:g.(?34526072)(34631468_?)del	Pathogenic
1075447	NM_001365088.1(SLC12A6):c.366T>G (p.Tyr122Ter)	Pathogenic
1075604	NM_001365088.1(SLC12A6):c.2002_2003insTGGA (p.Arg668fs)	Pathogenic
1076707	NM_001365088.1(SLC12A6):c.390dup (p.Lys131Ter)	Pathogenic
136175	NM_001365088.1(SLC12A6):c.1584_1585delinsG (p.Phe529fs)	Pathogenic
136176	NM_001365088.1(SLC12A6):c.2032dup (p.Tyr678fs)	Pathogenic
136177	NM_001365088.1(SLC12A6):c.1478_1485del (p.Phe493fs)	Pathogenic
1367443	NM_001365088.1(SLC12A6):c.1639del (p.Leu547fs)	Pathogenic
1368157	NM_001365088.1(SLC12A6):c.1620_1621del (p.Cys541fs)	Pathogenic
1409721	NM_001365088.1(SLC12A6):c.2142C>G (p.Tyr714Ter)	Pathogenic
1423567	NM_001365088.1(SLC12A6):c.1614del (p.Phe538fs)	Pathogenic
1448267	NM_001365088.1(SLC12A6):c.1962C>A (p.Tyr654Ter)	Pathogenic
1454033	NM_001365088.1(SLC12A6):c.2157C>G (p.Tyr719Ter)	Pathogenic
1454158	NM_001365088.1(SLC12A6):c.2036A>G (p.Tyr679Cys)	Pathogenic
1455015	NM_001365088.1(SLC12A6):c.550C>T (p.Gln184Ter)	Pathogenic
1458003	NM_001365088.1(SLC12A6):c.2015G>A (p.Trp672Ter)	Pathogenic
1708538	NM_001365088.1(SLC12A6):c.865G>A (p.Glu289Lys)	Pathogenic
1708540	NM_001365088.1(SLC12A6):c.2036A>C (p.Tyr679Ser)	Pathogenic
2010893	NM_001365088.1(SLC12A6):c.262_263del (p.Val88fs)	Pathogenic
2041240	NM_001365088.1(SLC12A6):c.2808G>A (p.Trp936Ter)	Pathogenic
2085742	NM_001365088.1(SLC12A6):c.1540A>T (p.Lys514Ter)	Pathogenic
2091121	NM_001365088.1(SLC12A6):c.563dup (p.Met189fs)	Pathogenic
2094419	NM_001365088.1(SLC12A6):c.629G>A (p.Trp210Ter)	Pathogenic
2102681	NM_001365088.1(SLC12A6):c.3146G>A (p.Trp1049Ter)	Pathogenic
2103220	NM_001365088.1(SLC12A6):c.3178C>T (p.Gln1060Ter)	Pathogenic
2103369	NM_001365088.1(SLC12A6):c.3196del (p.Glu1066fs)	Pathogenic
2110920	NM_001365088.1(SLC12A6):c.2180del (p.Gly727fs)	Pathogenic
2427223	NC_000015.9:g.(?34628591)(34628881_?)del	Pathogenic
2678741	NM_001365088.1(SLC12A6):c.3321del (p.Asn1107fs)	Pathogenic

SpliceAI

3006 predictions. Top by Δscore:

Variant	Effect	Δscore
15:34236008:AACTT:A	donor_loss	1.0000
15:34236009:ACTTA:A	donor_loss	1.0000
15:34236010:CTT:C	donor_loss	1.0000
15:34236011:TTA:T	donor_loss	1.0000
15:34236012:TAC:T	donor_loss	1.0000
15:34236013:A:AC	donor_gain	1.0000
15:34236013:A:C	donor_loss	1.0000
15:34236014:C:CA	donor_gain	1.0000
15:34236014:CG:C	donor_gain	1.0000
15:34236014:CGG:C	donor_gain	1.0000
15:34236014:CGGA:C	donor_gain	1.0000
15:34236033:T:TA	donor_gain	1.0000
15:34236045:T:TA	donor_gain	1.0000
15:34236195:TGTGC:T	acceptor_gain	1.0000
15:34236196:GTGC:G	acceptor_gain	1.0000
15:34236197:TGC:T	acceptor_gain	1.0000
15:34236198:GC:G	acceptor_gain	1.0000
15:34236199:CC:C	acceptor_gain	1.0000
15:34236200:C:CA	acceptor_loss	1.0000
15:34236200:C:CC	acceptor_gain	1.0000
15:34236201:T:G	acceptor_loss	1.0000
15:34236813:ATGCT:A	acceptor_loss	1.0000
15:34236814:TG:T	acceptor_gain	1.0000
15:34236816:C:CC	acceptor_gain	1.0000
15:34236820:C:CT	acceptor_gain	1.0000
15:34236821:A:AC	acceptor_gain	1.0000
15:34236821:A:C	acceptor_gain	1.0000
15:34236829:C:CT	acceptor_gain	1.0000
15:34236831:CA:C	acceptor_gain	1.0000
15:34236832:A:AC	acceptor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000021097 (15:34331273 G>T), RS1000034995 (15:34305631 A>T), RS1000047310 (15:34326595 T>C), RS1000069455 (15:34257048 G>A), RS1000070472 (15:34299612 T>A,C), RS1000075196 (15:34307767 A>T), RS1000089460 (15:34264163 C>A), RS1000168277 (15:34279309 G>A,C), RS1000236135 (15:34283067 G>A), RS1000253358 (15:34263534 A>G), RS1000268208 (15:34273730 T>C), RS1000282465 (15:34323620 C>A,T), RS1000375456 (15:34312258 G>C), RS1000380125 (15:34270114 A>T), RS1000420297 (15:34299269 A>G)

Disease associations

OMIM: gene MIM:604878 | disease phenotypes: MIM:218000, MIM:620068, MIM:118220, MIM:217990, MIM:276904

GenCC curated gene-disease

Disease	Classification	Inheritance
agenesis of the corpus callosum with peripheral neuropathy	Definitive	Autosomal recessive
Charcot-Marie-Tooth disease, axonal, IIa 2II	Strong	Autosomal dominant

Mondo (6): agenesis of the corpus callosum with peripheral neuropathy (MONDO:0000902), peripheral neuropathy (MONDO:0005244), Charcot-Marie-Tooth disease, axonal, IIa 2II (MONDO:0031068), Charcot-Marie-Tooth disease (MONDO:0015626), corpus callosum, agenesis of (MONDO:0009022), Usher syndrome type 1C (MONDO:0010171)

Orphanet (6): Corpus callosum agenesis-neuronopathy syndrome (Orphanet:1496), Charcot-Marie-Tooth disease/Hereditary motor and sensory neuropathy (Orphanet:166), Isolated corpus callosum agenesis (Orphanet:200), Autosomal recessive axonal hereditary motor and sensory neuropathy (Orphanet:91024), Usher syndrome type 1 (Orphanet:231169), Usher syndrome (Orphanet:886)

HPO phenotypes

87 total (30 of 87 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000218	High palate
HP:0000248	Brachycephaly
HP:0000252	Microcephaly
HP:0000262	Turricephaly
HP:0000276	Long face
HP:0000294	Low anterior hairline
HP:0000316	Hypertelorism
HP:0000324	Facial asymmetry
HP:0000327	Hypoplasia of the maxilla
HP:0000341	Narrow forehead
HP:0000400	Macrotia
HP:0000431	Wide nasal bridge
HP:0000486	Strabismus
HP:0000508	Ptosis
HP:0000545	Myopia
HP:0000565	Esotropia
HP:0000639	Nystagmus
HP:0000709	Psychosis
HP:0000762	Decreased nerve conduction velocity
HP:0000763	Sensory neuropathy
HP:0001182	Tapered finger
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001256	Mild intellectual disability
HP:0001257	Spasticity
HP:0001263	Global developmental delay
HP:0001270	Motor delay

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST006528_1	Barrett’s esophagus x pack-years of smoking exposure interaction	3.000000e-07

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0006526	pack-years measurement

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D061085	Agenesis of Corpus Callosum	C10.500.034; C16.131.666.034; C23.300.008
D002607	Charcot-Marie-Tooth Disease	C10.500.300.200; C10.574.500.495.200; C10.668.829.800.300.200; C16.131.666.300.200; C16.320.400.375.200
C536446	Corpus callosum agenesis neuronopathy (supp.)

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 — SLC12 family of cation-coupled chloride transporters

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	3
Cadmium Chloride	decreases expression, increases expression	3
(+)-JQ1 compound	increases expression	2
Cyclosporine	decreases expression, increases expression	2
FR900359	affects phosphorylation	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
arsenite	affects binding, decreases reaction	1
perfluorooctanoic acid	increases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
potassium chromate(VI)	decreases expression	1
avobenzone	increases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
oxamflatin	increases expression	1
apicidin	increases expression	1
dimethylarsinous acid	increases expression	1
NSC 689534	increases expression, affects binding	1
Resveratrol	affects cotreatment, increases expression	1
Norethindrone Acetate	affects cotreatment, increases expression	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Benzo(a)pyrene	increases methylation	1
Caffeine	decreases phosphorylation	1
Copper	affects binding, increases expression	1
Cytarabine	decreases expression	1
Dimethylnitrosamine	increases expression	1
Doxorubicin	decreases expression	1
Estradiol	affects cotreatment, increases expression	1
Manganese	affects cotreatment, decreases expression, increases abundance	1

Cellosaurus cell lines

5 cell lines: 3 cancer cell line, 2 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D4DJ	HEK-SLC12A6-KO-c4	Transformed cell line	Female
CVCL_D4DK	HEK-SLC12A6-KO-c5	Transformed cell line	Female
CVCL_D4HN	HCT116-SLC12A6-KO-c17	Cancer cell line	Male
CVCL_D4HP	HCT116-SLC12A6-KO-c19	Cancer cell line	Male
CVCL_TL54	HAP1 SLC12A6 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00380965	PHASE4	COMPLETED	Evaluation of the Efficacy of Cesamet™ for the Treatment of Pain in Patients With Chemotherapy-Induced Neuropathy
NCT00487981	PHASE4	TERMINATED	Spinal Cord Stimulation for Painful Diabetic Neuropathy
NCT00904202	PHASE4	COMPLETED	A Study Of Lidocaine Patch 5% Alone, Gabapentin Alone, And Lidocaine Patch 5% And Gabapentin In Combination For The Relief Of Pain In Patients With Diverse Peripheral Neuropathic Pain Conditions
NCT01192113	PHASE4	COMPLETED	Safety and Efficacy of Mecobalamin Injection in Peripheral Neuropathies Patients (Study JGAZSY091109)
NCT01373983	PHASE4	COMPLETED	Intrathecal Bolus Doses of Ziconotide
NCT01458015	PHASE4	TERMINATED	Tapentadol Versus Oxycodone - a Mechanism-based Treatment Approach in Neuropathic Pain
NCT02074267	PHASE4	COMPLETED	Clinical Study for Assessment of the Efficacy of Gabapentin (Carbatin and Neurontin) in Patients With Neuropathy Pain
NCT02372149	PHASE4	UNKNOWN	IVIg for Demyelination in Diabetes Mellitus
NCT02670161	PHASE4	ENROLLING_BY_INVITATION	Quality Improvement and Practice Based Research in Neurology Using the EMR
NCT07022938	PHASE4	COMPLETED	Nutritional Supplement for Treating Chemotherapy Induced Neuropathy
NCT07025005	PHASE4	RECRUITING	Fenofibrate Role in the Prophylaxis From Peripheral Neuropathy Induced by Bortezomib, Lenalidomide and Dexamethasone (VRd) Protocol in the Treatment of Patients With Multiple Myeloma (MM)
NCT00058071	PHASE3	COMPLETED	Amifostine in Treating Peripheral Neuropathy in Patients Who Have Received Chemotherapy for Cancer
NCT00125268	PHASE3	TERMINATED	Near Infrared Light for the Treatment of Painful Peripheral Neuropathy
NCT00195013	PHASE3	COMPLETED	Randomized Placebo-Controlled Trial of Glutamine for Breast Cancer Patients With Peripheral Neuropathy
NCT00232141	PHASE3	COMPLETED	Study of Pregabalin Versus Placebo in the Treatment of Nerve Pain Associated With HIV Neuropathy
NCT00264875	PHASE3	COMPLETED	Open Label Safety And Efficacy Study Of Pregabalin In Subjects With Nerve Pain Asociated With Human Immunodeficiency Virus (HIV) Neuropathy
NCT00369564	PHASE3	COMPLETED	Glutamic Acid in Reducing Nerve Damage Caused by Vincristine in Young Patients With Cancer
NCT00471445	PHASE3	COMPLETED	Topical Amitriptyline and Ketamine Cream in Treating Peripheral Neuropathy Caused by Chemotherapy in Cancer Patients
NCT00489411	PHASE3	COMPLETED	Duloxetine in Treating Peripheral Neuropathy Caused by Chemotherapy in Patients With Cancer
NCT00710554	PHASE3	COMPLETED	A Study of Sativex® for Pain Relief of Peripheral Neuropathic Pain, Associated With Allodynia
NCT00711880	PHASE3	COMPLETED	A Study of Sativex® for Relief of Peripheral Neuropathic Pain Associated With Allodynia.
NCT00713323	PHASE3	COMPLETED	A Study to Compare the Safety and Tolerability of Sativex® in Patients With Neuropathic Pain.
NCT00713817	PHASE3	COMPLETED	A Study to Determine the Maintenance of Effect After Long-term Treatment of Sativex® in Subjects With Neuropathic Pain
NCT00775645	PHASE3	COMPLETED	S0715: Acetyl-L-Carnitine in Preventing Neuropathy in Women With Stage I, II, or IIIA Breast Cancer Undergoing Chemo
NCT00872352	PHASE3	UNKNOWN	Evaluation of Bortezomib Induced Peripheral Neuropathy of Multiple Myeloma (MM) Patients
NCT00998738	PHASE3	TERMINATED	Calcium and Magnesium in Preventing Peripheral Neuropathy Caused by Ixabepilone in Patients With Breast Cancer
NCT01049217	PHASE3	TERMINATED	Pregabalin Versus Placebo In The Treatment Of Neuropathic Pain Associated With HIV Neuropathy
NCT01099449	PHASE3	COMPLETED	Calcium Gluconate and Magnesium Sulfate in Preventing Neurotoxicity in Patients With Colon Cancer or Rectal Cancer Receiving Oxaliplatin-Based Combination Chemotherapy
NCT01288937	PHASE3	TERMINATED	A Placebo Controlled, Randomized, Double Blind Trial of Milnacipran for the Treatment of Idiopathic Neuropathy Pain
NCT01492920	PHASE3	WITHDRAWN	Acetyl-L-Carnitine Hydrochloride in Preventing Peripheral Neuropathy in Patients With Recurrent Ovarian Epithelial Cancer, Primary Peritoneal Cavity Cancer, or Fallopian Tube Cancer Undergoing Chemotherapy
NCT01775449	PHASE3	COMPLETED	Prevention of Oxaliplatin-induced Neuropathic Pain by a Specific Diet
NCT02024191	PHASE3	UNKNOWN	The Role of Glutamine for Preventing Oxaliplatin-Induced Peripheral Neuropathy
NCT02217267	PHASE3	COMPLETED	Long Term Outcome After Serial Lidocaine Infusion in Peripheral Neuropathic Pain
NCT02294149	PHASE3	UNKNOWN	Vit D3 and Omega 3 in Chemo Induced Neuropathy
NCT02311907	PHASE3	COMPLETED	Glutathione in Preventing Peripheral Neuropathy Caused by Paclitaxel and Carboplatin in Patients With Ovarian Cancer, Fallopian Tube Cancer, and/or Primary Peritoneal Cancer
NCT06071936	PHASE3	UNKNOWN	Efficacy and Tolerability of AP707 in Patients With Chronic Pain Due to Traumatic or Post-operative Peripheral Neuropathy
NCT06071975	PHASE3	UNKNOWN	Long Term Efficacy and Tolerability of AP707 in Patients With Chronic Pain Due to Diabetic Polyneuropathy
NCT06071988	PHASE3	UNKNOWN	Long Term Efficacy and Tolerability of AP707 in Patients With Chronic Pain Due to Traumatic or Post-operative Peripheral Neuropathy
NCT06072573	PHASE3	UNKNOWN	Efficacy and Tolerability of AP707 in Patients With Chronic Pain Due to Diabetic Polyneuropathy
NCT07287592	PHASE3	NOT_YET_RECRUITING	Glutamine for the Prophylaxis of Vincristine-induced Neuropathy in Children and Adolescents With Cancer.