SLC7A8

Summary

SLC7A8 (solute carrier family 7 member 8, HGNC:11066) is a protein-coding gene on chromosome 14q11.2, encoding Large neutral amino acids transporter small subunit 2 (Q9UHI5). Associates with SLC3A2 to form a functional heterodimeric complex that translocates small and large neutral amino acids with broad specificity and a stoichiometry of 1:1.

Enables several functions, including neutral L-amino acid transmembrane transporter activity; protein heterodimerization activity; and secondary active transmembrane transporter activity. Involved in L-alanine import across plasma membrane; L-leucine import across plasma membrane; and thyroid hormone transport. Located in basolateral plasma membrane and microvillus membrane.

Source: NCBI Gene 23428 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 149 total — 3 likely-pathogenic
• Phenotypes (HPO): 1
• Druggable target: yes
• MANE Select transcript: NM_012244

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11066
Approved symbol	SLC7A8
Name	solute carrier family 7 member 8
Location	14q11.2
Locus type	gene with protein product
Status	Approved
Aliases	LPI-PC1, LAT2
Ensembl gene	ENSG00000092068
Ensembl biotype	protein_coding
OMIM	604235
Entrez	23428

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 7 protein_coding, 3 retained_intron, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000316902, ENST00000339733, ENST00000397310, ENST00000422941, ENST00000453702, ENST00000469263, ENST00000524758, ENST00000525062, ENST00000528186, ENST00000528806, ENST00000528860, ENST00000529705, ENST00000532568

RefSeq mRNA: 4 — MANE Select: NM_012244 NM_001267036, NM_001267037, NM_012244, NM_182728

CCDS: CCDS41924, CCDS58304, CCDS58305, CCDS9590

Canonical transcript exons

ENST00000316902 — 11 exons

Exon	Start	End
ENSE00001669751	23166336	23166540
ENSE00001735447	23165285	23165436
ENSE00002723095	23182764	23183660
ENSE00003484408	23143079	23143204
ENSE00003579777	23139424	23139547
ENSE00003583268	23128019	23128196
ENSE00003599192	23129650	23129799
ENSE00003610632	23140471	23140624
ENSE00003632303	23131461	23131557
ENSE00003650701	23125295	23127343
ENSE00003658249	23137921	23138024

Expression profiles

Bgee: expression breadth ubiquitous, 284 present calls, max score 97.58.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 26.0846 / max 1050.7974, expressed in 1375 samples.

FANTOM5 promoters (14 alternative TSS)

Promoter ID	TPM avg	Samples expressed
142334	17.2166	1008
142333	4.5476	728
142328	2.5442	819
142329	0.3853	200
142327	0.3245	183
142331	0.2211	103
142330	0.1628	85
142326	0.1521	79
142321	0.1440	81
142332	0.1409	67

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
islet of Langerhans	UBERON:0000006	97.58	gold quality
left uterine tube	UBERON:0001303	97.22	gold quality
type B pancreatic cell	CL:0000169	97.19	gold quality
mucosa of stomach	UBERON:0001199	96.83	gold quality
right ovary	UBERON:0002118	96.10	gold quality
adult mammalian kidney	UBERON:0000082	95.98	gold quality
left ovary	UBERON:0002119	95.64	gold quality
oocyte	CL:0000023	95.10	gold quality
pigmented layer of retina	UBERON:0001782	95.06	gold quality
decidua	UBERON:0002450	94.59	gold quality
body of uterus	UBERON:0009853	94.25	gold quality
lower esophagus mucosa	UBERON:0035834	93.82	gold quality
body of stomach	UBERON:0001161	93.72	gold quality
ectocervix	UBERON:0012249	93.66	gold quality
renal medulla	UBERON:0000362	93.46	gold quality
adult organism	UBERON:0007023	93.25	gold quality
ovary	UBERON:0000992	93.18	gold quality
kidney	UBERON:0002113	93.02	gold quality
pylorus	UBERON:0001166	92.99	gold quality
right lung	UBERON:0002167	92.80	gold quality
endocervix	UBERON:0000458	92.52	gold quality
esophagus mucosa	UBERON:0002469	92.36	gold quality
gastrocnemius	UBERON:0001388	92.27	gold quality
stomach	UBERON:0000945	92.23	gold quality
myometrium	UBERON:0001296	91.88	gold quality
skin of leg	UBERON:0001511	91.78	gold quality
prostate gland	UBERON:0002367	91.64	gold quality
right lobe of thyroid gland	UBERON:0001119	91.62	gold quality
cardia of stomach	UBERON:0001162	91.52	gold quality
lateral nuclear group of thalamus	UBERON:0002736	91.33	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-GEOD-109979	yes	290.70
E-GEOD-100618	yes	208.67
E-MTAB-6075	yes	196.64
E-MTAB-5061	yes	30.17
E-GEOD-81547	yes	24.74
E-MTAB-6678	yes	10.61
E-GEOD-83139	yes	10.05
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CTNNB1

miRNA regulators (miRDB)

161 targeting SLC7A8, 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-3613-3P	100.00	76.36	7965
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-432-3P	100.00	67.86	705
HSA-MIR-1193	100.00	65.93	529
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-1229-3P	99.97	66.49	906
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-4525	99.94	64.38	675
HSA-MIR-5010-5P	99.94	64.11	705

Literature-anchored findings (GeneRIF, showing 19)

• the interaction of CD98/LAT2 with ICAM-1, found to be expressed to the basolateral domain, and the potential of such interaction on intracellular signal activation in Caco2-BBE cell monolayers (PMID:12716892)
• identify LAT1 and LAT2 as members of system L that mediate transmembrane movement of l-CSNO (PMID:15769744)
• Genetic variation in LAT1 and LAT2 does not appear to be a major cause of inter-individual variability in pharmacokinetics and of adverse reactions to melphalan. (PMID:17558306)
• LAT2 genes may play important roles in leiomyoma cell proliferation and regulate leiomyoma growth (PMID:19808856)
• Compared with the adult cerebral cortex, mRNAs encoding OATP1A2, OATP1C1, OATP3A1 variant 2, OATP4A1, LAT2 and CD98 were reduced in fetal cortex at different gestational ages, whilst mRNAs encoding MCT8, MCT10, OATP3A1 variant 1 and LAT1 were similar. (PMID:21486766)
• The detergent-induced stabilization of the purified human 4F2hc-LAT2 complex presented here paves the way towards its crystallization and structure determination at high-resolution (PMID:25299125)
• LAT1 and LAT2 are present and functional in the syncytiotrophoblast MVM, whereas LAT2 is also expressed in the BM and in the fetal capillary endothelium. (PMID:26050671)
• LAT1 and LAT2 were overexpressed in both pheochromocytoma and medullary thyroid carcinoma by comparison with normal tissues. (PMID:27224648)
• These preliminary data suggest that a relevant proportion of age-related hearing loss cases could be explained by SLC7A8 mutations. (PMID:29355479)
• Data reveal that LAT2 functions as an oncogenic protein and could regulate glutamine-dependent mTOR activation to promote glycolysis and decrease GEM sensitivity in pancreatic cancer (PMID:30419950)
• Abnormalities in the genes that encode Large Amino Acid Transporters increase the risk of Autism Spectrum Disorder. (PMID:31701662)
• The solute carrier SLC7A8 is a marker of favourable prognosis in ER-positive low proliferative invasive breast cancer. (PMID:32200487)
• Sub-Nanometer Cryo-EM Density Map of the Human Heterodimeric Amino Acid Transporter 4F2hc-LAT2. (PMID:32993041)
• Small molecule inhibitors provide insights into the relevance of LAT1 and LAT2 in materno-foetal amino acid transport. (PMID:33001560)
• The Heavy Chain 4F2hc Modulates the Substrate Affinity and Specificity of the Light Chains LAT1 and LAT2. (PMID:33066406)
• Genomic and epigenomic evolution of acquired resistance to combination therapy in esophageal squamous cell carcinoma. (PMID:34494553)
• Identification and verification of microRNA signature and key genes in the development of osteosarcoma with lung metastasis. (PMID:36626488)
• SLC7A8 overexpression inhibits the growth and metastasis of lung adenocarcinoma and is correlated with a dismal prognosis. (PMID:38244585)
• Evidence for a relationship between genetic polymorphisms of the L-DOPA transporter LAT2/4F2hc and risk of hypertension in the context of chronic kidney disease. (PMID:38890684)

Cross-species orthologs

15 orthologs

Organism	Symbol	Gene ID
danio_rerio	slc7a8b	ENSDARG00000054343
danio_rerio	slc7a8a	ENSDARG00000075831
mus_musculus	Slc7a8	ENSMUSG00000022180
rattus_norvegicus	Slc7a8	ENSRNOG00000014311
drosophila_melanogaster	mnd	FBGN0002778
drosophila_melanogaster	CG7255	FBGN0036493
drosophila_melanogaster	CG5535	FBGN0036764
drosophila_melanogaster	slif	FBGN0037203
drosophila_melanogaster	CG1607	FBGN0039844
caenorhabditis_elegans		WBGENE00000002
caenorhabditis_elegans		WBGENE00000003
caenorhabditis_elegans		WBGENE00000005
caenorhabditis_elegans	aat-9	WBGENE00000010
caenorhabditis_elegans		WBGENE00015197
caenorhabditis_elegans		WBGENE00017747

Paralogs (12): SLC7A2 (ENSG00000003989), SLC7A14 (ENSG00000013293), SLC7A9 (ENSG00000021488), SLC7A4 (ENSG00000099960), SLC7A6 (ENSG00000103064), SLC7A5 (ENSG00000103257), SLC7A10 (ENSG00000130876), SLC7A1 (ENSG00000139514), SLC7A11 (ENSG00000151012), SLC7A7 (ENSG00000155465), SLC7A13 (ENSG00000164893), SLC7A3 (ENSG00000165349)

Protein

Protein identifiers

Large neutral amino acids transporter small subunit 2 — Q9UHI5 (reviewed: Q9UHI5)

Alternative names: L-type amino acid transporter 2, Solute carrier family 7 member 8

All UniProt accessions (6): Q9UHI5, E9PIC3, E9PLV9, E9PQT4, E9PS92, H0Y2X7

UniProt curated annotations — full annotation on UniProt →

Function. Associates with SLC3A2 to form a functional heterodimeric complex that translocates small and large neutral amino acids with broad specificity and a stoichiometry of 1:1. Functions as amino acid antiporter mediating the influx of extracellular essential amino acids mainly in exchange with the efflux of highly concentrated intracellular amino acids. Has relatively symmetrical selectivities but strongly asymmetrical substrate affinities at both the intracellular and extracellular sides of the transporter. This asymmetry allows SLC7A8 to regulate intracellular amino acid pools (mM concentrations) by exchange with external amino acids (uM concentration range), equilibrating the relative concentrations of different amino acids across the plasma membrane instead of mediating their net uptake. May play an essential role in the reabsorption of neutral amino acids from the epithelial cells to the bloodstream in the kidney. Involved in the uptake of methylmercury (MeHg) when administered as the L-cysteine or D,L-homocysteine complexes, and hence plays a role in metal ion homeostasis and toxicity. Involved in the cellular activity of small molecular weight nitrosothiols, via the stereoselective transport of L-nitrosocysteine (L-CNSO) across the transmembrane. Imports the thyroid hormone diiodothyronine (T2) and to a smaller extent triiodothyronine (T3) but not rT 3 or thyroxine (T4). Mediates the uptake of L-DOPA. May participate in auditory function.

Subunit / interactions. Disulfide-linked heterodimer composed of the catalytic light chain subunit SLC7A8 and the heavy chain subunit SLC3A2. SLC3A2 acts as chaperones for correct plasma membrane trafficking and stabilization of SLC7A8 and modulates the substrate affinity and specificity of SLC7A8. ICAM-1 associates with the heterodimer SLC3A2/SLC7A8; this interaction regulates SLC7A8 activity.

Subcellular location. Cell membrane. Basolateral cell membrane.

Tissue specificity. Strongest expression is observed in kidney and moderate expression in placenta and brain, followed by liver, prostate, testis, ovary, lymph node, thymus, spleen, skeletal muscle and heart. Also expressed in fetal liver as well as in the retinal pigment epithelial cell line ARPE-19 and the intestinal epithelial cell line Caco-2.

Activity regulation. Inhibited by the L-type inhibitor 2-Aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH).

Similarity. Belongs to the amino acid-polyamine-organocation (APC) superfamily. L-type amino acid transporter (LAT) (TC 2.A.3.8) family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q9UHI5-1	1	yes
Q9UHI5-2	2
Q9UHI5-3	3
Q9UHI5-4	4

RefSeq proteins (4): NP_001253965, NP_001253966, NP_036376, NP_877392 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002293	AA/rel_permease1	Family
IPR004760	L_AA_transporter	Family
IPR050598	AminoAcid_Transporter	Family

Pfam: PF13520

Catalyzed reactions (Rhea), 12 shown:

• L-histidine(in) + L-phenylalanine(out) = L-histidine(out) + L-phenylalanine(in) (RHEA:71003)
• L-tryptophan(in) + L-phenylalanine(out) = L-tryptophan(out) + L-phenylalanine(in) (RHEA:71007)
• L-isoleucine(in) + L-phenylalanine(out) = L-isoleucine(out) + L-phenylalanine(in) (RHEA:71011)
• L-valine(in) + L-phenylalanine(out) = L-valine(out) + L-phenylalanine(in) (RHEA:71019)
• L-leucine(in) + L-phenylalanine(out) = L-leucine(out) + L-phenylalanine(in) (RHEA:71023)
• L-glutamine(in) + L-phenylalanine(out) = L-glutamine(out) + L-phenylalanine(in) (RHEA:71027)
• L-cysteine(in) + L-phenylalanine(out) = L-cysteine(out) + L-phenylalanine(in) (RHEA:71031)
• L-phenylalanine(out) + L-serine(in) = L-phenylalanine(in) + L-serine(out) (RHEA:71035)
• L-phenylalanine(out) + L-methionine(in) = L-phenylalanine(in) + L-methionine(out) (RHEA:71039)
• L-phenylalanine(out) + L-alanine(in) = L-phenylalanine(in) + L-alanine(out) (RHEA:71043)
• L-phenylalanine(out) + glycine(in) = L-phenylalanine(in) + glycine(out) (RHEA:71047)
• L-leucine(out) + L-methionine(in) = L-leucine(in) + L-methionine(out) (RHEA:71051)

UniProt features (91 total): helix 22, topological domain 12, transmembrane region 12, mutagenesis site 8, strand 7, turn 7, binding site 4, sequence variant 4, splice variant 3, sequence conflict 3, region of interest 2, compositionally biased region 2, site 2, chain 1, modified residue 1, disulfide bond 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
7CMI	ELECTRON MICROSCOPY	2.9
8A6L	ELECTRON MICROSCOPY	3.18
7CMH	ELECTRON MICROSCOPY	3.4
7B00	ELECTRON MICROSCOPY	3.98

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UHI5-F1	82.95	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.

Catalytic / active sites (2): 134 (important for substrate specificity); 246 (important for substrate specificity)

Ligand- & substrate-binding residues (4): 53; 134; 246; 395

Post-translational modifications (1): 29

Disulfide bonds (1): 154

Mutagenesis-validated functional residues (8):

Position	Phenotype
93	nearly complete reduction of glycine, l-alanine, and l-glutamine uptake. minimal effect on the transport of l-isoleucine
134	reduces l-leucine uptake activity. abolishes l-tryptophan uptake.
134	the substrate specificity changed dramatically reducing l-glutamine, glycine and l-alanine uptake activity thus mimickin
174	does not affect protein expression, plasma membrane localization, or l-alanine uptake.
243	abolishes leucine and tryptophan transport activities.
246	strong decrease in the uptake of large substrates l-tryptophan, l-glutamine, and l-histidine but increases the uptake of
395	strongly reduces l-leucine uptake activity. strongly reduces l-tryptophan uptake activity.
396	strongly reduces l-leucine uptake activity.

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-210991	Basigin interactions
R-HSA-352230	Amino acid transport across the plasma membrane
R-HSA-109582	Hemostasis
R-HSA-202733	Cell surface interactions at the vascular wall
R-HSA-382551	Transport of small molecules
R-HSA-425393
R-HSA-425407	SLC-mediated transmembrane transport

MSigDB gene sets: 587 (showing top): GGGACCA_MIR133A_MIR133B, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_B_CELL_ACTIVATION, GCANCTGNY_MYOD_Q6, GOBP_ANTIGEN_RECEPTOR_MEDIATED_SIGNALING_PATHWAY, GOBP_REGULATION_OF_HORMONE_LEVELS, IVANOVA_HEMATOPOIESIS_MATURE_CELL, MORI_IMMATURE_B_LYMPHOCYTE_UP, GOBP_HORMONE_TRANSPORT, GOBP_VESICLE_MEDIATED_TRANSPORT, GNF2_LYN, GOBP_AMINO_ACID_TRANSMEMBRANE_TRANSPORT, GOBP_LEUKOCYTE_MEDIATED_IMMUNITY, CCATCCA_MIR432

GO Biological Process (16): amino acid transmembrane transport (GO:0003333), amino acid transport (GO:0006865), neutral amino acid transport (GO:0015804), glycine transport (GO:0015816), L-leucine transport (GO:0015820), tryptophan transport (GO:0015827), valine transport (GO:0015829), proline transmembrane transport (GO:0035524), thyroid hormone transport (GO:0070327), amino acid import across plasma membrane (GO:0089718), transport across blood-brain barrier (GO:0150104), L-leucine import across plasma membrane (GO:1903801), L-alanine import across plasma membrane (GO:1904273), L-amino acid transport (GO:0015807), transmembrane transport (GO:0055085), L-alpha-amino acid transmembrane transport (GO:1902475)

GO Molecular Function (14): obsolete organic cation transmembrane transporter activity (GO:0015101), amino acid transmembrane transporter activity (GO:0015171), neutral L-amino acid transmembrane transporter activity (GO:0015175), L-amino acid transmembrane transporter activity (GO:0015179), L-alanine transmembrane transporter activity (GO:0015180), glycine transmembrane transporter activity (GO:0015187), L-leucine transmembrane transporter activity (GO:0015190), antiporter activity (GO:0015297), thyroid hormone transmembrane transporter activity (GO:0015349), toxin transmembrane transporter activity (GO:0019534), peptide antigen binding (GO:0042605), protein heterodimerization activity (GO:0046982), protein binding (GO:0005515), transmembrane transporter activity (GO:0022857)

GO Cellular Component (6): plasma membrane (GO:0005886), basal plasma membrane (GO:0009925), basolateral plasma membrane (GO:0016323), apical plasma membrane (GO:0016324), microvillus membrane (GO:0031528), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Cell surface interactions at the vascular wall	1
SLC-mediated transport of amino acids	1
Hemostasis	1
Transport of small molecules	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
amino acid transport	4
neutral amino acid transport	4
amino acid transmembrane transport	4
nitrogen compound transport	3
plasma membrane region	3
transmembrane transport	2
transport	2
carboxylic acid transport	2
branched-chain amino acid transport	2
L-amino acid transport	2
carboxylic acid transmembrane transport	2
amino acid import across plasma membrane	2
L-alpha-amino acid transmembrane transport	2
transmembrane transporter activity	2
amino acid transmembrane transporter activity	2
carboxylic acid transmembrane transporter activity	2
L-amino acid transmembrane transporter activity	2
neutral L-amino acid transmembrane transporter activity	2
secondary active transmembrane transporter activity	2
aromatic amino acid transport	1
hormone transport	1
import across plasma membrane	1
vascular transport	1
L-leucine transport	1
L-alanine transmembrane transport	1
cellular process	1
L-alanine transport	1
alanine transmembrane transporter activity	1
glycine transport	1
branched-chain amino acid transmembrane transporter activity	1
thyroid hormone transport	1
antigen binding	1
peptide binding	1
protein dimerization activity	1
binding	1
transporter activity	1
membrane	1
cell periphery	1
basal part of cell	1
basal plasma membrane	1

Protein interactions and networks

STRING

1046 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC7A8	SLC3A2	P08195	999
SLC7A8	SLC43A1	O75387	943
SLC7A8	SLC16A2	P36021	839
SLC7A8	SLC43A2	Q8N370	806
SLC7A8	SLCO1C1	Q9NYB5	727
SLC7A8	SLC7A5	Q01650	712
SLC7A8	SLC16A10	Q8TF71	695
SLC7A8	SLC38A2	Q96QD8	671
SLC7A8	DIO3	P55073	665
SLC7A8	DIO2	Q92813	655
SLC7A8	SLC1A5	Q15758	653
SLC7A8	SLC38A1	Q9H2H9	633
SLC7A8	SLC3A1	Q07837	631
SLC7A8	SLC6A19	Q695T7	621
SLC7A8	SLC38A4	Q969I6	606

IntAct

100 interactions, top by confidence:

A	B	Type	Score
YIPF1	SLC7A8	psi-mi:“MI:0915”(physical association)	0.560
	SLC7A8	psi-mi:“MI:0915”(physical association)	0.560
SLC3A2	SLC7A8	psi-mi:“MI:0915”(physical association)	0.560
MFSD3	SLC7A8	psi-mi:“MI:0915”(physical association)	0.560
DERL1	SLC7A8	psi-mi:“MI:0915”(physical association)	0.560
SNORC	SLC7A8	psi-mi:“MI:0915”(physical association)	0.560
YIPF6	SLC7A8	psi-mi:“MI:0915”(physical association)	0.560
SIGLEC5	SLC7A8	psi-mi:“MI:0915”(physical association)	0.560
MFF	SLC7A8	psi-mi:“MI:0915”(physical association)	0.560
COMT	SLC7A8	psi-mi:“MI:0915”(physical association)	0.560
AQP6	SLC7A8	psi-mi:“MI:0915”(physical association)	0.560
AGPAT4	SLC7A8	psi-mi:“MI:0915”(physical association)	0.560
SLC30A2	SLC7A8	psi-mi:“MI:0915”(physical association)	0.560
SLC7A8	YIPF1	psi-mi:“MI:0915”(physical association)	0.560
SLC25A46	SLC7A8	psi-mi:“MI:0915”(physical association)	0.560
ABHD16A	SLC7A8	psi-mi:“MI:0915”(physical association)	0.560
NINJ2	SLC7A8	psi-mi:“MI:0915”(physical association)	0.560
TMEM208	SLC7A8	psi-mi:“MI:0915”(physical association)	0.560
TMEM65	SLC7A8	psi-mi:“MI:0915”(physical association)	0.560
REEP4	SLC7A8	psi-mi:“MI:0915”(physical association)	0.560
TMEM14B	SLC7A8	psi-mi:“MI:0915”(physical association)	0.560
SMPD2	SLC7A8	psi-mi:“MI:0915”(physical association)	0.560
SYNJ2BP	SLC7A8	psi-mi:“MI:0915”(physical association)	0.560
TMEM60	SLC7A8	psi-mi:“MI:0915”(physical association)	0.560
NDUFA3	SLC7A8	psi-mi:“MI:0915”(physical association)	0.560
SLC7A8	ERN1	psi-mi:“MI:0915”(physical association)	0.560
SLC7A8	FGFR3	psi-mi:“MI:0915”(physical association)	0.560
SLC7A8	FKBP1A	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (73): SLC7A8 (Two-hybrid), SLC7A8 (Two-hybrid), SLC7A8 (Two-hybrid), COMT (Two-hybrid), SIGLEC5 (Two-hybrid), TMEM60 (Two-hybrid), SMPD2 (Two-hybrid), DERL1 (Two-hybrid), TMEM14B (Two-hybrid), SLC30A2 (Two-hybrid), SLC25A46 (Two-hybrid), TMEM65 (Two-hybrid), MFSD3 (Two-hybrid), SLC3A2 (Two-hybrid), REEP4 (Two-hybrid)

ESM2 similar proteins: A1L3M3, A7MBD8, B3TP03, B5D5N9, D3ZMM8, O08812, O61369, P11170, P13866, P18581, P30823, P30825, P52569, P70423, P83740, Q01650, Q09143, Q1EHB4, Q22397, Q28I80, Q3ZMH1, Q49B93, Q59I64, Q5BL81, Q5PR34, Q5RAE3, Q5RAG7, Q5RKI7, Q63016, Q6DCE8, Q7SYH5, Q7T384, Q7YQK4, Q8BGK6, Q8BYF6, Q8N695, Q8TCU3, Q8WY07, Q91WN3, Q92536

Diamond homologs: A1L3M3, D3ZMM8, O34739, P63115, P63116, P82251, P82252, Q01650, Q22397, Q28I80, Q59I64, Q5RAE3, Q5RAG7, Q5RKI7, Q63016, Q7YQK4, Q8BGK6, Q8MH63, Q8TCU3, Q91WN3, Q92536, Q9GIP4, Q9N1Q4, Q9N1R6, Q9NS82, Q9QXA6, Q9QXW9, Q9R0S5, Q9UHI5, Q9UM01, Q9UPY5, Q9WTR6, Q9WVR6, Q9Z127, Q9Z1K8, A2RNI1, A2RNI5, B0B7U3, B0BC08, O32204

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	3
Uncertain significance	104
Likely benign	9
Benign	3

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
3253728	NM_012244.4(SLC7A8):c.1017-1G>T	Likely pathogenic
599499	NM_012244.4(SLC7A8):c.851A>G (p.Asn284Ser)	Likely pathogenic
599500	NM_012244.4(SLC7A8):c.730G>A (p.Ala244Thr)	Likely pathogenic

SpliceAI

3950 predictions. Top by Δscore:

Variant	Effect	Δscore
14:23127339:CAGCT:C	acceptor_gain	1.0000
14:23127341:GCTCT:G	acceptor_loss	1.0000
14:23127342:CT:C	acceptor_gain	1.0000
14:23127343:TCTG:T	acceptor_loss	1.0000
14:23127344:C:CC	acceptor_gain	1.0000
14:23127344:CTGTA:C	acceptor_loss	1.0000
14:23128012:AACTC:A	donor_loss	1.0000
14:23128013:ACTCA:A	donor_loss	1.0000
14:23128014:CTC:C	donor_loss	1.0000
14:23128015:TCAC:T	donor_loss	1.0000
14:23128016:CA:C	donor_loss	1.0000
14:23128017:ACC:A	donor_loss	1.0000
14:23128018:C:CA	donor_loss	1.0000
14:23129644:TCTCA:T	donor_loss	1.0000
14:23129645:CTCA:C	donor_loss	1.0000
14:23129646:TCA:T	donor_loss	1.0000
14:23129647:CACCT:C	donor_loss	1.0000
14:23129648:A:C	donor_loss	1.0000
14:23129649:C:A	donor_loss	1.0000
14:23129795:ATGCA:A	acceptor_gain	1.0000
14:23129796:TGCA:T	acceptor_gain	1.0000
14:23129797:GCA:G	acceptor_gain	1.0000
14:23129797:GCAC:G	acceptor_loss	1.0000
14:23129798:CA:C	acceptor_gain	1.0000
14:23129798:CAC:C	acceptor_gain	1.0000
14:23129798:CACT:C	acceptor_loss	1.0000
14:23129799:AC:A	acceptor_loss	1.0000
14:23129800:C:CC	acceptor_gain	1.0000
14:23129801:T:G	acceptor_loss	1.0000
14:23131459:A:AC	donor_gain	1.0000

AlphaMissense

3448 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:23137933:A:G	F335S	1.000
14:23137936:A:G	L334P	1.000
14:23137942:C:T	G332E	1.000
14:23137943:C:A	G332W	1.000
14:23137944:A:C	N331K	1.000
14:23137944:A:T	N331K	1.000
14:23137954:C:T	G328E	1.000
14:23137969:G:T	A323D	1.000
14:23137972:A:T	V322D	1.000
14:23139428:G:T	A303D	1.000
14:23140503:A:C	N252K	1.000
14:23140503:A:T	N252K	1.000
14:23140517:A:G	W248R	1.000
14:23140517:A:T	W248R	1.000
14:23140530:A:C	F243L	1.000
14:23140530:A:T	F243L	1.000
14:23140532:A:G	F243L	1.000
14:23143100:C:G	G205R	1.000
14:23143100:C:T	G205R	1.000
14:23143185:G:C	N176K	1.000
14:23143185:G:T	N176K	1.000
14:23165423:A:G	W124R	1.000
14:23165423:A:T	W124R	1.000
14:23165425:A:G	L123P	1.000
14:23166445:C:G	G83R	1.000
14:23166457:A:G	W79R	1.000
14:23166457:A:T	W79R	1.000
14:23166515:A:C	F59L	1.000
14:23166515:A:T	F59L	1.000
14:23166516:A:C	F59C	1.000

dbSNP variants (sampled 300 via entrez): RS1000017678 (14:23157505 C>G), RS1000087111 (14:23142234 C>T), RS1000156120 (14:23136620 G>A,T), RS1000224405 (14:23180485 T>A), RS1000264096 (14:23155611 C>T), RS1000413794 (14:23184259 A>G,T), RS1000482608 (14:23156033 T>C), RS1000503153 (14:23147766 C>T), RS1000567601 (14:23149297 C>T), RS1000602819 (14:23154417 G>A,C), RS1000763811 (14:23160121 G>A), RS1000793636 (14:23137724 G>A,T), RS1000805784 (14:23126041 T>C), RS1000834428 (14:23161282 C>A,G,T), RS1000948841 (14:23162648 C>T)

Disease associations

OMIM: gene MIM:604235 | disease phenotypes: MIM:116200

GenCC curated gene-disease

Mondo (1): cataract (MONDO:0005129)

Orphanet (0):

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0000518	Cataract

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST005831_3	Systemic lupus erythematosus	4.000000e-08
GCST012490_547	Femur bone mineral density x serum urate levels interaction	5.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004531	urate measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D002386	Cataract	C11.510.245

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4301 (SINGLE PROTEIN)

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs7141505	RNF212B, SLC7A8		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: transporter — SLC7 family

Binding affinities (BindingDB)

17 measured of 17 human assays (17 total across all organisms); most potent 17 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
(5R)-5-phenyl-5-[4-(trifluoromethoxy)phenoxy]pentan-1-amine	IC50	10400 nM	US-9771316: Phenoxyalkylamine compound
(5R)-5-[3-fluoro-4-(trifluoromethoxy)phenoxy]-5-phenylpentan-1-amine	IC50	36400 nM	US-9771316: Phenoxyalkylamine compound
5-phenyl-5-[4-(trifluoromethoxy)phenoxy]pentan-1-amine	IC50	39400 nM	US-9771316: Phenoxyalkylamine compound
5-thiophen-2-yl-5-[4-(trifluoromethyl)phenoxy]pentan-1-amine	IC50	56600 nM	US-9771316: Phenoxyalkylamine compound
5-(4-butan-2-ylphenoxy)-5-phenylpentan-1-amine	IC50	57000 nM	US-9771316: Phenoxyalkylamine compound
5-phenyl-5-[4-(trifluoromethyl)phenoxy]pentan-1-amine	IC50	57500 nM	US-9771316: Phenoxyalkylamine compound
(5R)-5-phenyl-5-[4-(trifluoromethyl)phenoxy]pentan-1-amine	IC50	62800 nM	US-9771316: Phenoxyalkylamine compound
5-(3-fluorophenyl)-5-[4-(trifluoromethyl)phenoxy]pentan-1-amine	IC50	63000 nM	US-9771316: Phenoxyalkylamine compound
(5S)-5-[3-fluoro-4-(trifluoromethyl)phenoxy]-5-phenylpentan-1-amine	IC50	69000 nM	US-9771316: Phenoxyalkylamine compound
5-[3-fluoro-4-(trifluoromethyl)phenoxy]-5-phenylpentan-1-amine	IC50	76000 nM	US-9771316: Phenoxyalkylamine compound
6-phenyl-6-[4-(trifluoromethyl)phenoxy]hexan-1-amine	IC50	89100 nM	US-9771316: Phenoxyalkylamine compound
(5S)-5-phenyl-5-[4-(trifluoromethyl)phenoxy]pentan-1-amine	IC50	96200 nM	US-9771316: Phenoxyalkylamine compound
5-thiophen-2-yl-5-[4-(trifluoromethoxy)phenoxy]pentan-1-amine	IC50	123000 nM	US-9771316: Phenoxyalkylamine compound
5-[3-fluoro-4-(trifluoromethoxy)phenoxy]-5-thiophen-2-ylpentan-1-amine	IC50	146000 nM	US-9771316: Phenoxyalkylamine compound
5-[3-fluoro-4-(trifluoromethyl)phenoxy]-5-thiophen-2-ylpentan-1-amine	IC50	177000 nM	US-9771316: Phenoxyalkylamine compound
(5S)-5-phenyl-5-[4-(trifluoromethoxy)phenoxy]pentan-1-amine	IC50	244000 nM	US-9771316: Phenoxyalkylamine compound
5-(4-butan-2-ylphenoxy)-5-thiophen-2-ylpentan-1-amine	IC50	261000 nM	US-9771316: Phenoxyalkylamine compound

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, affects cotreatment, decreases expression, affects expression	5
bisphenol A	decreases expression, decreases methylation, increases expression, increases methylation	3
trichostatin A	affects cotreatment, decreases expression	3
Progesterone	affects cotreatment, increases expression	3
bisphenol F	affects cotreatment, increases methylation, increases expression	2
sodium arsenite	increases expression	2
Calcitriol	decreases expression	2
Estradiol	affects cotreatment, decreases expression, increases expression	2
FR900359	affects phosphorylation	1
allyl 2,4,6-tribromophenyl ether	decreases expression	1
triphenyl phosphate	affects expression	1
lead acetate	increases expression	1
arsenite	increases methylation	1
zinc chromate	increases abundance, increases expression	1
nickel sulfate	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
chromium hexavalent ion	increases abundance, increases expression	1
CGP 52608	increases reaction, affects binding	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
licochalcone B	decreases expression	1
bisphenol S	decreases methylation	1
incobotulinumtoxinA	increases expression	1
2,3-dibromopropyl-2,4,6-tribromophenyl ether	decreases expression	1
NSC 689534	affects binding, decreases expression	1
Sunitinib	increases expression	1
Arsenic Trioxide	increases expression	1
Fulvestrant	increases methylation, affects cotreatment	1
Acetaminophen	affects expression	1

ChEMBL screening assays

3 unique, capped per target: 3 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4425984	Binding	Competitive inhibition of [14C]-L-alanine uptake at LAT2 in human MCF7 cells at 25 uM preincubated for 5 mins followed by addition of substrate measured during 5 mins by liquid scintillation counting	A Selective and Slowly Reversible Inhibitor of l-Type Amino Acid Transporter 1 (LAT1) Potentiates Antiproliferative Drug Efficacy in Cancer Cells. — J Med Chem

Cellosaurus cell lines

5 cell lines: 5 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_DX59	HAP1 SLC7A5 (-) SLC7A8 (-) 1	Cancer cell line	Male
CVCL_DX60	HAP1 SLC7A5 (-) SLC7A8 (-) 2	Cancer cell line	Male
CVCL_TP16	HAP1 SLC7A8 (-) 1	Cancer cell line	Male
CVCL_XT36	HAP1 SLC7A8 (-) 2	Cancer cell line	Male
CVCL_XT37	HAP1 SLC7A8 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00273221	PHASE4	UNKNOWN	Combined Phacotube vs Phacotrabeculectomy:A Randomized Controlled Trial
NCT00312299	PHASE4	COMPLETED	Posterior Capsule Opacification Study
NCT00345046	PHASE4	COMPLETED	A Comparison of Three Different Formulations of Prednisolone Acetate 1%
NCT00347243	PHASE4	COMPLETED	Wavefront Analisys and Contrast Sensitivity of Spherical and Aspherical Intraocular Lenses
NCT00347503	PHASE4	COMPLETED	Aqueous Concentrations and PGE2 Inhibition of Ketorolac 0.4% vs. Bromfenac 0.09% in Cataract Patients
NCT00348244	PHASE4	COMPLETED	Ketorolac vs. Steroid in the Prevention of CME
NCT00348270	PHASE4	COMPLETED	Comparison of the Quality of Vision Provided by AMO Tecnis Z9000 and Alcon Laboratories MA60 Acrysof Posterior Chamber Intraocular Lenses
NCT00348582	PHASE4	COMPLETED	Acular LS vs. Nevanac in Post op Inflammation Following Cataract Surgery
NCT00348621	PHASE4	COMPLETED	A Study of Interventions to Reduce Disability From Visual Loss in Nursing Home Residents
NCT00349583	PHASE4	COMPLETED	Efficacy of Topical Cyclosporine Versus Tears for Improving Visual Outcomes Following Multifocal IOL Implantation
NCT00355446	PHASE4	COMPLETED	Bioavailability of Bimatoprost Ophthalmic Solution in Human Aqueous.
NCT00386438	PHASE4	COMPLETED	Efficacy of Honan Balloon in Intraocular Pressure Reduction Before Phacoemulsification
NCT00392275	PHASE4	COMPLETED	Penetrance of Third Generation Fluoroquinolones in Eyes With Functioning Filtering Blebs
NCT00428363	PHASE4	COMPLETED	Effect of Optic Edge Design in a Silicone Intraocular Lens on Posterior Capsule Opacification
NCT00449267	PHASE4	COMPLETED	Aurolab Hydrophobic Foldable Intraocular Lens Study
NCT00459303	PHASE4	COMPLETED	Comparison of Functional Vision Provided by AMO Tecnis Z9000 and Alcon SA60AT Acrysof
NCT00469690	PHASE4	COMPLETED	Aqueous Concentrations and PGE2 Inhibition of Ketorolac 0.4% vs. Bromfenac 0.09% in Cataract Patients: Trough Drug Effects
NCT00576485	PHASE4	COMPLETED	Spherical Aberration and Contrast Sensitivity in IOLs
NCT00612729	PHASE4	COMPLETED	Light Filters in Intraocular Lenses (IOLs) and Its Influence on Colour and Contrast Vision.
NCT00612781	PHASE4	COMPLETED	Yellow Versus White Study
NCT00630019	PHASE4	COMPLETED	Ocular Tissue Levels of 1.5% Levofloxacin Ophthalmic Solution Compared to an Active Comparator
NCT00673803	PHASE4	COMPLETED	Influence of Two Different Preloaded Intraocular Lens (IOLs) on Posterior Capsule Opacification
NCT00684138	PHASE4	COMPLETED	ACRYSOF® ReSTOR® Aspheric +3.0 D Add Power Intraocular Lens (IOL)
NCT00698724	PHASE4	COMPLETED	Comparing Optical Coherence Tomography (OCT) and Visual Acuity Outcomes in Subjects Undergoing Cataract Surgery, Who Receive Xibrom Ophthalmic Solution and Standard Presurgical Care vs. Xibrom Ophthalmic Solution Plus Prednisolone Acetate 1% and Standard Presurgical Care
NCT00710905	PHASE4	TERMINATED	Visual Function With Contralateral AcrySof® ReSTOR® Aspheric SN6AD1 and SN6AD3
NCT00710931	PHASE4	COMPLETED	Visual Function With Bilateral AcrySof® ReSTOR® Aspheric SN6AD1
NCT00711347	PHASE4	COMPLETED	Intraoperative Floppy Iris Syndrome
NCT00712244	PHASE4	COMPLETED	DisCoVisc Versus DuoVisc, Healon5 and AmVisc Plus
NCT00717080	PHASE4	COMPLETED	The Role of Capsular Tension Ring (CTR) in Anterior Capsular Contraction
NCT00719732	PHASE4	COMPLETED	Visual Function After Implantation of Bilateral AcrySof ReSTOR Aspheric +3
NCT00721253	PHASE4	COMPLETED	Visual Outcomes of Subjects Bilaterally Implanted With ReSTOR Aspheric +4 vs. Tecnis or Acri.LISA
NCT00731640	PHASE4	COMPLETED	Contralateral ReSTOR / Monofocal or Phakic Eye
NCT00732030	PHASE4	COMPLETED	Low Cylinder Toric
NCT00758199	PHASE4	COMPLETED	Determination of Optimum Duration of Treatment With Bromfenac (Xibrom) Eyedrops Following Cataract Surgery
NCT00760058	PHASE4	WITHDRAWN	Visual Outcome and Visual Quality After Bilateral Implantation of the AcrySof® IQ IOL Compared to MI60® and Tecnis® IOL
NCT00760487	PHASE4	COMPLETED	Visual Function After Implantation of Bilateral AcrySof® Toric Natural Intraocular Lens
NCT00761488	PHASE4	WITHDRAWN	Recommendations for Monitoring Clinical Experience Following Implantation of the AcrySof® Toric
NCT00763360	PHASE4	COMPLETED	To Compare the Ability of DiscoVisc® OVD to Protect the Corneal Endothelium and Maintain Anterior Chamber Space With Healon® and Amvisc® PLUS During Cataract Surgery.
NCT00786370	PHASE4	COMPLETED	Dexmedetomidine vs. Propofol for Cataract Surgery
NCT00786565	PHASE4	COMPLETED	Clinical Evaluation of a New Aspheric Intraocular Lens.