SLC13A5

Summary

SLC13A5 (solute carrier family 13 member 5, HGNC:23089) is a protein-coding gene on chromosome 17p13.1, encoding Na(+)/citrate cotransporter (Q86YT5). High-affinity sodium/citrate cotransporter that mediates the entry of citrate into cells, which is a critical participant of biochemical pathways.

This gene encodes a protein belonging to the solute carrier family 13 group of proteins. This family member is a sodium-dependent citrate cotransporter that may regulate metabolic processes. Mutations in this gene cause early infantile epileptic encephalopathy 25. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 284111 — RefSeq curated summary.

At a glance

• Gene–disease (curated): developmental and epileptic encephalopathy, 25 (Definitive, GenCC) — +3 more curated relationships
• GWAS associations: 2
• Clinical variants (ClinVar): 818 total — 35 pathogenic, 24 likely-pathogenic
• Phenotypes (HPO): 69
• Druggable target: yes
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_177550

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23089
Approved symbol	SLC13A5
Name	solute carrier family 13 member 5
Location	17p13.1
Locus type	gene with protein product
Status	Approved
Aliases	NACT, INDY, mINDY
Ensembl gene	ENSG00000141485
Ensembl biotype	protein_coding
OMIM	608305
Entrez	284111

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 10 protein_coding, 2 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000293800, ENST00000381074, ENST00000433363, ENST00000570687, ENST00000572094, ENST00000572352, ENST00000572727, ENST00000573648, ENST00000574580, ENST00000574824, ENST00000575230, ENST00000576323, ENST00000898130, ENST00000898131, ENST00000898132, ENST00000949501

RefSeq mRNA: 4 — MANE Select: NM_177550 NM_001143838, NM_001284509, NM_001284510, NM_177550

CCDS: CCDS11079, CCDS45593, CCDS67136, CCDS67137

Canonical transcript exons

ENST00000433363 — 12 exons

Exon	Start	End
ENSE00000949009	6707028	6707156
ENSE00001314051	6695726	6695941
ENSE00001699681	6687529	6687666
ENSE00001813353	6684719	6686338
ENSE00002648639	6713232	6713369
ENSE00002756164	6693044	6693162
ENSE00002866825	6690779	6690940
ENSE00002970000	6694097	6694197
ENSE00003544988	6702970	6703138
ENSE00003586352	6706642	6706778
ENSE00003619518	6703878	6704056
ENSE00003678283	6701004	6701126

Expression profiles

Bgee: expression breadth ubiquitous, 148 present calls, max score 99.05.

FANTOM5 (CAGE): breadth broad, TPM avg 4.8056 / max 1859.4846, expressed in 234 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
164066	4.6144	224
164063	0.1912	21

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	99.05	gold quality
liver	UBERON:0002107	98.60	gold quality
parotid gland	UBERON:0001831	97.85	gold quality
tibia	UBERON:0000979	87.83	gold quality
ileal mucosa	UBERON:0000331	79.42	silver quality
nucleus accumbens	UBERON:0001882	76.63	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	75.32	silver quality
right frontal lobe	UBERON:0002810	74.12	gold quality
tibialis anterior	UBERON:0001385	73.82	silver quality
caudate nucleus	UBERON:0001873	73.22	gold quality
anterior cingulate cortex	UBERON:0009835	72.63	gold quality
Brodmann (1909) area 9	UBERON:0013540	71.77	gold quality
prefrontal cortex	UBERON:0000451	71.28	gold quality
putamen	UBERON:0001874	70.50	gold quality
ganglionic eminence	UBERON:0004023	70.43	gold quality
lower esophagus mucosa	UBERON:0035834	69.62	gold quality
neocortex	UBERON:0001950	69.57	gold quality
ventricular zone	UBERON:0003053	69.54	gold quality
frontal cortex	UBERON:0001870	69.50	gold quality
amygdala	UBERON:0001876	69.49	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	69.33	gold quality
pancreatic ductal cell	CL:0002079	68.83	silver quality
primary visual cortex	UBERON:0002436	67.44	gold quality
cerebral cortex	UBERON:0000956	66.87	gold quality
hypothalamus	UBERON:0001898	66.84	gold quality
forebrain	UBERON:0001890	66.72	gold quality
spleen	UBERON:0002106	66.30	gold quality
right adrenal gland	UBERON:0001233	66.07	gold quality
left adrenal gland	UBERON:0001234	65.88	gold quality
brain	UBERON:0000955	65.32	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-MTAB-7249	no	50.55
E-ANND-3	no	3.56

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NR1I3

miRNA regulators (miRDB)

74 targeting SLC13A5, 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-6867-5P	100.00	82.21	3464
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-4493	99.90	66.48	977
HSA-MIR-4779	99.86	66.50	1583
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-378G	99.71	64.90	1106
HSA-MIR-12124	99.68	69.17	2700
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-4756-3P	99.62	66.30	1319
HSA-MIR-3136-3P	99.57	66.59	781
HSA-MIR-7155-3P	99.57	66.48	794
HSA-MIR-4472	99.56	66.08	1478
HSA-MIR-516B-5P	99.56	66.33	1495
HSA-MIR-3153	99.55	67.59	2337
HSA-MIR-4761-5P	99.51	66.69	804
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-766-5P	99.47	67.91	2225
HSA-MIR-5697	99.39	67.74	1249
HSA-MIR-3911	99.38	66.95	1087
HSA-MIR-4318	99.38	66.94	1505
HSA-MIR-1912-3P	99.32	67.40	936
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-7974	99.24	65.48	1137
HSA-MIR-642A-3P	99.23	67.67	1258
HSA-MIR-642B-3P	99.23	67.67	1258
HSA-MIR-5787	99.22	67.86	2628

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 24)

• This paper describes the cloning and functional characterization of the human Na(+)-coupled citrate transporter (NaCT). (PMID:12445824)
• mediates the utilization of extracellular citrate for fat synthesis in human liver cells, and that the process is stimulated by lithium (PMID:12826022)
• Expression and function of NaCT in a cell line and in primary hepatocytes. (PMID:16973915)
• Screening of 68 additional unrelated individuals with early-onset epileptic encephalopathy for SLC13A5 mutations led to identification of one additional subject with heterozygous mutations of SLC13A5 and a similar clinical presentation as index subjects (PMID:24995870)
• SLC13A5 is a novel target gene of PXR and may contribute to drug-induced steatosis and metabolic disorders in humans. (PMID:25628225)
• Eight patients from four families with SLC13A5 mutation are described. They have neonatal epilepsy, tooth hypoplasia, and developmental delay. (PMID:26384929)
• Discovery and characterization of novel inhibitors of the sodium-coupled citrate transporter (NaCT or SLC13A5). (PMID:26620127)
• Study identified additional SLC13A5 mutations in patients with chronic epilepsy starting in the neonatal period, with the mutations producing inactive Na+/citrate transporters. (PMID:27261973)
• SLC13A5 is the second major gene associated with the clinical diagnosis of KTZS. (PMID:27600704)
• In infants presenting with therapy resistant seizures in the first days after birth, without a clear history of hypoxic-ischemic encephalopathy, but with Punctate White Matter Lesions on their neonatal MRI, a diagnosis of SCL13A5 related epileptic encephalopathy should be considered. (PMID:27913086)
• Studies show that SLC13A5 is a transporter in the plasma membrane that mediates the uptake of citrate into cells. It is expressed in hepatocytes, neurons, and spermatozoa. Its loss-of-function mutations are associated with neonatal epilepsy in humans. This is a single-gene disease with epilepsy resulting solely from the inactivity of SLC13A5. [review] (PMID:28264506)
• Data suggest that SLC13A5 plays a role in progression/cell proliferation of human hepatocellular carcinoma cells; here, RNA interference using shRNA against SLC13A5 decreased tumor burden in treatment of hepatocarcinoma in a xenograft tumor model in nude mice. (PMID:28655760)
• Data suggest that SLC13A5 plays a role in progression/proliferation of human hepatocellular carcinoma cells; RNA interference using shRNA against SLC13A5 decreased tumor burden in treatment of hepatocarcinoma in a xenograft tumor model in nude mice. [REVIEW] (PMID:28821606)
• We demonstrated that all proteins were synthesized with an identical molecular weight as the wild-type transporter but several mutations (NaCTp.G219R, -p.G219E, -p.T227M, -p.L420P and -p.L488P) lead to a complete loss of NaCT-mediated citrate transport. This loss of transport activity can be explained on the basis of the developed structural model. (PMID:30054523)
• A dynamic anchor domain in slc13 transporters controls metabolite transport. (PMID:32152229)
• Neonatal developmental and epileptic encephalopathy due to autosomal recessive variants in SLC13A5 gene. (PMID:33063863)
• Adult phenotype of the homozygous missense mutation c.655G>A, p.Gly219Arg in SLC13A5: A case report. (PMID:33200910)
• Consequences of NaCT/SLC13A5/mINDY deficiency: good versus evil, separated only by the blood-brain barrier. (PMID:33544126)
• Structure and inhibition mechanism of the human citrate transporter NaCT. (PMID:33597751)
• A novel homozygous SLC13A5 whole-gene deletion generated by Alu/Alu-mediated rearrangement in an Iraqi family with epileptic encephalopathy. (PMID:33797191)
• Regulation on Citrate Influx and Metabolism through Inhibiting SLC13A5 and ACLY: A Novel Mechanism Mediating the Therapeutic Effects of Curcumin on NAFLD. (PMID:34323067)
• NaCT/SLC13A5 facilitates citrate import and metabolism under nutrient-limited conditions. (PMID:34525352)
• The citrate transporters SLC13A5 and SLC25A1 elicit different metabolic responses and phenotypes in the mouse. (PMID:37689798)
• Novel Homozygous Variants of SLC13A5 Expand the Functional Heterogeneity of a Homogeneous Syndrome of Early Infantile Epileptic Encephalopathy. (PMID:38113697)

Cross-species orthologs

12 orthologs

Organism	Symbol	Gene ID
danio_rerio	slc13a5b	ENSDARG00000039999
danio_rerio	slc13a5a	ENSDARG00000077691
mus_musculus	Slc13a5	ENSMUSG00000020805
rattus_norvegicus	Slc13a5	ENSRNOG00000014870
drosophila_melanogaster	CG7309	FBGN0032314
drosophila_melanogaster	Indy	FBGN0036816
drosophila_melanogaster	CG33934	FBGN0064119
drosophila_melanogaster	Indy-2	FBGN0260466
caenorhabditis_elegans		WBGENE00003517
caenorhabditis_elegans		WBGENE00003518
caenorhabditis_elegans		WBGENE00003519
caenorhabditis_elegans		WBGENE00007138

Paralogs (5): SLC13A2 (ENSG00000007216), SLC13A1 (ENSG00000081800), OCA2 (ENSG00000104044), SLC13A3 (ENSG00000158296), SLC13A4 (ENSG00000164707)

Protein

Protein identifiers

Na(+)/citrate cotransporter — Q86YT5 (reviewed: Q86YT5)

Alternative names: Sodium-coupled citrate transporter, Sodium-dependent citrate transporter, Solute carrier family 13 member 5

All UniProt accessions (5): Q86YT5, I3L2Y7, I3L424, I3L4S9, I3L4X6

UniProt curated annotations — full annotation on UniProt →

Function. High-affinity sodium/citrate cotransporter that mediates the entry of citrate into cells, which is a critical participant of biochemical pathways. May function in various metabolic processes in which citrate has a critical role such as energy production (Krebs cycle), fatty acid synthesis, cholesterol synthesis, glycolysis, and gluconeogenesis. Transports citrate into the cell in a Na(+)-dependent manner, recognizing the trivalent form of citrate (physiological pH) rather than the divalent form. Can recognize succinate as a substrate, but its affinity for succinate is several fold lower than for citrate. The stoichiometry is probably 4 Na(+) for each carboxylate, irrespective of whether the translocated substrate is divalent or trivalent, rendering the process electrogenic. Involved in the regulation of citrate levels in the brain.

Subunit / interactions. Homodimer; the dimer shifts between outward and inward conformations to generate an elevator-type movement for substrate transport. The dimer can simultaneously bind four Na(+) ions, two in each protomer.

Subcellular location. Cell membrane.

Tissue specificity. Expressed most predominantly in the liver, with moderate expression detectable in the brain and testis.

Disease relevance. Developmental and epileptic encephalopathy 25, with amelogenesis imperfecta (DEE25) [MIM:615905] An autosomal recessive disease characterized by subclinical seizures appearing in the first days of life, evolving to severe epileptic disease. Affected individuals have profound or severe delayed development with lack of speech, and most patients do not acquire the ability to sit. Additional variable features include axial hypotonia, peripheral hypertonia, and abnormal involuntary movements such as dystonia and choreoathetosis. Dental abnormalities, including delayed eruption, hypodontia, tooth hypoplasia, yellow discoloration, thin enamel, and enamel chipping are observed in most patients. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Inhibited by (R)-2-(4-(tert-butyl)phenethyl)-2-hydroxysuccinic acid (also known as PF-06649298). Stimulated by Li(+) in the presence of Na(+), moreover changes stoichiometry from 4:1 to 2:1 Na(+):citrate.

Domain organisation. The SNT motif and TXP motif are essential for substrate recognition.

Similarity. Belongs to the SLC13A/DASS transporter (TC 2.A.47) family. NADC subfamily.

Isoforms (4)

UniProt ID	Names	Canonical?
Q86YT5-1	1	yes
Q86YT5-2	2
Q86YT5-3	3
Q86YT5-4	4

RefSeq proteins (4): NP_001137310, NP_001271438, NP_001271439, NP_808218* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001898	SLC13A/DASS	Family
IPR031312	Na/sul_symport_CS	Conserved_site

Pfam: PF00939

Catalyzed reactions (Rhea), 1 shown:

• citrate(out) + 4 Na(+)(out) = citrate(in) + 4 Na(+)(in) (RHEA:65664)

UniProt features (94 total): helix 29, topological domain 14, transmembrane region 11, sequence variant 11, binding site 7, sequence conflict 5, splice variant 3, mutagenesis site 3, turn 3, intramembrane region 2, short sequence motif 2, strand 2, chain 1, glycosylation site 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
8UVB	ELECTRON MICROSCOPY	2.13
8UVH	ELECTRON MICROSCOPY	2.33
7JSK	ELECTRON MICROSCOPY	3.04
7JSJ	ELECTRON MICROSCOPY	3.12

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86YT5-F1	85.97	0.59

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 (7): 136; 141; 226; 460; 463; 465; 507

Glycosylation sites (1): 562

Mutagenesis-validated functional residues (3):

Position	Phenotype
409	no effect on its function in citrate transport.
410	significant loss of function in citrate transport.
410	no effect on its function in citrate transport.

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-9955298	SLC-mediated transport of organic anions
R-HSA-433137	Sodium-coupled sulphate, di- and tri-carboxylate transporters
R-HSA-382551	Transport of small molecules
R-HSA-425366
R-HSA-425407	SLC-mediated transmembrane transport

MSigDB gene sets: 193 (showing top): FXR_IR1_Q6, LFA1_Q6, GOBP_SODIUM_ION_TRANSMEMBRANE_TRANSPORT, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_ORGANIC_ACID_TRANSPORT, GOBP_RESPONSE_TO_METAL_ION, SOX9_B1, GOBP_ORGANIC_ANION_TRANSPORT, GOBP_DICARBOXYLIC_ACID_TRANSPORT, RYTTCCTG_ETS2_B, GOBP_RESPONSE_TO_LITHIUM_ION, GOBP_TRANSMEMBRANE_TRANSPORT, GOBP_SODIUM_ION_TRANSPORT, NUYTTEN_EZH2_TARGETS_DN, GOMF_METAL_ION_TRANSMEMBRANE_TRANSPORTER_ACTIVITY

GO Biological Process (14): oxaloacetate transport (GO:0015729), fumarate transport (GO:0015741), alpha-ketoglutarate transport (GO:0015742), succinate transport (GO:0015744), citrate transport (GO:0015746), transmembrane transport (GO:0055085), cellular response to lithium ion (GO:0071285), monoatomic ion transport (GO:0006811), sodium ion transport (GO:0006814), tricarboxylic acid transport (GO:0006842), tricarboxylic acid transmembrane transport (GO:0035674), sodium ion transmembrane transport (GO:0035725), succinate transmembrane transport (GO:0071422), obsolete organic acid transmembrane transport (GO:1903825)

GO Molecular Function (10): organic acid:sodium symporter activity (GO:0005343), citrate transmembrane transporter activity (GO:0015137), succinate transmembrane transporter activity (GO:0015141), sodium:dicarboxylate symporter activity (GO:0017153), identical protein binding (GO:0042802), protein binding (GO:0005515), tricarboxylic acid transmembrane transporter activity (GO:0015142), symporter activity (GO:0015293), solute:sodium symporter activity (GO:0015370), transmembrane transporter activity (GO:0022857)

GO Cellular Component (4): nucleoplasm (GO:0005654), cytosol (GO:0005829), plasma membrane (GO:0005886), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
SLC-mediated transmembrane transport	1
SLC-mediated transport of inorganic anions	1
Transport of small molecules	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
C4-dicarboxylate transport	3
cellular anatomical structure	3
tricarboxylic acid transport	2
transport	2
carboxylic acid transmembrane transport	2
dicarboxylic acid transport	1
cellular process	1
response to lithium ion	1
cellular response to metal ion	1
metal ion transport	1
carboxylic acid transport	1
sodium ion transport	1
monoatomic cation transmembrane transport	1
succinate transport	1
solute:sodium symporter activity	1
tricarboxylic acid transmembrane transporter activity	1
citrate transport	1
C4-dicarboxylate transmembrane transporter activity	1
succinate transmembrane transport	1
dicarboxylic acid transmembrane transporter activity	1
organic acid:sodium symporter activity	1
protein binding	1
binding	1
tricarboxylic acid transmembrane transport	1
carboxylic acid transmembrane transporter activity	1
secondary active transmembrane transporter activity	1
sodium ion transmembrane transporter activity	1
solute:monoatomic cation symporter activity	1
transporter activity	1
transmembrane transport	1
nuclear lumen	1
cytoplasm	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

1476 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC13A5	SLC15A5	A6NIM6	953
SLC13A5	MINDY1	Q8N5J2	790
SLC13A5	DYRK1A	Q13627	702
SLC13A5	SLC25A1	P53007	667
SLC13A5	DYRK1B	Q9Y463	658
SLC13A5	COPS5	Q92905	654
SLC13A5	JOSD2	Q8TAC2	646
SLC13A5	JOSD1	Q15040	643
SLC13A5	ZUP1	Q96AP4	623
SLC13A5	DYRK4	Q9NR20	586
SLC13A5	DYRK2	Q92630	582
SLC13A5	NR1I2	O75469	497
SLC13A5	ROGDI	Q9GZN7	474
SLC13A5	CLK4	Q9HAZ1	462
SLC13A5	GCG	P01275	456

IntAct

58 interactions, top by confidence:

A	B	Type	Score
SLC13A5	EEF1A2	psi-mi:“MI:0915”(physical association)	0.590
SLC13A5	KRTAP3-2	psi-mi:“MI:0915”(physical association)	0.560
KRTAP12-3	SLC13A5	psi-mi:“MI:0915”(physical association)	0.560
KRTAP1-3	SLC13A5	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-8	SLC13A5	psi-mi:“MI:0915”(physical association)	0.560
SLC13A5	KRTAP9-2	psi-mi:“MI:0915”(physical association)	0.560
ADAMTSL4	SLC13A5	psi-mi:“MI:0915”(physical association)	0.560
KRTAP5-9	SLC13A5	psi-mi:“MI:0915”(physical association)	0.560
SLC13A5	KRTAP9-3	psi-mi:“MI:0915”(physical association)	0.560
KRTAP12-2	SLC13A5	psi-mi:“MI:0915”(physical association)	0.560
KRTAP5-2	SLC13A5	psi-mi:“MI:0915”(physical association)	0.560
SLC13A5	KRTAP11-1	psi-mi:“MI:0915”(physical association)	0.560
SLC13A5	KLHL20	psi-mi:“MI:0915”(physical association)	0.560
SLC13A5	KRTAP9-8	psi-mi:“MI:0915”(physical association)	0.560
SLC13A5	GOLM1	psi-mi:“MI:0915”(physical association)	0.560
GJA8	SLC13A5	psi-mi:“MI:0915”(physical association)	0.560
CYSRT1	SLC13A5	psi-mi:“MI:0915”(physical association)	0.560
SLC13A5	MDFI	psi-mi:“MI:0915”(physical association)	0.560
CD79A	SLC13A5	psi-mi:“MI:0915”(physical association)	0.560
SLC13A5	POLR3A	psi-mi:“MI:0914”(association)	0.350
SLC13A5	KRTAP3-2	psi-mi:“MI:0915”(physical association)	0.000
SLC13A5	KRTAP12-3	psi-mi:“MI:0915”(physical association)	0.000
SLC13A5	KRTAP1-3	psi-mi:“MI:0915”(physical association)	0.000
SLC13A5	KRTAP10-8	psi-mi:“MI:0915”(physical association)	0.000
SLC13A5	KRTAP9-2	psi-mi:“MI:0915”(physical association)	0.000
SLC13A5	CYSRT1	psi-mi:“MI:0915”(physical association)	0.000
SLC13A5	ADAMTSL4	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (40): SLC13A5 (Affinity Capture-MS), EEF1A2 (Affinity Capture-MS), SLC13A5 (Two-hybrid), SLC13A5 (Two-hybrid), SLC13A5 (Two-hybrid), SLC13A5 (Two-hybrid), SLC13A5 (Two-hybrid), ADAMTSL4 (Two-hybrid), KRTAP11-1 (Two-hybrid), KRTAP9-8 (Two-hybrid), KRTAP10-8 (Two-hybrid), CYSRT1 (Two-hybrid), KRTAP9-3 (Two-hybrid), KRTAP12-3 (Two-hybrid), KRTAP5-2 (Two-hybrid)

ESM2 similar proteins: A0A075B734, A2IBY8, A4L9J0, A8W649, A9Y006, B0D4E4, B0D4K0, I1Z8E7, I1Z8E8, O14520, O43315, O54794, O62735, O77697, O77714, O77722, O77740, P06624, P09011, P30301, P34080, P41181, P47862, P47864, P51180, P55064, P56402, P56403, P79099, P79144, P79164, P79165, P79168, P79200, P79213, P79229, P79803, Q08DE6, Q4R691, Q6J8I9

Diamond homologs: P0AFU2, P0AFU3, P32739, P46556, P70545, Q13183, Q21339, Q28615, Q49YW0, Q67BT3, Q86YT5, Q8CJ44, Q8WWT9, Q91Y63, Q93655, Q9ES88, Q9VDQ0, Q9VVT2, Q9Z0Z5, P39535, Q07782, Q9BZW2, Q9JHI4, O59712, P25360, P72958, Q2FFH9, Q2FWY4, Q2YU56, Q5HEK4, Q6G816, Q6GFE0, Q7A4P8, Q8LG88, Q8NVS5, Q99SX1, Q9UKG4, Q57486, Q58086, P27514

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 20 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.

Reactome pathways:

Pathway	Partners	Fold	FDR
Keratinization	11	34.0×	5e-14

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	35
Likely pathogenic	24
Uncertain significance	294
Likely benign	360
Benign	56

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1070161	NC_000017.10:g.(?6616531)(6616672_?)del	Pathogenic
1186028	NM_177550.5(SLC13A5):c.1115C>A (p.Ser372Ter)	Pathogenic
1352224	NM_177550.5(SLC13A5):c.1056-1G>C	Pathogenic
1402016	NM_177550.5(SLC13A5):c.1475del (p.Leu492fs)	Pathogenic
1455896	NM_177550.5(SLC13A5):c.1117C>T (p.Gln373Ter)	Pathogenic
1956988	NM_177550.5(SLC13A5):c.1412del (p.Leu471fs)	Pathogenic
2030414	NM_177550.5(SLC13A5):c.414G>A (p.Trp138Ter)	Pathogenic
2071759	NM_177550.5(SLC13A5):c.758G>A (p.Trp253Ter)	Pathogenic
2101634	NM_177550.5(SLC13A5):c.85_101delinsT (p.Ile29fs)	Pathogenic
218172	NM_177550.5(SLC13A5):c.1207_1217dup (p.Pro407fs)	Pathogenic
218174	NM_177550.5(SLC13A5):c.1570G>C (p.Asp524His)	Pathogenic
2427555	NC_000017.10:g.(?6607177)(6607395_?)del	Pathogenic
2579197	GRCh38/hg38 17p13.1(chr17:6690682-6696039)x0	Pathogenic
2707561	NM_177550.5(SLC13A5):c.1096del (p.Leu366fs)	Pathogenic
2760744	NM_177550.5(SLC13A5):c.15_19del (p.Ser6fs)	Pathogenic
2802014	NM_177550.5(SLC13A5):c.646del (p.Ala216fs)	Pathogenic
2983161	NM_177550.5(SLC13A5):c.812G>A (p.Trp271Ter)	Pathogenic
3239356	NM_177550.5(SLC13A5):c.1157-1G>T	Pathogenic
3243104	NC_000017.10:g.(?6609941)(6616652_?)del	Pathogenic
3243105	NC_000017.10:g.(?6607177)(6610495_?)del	Pathogenic
3256119	Single allele	Pathogenic
3639979	NM_177550.5(SLC13A5):c.395_396del (p.Thr132fs)	Pathogenic
3641048	NM_177550.5(SLC13A5):c.1354_1358dup (p.Leu454fs)	Pathogenic
3664328	NM_177550.5(SLC13A5):c.806G>A (p.Trp269Ter)	Pathogenic
372505	NM_177550.5(SLC13A5):c.511del (p.Glu171fs)	Pathogenic
373238	NM_177550.5(SLC13A5):c.1227dup (p.Ile410fs)	Pathogenic
442539	GRCh37/hg19 17p13.1(chr17:6564810-6660724)x0	Pathogenic
4715028	NM_177550.5(SLC13A5):c.1118del (p.Gln373fs)	Pathogenic
4715742	NM_177550.5(SLC13A5):c.238_239del (p.Val80fs)	Pathogenic
4719971	NM_177550.5(SLC13A5):c.1487_1502del (p.Leu496fs)	Pathogenic

SpliceAI

2290 predictions. Top by Δscore:

Variant	Effect	Δscore
17:6690773:ACTT:A	donor_loss	1.0000
17:6690774:CTT:C	donor_loss	1.0000
17:6690775:TTACC:T	donor_loss	1.0000
17:6690776:T:TG	donor_loss	1.0000
17:6690777:A:AC	donor_gain	1.0000
17:6690778:C:A	donor_loss	1.0000
17:6690778:C:CC	donor_gain	1.0000
17:6694092:CTTA:C	donor_loss	1.0000
17:6694093:TTA:T	donor_loss	1.0000
17:6694094:TA:T	donor_loss	1.0000
17:6694095:A:AC	donor_gain	1.0000
17:6694095:ACCTT:A	donor_gain	1.0000
17:6694096:C:CC	donor_gain	1.0000
17:6694096:C:CT	donor_loss	1.0000
17:6694096:CCTT:C	donor_gain	1.0000
17:6694096:CCTTC:C	donor_gain	1.0000
17:6694193:CATAC:C	acceptor_gain	1.0000
17:6694195:TAC:T	acceptor_gain	1.0000
17:6694195:TACCT:T	acceptor_loss	1.0000
17:6694196:ACC:A	acceptor_loss	1.0000
17:6694197:CCT:C	acceptor_loss	1.0000
17:6694198:CTAG:C	acceptor_loss	1.0000
17:6694199:T:C	acceptor_loss	1.0000
17:6695724:A:AC	donor_gain	1.0000
17:6695725:C:CC	donor_gain	1.0000
17:6701002:A:AC	donor_gain	1.0000
17:6701003:C:CC	donor_gain	1.0000
17:6702968:A:AC	donor_gain	1.0000
17:6702969:C:CA	donor_gain	1.0000
17:6702969:CT:C	donor_gain	1.0000

AlphaMissense

3715 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:6703010:C:A	G226W	0.997
17:6704013:A:G	W138R	0.997
17:6704013:A:T	W138R	0.997
17:6701086:A:G	W253R	0.996
17:6701086:A:T	W253R	0.996
17:6702996:G:C	N230K	0.996
17:6702996:G:T	N230K	0.996
17:6703021:G:T	A222D	0.996
17:6690824:G:C	S464R	0.995
17:6690824:G:T	S464R	0.995
17:6690826:T:G	S464R	0.995
17:6693097:A:G	W408R	0.995
17:6693097:A:T	W408R	0.995
17:6703030:C:T	G219E	0.995
17:6703031:C:A	G219W	0.995
17:6703035:G:C	S217R	0.995
17:6703035:G:T	S217R	0.995
17:6703037:T:G	S217R	0.995
17:6703047:G:C	C213W	0.995
17:6704002:G:C	N141K	0.995
17:6704002:G:T	N141K	0.995
17:6704018:G:A	S136F	0.995
17:6687571:A:C	N511K	0.994
17:6687571:A:T	N511K	0.994
17:6687598:G:C	F502L	0.994
17:6687598:G:T	F502L	0.994
17:6687600:A:G	F502L	0.994
17:6690821:G:C	N465K	0.994
17:6690821:G:T	N465K	0.994
17:6693063:G:T	A419D	0.994

dbSNP variants (sampled 300 via entrez): RS1000130885 (17:6708852 G>A), RS1000153477 (17:6705524 T>C), RS1000315138 (17:6714742 CTTTTTTAT>C), RS1000451205 (17:6701716 A>C,G), RS1000556764 (17:6697822 T>C), RS1000561491 (17:6698755 G>A), RS1000686772 (17:6714423 C>A,T), RS1000755770 (17:6698019 G>A), RS1000788000 (17:6687398 C>T), RS1000827878 (17:6696917 T>G), RS1000920206 (17:6686395 G>A), RS1000926381 (17:6687084 G>T), RS1001116446 (17:6688470 T>A), RS1001147167 (17:6692749 T>C,G), RS1001163546 (17:6707929 T>C)

Disease associations

OMIM: gene MIM:608305 | disease phenotypes: MIM:615905

GenCC curated gene-disease

Disease	Classification	Inheritance
developmental and epileptic encephalopathy, 25	Definitive	Autosomal recessive
amelocerebrohypohidrotic syndrome	Supportive	Autosomal recessive
pyridoxine-dependent epilepsy	Supportive	Autosomal recessive
undetermined early-onset epileptic encephalopathy	Supportive	Autosomal dominant

Mondo (7): developmental and epileptic encephalopathy, 25 (MONDO:0014392), undetermined early-onset epileptic encephalopathy (MONDO:0018614), chronic kidney disease (MONDO:0005300), intellectual disability (MONDO:0001071), microcephaly (MONDO:0001149), amelocerebrohypohidrotic syndrome (MONDO:0009185), pyridoxine-dependent epilepsy (MONDO:0009945)

Orphanet (2): Non-specific early-onset epileptic encephalopathy (Orphanet:442835), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

69 total (30 of 69 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000238	Hydrocephalus
HP:0000252	Microcephaly
HP:0000348	High forehead
HP:0000494	Downslanted palpebral fissures
HP:0000504	Abnormality of vision
HP:0000508	Ptosis
HP:0000546	Retinal degeneration
HP:0000639	Nystagmus
HP:0000648	Optic atrophy
HP:0000668	Hypodontia
HP:0000682	Abnormal dental enamel morphology
HP:0000684	Delayed eruption of teeth
HP:0000705	Amelogenesis imperfecta
HP:0000708	Atypical behavior
HP:0000717	Autism
HP:0000726	Dementia
HP:0000750	Delayed speech and language development
HP:0000817	Reduced eye contact
HP:0000966	Hypohidrosis
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001257	Spasticity
HP:0001263	Global developmental delay
HP:0001265	Hyporeflexia
HP:0001266	Choreoathetosis
HP:0001268	Mental deterioration
HP:0001273	Abnormal corpus callosum morphology
HP:0001288	Gait disturbance

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST001511_10	Economic and political preferences (time)	5.000000e-06
GCST009617_2	LDL cholesterol levels x thiazide or thiazide-like diuretics use interaction	1.000000e-07

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004827	economic and social preference
EFO:0004611	low density lipoprotein cholesterol measurement

MeSH disease descriptors (5)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D007676	Kidney Failure, Chronic	C12.050.351.968.419.780.750.500; C12.200.777.419.780.750.500; C12.950.419.780.750.500; C23.550.291.500.906.500
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500
C537213	Kohlschutter Tonz syndrome (supp.)
C536254	Pyridoxine-dependent epilepsy (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3769293 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: transporter — SLC13 family of sodium-dependent sulphate/carboxylate transporters

Most potent curated ligand interactions (5 total), top 5:

Ligand	Action	Affinity	Parameter
compound 7 [PMID: 37428122]	Inhibition	7.3	pIC50
BI01383298	Inhibition	7.25	pIC50
ETG-5773	Inhibition	6.8	pIC50
PF-06649298	Inhibition	6.4	pIC50
PF-06761281	Inhibition	6.29	pIC50

Binding affinities (BindingDB)

4 measured of 4 human assays (4 total across all organisms); most potent 4 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
5-[2-(1-adamantyl)-1,3-thiazol-4-yl]-2H-triazole-4-carbonitrile	EC50	620 nM	US-10626095: Cyanotriazole compounds
3-[(3-hydroxy-1-adamantyl)methoxymethyl]benzaldehyde	EC50	1090 nM	US-10626095: Cyanotriazole compounds
[3-(oxan-2-yloxy)-1-adamantyl]methanol	EC50	2350 nM	US-10626095: Cyanotriazole compounds
3-[(3-methoxy-1-adamantyl)methoxymethyl]benzaldehyde	EC50	2470 nM	US-10626095: Cyanotriazole compounds

ChEMBL bioactivities

49 potent at pChembl≥5 of 52 total, top 47 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.66	IC50	22	nM	CHEMBL5723572
7.62	IC50	24	nM	CHEMBL4757114
7.25	IC50	56	nM	CHEMBL4757114
7.25	IC50	56	nM	CHEMBL5723572
7.17	IC50	67	nM	CHEMBL5564833
7.14	IC50	73	nM	CHEMBL5571867
6.96	IC50	110	nM	CHEMBL3771175
6.96	IC50	110	nM	CHEMBL3770609
6.96	IC50	110	nM	CHEMBL5590742
6.90	IC50	125.9	nM	CHEMBL3771175
6.90	IC50	125.9	nM	CHEMBL3770609
6.89	IC50	130	nM	CHEMBL5568900
6.82	IC50	150	nM	CHEMBL5563872
6.80	IC50	160	nM	CHEMBL5574508
6.72	IC50	190	nM	CHEMBL3770497
6.72	IC50	190	nM	CHEMBL5569653
6.70	IC50	199.5	nM	CHEMBL3770497
6.68	IC50	210	nM	CHEMBL5571351
6.57	IC50	270	nM	CHEMBL5590896
6.54	IC50	290	nM	CHEMBL5565504
6.51	IC50	310	nM	CHEMBL5564000
6.50	IC50	316.2	nM	CHEMBL3770370
6.50	IC50	316.2	nM	CHEMBL3770675
6.50	IC50	316.2	nM	CHEMBL3770609
6.48	IC50	330	nM	CHEMBL3770675
6.48	IC50	330	nM	CHEMBL3770609
6.47	IC50	340	nM	CHEMBL5569072
6.46	IC50	350	nM	CHEMBL5562640
6.39	IC50	410	nM	CHEMBL3769578
6.36	IC50	440	nM	CHEMBL5565519
6.30	IC50	501.2	nM	CHEMBL3769578
6.30	IC50	501.2	nM	CHEMBL3771118
6.29	IC50	510	nM	CHEMBL3771118
6.24	IC50	570	nM	CHEMBL3769578
6.19	IC50	650	nM	CHEMBL3770370
6.13	IC50	740	nM	CHEMBL3771118
6.10	IC50	800	nM	CHEMBL3769514
6.10	IC50	794.3	nM	CHEMBL3769514
6.10	IC50	794.3	nM	CHEMBL3771118
6.07	IC50	860	nM	CHEMBL5574021
6.07	IC50	860	nM	CHEMBL5572112
5.93	IC50	1180	nM	CHEMBL5564637
5.80	IC50	1585	nM	CHEMBL3769911
5.78	IC50	1650	nM	CHEMBL3769911
5.71	IC50	1970	nM	CHEMBL5590508
5.50	IC50	3162	nM	CHEMBL3769766
5.47	IC50	3370	nM	CHEMBL3769766

PubChem BioAssay actives

46 with measured affinity, of 65 total; 30 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
1-(3,5-dichlorophenyl)sulfonyl-N-[(4-fluorophenyl)methyl]piperidine-4-carboxamide	1997684: Inhibition of SLC13A5 in human HepG2 cells assessed as reduction in citrate uptake	ic50	0.0240	uM
3-chloro-1-(cyanomethylamino)-7-[1-[6-(difluoromethoxy)-2-methyl-3-pyridinyl]ethyl]-6,8-dihydro-5H-2,7-naphthyridine-4-carbonitrile	1997685: Inhibition of recombinant human SLC13A5 in HEK293T cells	ic50	0.0500	uM
2-hydroxy-2-[2-(4-phenylphenyl)ethyl]butanedioic acid	2104010: Inhibition of human SLC13A5 transfected in HEK293T cells incubated for 30 mins by D4-citrate uptake assay	ic50	0.0670	uM
2-hydroxy-2-(2-naphthalen-2-ylethyl)butanedioic acid	2104010: Inhibition of human SLC13A5 transfected in HEK293T cells incubated for 30 mins by D4-citrate uptake assay	ic50	0.0730	uM
2-[2-(2-ethoxy-3-pyridinyl)ethyl]-2-hydroxybutanedioic acid	1280696: Inhibition of NaCT (unknown origin) expressed in HEK293 cells assessed as inhibition of [14C]citrate uptake by microbeta plate reader analysis	ic50	0.1100	uM
(2R)-2-[2-(2-ethoxy-3-pyridinyl)ethyl]-2-hydroxybutanedioic acid	1280696: Inhibition of NaCT (unknown origin) expressed in HEK293 cells assessed as inhibition of [14C]citrate uptake by microbeta plate reader analysis	ic50	0.1100	uM
2-[2-[4-(1,3-benzodioxol-5-yl)phenyl]ethyl]-2-hydroxybutanedioic acid	2104010: Inhibition of human SLC13A5 transfected in HEK293T cells incubated for 30 mins by D4-citrate uptake assay	ic50	0.1100	uM
2-[2-[4-(2-ethylpyrazol-3-yl)phenyl]ethyl]-2-hydroxybutanedioic acid	2104010: Inhibition of human SLC13A5 transfected in HEK293T cells incubated for 30 mins by D4-citrate uptake assay	ic50	0.1300	uM
2-hydroxy-2-[2-[4-[3-(trifluoromethyl)phenyl]phenyl]ethyl]butanedioic acid	2104010: Inhibition of human SLC13A5 transfected in HEK293T cells incubated for 30 mins by D4-citrate uptake assay	ic50	0.1500	uM
2-[2-(1,3-benzothiazol-2-yl)ethyl]-2-hydroxybutanedioic acid	2104010: Inhibition of human SLC13A5 transfected in HEK293T cells incubated for 30 mins by D4-citrate uptake assay	ic50	0.1600	uM
2-[2-(2-ethoxy-5-methyl-3-pyridinyl)ethyl]-2-hydroxybutanedioic acid	1280696: Inhibition of NaCT (unknown origin) expressed in HEK293 cells assessed as inhibition of [14C]citrate uptake by microbeta plate reader analysis	ic50	0.1900	uM
2-hydroxy-2-[2-[4-[3-(trifluoromethoxy)phenyl]phenyl]ethyl]butanedioic acid	2104010: Inhibition of human SLC13A5 transfected in HEK293T cells incubated for 30 mins by D4-citrate uptake assay	ic50	0.1900	uM
2-hydroxy-2-[2-[4-[2-(trifluoromethyl)phenyl]phenyl]ethyl]butanedioic acid	2104010: Inhibition of human SLC13A5 transfected in HEK293T cells incubated for 30 mins by D4-citrate uptake assay	ic50	0.2100	uM
2-hydroxy-2-[2-[4-(3-propoxyphenyl)phenyl]ethyl]butanedioic acid	2104010: Inhibition of human SLC13A5 transfected in HEK293T cells incubated for 30 mins by D4-citrate uptake assay	ic50	0.2700	uM
2-hydroxy-2-[2-[4-(2-methoxyphenyl)phenyl]ethyl]butanedioic acid	2104010: Inhibition of human SLC13A5 transfected in HEK293T cells incubated for 30 mins by D4-citrate uptake assay	ic50	0.2900	uM
2-[2-[4-(3-ethoxyphenyl)phenyl]ethyl]-2-hydroxybutanedioic acid	2104010: Inhibition of human SLC13A5 transfected in HEK293T cells incubated for 30 mins by D4-citrate uptake assay	ic50	0.3100	uM
2-hydroxy-2-[2-(2-methoxy-5-methyl-3-pyridinyl)ethyl]butanedioic acid	1280696: Inhibition of NaCT (unknown origin) expressed in HEK293 cells assessed as inhibition of [14C]citrate uptake by microbeta plate reader analysis	ic50	0.3162	uM
2-hydroxy-2-[2-(2-propan-2-yloxy-3-pyridinyl)ethyl]butanedioic acid	1280696: Inhibition of NaCT (unknown origin) expressed in HEK293 cells assessed as inhibition of [14C]citrate uptake by microbeta plate reader analysis	ic50	0.3162	uM
2-hydroxy-2-[2-[4-(3-methoxyphenyl)phenyl]ethyl]butanedioic acid	2104010: Inhibition of human SLC13A5 transfected in HEK293T cells incubated for 30 mins by D4-citrate uptake assay	ic50	0.3400	uM
2-hydroxy-2-[2-[4-(1,2,3,4-tetrahydroquinolin-8-yl)phenyl]ethyl]butanedioic acid	2104010: Inhibition of human SLC13A5 transfected in HEK293T cells incubated for 30 mins by D4-citrate uptake assay	ic50	0.3500	uM
(2R)-2-[2-(4-tert-butylphenyl)ethyl]-2-hydroxybutanedioic acid	1280696: Inhibition of NaCT (unknown origin) expressed in HEK293 cells assessed as inhibition of [14C]citrate uptake by microbeta plate reader analysis	ic50	0.4100	uM
2-hydroxy-2-[2-[4-(3-propan-2-yloxyphenyl)phenyl]ethyl]butanedioic acid	2104010: Inhibition of human SLC13A5 transfected in HEK293T cells incubated for 30 mins by D4-citrate uptake assay	ic50	0.4400	uM
(2R)-2-hydroxy-2-[2-(2-methoxy-5-methyl-3-pyridinyl)ethyl]butanedioic acid	1280696: Inhibition of NaCT (unknown origin) expressed in HEK293 cells assessed as inhibition of [14C]citrate uptake by microbeta plate reader analysis	ic50	0.5012	uM
2-[2-(4-tert-butylphenyl)ethyl]-2-hydroxybutanedioic acid	1280696: Inhibition of NaCT (unknown origin) expressed in HEK293 cells assessed as inhibition of [14C]citrate uptake by microbeta plate reader analysis	ic50	0.7943	uM
2-hydroxy-2-[2-(4-morpholin-4-ylphenyl)ethyl]butanedioic acid	2104010: Inhibition of human SLC13A5 transfected in HEK293T cells incubated for 30 mins by D4-citrate uptake assay	ic50	0.8600	uM
2-hydroxy-2-[2-[4-(2-methoxy-4-pyridinyl)phenyl]ethyl]butanedioic acid	2104010: Inhibition of human SLC13A5 transfected in HEK293T cells incubated for 30 mins by D4-citrate uptake assay	ic50	0.8600	uM
2-hydroxy-2-[2-[4-(1H-pyrazol-5-yl)phenyl]ethyl]butanedioic acid	2104010: Inhibition of human SLC13A5 transfected in HEK293T cells incubated for 30 mins by D4-citrate uptake assay	ic50	1.1800	uM
2-hydroxy-2-[2-(2-methoxy-5-methylphenyl)ethyl]butanedioic acid	1280696: Inhibition of NaCT (unknown origin) expressed in HEK293 cells assessed as inhibition of [14C]citrate uptake by microbeta plate reader analysis	ic50	1.5849	uM
2-hydroxy-2-[2-[4-(2-methylpyrazol-3-yl)phenyl]ethyl]butanedioic acid	2104010: Inhibition of human SLC13A5 transfected in HEK293T cells incubated for 30 mins by D4-citrate uptake assay	ic50	1.9700	uM
2-hydroxy-2-[2-(2-methoxy-3-pyridinyl)ethyl]butanedioic acid	1280696: Inhibition of NaCT (unknown origin) expressed in HEK293 cells assessed as inhibition of [14C]citrate uptake by microbeta plate reader analysis	ic50	3.1623	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects cotreatment, increases expression, increases reaction, decreases expression, increases methylation	3
Resveratrol	affects cotreatment, decreases expression	2
Acetaminophen	decreases expression	2
Cisplatin	affects expression, decreases response to substance	2
Rifampin	increases expression	2
Valproic Acid	affects expression, increases expression	2
Cyclosporine	decreases expression	2
bisphenol A	affects expression	1
sodium arsenate	decreases expression, increases abundance	1
terbufos	increases methylation	1
arsenite	increases methylation	1
acetoacetic acid	decreases abundance	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
butyraldehyde	increases expression	1
ferrous chloride	decreases expression	1
pentanal	increases expression	1
K 7174	decreases expression	1
obeticholic acid	decreases expression	1
Sorafenib	decreases response to substance	1
Decitabine	affects expression	1
Arsenic	decreases expression, increases abundance	1
Copper	affects cotreatment, decreases expression	1
Doxorubicin	decreases response to substance	1
Fonofos	increases methylation	1
Estradiol	affects cotreatment, increases expression	1
Fluorouracil	decreases response to substance	1
Parathion	increases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Quercetin	decreases expression	1
Testosterone	decreases expression	1

ChEMBL screening assays

14 unique, capped per target: 11 binding, 3 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3773091	Binding	Inhibition of NaCT (unknown origin) expressed in HEK293 cells assessed as inhibition of [14C]citrate uptake by microbeta plate reader analysis	Optimization of a Dicarboxylic Series for in Vivo Inhibition of Citrate Transport by the Solute Carrier 13 (SLC13) Family. — J Med Chem
CHEMBL5723547	Functional	Affinity On-target Cellular interaction: (Radiolabelled uptake assay with [14C]citrate, HEPG2 cells) EUB0002721a SLC13A5	Affinity On-target Cellular Literature for EUbOPEN Chemogenomic Library

Cellosaurus cell lines

8 cell lines: 5 transformed cell line, 2 cancer cell line, 1 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_D4DL	HEK-SLC13A5-KO-c12	Transformed cell line	Female
CVCL_D4RQ	HuH7-SLC13A5-KO-c4	Cancer cell line	Male
CVCL_D4RR	HuH7-SLC13A5-KO-c5	Cancer cell line	Male
CVCL_D6Z3	GM28920	Induced pluripotent stem cell	Female
CVCL_YN37	GM27288	Transformed cell line	Female
CVCL_YN38	GM27289	Transformed cell line	Male
CVCL_YN39	GM27290	Transformed cell line	Female
CVCL_YN40	GM27299	Transformed cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00073710	PHASE4	COMPLETED	Study to Evaluate the Effects of Zemplar Injection and Calcijex on Intestinal Absorption of Calcium
NCT00125593	PHASE4	COMPLETED	Study of Heart and Renal Protection
NCT00132431	PHASE4	COMPLETED	START: Sensipar Treatment Algorithm to Reach K/DOQI Targets in Chronic Kidney Disease Subjects With Secondary Hyperparathyroidism
NCT00155246	PHASE4	COMPLETED	Efficacy of Pentoxifylline on Chronic Kidney Disease
NCT00175149	PHASE4	TERMINATED	Active Vitamin D Effect on Left Ventricular Hypertrophy
NCT00184769	PHASE4	COMPLETED	Growth Hormone Treatment in Infants Aged 1 to 2 Years With Chronic Renal Insufficiency (CRI) and Growth Retardation.
NCT00190580	PHASE4	COMPLETED	Kanagawa Valsartan Trial (KVT): Effects of Valsartan on Renal and Cardiovascular Disease
NCT00194961	PHASE4	TERMINATED	Effect of Growth Hormone on Leptin, Cytokines and Body Composition of Children With Growth Failure Due to Chronic Kidney Disease
NCT00239642	PHASE4	COMPLETED	Safety and Efficacy of Iron Sucrose in Children
NCT00324571	PHASE4	COMPLETED	Dialysis Clinical Outcomes Revisited (DCOR) Trial
NCT00364884	PHASE4	UNKNOWN	Keto-/Amino Acid Supplemented Low Protein Diet in Patients With Chronic Kidney Disease
NCT00368901	PHASE4	COMPLETED	STAAR-2 Clinical Study
NCT00369733	PHASE4	COMPLETED	STAAR-3 Clinical Study
NCT00369772	PHASE4	COMPLETED	STAAR-1 Clinical Study
NCT00379899	PHASE4	COMPLETED	ADVANCE: Study to Evaluate Cinacalcet Plus Low Dose Vitamin D on Vascular Calcification in Subjects With Chronic Kidney Disease Receiving Hemodialysis
NCT00384618	PHASE4	TERMINATED	Anti-Oxidant Therapy In Chronic Renal Insufficiency (ATIC) Study
NCT00478543	PHASE4	COMPLETED	Loop Diuretics in Chronic Kidney Disease
NCT00632125	PHASE4	COMPLETED	Post-authorization Safety Study in CKD Subjects Receiving HX575 i.v.
NCT00644046	PHASE4	COMPLETED	Chronic Kidney Disease Prevention of An-Lo District, Keelung
NCT00719316	PHASE4	UNKNOWN	Aliskiren and Muscle Sympathetic Nerve Activity
NCT00725517	PHASE4	COMPLETED	Efficacy and Safety of a 7.5% Icodextrin Peritoneal Dialysis Solution in Once-Daily Long Dwell Exchange
NCT00741585	PHASE4	COMPLETED	Prognostic Value of the Circadian Pattern of Ambulatory Blood Pressure for Multiple Risk Assessment
NCT00749736	PHASE4	COMPLETED	The Role of Vitamin D in Immune Function in Patients With Chronic Kidney Disease (CKD) Stages 3 and 4.
NCT00752102	PHASE4	COMPLETED	Vitamin D and Coronary Calcification Study
NCT00756145	PHASE4	COMPLETED	The Use of Low Molecular Weight Heparin in Hemodiafiltration
NCT00768638	PHASE4	COMPLETED	Study of Atorvastatin Dose Dependent Reduction of Proteinuria
NCT00786136	PHASE4	COMPLETED	Rosuvastatin Prevent Contrast Induced Acute Kidney Injury in Patients With Diabetes
NCT00803712	PHASE4	COMPLETED	20070360 Incident Dialysis
NCT00812123	PHASE4	COMPLETED	Calcineurin Free Immunosuppression in Renal Transplant Recipients
NCT00823303	PHASE4	COMPLETED	Paricalcitol Versus Calcitriol for Efficacy and Safety in Stage 3/4 Chronic Kidney Disease (CKD) With Secondary Hyperparathyroidism (SHPT)
NCT00830037	PHASE4	TERMINATED	A Clinical Trial of Oral Versus IV Iron in Patients With Chronic Kidney Disease
NCT00852969	PHASE4	COMPLETED	Niacin and Endothelial Function in Early CKD
NCT00858299	PHASE4	UNKNOWN	The Change of Urinary Angiotensinogen Excretion After Valsartan Treatment in Patients With Persistent Proteinuria
NCT00860431	PHASE4	COMPLETED	Kremezin Study Against Renal Disease Progression in Korea
NCT00882401	PHASE4	COMPLETED	Vitamin D, Chronic Kidney Disease (CKD) and the Microcirculation
NCT00889629	PHASE4	COMPLETED	Pilot Study Evaluating Doxercalciferol Replacement Therapy in Kidney Transplant Recipients
NCT00892892	PHASE4	WITHDRAWN	Sympathetic Nerve Activity in Renal Failure
NCT00893425	PHASE4	COMPLETED	Effect of Renin Angiotensin System Blockade on the Fas Antigen (CD95) and Asymmetric Dimethylarginine (ADMA) Levels in Type-2 Diabetic Patients With Proteinuria
NCT00908310	PHASE4	COMPLETED	Post-marketing Safety Study in Patients With Moderate Renal Insufficiency Who Receive Omniscan for Contrast-enhanced Magnetic Resonance Imaging (MRI)
NCT00958451	PHASE4	COMPLETED	Vitamin D Deficiency in Chronic Kidney Disease (CKD) Patients