SLC5A7

Summary

SLC5A7 (solute carrier family 5 member 7, HGNC:14025) is a protein-coding gene on chromosome 2q12.3, encoding High affinity choline transporter 1 (Q9GZV3). High-affinity Na(+)-coupled choline transmembrane symporter.

This gene encodes a sodium ion- and chloride ion-dependent high-affinity transporter that mediates choline uptake for acetylcholine synthesis in cholinergic neurons. The protein transports choline from the extracellular space into presynaptic terminals for synthesis into acetylcholine. Increased choline uptake results from increased density of this protein in synaptosomal plasma membranes in response to depolarization of cholinergic terminals. Dysfunction of cholinergic signaling has been implicated in various disorders including depression, attention-deficit disorder, and schizophrenia. An allelic variant of this gene is associated with autosomal dominant distal hereditary motor neuronopathy type VIIA. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 60482 — RefSeq curated summary.

At a glance

• Gene–disease (curated): congenital myasthenic syndrome 20 (Strong, GenCC) — +3 more curated relationships
• Clinical variants (ClinVar): 591 total — 6 pathogenic, 13 likely-pathogenic
• Phenotypes (HPO): 92
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_021815

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14025
Approved symbol	SLC5A7
Name	solute carrier family 5 member 7
Location	2q12.3
Locus type	gene with protein product
Status	Approved
Aliases	hCHT, CHT1, ChT
Ensembl gene	ENSG00000115665
Ensembl biotype	protein_coding
OMIM	608761
Entrez	60482

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000264047, ENST00000409059, ENST00000950055

RefSeq mRNA: 4 — MANE Select: NM_021815 NM_001305005, NM_001305006, NM_001305007, NM_021815

CCDS: CCDS2074

Canonical transcript exons

ENST00000264047 — 9 exons

Exon	Start	End
ENSE00000963446	107997838	107997986
ENSE00000963447	108001897	108002040
ENSE00000963448	108006049	108006202
ENSE00000963449	108008465	108008682
ENSE00000963450	108010232	108013994
ENSE00001009231	107986524	107986763
ENSE00001337491	107988105	107988333
ENSE00003578546	107992972	107993127
ENSE00003588062	107992106	107992219

Expression profiles

Bgee: expression breadth ubiquitous, 101 present calls, max score 76.38.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 3.7716 / max 2744.5919, expressed in 146 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
21848	2.9575	104
21845	0.5317	59
21847	0.1065	15
21844	0.0889	9
21846	0.0706	13
21849	0.0164	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	76.38	gold quality
pancreatic ductal cell	CL:0002079	67.66	silver quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	65.51	gold quality
muscle layer of sigmoid colon	UBERON:0035805	65.02	gold quality
colonic epithelium	UBERON:0000397	63.42	silver quality
choroid plexus epithelium	UBERON:0003911	63.04	silver quality
putamen	UBERON:0001874	60.40	gold quality
lower esophagus muscularis layer	UBERON:0035833	60.20	gold quality
lower esophagus	UBERON:0013473	60.16	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	60.10	gold quality
urinary bladder	UBERON:0001255	60.00	gold quality
mucosa of urinary bladder	UBERON:0001259	59.17	gold quality
caudate nucleus	UBERON:0001873	58.69	gold quality
rectum	UBERON:0001052	56.72	gold quality
superior vestibular nucleus	UBERON:0007227	55.61	silver quality
smooth muscle tissue	UBERON:0001135	55.50	gold quality
mucosa of paranasal sinus	UBERON:0005030	55.47	gold quality
mucosa of stomach	UBERON:0001199	54.81	gold quality
colon	UBERON:0001155	54.38	gold quality
large intestine	UBERON:0000059	53.94	gold quality
vermiform appendix	UBERON:0001154	52.72	gold quality
epithelial cell of pancreas	CL:0000083	52.52	gold quality
intestine	UBERON:0000160	52.44	gold quality
nucleus accumbens	UBERON:0001882	52.04	gold quality
tibialis anterior	UBERON:0001385	51.42	silver quality
caecum	UBERON:0001153	51.07	gold quality
cervix squamous epithelium	UBERON:0006922	50.88	gold quality
hypothalamus	UBERON:0001898	50.76	gold quality
cortical plate	UBERON:0005343	50.61	gold quality
germinal epithelium of ovary	UBERON:0001304	50.59	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.53

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

166 targeting SLC5A7, 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-1277-5P	100.00	73.95	5056
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-574-5P	100.00	66.01	989
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-1468-3P	99.96	72.74	3797

Literature-anchored findings (GeneRIF, showing 27)

• Results describe the identification and functional characterization of a single nucleotide polymorphism in the high affinity choline transporter (CHT1) gene. (PMID:12237312)
• high-affinity choline transporter, choline transporter 1, in nerve fibers and epithelial cells in the human and rat skin supporting the pivotal role of this transporter in both the neuronal and non-neuronal cholinergic system of the skin. (PMID:12406342)
• CHT1 binds to Par-4 and inhibits choline uptake when its incorporation is reduced on the cell surface (PMID:15090548)
• CHT1 variation is related to differences in a distributed corticolimbic circuitry mediating behavioral and physiologic arousal. (PMID:16876130)
• The charge/choline ratio of hCHT varies from 10e/choline at -80 mV to 3e/choline at -20 mV. Choline uptake & choline-induced current are Na+ & Cl- dependent. External protons reduce hCHT current, transport, & binding with a similar pKa of 7.4. (PMID:17005849)
• The colocalisation of CHT1 immunoreactivity with VAChT immunoreactivity in cholinergic enteric nerves in the human bowel thus suggests that CHT1 represents another marker of cholinergic nerves. (PMID:20490865)
• overexpressed ChAT enhanced transcription of the CHT1 gene but not the VACHT gene (PMID:21163949)
• Polymorphic variation in the CHT1 gene can predict early, subclinical measures of carotid atherosclerosis. (PMID:21337021)
• Nedd4-2 mediated ubiquitination regulates the cell surface expression of CHT1 in HEK293 cells. (PMID:22361880)
• This mini-review discusses structural requirements for both organic cationic transporters OCT1 and OCT2 versus the blood-brain barrier choline transporter (BBBCHT) are discussed and compared. (PMID:22483271)
• [review] The critical role of CHT in maintaining cholinergic transmission indicates that it could be a target for therapeutic intervention to promote acetylcholine synthesis, the accomplishment of which has not been adequately addressed. (PMID:22483273)
• CHT1 forms a homo-oligomer on the cell surface in cultured cells. (PMID:23132865)
• Our findings compel consideration of mutations in SLC5A7 or its functional partners in relation to unexplained motor neuronopathies. (PMID:23141292)
• In transgenic animals with a heterozygous deletion of the choline transporter there is impairment in performing sustained attention tasks. (PMID:23392663)
• This study demonstrated a specific impairment in cognitive control associated with the Ile89Val polymorphism of SLC5A7. (PMID:24666128)
• These data show that acute exposure of depolarized cells to insulin is coupled to transiently increased levels of CHT proteins at the cell surface, and that this is attenuated by chronic insulin exposure. (PMID:26161852)
• Impaired Presynaptic High-Affinity Choline Transporter Causes a Congenital Myasthenic Syndrome with Episodic Apnea: this study broadens the clinical spectrum of human diseases resulting from reduced CHT activity and highlights the complexity of cholinergic metabolism at the synapse (PMID:27569547)
• Lack of association between SLC5A7 polymorphisms and Tourette syndrome in a Chinese Han population (PMID:28830823)
• Here we describe an autosomal recessive presynaptic congenital myasthenic syndrome presenting with a broad clinical phenotype due to homozygous SLC5a7 missense mutations. Phenotype ranges from classical presentation of a congenital myasthenic syndrome in one patient (p.Pro210Leu), to severe neurodevelopmental delay with brain atrophy (p.Ser94Arg) and extend the clinical outcomes to infantile lethality (p.Val112Glu). (PMID:29088354)
• Biallelic loss-of-function SLC5A7 variants cause congenital myasthenic syndrome, while a monoallelic truncatingvariant in the last exon of SLC5A7 was reported in 2 unrelated hereditary motor neuropathy 7 families from Wales (PMID:29782645)
• SLC5A7 genotype significantly predicted respiratory sinus arrhythmia (RSA) stress responsivity (beta=-0.023; p=0.028) and heart rate (HR) stress responsivity (beta=0.004; p=0.002). T-allele carriers exhibited RSA suppression and HR acceleration in response to stress while G/G homozygotes did not suppress RSA and exhibited less HR acceleration. (PMID:30005279)
• Our observation regarding defective myelination in the recessive form of the SLC5A7-related disorder could suggest that pathogenicity of CHT1 variants is not limited strictly to the transport of choline but may also influence myelination with a combined functional effect. (PMID:31299140)
• Choline-induced SLC5A7 impairs colorectal cancer growth by stabilizing p53 protein. (PMID:34562520)
• Targeted demethylation of the SLC5A7 promotor inhibits colorectal cancer progression. (PMID:35858918)
• CircFBXW4 Suppresses Colorectal Cancer Progression by Regulating the MiR-338-5p/SLC5A7 Axis. (PMID:38461489)
• Genetic analysis of a family affected by congenital myasthenic syndrome due to a Novel mutation in the SLC5A7 gene. (PMID:38886633)
• Congenital myasthenic syndrome secondary to pathogenic variants in the SLC5A7 gene: report of two cases. (PMID:39135055)

Cross-species orthologs

14 orthologs

Organism	Symbol	Gene ID
danio_rerio	slc5a7a	ENSDARG00000074860
danio_rerio	SLC5A7	ENSDARG00000102336
mus_musculus	Slc5a7	ENSMUSG00000023945
rattus_norvegicus	Slc5a7	ENSRNOG00000010597
drosophila_melanogaster	CG2187	FBGN0017448
drosophila_melanogaster	rumpel	FBGN0029950
drosophila_melanogaster	SLC5A11	FBGN0031998
drosophila_melanogaster	bumpel	FBGN0037895
drosophila_melanogaster	salt	FBGN0039872
drosophila_melanogaster	Smvt	FBGN0039873
drosophila_melanogaster	CG31262	FBGN0051262
drosophila_melanogaster	CG31668	FBGN0051668
drosophila_melanogaster	CG33124	FBGN0053124
drosophila_melanogaster	kumpel	FBGN0250757

Paralogs (12): SLC5A1 (ENSG00000100170), SLC5A4 (ENSG00000100191), SLC5A5 (ENSG00000105641), SLC5A9 (ENSG00000117834), SLC5A6 (ENSG00000138074), SLC5A2 (ENSG00000140675), SLC5A12 (ENSG00000148942), SLC5A10 (ENSG00000154025), SLC5A11 (ENSG00000158865), SLC5A3 (ENSG00000198743), SLC5A8 (ENSG00000256870), (ENSG00000293606)

Protein

Protein identifiers

High affinity choline transporter 1 — Q9GZV3 (reviewed: Q9GZV3)

Alternative names: Hemicholinium-3-sensitive choline transporter, Solute carrier family 5 member 7

All UniProt accessions (1): Q9GZV3

UniProt curated annotations — full annotation on UniProt →

Function. High-affinity Na(+)-coupled choline transmembrane symporter. Functions as an electrogenic, voltage-dependent transporter with variable charge/choline stoichiometry. Choline uptake and choline-induced current is also Cl(-)-dependent where Cl(-) is likely a regulatory ion rather than cotransported ion. Plays a critical role in acetylcholine (ACh) synthesis by taking up the substrate choline from the synaptic cleft into the presynaptic nerve terminals after neurotransmitter release. SLC5A7/CHT1-mediated choline high-affinity transport in cholinergic neurons is the rate-limiting step for production of ACh, thereby facilitating communication by subsequent action potentials. Localized predominantly in presynaptic terminal intracellular organelles, and translocated to the plasma membrane in active form in response to neuronal activity.

Subunit / interactions. Homooligomerizes at cell surface. Interacts with SEC14L1; may regulate SLC5A7.

Subcellular location. Presynaptic cell membrane. Cell projection. Axon. Early endosome membrane. Cytoplasmic vesicle. Secretory vesicle. Synaptic vesicle membrane.

Tissue specificity. Expressed in putamen, spinal cord and medulla. Expressed in cholinergic neurons.

Post-translational modifications. Phosphorylated.

Disease relevance. Neuronopathy, distal hereditary motor, autosomal dominant 7 (HMND7) [MIM:158580] A form of distal hereditary motor neuronopathy, a heterogeneous group of neuromuscular disorders caused by selective degeneration of motor neurons in the anterior horn of the spinal cord, without sensory deficit in the posterior horn. The overall clinical picture consists of a classical distal muscular atrophy syndrome in the legs without clinical sensory loss. The disease starts with weakness and wasting of distal muscles of the anterior tibial and peroneal compartments of the legs. Later on, weakness and atrophy may expand to the proximal muscles of the lower limbs and/or to the distal upper limbs. HMND7 is characterized by onset in the second decade of progressive distal muscle wasting and weakness affecting the upper and lower limbs and resulting in walking difficulties and hand grip. There is significant muscle atrophy of the hands and lower limbs. The disorder is associated with vocal cord paresis due to involvement of the tenth cranial nerve. The disease is caused by variants affecting the gene represented in this entry. Myasthenic syndrome, congenital, 20, presynaptic (CMS20) [MIM:617143] A form of congenital myasthenic syndrome, a group of disorders characterized by failure of neuromuscular transmission, including pre-synaptic, synaptic, and post-synaptic disorders that are not of autoimmune origin. Clinical features are easy fatigability and muscle weakness. CMS20 is an autosomal recessive, pre-synaptic form characterized by severe hypotonia and episodic apnea soon after birth, generalized limb fatigability and weakness, delayed walking, ptosis, poor sucking and swallowing. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Choline uptake activity is regulated by SLC5A7/CHT1 internalization (inactive form) from the cell surface and recycling of internalized SLC5A7/CHT1 into the cell surface (active form). Activated by extracellular chloride ion. Specifically inhibited by nanomolar concentrations of hemicholinium 3.

Domain organisation. The C-terminal dileucine-like motif (DKTILV) controls SLC5A7/CHT1 internalization in clathrin-coated vesicles to early endosomes as well as choline transporter activity.

Similarity. Belongs to the sodium:solute symporter (SSF) (TC 2.A.21) family.

RefSeq proteins (4): NP_001291934, NP_001291935, NP_001291936, NP_068587* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001734	Na/solute_symporter	Family
IPR038377	Na/Glc_symporter_sf	Homologous_superfamily
IPR052244	Choline_transporter	Family

Pfam: PF00474

Catalyzed reactions (Rhea), 1 shown:

• choline(out) + n Na(+)(out) = choline(in) + n Na(+)(in) (RHEA:76443)

UniProt features (86 total): helix 25, topological domain 14, transmembrane region 13, sequence variant 11, mutagenesis site 7, turn 6, strand 6, chain 1, region of interest 1, short sequence motif 1, glycosylation site 1

Structure

Experimental structures (PDB)

12 structures.

PDB	Method	Resolution (Å)
9BFJ	ELECTRON MICROSCOPY	2.35
8ZQQ	ELECTRON MICROSCOPY	2.5
9BFI	ELECTRON MICROSCOPY	2.66
8ZQO	ELECTRON MICROSCOPY	2.8
9BFK	ELECTRON MICROSCOPY	2.85
8ZQP	ELECTRON MICROSCOPY	3.1
8J74	ELECTRON MICROSCOPY	3.6
8J75	ELECTRON MICROSCOPY	3.6
8ZQR	ELECTRON MICROSCOPY	3.6
9BIM	ELECTRON MICROSCOPY	3.67
8J76	ELECTRON MICROSCOPY	3.7
8J77	ELECTRON MICROSCOPY	3.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9GZV3-F1	84.35	0.55

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): 301

Mutagenesis-validated functional residues (7):

Position	Phenotype
89	decreased choline transmembrane transporter activity, only 20% of wild-type choline uptake activity.
451	decreased choline transmembrane transporter activity, only 5% of wild-type choline uptake activity.
530	no change in protein internalization. no change in choline transmembrane transporter activity.
531–532	decreased protein internalization; when associated with v-538. increased choline transmembrane transporter activity; whe
531	loss of protein internalization to vesicular structures in neurons. increased choline transmembrane transporter activity
532	decreased protein internalization. increased choline transmembrane transporter activity.
538	decreased protein internalization; when associated with 531-l-v-532. increased choline transmembrane transporter activit

Function

Pathways and Gene Ontology

Reactome pathways

13 pathways

ID	Pathway
R-HSA-264642	Acetylcholine Neurotransmitter Release Cycle
R-HSA-5619114	Defective SLC5A7 in the neurotransmitter release cycle causes distal hereditary motor neuronopathy 7A (HMN7A)
R-HSA-5658471	Defective transport by SLC5A7 causes distal hereditary motor neuronopathy 7A (HMN7A)
R-HSA-9958517	SLC-mediated bile acid transport
R-HSA-425366
R-HSA-112310	Neurotransmitter release cycle
R-HSA-112315	Transmission across Chemical Synapses
R-HSA-112316	Neuronal System
R-HSA-1643685	Disease
R-HSA-382551	Transport of small molecules
R-HSA-425407	SLC-mediated transmembrane transport
R-HSA-5619102	SLC transporter disorders
R-HSA-5619115	Disorders of transmembrane transporters

MSigDB gene sets: 305 (showing top): GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, chr2q12, AAGCCAT_MIR135A_MIR135B, GOBP_SYNAPTIC_TRANSMISSION_CHOLINERGIC, GOBP_NEUROTRANSMITTER_TRANSPORT, GAUSSMANN_MLL_AF4_FUSION_TARGETS_E_UP, CAGCTG_AP4_Q5, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_CELL_CELL_SIGNALING, GOBP_IN_UTERO_EMBRYONIC_DEVELOPMENT, GOBP_SYNAPTIC_SIGNALING, GOBP_ORGANIC_CATION_TRANSPORT, GOCC_NEURON_PROJECTION, GOBP_EMBRYO_DEVELOPMENT, HNF1_01

GO Biological Process (9): in utero embryonic development (GO:0001701), neurotransmitter transport (GO:0006836), synaptic transmission, cholinergic (GO:0007271), neuromuscular synaptic transmission (GO:0007274), acetylcholine biosynthetic process (GO:0008292), choline transport (GO:0015871), transmembrane transport (GO:0055085), monoatomic ion transport (GO:0006811), sodium ion transport (GO:0006814)

GO Molecular Function (5): choline:sodium symporter activity (GO:0005307), choline transmembrane transporter activity (GO:0015220), choline binding (GO:0033265), symporter activity (GO:0015293), transmembrane transporter activity (GO:0022857)

GO Cellular Component (15): plasma membrane (GO:0005886), membrane (GO:0016020), axon (GO:0030424), dendrite (GO:0030425), synaptic vesicle membrane (GO:0030672), neuromuscular junction (GO:0031594), early endosome membrane (GO:0031901), presynaptic membrane (GO:0042734), perikaryon (GO:0043204), synapse (GO:0045202), endosome (GO:0005768), cytoplasmic vesicle (GO:0031410), cell projection (GO:0042995), neuronal cell body (GO:0043025), presynapse (GO:0098793)

Reactome top-level categories

Rollup of top-8 pathways:

Category	Pathways
SLC transporter disorders	2
Neurotransmitter release cycle	1
SLC-mediated transport of organic anions	1
Transmission across Chemical Synapses	1
Neuronal System	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
cellular anatomical structure	4
transport	3
chemical synaptic transmission	2
neuron projection	2
synapse	2
chordate embryonic development	1
acetylcholine metabolic process	1
biosynthetic process	1
nitrogen compound transport	1
cellular process	1
metal ion transport	1
choline transmembrane transporter activity	1
solute:sodium symporter activity	1
choline transport	1
transmembrane transporter activity	1
cation binding	1
secondary active transmembrane transporter activity	1
transporter activity	1
transmembrane transport	1
membrane	1
cell periphery	1
dendritic tree	1
synaptic vesicle	1
exocytic vesicle membrane	1
early endosome	1
endosome membrane	1
synaptic membrane	1
presynapse	1
neuronal cell body	1
cell junction	1
endomembrane system	1
cytoplasmic vesicle	1
cytoplasm	1
intracellular vesicle	1
somatodendritic compartment	1
cell body	1

Protein interactions and networks

STRING

1505 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC5A7	SLC18A3	Q16572	854
SLC5A7	KIF23	Q02241	782
SLC5A7	CHAT	P28329	749
SLC5A7	RANBP2	P49792	737
SLC5A7	SLC44A1	Q8WWI5	693
SLC5A7	CHIT1	Q13231	665
SLC5A7	CTRB2	Q6GPI1	628
SLC5A7	CTRB1	P17538	627
SLC5A7	CTRL	P40313	587
SLC5A7	SLC5A6	Q9Y289	581
SLC5A7	SLC44A2	Q8IWA5	565
SLC5A7	ACHE	P22303	563
SLC5A7	SLC44A5	Q8NCS7	534
SLC5A7	SLC10A4	Q96EP9	534
SLC5A7	SLC44A3	Q8N4M1	520

IntAct

4 interactions, top by confidence:

A	B	Type	Score
ZMYND11	SLC5A7	psi-mi:“MI:0407”(direct interaction)	0.440
SLC5A7	KIAA1549	psi-mi:“MI:0915”(physical association)	0.400
SLC5A7	FUT4	psi-mi:“MI:0914”(association)	0.350

BioGRID (27): SLC5A7 (Affinity Capture-Western), PAWR (Affinity Capture-Western), SLC5A7 (Affinity Capture-MS), SEC14L1 (Two-hybrid), SEC14L1 (Affinity Capture-Western), SLC5A7 (Affinity Capture-Western), KIAA1549 (Affinity Capture-MS), SLC5A7 (Affinity Capture-Western), TP53 (Affinity Capture-Western), SLC5A7 (Two-hybrid), AMFR (Affinity Capture-MS), BCAP29 (Affinity Capture-MS), BCAP31 (Affinity Capture-MS), CHPF2 (Affinity Capture-MS), CHSY1 (Affinity Capture-MS)

ESM2 similar proteins: A0A1D8PDB5, A0A1D8PNR5, A1AIQ8, A1JIK1, A4TS08, A7FNG3, A8AN31, A9R563, B1JNK6, B1LPN2, B1XCV3, B2K137, B2TXA0, B6I5T5, B7LB16, B7MJT5, B7MSH6, B7NSM7, B7UPN5, C6D930, D3ZIS0, F4KD71, O59813, O94469, P11170, P26429, P31636, P33413, P53790, P53791, Q0T9Y2, Q1C0M8, Q1CE35, Q1R3J9, Q31TS7, Q3YUR7, Q42400, Q66FN0, Q6D913, Q7XBS0

Diamond homologs: O02228, Q8BGY9, Q8UWF0, Q9GZV3, Q9JMD7, Q9VE46

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	6
Likely pathogenic	13
Uncertain significance	320
Likely benign	207
Benign	22

Top pathogenic / likely-pathogenic (19)

Variant ID	HGVS	Classification
1426671	NM_021815.5(SLC5A7):c.364dup (p.Tyr122fs)	Pathogenic
265765	NM_021815.5(SLC5A7):c.143A>G (p.Asp48Gly)	Pathogenic
3752933	NM_021815.5(SLC5A7):c.719G>A (p.Trp240Ter)	Pathogenic
3756992	NM_021815.5(SLC5A7):c.134del (p.Gly45fs)	Pathogenic
4784269	NM_021815.5(SLC5A7):c.836del (p.Phe279fs)	Pathogenic
4788433	NM_021815.5(SLC5A7):c.101dup (p.Ser34fs)	Pathogenic
1009672	NM_021815.5(SLC5A7):c.292+1G>A	Likely pathogenic
1027324	NM_021815.5(SLC5A7):c.895+1G>C	Likely pathogenic
1299689	NM_021815.5(SLC5A7):c.1113+2T>A	Likely pathogenic
1415144	NM_021815.5(SLC5A7):c.179-2A>G	Likely pathogenic
2500960	NM_021815.5(SLC5A7):c.742-2A>G	Likely pathogenic
265763	NM_021815.5(SLC5A7):c.1082G>A (p.Arg361Gln)	Likely pathogenic
265764	NM_021815.5(SLC5A7):c.123_126del (p.Ala41_Ile42insTer)	Likely pathogenic
2687476	NM_021815.5(SLC5A7):c.178+2T>C	Likely pathogenic
2687766	NM_021815.5(SLC5A7):c.1207T>C (p.Tyr403His)	Likely pathogenic
2687767	NM_021815.5(SLC5A7):c.1349G>A (p.Gly450Glu)	Likely pathogenic
2691886	NM_021815.5(SLC5A7):c.1503_1506del (p.Phe502fs)	Likely pathogenic
4293912	NM_021815.5(SLC5A7):c.881T>C (p.Ile294Thr)	Likely pathogenic
872332	NM_021815.5(SLC5A7):c.1231G>A (p.Asp411Asn)	Likely pathogenic

SpliceAI

1970 predictions. Top by Δscore:

Variant	Effect	Δscore
2:107986759:TCCAG:T	donor_loss	1.0000
2:107986760:CCAG:C	donor_loss	1.0000
2:107986761:CAGG:C	donor_loss	1.0000
2:107986762:AGGTA:A	donor_loss	1.0000
2:107986763:GG:G	donor_loss	1.0000
2:107986764:G:GA	donor_loss	1.0000
2:107986765:T:G	donor_loss	1.0000
2:107997832:TTTCA:T	acceptor_loss	1.0000
2:107997833:TTCAG:T	acceptor_loss	1.0000
2:107997835:CA:C	acceptor_loss	1.0000
2:107997836:A:AG	acceptor_gain	1.0000
2:107997837:G:GG	acceptor_gain	1.0000
2:107997837:GGA:G	acceptor_gain	1.0000
2:108008463:A:AG	acceptor_gain	1.0000
2:108008464:G:GG	acceptor_gain	1.0000
2:107988103:A:AG	acceptor_gain	0.9900
2:107988104:G:GG	acceptor_gain	0.9900
2:107988104:GAA:G	acceptor_gain	0.9900
2:107988206:A:AG	acceptor_gain	0.9900
2:107988214:T:A	acceptor_gain	0.9900
2:107993139:C:G	donor_gain	0.9900
2:107997836:AG:A	acceptor_gain	0.9900
2:107997837:GG:G	acceptor_gain	0.9900
2:108005736:TGG:T	donor_gain	0.9900
2:108005738:G:GT	donor_gain	0.9900
2:108008459:CAACA:C	acceptor_loss	0.9900
2:108008461:ACAG:A	acceptor_loss	0.9900
2:108008462:CAGAC:C	acceptor_loss	0.9900
2:108008463:A:T	acceptor_loss	0.9900
2:108008463:AGACT:A	acceptor_gain	0.9900

AlphaMissense

3745 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:107997951:G:C	D188H	1.000
2:107997951:G:T	D188Y	1.000
2:107997952:A:C	D188A	1.000
2:108008469:G:C	W300C	1.000
2:108008469:G:T	W300C	1.000
2:108008594:C:A	A342D	1.000
2:108008597:C:A	A343D	1.000
2:107988219:G:A	G22R	0.999
2:107988219:G:C	G22R	0.999
2:107988220:G:A	G22E	0.999
2:107988315:G:C	G54R	0.999
2:107988316:G:A	G54D	0.999
2:107988325:C:T	T57I	0.999
2:107988333:G:C	A60P	0.999
2:107992106:C:A	A60D	0.999
2:107992109:C:T	T61I	0.999
2:107992111:T:A	W62R	0.999
2:107992111:T:C	W62R	0.999
2:107992136:G:A	G70D	0.999
2:107992142:C:A	A72D	0.999
2:107992207:A:C	S94R	0.999
2:107992209:T:A	S94R	0.999
2:107992209:T:G	S94R	0.999
2:107992211:T:C	L95P	0.999
2:107992998:C:A	R107S	0.999
2:107992999:G:C	R107P	0.999
2:107997904:C:A	A172D	0.999
2:107997925:G:A	G179E	0.999
2:107997943:C:A	A185D	0.999
2:107997952:A:G	D188G	0.999

dbSNP variants (sampled 300 via entrez): RS1000048052 (2:107992264 C>A,G,T), RS1000227125 (2:107994359 G>A), RS1000296097 (2:108012089 T>C), RS1000327849 (2:108012244 A>G), RS1000484135 (2:107998682 A>G), RS1000501508 (2:108009330 CTTTT>C), RS1000508223 (2:108005531 G>A), RS1000537451 (2:107999020 A>C), RS1000706379 (2:107986205 T>C), RS1000830853 (2:107993217 G>A), RS1000880140 (2:108005179 C>A), RS1000980284 (2:107986760 C>G), RS1001047668 (2:107990619 C>T), RS1001078727 (2:107990951 C>A,T), RS1001096086 (2:107992904 G>A)

Disease associations

OMIM: gene MIM:608761 | disease phenotypes: MIM:158580, MIM:617143, MIM:118220

GenCC curated gene-disease

Disease	Classification	Inheritance
neuronopathy, distal hereditary motor, type 7A	Strong	Autosomal dominant
congenital myasthenic syndrome 20	Strong	Autosomal recessive
distal hereditary motor neuropathy type 7	Supportive	Autosomal dominant
presynaptic congenital myasthenic syndrome	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
neuronopathy, distal hereditary motor, type 7A	Moderate	AD

Mondo (8): neuronopathy, distal hereditary motor, type 7A (MONDO:0008024), congenital myasthenic syndrome 20 (MONDO:0014939), Charcot-Marie-Tooth disease type 2 (MONDO:0018993), prostate cancer (MONDO:0008315), Charcot-Marie-Tooth disease (MONDO:0015626), distal hereditary motor neuropathy (MONDO:0018894), distal hereditary motor neuropathy type 7 (MONDO:0015355), (MONDO:0020345)

Orphanet (5): Distal hereditary motor neuropathy type 7 (Orphanet:139589), Autosomal dominant Charcot-Marie-Tooth disease type 2 (Orphanet:64746), Familial prostate cancer (Orphanet:1331), Charcot-Marie-Tooth disease/Hereditary motor and sensory neuropathy (Orphanet:166), Distal hereditary motor neuropathy (Orphanet:53739)

HPO phenotypes

92 total (30 of 92 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000218	High palate
HP:0000276	Long face
HP:0000308	Microretrognathia
HP:0000369	Low-set ears
HP:0000407	Sensorineural hearing impairment
HP:0000467	Neck muscle weakness
HP:0000508	Ptosis
HP:0000565	Esotropia
HP:0000597	Ophthalmoparesis
HP:0000602	Ophthalmoplegia
HP:0000639	Nystagmus
HP:0000651	Diplopia
HP:0000768	Pectus carinatum
HP:0000961	Cyanosis
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001265	Hyporeflexia
HP:0001270	Motor delay
HP:0001283	Bulbar palsy
HP:0001284	Areflexia
HP:0001288	Gait disturbance
HP:0001324	Muscle weakness
HP:0001337	Tremor
HP:0001374	Congenital hip dislocation
HP:0001382	Joint hypermobility
HP:0001558	Decreased fetal movement

GWAS associations

0 associations (top):

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
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
D011471	Prostatic Neoplasms	C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750
C563562	Neuropathy, Distal Hereditary Motor, Type VIIA (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4507 (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: 50,135 (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
CHEMBL282468	CHOLINE CHLORIDE	3	50,135

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

PharmGKB variants

4 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs6542746	SLC5A7		0.00	0
rs6720783	SLC5A7		0.00	0
rs11685873	SLC5A7		0.00	0
rs1013940	SLC5A7		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: transporter — Choline transporter

Most potent curated ligand interactions (2 total), top 2:

Ligand	Action	Affinity	Parameter
[3H]hemicholinium-3		8.4	pKd
hemicholinium-3	Inhibition	8.0	pKi

Binding affinities (BindingDB)

72 measured of 73 human assays (75 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
SMR000658847	IC50	18.9 nM
N-[(4,5-dimethyl-1,3-thiazol-2-yl)methyl]-4-methoxy-3-(1-propan-2-ylpiperidin-4-yl)oxybenzamide	IC50	303 nM
cid_1744440	IC50	447 nM
MLS001081265	IC50	864 nM
N-(furan-2-ylmethyl)-2-piperidin-1-yl-quinazolin-4-amine;hydrochloride	EC50	1790 nM
N-(1-phenylethyl)-4-{[1-(pyridin-2-ylmethyl)piperidin-4-yl]oxy}benzamide	IC50	1790 nM
N-(2,3-dihydro-1H-inden-1-yl)-4-methoxy-3-[(1-propan-2-yl-4-piperidinyl)oxy]benzamide	IC50	2120 nM
2,4-dichloro-N-{4-[(2-quinoxalinylamino)sulfonyl]phenyl}benzamide	IC50	2820 nM
5-(3-bromanyl-4-methoxy-phenyl)-N-(4-ethylphenyl)-4-phenyl-1,3,4-thiadiazol-4-ium-2-amine;chloride	EC50	2850 nM
SMR000664527	IC50	3760 nM
2-chloro-4-nitro-N-[4-(2-pyridinylsulfamoyl)phenyl]benzamide;2,2,2-trifluoroacetic acid	IC50	3850 nM
MLS000829787	IC50	4220 nM
N-[3-(2,2-dimethyltetrahydro-2H-pyran-4-yl)-3-phenylpropyl]-N-(1-phenylethyl)-2-furamide	EC50	5670 nM
MLS001201576	EC50	5760 nM
methyl (4R,5R,6R)-1-ethyl-2-[2-(1H-indol-3-yl)ethylamino]-6-methyl-4-phenyl-5,6-dihydro-4H-pyrimidine-5-carboxylate	IC50	6290 nM
SMR000317543	EC50	6690 nM
2-(4-ethoxyphenyl)-1-phenyl-6,7,8,9-tetrahydro-5H-imidazo[1,2-a]azepin-4-ium;bromide	EC50	6830 nM
4-methoxy-3-(1-propan-2-ylpiperidin-4-yl)oxy-N-(1-pyrazin-2-ylpropan-2-yl)benzamide	IC50	7510 nM
MLS000578592	EC50	7730 nM
2-[[5-(1,3-benzodioxol-5-yl)-1,2-oxazol-3-yl]methoxy]-N-butyl-ethanamide	EC50	8040 nM
SMR000316090	EC50	8220 nM
2-[4-[[1-(5-chloro-2-pyridinyl)-2-pyrrolyl]methyl]-1-(2-methylpropyl)-2-piperazinyl]ethanol	EC50	8240 nM
MLS001000473	EC50	8400 nM
SMR000710522	IC50	8420 nM
cid_24791264	IC50	8430 nM
1-(4-Chloro-benzoyl)-1-ethyl-2-oxo-1,7b-dihydro-cyclopropa[c]chromene-1a-carboxylic acid phenylamide	EC50	8440 nM
cid_5346381	EC50	9060 nM
3-chloranyl-N-[3-[4-[3-[(3-chlorophenyl)carbonylamino]propyl]piperazin-1-yl]propyl]benzamide	EC50	9440 nM
cid_16196246	EC50	9580 nM
SMR000420198	EC50	9770 nM
2,7-bis(azanyl)-4-(3,4,5-trimethoxyphenyl)-4H-chromene-3-carbonitrile	IC50	10500 nM
MLS000948498	EC50	12100 nM
diisobutyl [anilino(4-fluorophenyl)methyl]phosphonate	EC50	12200 nM
methyl 4-[(E,4R)-5-[(3,4-dimethoxyphenyl)methylamino]-2,4-dimethyl-5-oxidanylidene-1-(phenylmethoxycarbonylamino)pent-2-enyl]benzoate	EC50	12300 nM
1-[3-[2-(diethylamino)ethyl]-2-imino-1-benzimidazolyl]-3-(3-methylphenoxy)-2-propanol;hydrochloride	EC50	12400 nM
2,4-dichloro-N-[4-(2-pyridinylsulfamoyl)phenyl]benzamide	IC50	12800 nM
cid_1091621	EC50	12900 nM
2-(1-ethyl-6-methyl-3,4-dihydropyrrolo[1,2-a]pyrazin-2-ium-2-yl)-1-(4-methylphenyl)ethanone;bromide	EC50	13000 nM
N-[2-[(3S,6R)-3-benzyl-6-[(4-hydroxyphenyl)methyl]-2,3,5,6-tetrahydroimidazo[1,2-a]imidazol-7-yl]ethyl]-3-cyclohexylpropanamide	EC50	13400 nM
SMR000539538	EC50	13600 nM
cid_2962652	EC50	13800 nM
SMR000338095	EC50	13900 nM
cid_647543	EC50	14000 nM
MLS001242871	EC50	14100 nM
N-[(5-bromanyl-2-prop-2-enoxy-phenyl)methyl]-3-morpholin-4-yl-propan-1-amine;hydrochloride	EC50	14200 nM
SMR000175096	EC50	14300 nM
cid_3193712	EC50	14500 nM
MLS001140154	EC50	14600 nM
2-(2-cyanophenyl)sulfanyl-N-[(3-fluorophenyl)methyl]-N-methylbenzamide	EC50	15000 nM
N-(6-amino-1-benzyl-2,4-dioxopyrimidin-5-yl)-N-[2-(cyclohexen-1-yl)ethyl]-2-phenoxypropanamide	EC50	15000 nM

ChEMBL bioactivities

40 potent at pChembl≥5 of 41 total, top 40 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.17	Ki	68	nM	CHEMBL4217988
7.14	IC50	72	nM	CHEMBL3304438
7.05	IC50	90	nM	CHEMBL3304438
7.00	IC50	100	nM	CHEMBL1872483
6.92	IC50	120	nM	CHEMBL4217988
6.62	IC50	240	nM	CHEMBL1872483
6.57	IC50	270	nM	CHEMBL3304438
6.57	IC50	270	nM	CHEMBL3933906
6.33	IC50	467	nM	CHEMBL3899143
6.28	IC50	530	nM	CHEMBL3303792
6.22	IC50	600	nM	CHEMBL1340914
6.19	IC50	640	nM	CHEMBL3959257
6.12	IC50	760	nM	CHEMBL1887357
6.12	IC50	760	nM	CHEMBL3303792
6.04	IC50	910	nM	CHEMBL3182315
5.99	IC50	1020	nM	CHEMBL3187862
5.90	IC50	1260	nM	CHEMBL1381708
5.90	IC50	1250	nM	CHEMBL3303292
5.81	IC50	1560	nM	CHEMBL3183447
5.80	IC50	1580	nM	CHEMBL3182315
5.79	IC50	1640	nM	CHEMBL3187348
5.76	IC50	1730	nM	CHEMBL3188567
5.75	IC50	1770	nM	CHEMBL3303803
5.74	IC50	1840	nM	CHEMBL3923550
5.73	IC50	1850	nM	CHEMBL3183383
5.67	IC50	2130	nM	CHEMBL3183447
5.60	IC50	2510	nM	CHEMBL3186365
5.50	IC50	3200	nM	CHEMBL2203622
5.50	IC50	3160	nM	CHEMBL1498691
5.47	IC50	3360	nM	CHEMBL1409183
5.47	IC50	3350	nM	CHEMBL3970338
5.46	IC50	3480	nM	CHEMBL3187862
5.38	IC50	4220	nM	CHEMBL1507715
5.38	IC50	4120	nM	CHEMBL3188567
5.35	IC50	4470	nM	CHEMBL1580921
5.34	IC50	4540	nM	CHEMBL3303292
5.31	IC50	4930	nM	CHEMBL3187348
5.21	IC50	6120	nM	CHEMBL3303803
5.09	IC50	8090	nM	CHEMBL3186365
5.03	IC50	9270	nM	CHEMBL3183383

PubChem BioAssay actives

40 with measured affinity, of 123 total; 26 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
3-cyano-4-[2-[2-[(2-piperidin-4-ylethylamino)methyl]-4-pyridinyl]-4-[3-(trifluoromethyl)phenyl]phenoxy]-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide	1366025: Displacement of [3H]hemicholinium-3 from recombinant human choline transporter after 60 mins by scintillation counting method	ki	0.0680	uM
4-methoxy-3-(1-methylpiperidin-4-yl)oxy-N-[(3-propan-2-yl-1,2-oxazol-5-yl)methyl]benzamide	1321413: Inhibition of [3H]choline uptake at human choline transporter expressed in HEK293 cells preincubated for 15 mins followed by [3H]choline addition measured after 10 to 15 mins by scintillation proximity assay	ic50	0.0720	uM
4-methoxy-N-[(3-propan-2-yl-1,2-oxazol-5-yl)methyl]-3-(1-propan-2-ylpiperidin-4-yl)oxybenzamide	1194465: Inhibition of human CHT Leu530Ala and Val531Ala mutant expressed in HEK293 cells assessed as remaining transporter activity in presence of 10 uM [3H]choline by [3H]choline uptake assay	ic50	0.1000	uM
4-chloro-3-(1-methylpiperidin-4-yl)oxy-N-[(3-propan-2-yl-1,2-oxazol-5-yl)methyl]benzamide	1321413: Inhibition of [3H]choline uptake at human choline transporter expressed in HEK293 cells preincubated for 15 mins followed by [3H]choline addition measured after 10 to 15 mins by scintillation proximity assay	ic50	0.2700	uM
4-fluoro-3-(1-methylpiperidin-4-yl)oxy-N-[(3-propan-2-yl-1,2-oxazol-5-yl)methyl]benzamide	1321413: Inhibition of [3H]choline uptake at human choline transporter expressed in HEK293 cells preincubated for 15 mins followed by [3H]choline addition measured after 10 to 15 mins by scintillation proximity assay	ic50	0.4670	uM
4-methoxy-3-(2-piperidin-1-ylethoxy)-N-[(3-propan-2-yl-1,2-oxazol-5-yl)methyl]benzamide	1194465: Inhibition of human CHT Leu530Ala and Val531Ala mutant expressed in HEK293 cells assessed as remaining transporter activity in presence of 10 uM [3H]choline by [3H]choline uptake assay	ic50	0.5300	uM
N-[(3-ethyl-1,2-oxazol-5-yl)methyl]-4-methoxy-3-(1-propan-2-ylpiperidin-4-yl)oxybenzamide	1194461: Inhibition of human CHT Leu530Ala and Val531Ala mutant expressed in HEK293 cells by membrane depolarization assay	ic50	0.6000	uM
3-(1-methylpiperidin-4-yl)oxy-N-[(3-propan-2-yl-1,2-oxazol-5-yl)methyl]benzamide	1321413: Inhibition of [3H]choline uptake at human choline transporter expressed in HEK293 cells preincubated for 15 mins followed by [3H]choline addition measured after 10 to 15 mins by scintillation proximity assay	ic50	0.6400	uM
N-[(4,5-dimethyl-1,3-thiazol-2-yl)methyl]-4-methoxy-3-(1-propan-2-ylpiperidin-4-yl)oxybenzamide	1194461: Inhibition of human CHT Leu530Ala and Val531Ala mutant expressed in HEK293 cells by membrane depolarization assay	ic50	0.7600	uM
N-[(1-ethyl-3,5-dimethylpyrazol-4-yl)methyl]-4-methoxy-3-(1-propan-2-ylpiperidin-4-yl)oxybenzamide	1194465: Inhibition of human CHT Leu530Ala and Val531Ala mutant expressed in HEK293 cells assessed as remaining transporter activity in presence of 10 uM [3H]choline by [3H]choline uptake assay	ic50	0.9100	uM
4-methoxy-N-[(4-methyl-1,3-thiazol-2-yl)methyl]-3-(1-propan-2-ylpiperidin-4-yl)oxybenzamide	1194465: Inhibition of human CHT Leu530Ala and Val531Ala mutant expressed in HEK293 cells assessed as remaining transporter activity in presence of 10 uM [3H]choline by [3H]choline uptake assay	ic50	1.0200	uM
4-methoxy-3-(1-methylpiperidin-3-yl)oxy-N-[(3-propan-2-yl-1,2-oxazol-5-yl)methyl]benzamide	1194464: Inhibition of human CHT Leu530Ala and Val531Ala mutant expressed in HEK293 cells assessed as remaining transporter activity in presence of 100 nM [3H]choline by [3H]choline uptake assay	ic50	1.2500	uM
N-(1-phenylethyl)-4-[1-(pyridin-2-ylmethyl)piperidin-4-yl]oxybenzamide	1194461: Inhibition of human CHT Leu530Ala and Val531Ala mutant expressed in HEK293 cells by membrane depolarization assay	ic50	1.2600	uM
4-methoxy-3-(1-propan-2-ylpiperidin-4-yl)oxy-N-(2-pyrrolidin-1-ylethyl)benzamide	1194465: Inhibition of human CHT Leu530Ala and Val531Ala mutant expressed in HEK293 cells assessed as remaining transporter activity in presence of 10 uM [3H]choline by [3H]choline uptake assay	ic50	1.5600	uM
4-methoxy-N-[(2-methyl-1,3-thiazol-4-yl)methyl]-3-(1-propan-2-ylpiperidin-4-yl)oxybenzamide	1194465: Inhibition of human CHT Leu530Ala and Val531Ala mutant expressed in HEK293 cells assessed as remaining transporter activity in presence of 10 uM [3H]choline by [3H]choline uptake assay	ic50	1.6400	uM
4-methoxy-3-(1-propan-2-ylpiperidin-4-yl)oxy-N-(1-pyridin-2-ylpropan-2-yl)benzamide	1194465: Inhibition of human CHT Leu530Ala and Val531Ala mutant expressed in HEK293 cells assessed as remaining transporter activity in presence of 10 uM [3H]choline by [3H]choline uptake assay	ic50	1.7300	uM
4-methoxy-3-(2-morpholin-4-ylethoxy)-N-[(3-propan-2-yl-1,2-oxazol-5-yl)methyl]benzamide	1194465: Inhibition of human CHT Leu530Ala and Val531Ala mutant expressed in HEK293 cells assessed as remaining transporter activity in presence of 10 uM [3H]choline by [3H]choline uptake assay	ic50	1.7700	uM
N-[(3-propan-2-yl-1,2-oxazol-5-yl)methyl]-3-(1-propan-2-ylpiperidin-4-yl)oxybenzamide	1321413: Inhibition of [3H]choline uptake at human choline transporter expressed in HEK293 cells preincubated for 15 mins followed by [3H]choline addition measured after 10 to 15 mins by scintillation proximity assay	ic50	1.8400	uM
N-[(1-ethylpyrazol-4-yl)methyl]-4-methoxy-3-(1-propan-2-ylpiperidin-4-yl)oxybenzamide	1194465: Inhibition of human CHT Leu530Ala and Val531Ala mutant expressed in HEK293 cells assessed as remaining transporter activity in presence of 10 uM [3H]choline by [3H]choline uptake assay	ic50	1.8500	uM
N-[(1,5-dimethylpyrazol-3-yl)methyl]-4-methoxy-3-(1-propan-2-ylpiperidin-4-yl)oxybenzamide	1194465: Inhibition of human CHT Leu530Ala and Val531Ala mutant expressed in HEK293 cells assessed as remaining transporter activity in presence of 10 uM [3H]choline by [3H]choline uptake assay	ic50	2.5100	uM
N-[2-(cyclohexen-1-yl)ethyl]-4-methoxy-3-(1-propan-2-ylpiperidin-4-yl)oxybenzamide	1194461: Inhibition of human CHT Leu530Ala and Val531Ala mutant expressed in HEK293 cells by membrane depolarization assay	ic50	3.1600	uM
(13Z)-21-methyl-8,17-dioxa-19,21-diazatricyclo[16.2.1.02,7]henicosa-1(20),2,4,6,13,18-hexaene	711458: Antagonist activity at CHT1	ic50	3.2000	uM
4-cyano-3-(1-methylpiperidin-4-yl)oxy-N-[(3-propan-2-yl-1,2-oxazol-5-yl)methyl]benzamide	1321413: Inhibition of [3H]choline uptake at human choline transporter expressed in HEK293 cells preincubated for 15 mins followed by [3H]choline addition measured after 10 to 15 mins by scintillation proximity assay	ic50	3.3500	uM
N-(2,3-dihydro-1H-inden-1-yl)-4-methoxy-3-(1-propan-2-ylpiperidin-4-yl)oxybenzamide	1194461: Inhibition of human CHT Leu530Ala and Val531Ala mutant expressed in HEK293 cells by membrane depolarization assay	ic50	3.3600	uM
N-(2-phenylethyl)-3-(1-propylpiperidin-4-yl)oxybenzamide	1194461: Inhibition of human CHT Leu530Ala and Val531Ala mutant expressed in HEK293 cells by membrane depolarization assay	ic50	4.2200	uM
4-methoxy-3-(1-propan-2-ylpiperidin-4-yl)oxy-N-(1-pyrazin-2-ylpropan-2-yl)benzamide	1194461: Inhibition of human CHT Leu530Ala and Val531Ala mutant expressed in HEK293 cells by membrane depolarization assay	ic50	4.4700	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
arsenite	increases methylation	1
Acetaminophen	increases expression	1
Arsenic	decreases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Thimerosal	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	increases expression	1
Triclosan	increases expression	1
Valproic Acid	affects expression	1
8-Bromo Cyclic Adenosine Monophosphate	increases expression	1
Sodium Selenite	decreases expression	1
Antirheumatic Agents	decreases expression	1

ChEMBL screening assays

34 unique, capped per target: 24 binding, 10 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1015805	Binding	Inhibition of choline transporter at 10 uM	2-Cyclohexylcarbonylbenzimidazoles as potent, orally available and brain-penetrable opioid receptor-like 1 (ORL1) antagonists. — Bioorg Med Chem Lett
CHEMBL1794362	Functional	PUBCHEM_BIOASSAY: Dose responses of compounds that inhibit the Choline Transporter (CHT) - 5 point CRC. (Class of assay: confirmatory) [Related pubchem assays (depositor defined):AID488975, AID488997, AID493221, AID493222]	PubChem BioAssay data set

Cellosaurus cell lines

4 cell lines: 2 transformed cell line, 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E7VP	HEK293-hCHT LV-AA	Transformed cell line	Female
CVCL_E7VQ	HEK293-hCHT	Transformed cell line	Female
CVCL_TP02	HAP1 SLC5A7 (-) 1	Cancer cell line	Male
CVCL_TP03	HAP1 SLC5A7 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00029224	PHASE4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00035997	PHASE4	COMPLETED	Open-label Trial on the Effect of I.V. Zoledronic Acid 4 mg on Bone Density in Hormone Sensitive Prostate Cancer Patients With Bone Metastasis
NCT00063609	PHASE4	COMPLETED	The Effect of Zoledronic Acid on Bone Loss in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy
NCT00103623	PHASE4	SUSPENDED	The Plenaxis® Experience Study
NCT00106392	PHASE4	COMPLETED	A Safety and Efficacy Study of Prograf in the Prevention of Erectile Dysfunction After Radical Prostatectomy
NCT00185029	PHASE4	UNKNOWN	MR-Lymphography and Lymph Node Staging in Prostate Cancer
NCT00199485	PHASE4	COMPLETED	Angelica Sinensis for the Treatment of Hot Flashes in Men Undergoing LHRH Therapy for Prostate Cancer
NCT00219219	PHASE4	COMPLETED	Zoledronic Acid in the Prevention of Skeletal-related Events in Hormone Refractory and Hormone-sensitive Prostate Cancer Patients With Bone Metastases
NCT00219271	PHASE4	COMPLETED	Effect Of Zoledronic Acid On Circulating And Bone Marrow-Residing Prostate Cancer Cells In Patients With Clinically Localized Prostate Cancer
NCT00237146	PHASE4	COMPLETED	Study to Evaluate Zoledronic Acid on Quality of Life and Skeletal-related Events as Adjuvant Treatment in Patients With Hormone-naïve Prostate Cancer and Bone Metastasis Who Have Undergone Orchiectomy
NCT00242554	PHASE4	COMPLETED	Open-label Phase IV Clinical Trial to Evaluate the Safety and Tolerability of Zoledronic Acid in Patients With Prostate Cancer and Bone Metastases
NCT00280098	PHASE4	COMPLETED	Docetaxel in the Treatment of Hormone Refractory Prostate Cancer
NCT00293696	PHASE4	COMPLETED	Casodex/Zoladex Biomarkers in Localised Prostate Cancer
NCT00334139	PHASE4	COMPLETED	Effect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer
NCT00375765	PHASE4	COMPLETED	Effects On Dihydrotestosterone Regulated Gene Expression In Benign Prostatic Hyperplasia Or Prostate Cancer
NCT00391690	PHASE4	COMPLETED	Evaluation of Bone Markers as Diagnostic Tools for Early Detection of Bone Metastases in Patients With High Risk Prostate Cancer
NCT00422708	PHASE4	COMPLETED	Local Anesthesia for Prostate Biopsy
NCT00526331	PHASE4	COMPLETED	Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
NCT00590213	PHASE4	COMPLETED	Compare the Value of Prophylactic Versus Therapeutic Breast Radiotherapy in CASODEX
NCT00629330	PHASE4	TERMINATED	Dissemination of Prostate Cancer Screening to PCP’s in African American Communities
NCT00771966	PHASE4	COMPLETED	Radical Prostatectomy and Perioperative Fluid Therapy
NCT00805701	PHASE4	COMPLETED	Study Assessing The Efficacy And Safety Of Avodart (Dutasteride) At Improving Urinary Symptoms In Men With Prostate Cancer Who Are Undergoing Seed Implantation
NCT00859027	PHASE4	COMPLETED	Effect Of Risedronate On Bone Mass In Older Men Receiving Neoadjuvant Therapy For Prostate Cancer
NCT00906269	PHASE4	UNKNOWN	Can Hyperbaric Oxygen Improve Erectile Function Following Surgery for Prostate Cancer
NCT00953277	PHASE4	COMPLETED	Study of Nerve Reconstruction Using AVANCE in Subjects Who Undergo Robotic Assisted Prostatectomy for Treatment of Prostate Cancer
NCT00982800	PHASE4	COMPLETED	Does Postoperative Gabapentin Reduce Pain, Opioid Consumption and Anxiety and Have a Positive Effect on Health Related Quality of Life After Radical Prostatectomy?
NCT01083199	PHASE4	COMPLETED	Global Performance Evaluation of the AMS CONTINUUM™ Device
NCT01136226	PHASE4	COMPLETED	Evaluate Recovery of Testosterone for Patients Using Eligard
NCT01161563	PHASE4	COMPLETED	Randomized Crossover Trial to Assess the Tolerability of Gonadotropin Releasing Hormone (GnRH) Analogue Administration
NCT01230905	PHASE4	COMPLETED	Study to Monitor the Effects of Androgen Suppression Treatment on the Heart
NCT01296672	PHASE4	COMPLETED	3 Month Finasteride Challenge Test Can Significantly Improve the Performance of Screening for Prostate Cancer
NCT01365143	PHASE4	TERMINATED	Prospective Randomized Trial Comparing Robotic Versus Open Radical Prostatectomy
NCT01379742	PHASE4	UNKNOWN	Comparison of Between ThinSeed™ and OncoSeed™ for Permanent Prostate Brachytherapy
NCT01486563	PHASE4	COMPLETED	Hydroxyethyl Starch and Renal Function After Radical Prostatectomy
NCT01511874	PHASE4	COMPLETED	Efficacy and Safety Study of ELIGARD 22.5mg With Prostate Cancer
NCT01512472	PHASE4	TERMINATED	Firmagon (Degarelix) Intermittent Therapy
NCT01547416	PHASE4	COMPLETED	The Effect of Combined General/Epidural Anesthesia Versus General Anesthesia on Diaphragmatic Function
NCT01571544	PHASE4	COMPLETED	The Use of Thermal Suits as Preventing Hypothermia During Surgery
NCT01581749	PHASE4	UNKNOWN	Evaluation of Truebeam for Low-Intermediate Risk Prostate Cancer
NCT01649635	PHASE4	COMPLETED	Study of Cabazitaxel Combined With Prednisone and Prophylaxis of Neutropenia Complications in the Treatment of Patients With Metastatic Castration-resistant Prostate Cancer