SLC7A1

Summary

SLC7A1 (solute carrier family 7 member 1, HGNC:11057) is a protein-coding gene on chromosome 13q12.3, encoding High affinity cationic amino acid transporter 1 (P30825). High-affinity, low capacity permease involved in the transport of the cationic amino acids (arginine, lysine and ornithine) in non-hepatic tissues. It is a selective cancer dependency (DepMap: 17.3% of cell lines).

Enables L-arginine transmembrane transporter activity; L-histidine transmembrane transporter activity; and L-lysine transmembrane transporter activity. Involved in carboxylic acid transport. Located in apical plasma membrane and basolateral plasma membrane. Part of protein-containing complex.

Source: NCBI Gene 6541 — RefSeq curated summary.

At a glance

• GWAS associations: 11
• Clinical variants (ClinVar): 73 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 17.3% of screened cell lines
• MANE Select transcript: NM_003045

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11057
Approved symbol	SLC7A1
Name	solute carrier family 7 member 1
Location	13q12.3
Locus type	gene with protein product
Status	Approved
Aliases	CAT-1, HCAT1, REC1L
Ensembl gene	ENSG00000139514
Ensembl biotype	protein_coding
OMIM	104615
Entrez	6541

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 10 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000380752, ENST00000450494, ENST00000473577, ENST00000907882, ENST00000907883, ENST00000907884, ENST00000907885, ENST00000936268, ENST00000936269, ENST00000936270, ENST00000936271

RefSeq mRNA: 1 — MANE Select: NM_003045 NM_003045

CCDS: CCDS9333

Canonical transcript exons

ENST00000380752 — 13 exons

Exon	Start	End
ENSE00000938506	29532824	29532982
ENSE00000938507	29530538	29530712
ENSE00000938508	29524132	29524253
ENSE00000938509	29523266	29523488
ENSE00000938511	29519447	29519549
ENSE00000938513	29517144	29517310
ENSE00000938514	29516138	29516246
ENSE00001132166	29522317	29522456
ENSE00001361445	29553761	29553860
ENSE00001361454	29595416	29595688
ENSE00001486139	29509414	29514583
ENSE00001486219	29535819	29536202
ENSE00003639860	29517573	29517790

Expression profiles

Bgee: expression breadth ubiquitous, 287 present calls, max score 99.43.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 29.6831 / max 301.9638, expressed in 1802 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
136602	10.9424	1676
136603	9.1830	1715
136600	6.7944	1616
136605	0.6078	374
136599	0.5206	92
136595	0.4536	240
136601	0.4059	209
136604	0.3388	152
136593	0.2851	127
136594	0.0934	28

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tongue squamous epithelium	UBERON:0006919	99.43	gold quality
gingiva	UBERON:0001828	98.55	gold quality
gingival epithelium	UBERON:0001949	98.50	gold quality
squamous epithelium	UBERON:0006914	97.98	gold quality
esophagus squamous epithelium	UBERON:0006920	97.96	gold quality
endothelial cell	CL:0000115	97.88	gold quality
epithelium of esophagus	UBERON:0001976	97.83	gold quality
buccal mucosa cell	CL:0002336	97.79	gold quality
parotid gland	UBERON:0001831	97.56	gold quality
pharyngeal mucosa	UBERON:0000355	97.44	gold quality
oral cavity	UBERON:0000167	97.20	gold quality
corpus epididymis	UBERON:0004359	97.12	gold quality
choroid plexus epithelium	UBERON:0003911	96.92	gold quality
cervix squamous epithelium	UBERON:0006922	96.58	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	96.55	gold quality
oviduct epithelium	UBERON:0004804	96.48	gold quality
cartilage tissue	UBERON:0002418	96.06	gold quality
hair follicle	UBERON:0002073	95.88	gold quality
mucosa of sigmoid colon	UBERON:0004993	95.84	gold quality
penis	UBERON:0000989	95.79	gold quality
Brodmann (1909) area 23	UBERON:0013554	95.66	gold quality
type B pancreatic cell	CL:0000169	95.53	gold quality
cauda epididymis	UBERON:0004360	95.17	gold quality
endometrium epithelium	UBERON:0004811	95.10	gold quality
pigmented layer of retina	UBERON:0001782	94.89	gold quality
pons	UBERON:0000988	94.68	gold quality
medial globus pallidus	UBERON:0002477	94.45	gold quality
skin of hip	UBERON:0001554	94.15	gold quality
trabecular bone tissue	UBERON:0002483	94.09	gold quality
entorhinal cortex	UBERON:0002728	94.08	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NRIP1

miRNA regulators (miRDB)

238 targeting SLC7A1, 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-4262	100.00	73.26	3931
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-6740-5P	100.00	65.64	932
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-6759-5P	99.99	66.54	785
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-6793-5P	99.97	65.95	758
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-6825-5P	99.96	69.81	3431
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-4487	99.96	64.58	1252

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 17.3% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 29)

• analysis of the genomic organization (PMID:11665818)
• Stable polarized expression of hCAT-1 in an epithelial cell line. (PMID:11891586)
• Keratinocytes express cationic amino acid transporters 1 and 2. Cationic amino acid transporter mediated L-arginine essential for inducible nitric oxide synthase and arginase enzyme, which modulate proliferation and differentiation of epidermal cells. (PMID:12787129)
• Insulin-mediated stimulation of the L-arginine/NO pathway is thus associated with increased hCAT-1 and hCAT-2B mRNA, and eNOS expression (PMID:15064952)
• Glomerular arginine uptake is elevated through modulation of CAT-1 expression, thus, contributing to the pathogenesis of hyperfiltration. Increased nitric oxide formation may play a role in this process. (PMID:15086470)
• protein kinase C(PKC) did not phosphorylate human cationic amino acid transporter hCAT-1 directly as evidenced by in vivo phosphorylation experiments and mutational analysis, indicating an indirect action of PKC on hCAT-1 (PMID:15491978)
• The CAT-1 is thought to supply substrate to endothelial NOS by virtue of its co-localisation with this enzyme. (PMID:15631944)
• The present study identifies a key functionally active polymorphism in the 3’UTR of SLC7A1 [which] may account for the apparent link between altered endothelial function, L-arginine, and nitric oxide metabolism and predisposition to essential hypertension (PMID:17325243)
• Ornithine uptake in retinal pigment epithelium is depdendent on induction of SLC7A1 mRNA and spermine. (PMID:17494634)
• distribution of human cationic amino acid transporters 1 (hCAT1) and 2 (hCAT2) in healthy skin and compared it to psoriatic skin lesions by means of immunohistochemistry (PMID:18172665)
• CAT1 is directly involved in erythropoiesis through supplying arginine to the blood cells. (PMID:18574322)
• Data provide novel insights into the mechanism by which ss52051869 influences SLC7A1 gene expression. (PMID:19067360)
• PKC activation also resulted in ubiquitination of CAT-1 (PMID:21212261)
• Insulin increased hCATs-L-arginine transport, maximal transport capacity, and hCAT-1 expression. Sp1 nuclear protein abundance and binding to DNA, and SLC7A1 promoter activity was increased by insulin. (PMID:21302286)
• Data show that the CAT-1 isoform plays a role in arginine uptake. (PMID:21308737)
• In acute congestive heart failure acute renal impairment function and the modulation of metabolism and extracellular transport by the DDAH-1/CAT-1 system determine high ADMA and SDMA levels after therapy for acute congestive heart failure. (PMID:21722652)
• In hypoxic human pulmonary microvascular endothelial cells, overexpression of CAT-1 resulted in significantly greater L-arginine transport and NO production (PMID:21923750)
• The data demonstrates that CAT1 significantly (but most likely not exclusively) contributes to the cellular uptake of asymmetric dimethylarginine. (PMID:22705145)
• CAT1, CAT2, and CAT3 localized in adult brains but with uneven distribution. (PMID:22870827)
• mRNA levels for high-affinity CAT-1, expressed as a percentage of the wild-type value, are increased by an average 12% and 32% in mdx and transgenic mdx:utr mice respectively. (PMID:23009292)
• The rs41318021 polymorphism in the SLC7A1 gene was not associated with essential hypertension in 50-year-old subjects. (PMID:23841815)
• Overexpression of arginine transporter CAT-1 is associated with accumulation of L-arginine and cell growth in human colorectal cancer tissue. (PMID:24040099)
• Estradiol increases arginine transport and CAT-1 activity through modulation of constitutive signaling transduction pathways involving ERK. Progesterone inhibits arginine transport and CAT-1 via both PKCalpha and ERK1/2 phosphorylation. (PMID:26062636)
• L-homoarginine is a substrate of the cationic amino acid transporters CAT1, CAT2A and CAT2B. (PMID:28684763)
• Human cationic amino acid transporters are not affected by direct nitros(yl)ation. (PMID:32008093)
• High total cholesterol and triglycerides levels increase arginases metabolism, impairing nitric oxide signaling and worsening fetoplacental endothelial dysfunction in gestational diabetes mellitus pregnancies. (PMID:34314821)
• Oncogenic KRAS Induces Arginine Auxotrophy and Confers a Therapeutic Vulnerability to SLC7A1 Inhibition in Non-Small Cell Lung Cancer. (PMID:38502865)
• The solute carrier SLC7A1 may act as a protein transporter at the blood-brain barrier. (PMID:38547677)
• High expression of SLC7A1 in high-grade serous ovarian cancer promotes tumor progression and is involved in MAPK/ERK pathway and EMT. (PMID:38752472)

Cross-species orthologs

15 orthologs

Organism	Symbol	Gene ID
danio_rerio	slc7a1a	ENSDARG00000016439
danio_rerio	SLC7A1	ENSDARG00000100227
mus_musculus	Slc7a1	ENSMUSG00000041313
rattus_norvegicus	Slc7a1	ENSRNOG00000000924
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), SLC7A8 (ENSG00000092068), SLC7A4 (ENSG00000099960), SLC7A6 (ENSG00000103064), SLC7A5 (ENSG00000103257), SLC7A10 (ENSG00000130876), SLC7A11 (ENSG00000151012), SLC7A7 (ENSG00000155465), SLC7A13 (ENSG00000164893), SLC7A3 (ENSG00000165349)

Protein

Protein identifiers

High affinity cationic amino acid transporter 1 — P30825 (reviewed: P30825)

Alternative names: Ecotropic retroviral leukemia receptor homolog, Ecotropic retrovirus receptor homolog, Solute carrier family 7 member 1, System Y+ basic amino acid transporter

All UniProt accessions (2): P30825, Q5JR49

UniProt curated annotations — full annotation on UniProt →

Function. High-affinity, low capacity permease involved in the transport of the cationic amino acids (arginine, lysine and ornithine) in non-hepatic tissues.

Subunit / interactions. Interacts with TM4SF5; the interaction is negatively regulated by arginine. Forms tissue-specific complexes with ASL, ASS1 and nitric oxide synthase NOS1 or NOS3; the complex regulates cell-autonomous L-arginine synthesis and citrulline recycling while channeling extracellular L-arginine to nitric oxide synthesis pathway.

Subcellular location. Cell membrane.

Tissue specificity. Ubiquitous.

Similarity. Belongs to the amino acid-polyamine-organocation (APC) superfamily. Cationic amino acid transporter (CAT) (TC 2.A.3.3) family.

RefSeq proteins (1): NP_003036* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002293	AA/rel_permease1	Family
IPR004755	Cat_AA_permease	Family
IPR029485	CAT_C	Domain

Pfam: PF13520, PF13906

Catalyzed reactions (Rhea), 4 shown:

• L-arginine(in) = L-arginine(out) (RHEA:32143)
• L-lysine(in) = L-lysine(out) (RHEA:70935)
• L-ornithine(in) = L-ornithine(out) (RHEA:71199)
• L-homoarginine(in) = L-homoarginine(out) (RHEA:71203)

UniProt features (33 total): topological domain 15, transmembrane region 14, glycosylation site 2, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P30825-F1	82.11	0.44

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 (2): 226, 235

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-352230	Amino acid transport across the plasma membrane

MSigDB gene sets: 359 (showing top): GSE45365_NK_CELL_VS_BCELL_UP, GOBP_REGULATION_OF_CELL_ACTIVATION, AGGAAGC_MIR5163P, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_CIRCULATORY_SYSTEM_PROCESS, MITSIADES_RESPONSE_TO_APLIDIN_DN, BROWNE_HCMV_INFECTION_16HR_UP, GOBP_AMINO_ACID_TRANSMEMBRANE_TRANSPORT, EFC_Q6, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_ORGANIC_ACID_TRANSPORT, GOBP_POSITIVE_REGULATION_OF_CELL_ADHESION, PUJANA_CHEK2_PCC_NETWORK, GOBP_POSITIVE_REGULATION_OF_LEUKOCYTE_PROLIFERATION

GO Biological Process (15): amino acid transport (GO:0006865), L-amino acid transport (GO:0015807), lysine transport (GO:0015819), ornithine transport (GO:0015822), positive regulation of T cell proliferation (GO:0042102), amino acid import across plasma membrane (GO:0089718), L-arginine import across plasma membrane (GO:0097638), monoatomic cation transmembrane transport (GO:0098655), transport across blood-brain barrier (GO:0150104), L-ornithine transmembrane transport (GO:1903352), L-lysine transmembrane transport (GO:1903401), L-histidine import across plasma membrane (GO:1903810), L-arginine transmembrane transport (GO:1903826), symbiont entry into host cell (GO:0046718), transmembrane transport (GO:0055085)

GO Molecular Function (9): L-ornithine transmembrane transporter activity (GO:0000064), virus receptor activity (GO:0001618), L-histidine transmembrane transporter activity (GO:0005290), amino acid transmembrane transporter activity (GO:0015171), basic amino acid transmembrane transporter activity (GO:0015174), L-lysine transmembrane transporter activity (GO:0015189), L-arginine transmembrane transporter activity (GO:0061459), protein binding (GO:0005515), transmembrane transporter activity (GO:0022857)

GO Cellular Component (6): plasma membrane (GO:0005886), basal plasma membrane (GO:0009925), membrane (GO:0016020), basolateral plasma membrane (GO:0016323), apical plasma membrane (GO:0016324), protein-containing complex (GO:0032991)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
SLC-mediated transport of amino acids	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
L-amino acid transmembrane transporter activity	4
L-alpha-amino acid transmembrane transport	3
basic amino acid transmembrane transporter activity	3
plasma membrane region	3
transport	2
amino acid transport	2
carboxylic acid transport	2
nitrogen compound transport	2
L-lysine transport	2
amino acid transmembrane transport	2
amino acid import across plasma membrane	2
L-arginine transmembrane transport	2
L-histidine transmembrane transport	2
basic amino acid transmembrane transport	2
basic amino acid transport	1
T cell proliferation	1
regulation of T cell proliferation	1
positive regulation of lymphocyte proliferation	1
positive regulation of T cell activation	1
import across plasma membrane	1
monoatomic cation transport	1
monoatomic ion transmembrane transport	1
vascular transport	1
ornithine transport	1
viral life cycle	1
symbiont entry into host	1
cellular process	1
L-ornithine transmembrane transport	1
symbiont entry into host cell	1
exogenous protein binding	1
aromatic amino acid transmembrane transporter activity	1
azole transmembrane transporter activity	1
transmembrane transporter activity	1
amino acid transmembrane transporter activity	1
L-lysine transmembrane transport	1
binding	1
transporter activity	1
transmembrane transport	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

1844 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC7A1	ESRRG	P62508	931
SLC7A1	PPARGC1A	Q9UBK2	905
SLC7A1	PPARGC1B	Q86YN6	904
SLC7A1	ESRRA	P11474	847
SLC7A1	ESRRB	O95718	842
SLC7A1	NRIP1	P48552	792
SLC7A1	RAD1	O60671	712
SLC7A1	SLC1A4	P43007	703
SLC7A1	SLC1A5	Q15758	690
SLC7A1	ASS1	P00966	645
SLC7A1	SLC43A2	Q8N370	643
SLC7A1	ELAVL1	Q15717	640
SLC7A1	SLC38A2	Q96QD8	629
SLC7A1	SLC3A2	P08195	628
SLC7A1	ESR1	P03372	628

IntAct

232 interactions, top by confidence:

A	B	Type	Score
SLC7A1	YIPF4	psi-mi:“MI:0915”(physical association)	0.740
HS2ST1	SLC7A1	psi-mi:“MI:0914”(association)	0.730
SLC7A1	FATE1	psi-mi:“MI:0915”(physical association)	0.720
COMT	SLC7A1	psi-mi:“MI:0915”(physical association)	0.670
SLC7A1	SACM1L	psi-mi:“MI:0915”(physical association)	0.670
CD40	SLC7A1	psi-mi:“MI:0915”(physical association)	0.670
SLC7A1	STIM1	psi-mi:“MI:0915”(physical association)	0.670
CD27	TCAF2	psi-mi:“MI:0914”(association)	0.640
SLC7A1	MGST3	psi-mi:“MI:0915”(physical association)	0.560
SLC7A1	PDCD1LG2	psi-mi:“MI:0915”(physical association)	0.560
SLC39A2	SLC7A1	psi-mi:“MI:0915”(physical association)	0.560
LEPROTL1	SLC7A1	psi-mi:“MI:0915”(physical association)	0.560
CCL4L1	SLC7A1	psi-mi:“MI:0915”(physical association)	0.560
C8A	SLC7A1	psi-mi:“MI:0915”(physical association)	0.560
FAM241B	SLC7A1	psi-mi:“MI:0915”(physical association)	0.560
SLC7A1		psi-mi:“MI:0915”(physical association)	0.560
TMEM19	SLC7A1	psi-mi:“MI:0915”(physical association)	0.560
MS4A13	SLC7A1	psi-mi:“MI:0915”(physical association)	0.560
SLC30A2	SLC7A1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (476): FATE1 (Two-hybrid), SLC7A1 (Proximity Label-MS), SLC7A1 (Affinity Capture-MS), SLC7A1 (Affinity Capture-MS), RAC3 (Affinity Capture-MS), BCL2L13 (Affinity Capture-MS), METTL7A (Affinity Capture-MS), MTCH2 (Affinity Capture-MS), DGAT1 (Affinity Capture-MS), ZDHHC21 (Affinity Capture-MS), TMEM120B (Affinity Capture-MS), TMEM11 (Affinity Capture-MS), STX4 (Affinity Capture-MS), LEMD2 (Affinity Capture-MS), AGPAT3 (Affinity Capture-MS)

ESM2 similar proteins: A0JNI9, A8I499, B0UYF2, B3TP03, B5D5N9, O08812, O54701, O64759, O80668, P18581, P30823, P30825, P31637, P52569, P53793, P53794, P70423, Q08469, Q09143, Q09573, Q28677, Q28E01, Q5PR34, Q5R9C2, Q5RK27, Q63632, Q63633, Q6A4L1, Q6DCE8, Q80UP8, Q84MA5, Q8BG16, Q8BXR1, Q8GYB4, Q8TBB6, Q8W4K3, Q8WY07, Q91V14, Q924N4, Q9ASS7

Diamond homologs: A0JNI9, A8I499, B0UYF2, B3TP03, B5D5N9, O07576, O08812, O43246, O64759, P18581, P30823, P30825, P52569, P70423, Q09143, Q5PR34, Q6DCE8, Q797A7, Q84MA5, Q8BLQ7, Q8BXR1, Q8GYB4, Q8TBB6, Q8W4K3, Q8WY07, Q9C5D6, Q9LZ20, Q9SHH0, Q9SQZ0, A2RHI9, Q9ASS7, Q8MH63, Q9GIP4, A0A1D8PPG4, A0A1D8PPI5, P43059, P37103, A1L3M3, D3ZMM8, O34739

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	53
Likely benign	5
Benign	6

Top pathogenic / likely-pathogenic (0)

SpliceAI

2586 predictions. Top by Δscore:

Variant	Effect	Δscore
13:29516133:CATA:C	donor_loss	1.0000
13:29516134:ATAC:A	donor_loss	1.0000
13:29516135:TA:T	donor_loss	1.0000
13:29516136:A:AT	donor_loss	1.0000
13:29516137:C:CA	donor_loss	1.0000
13:29516244:AACC:A	acceptor_loss	1.0000
13:29516247:C:CC	acceptor_gain	1.0000
13:29516247:C:CG	acceptor_loss	1.0000
13:29517307:ACAG:A	acceptor_gain	1.0000
13:29517308:CAG:C	acceptor_gain	1.0000
13:29517308:CAGC:C	acceptor_gain	1.0000
13:29517309:AG:A	acceptor_gain	1.0000
13:29517309:AGCTA:A	acceptor_loss	1.0000
13:29517310:GC:G	acceptor_loss	1.0000
13:29517311:C:CC	acceptor_gain	1.0000
13:29517311:CTAA:C	acceptor_loss	1.0000
13:29519545:CACAG:C	acceptor_gain	1.0000
13:29519547:CAG:C	acceptor_gain	1.0000
13:29519550:C:CC	acceptor_gain	1.0000
13:29519550:CT:C	acceptor_loss	1.0000
13:29519551:T:G	acceptor_loss	1.0000
13:29523261:CTCAC:C	donor_loss	1.0000
13:29523262:TCAC:T	donor_loss	1.0000
13:29523263:CA:C	donor_loss	1.0000
13:29523264:AC:A	donor_loss	1.0000
13:29523265:CCTGG:C	donor_gain	1.0000
13:29523308:TTGG:T	donor_gain	1.0000
13:29523309:TGGC:T	donor_gain	1.0000
13:29523486:CAC:C	acceptor_gain	1.0000
13:29523489:C:CC	acceptor_gain	1.0000

AlphaMissense

4072 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
13:29519489:A:G	L417P	1.000
13:29524151:A:C	F269L	1.000
13:29524151:A:T	F269L	1.000
13:29524153:A:G	F269L	1.000
13:29524172:G:C	C262W	1.000
13:29535846:A:G	W115R	1.000
13:29535846:A:T	W115R	1.000
13:29535848:C:T	G114D	1.000
13:29535872:C:A	G106V	1.000
13:29535872:C:T	G106E	1.000
13:29535920:C:G	R90P	1.000
13:29535929:A:G	F87S	1.000
13:29535940:G:C	C83W	1.000
13:29536068:C:A	G41W	1.000
13:29516150:A:G	W592R	0.999
13:29516150:A:T	W592R	0.999
13:29516194:A:G	L577P	0.999
13:29516202:G:C	N574K	0.999
13:29516202:G:T	N574K	0.999
13:29516214:G:C	S570R	0.999
13:29516214:G:T	S570R	0.999
13:29516216:T:G	S570R	0.999
13:29517147:A:C	F558L	0.999
13:29517147:A:T	F558L	0.999
13:29517149:A:G	F558L	0.999
13:29519447:C:G	R431P	0.999
13:29519461:A:C	C426W	0.999
13:29519462:C:T	C426Y	0.999
13:29519463:A:G	C426R	0.999
13:29519489:A:T	L417H	0.999

dbSNP variants (sampled 300 via entrez): RS1000059684 (13:29533323 T>C), RS1000066098 (13:29567753 G>A), RS1000082654 (13:29535281 A>G), RS1000096565 (13:29567977 C>T), RS1000102949 (13:29521546 G>A), RS1000114577 (13:29518722 T>G), RS1000151118 (13:29535010 G>C), RS1000151451 (13:29576215 C>A,T), RS1000187517 (13:29557213 T>C), RS1000285174 (13:29544705 A>C), RS1000381047 (13:29529187 C>T), RS1000400029 (13:29564684 T>C), RS1000402158 (13:29574090 G>A), RS1000479683 (13:29527333 A>T), RS1000489072 (13:29586862 C>T)

Disease associations

OMIM: gene MIM:104615 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST004267_6	Blood osmolality (transformed sodium)	5.000000e-06
GCST007094_190	Diastolic blood pressure	1.000000e-11
GCST007095_93	Systolic blood pressure	3.000000e-06
GCST007098_32	Diastolic blood pressure	4.000000e-10
GCST007098_33	Diastolic blood pressure	1.000000e-07
GCST007099_201	Systolic blood pressure	9.000000e-09
GCST007267_135	Systolic blood pressure	1.000000e-09
GCST007928_12	Medication use (diuretics)	2.000000e-10
GCST007930_161	Medication use (agents acting on the renin-angiotensin system)	7.000000e-10
GCST009391_1235	Metabolite levels	2.000000e-06
GCST90000025_1040	Appendicular lean mass	3.000000e-16

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0006336	diastolic blood pressure
EFO:0006335	systolic blood pressure
EFO:0009928	Diuretic use measurement
EFO:0009931	Agents acting on the renin-angiotensin system use measurement
EFO:0010422	triacylglycerol 54:4 measurement
EFO:0004980	appendicular lean mass

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066921 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: transporter — SLC7 family

ChEMBL bioactivities

4 potent at pChembl≥5 of 4 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.78	Kd	1675	nM	CHEMBL5653589
5.78	ED50	1675	nM	CHEMBL5653589
5.39	Kd	4060	nM	CHEMBL3752910
5.39	ED50	4060	nM	CHEMBL3752910

PubChem BioAssay actives

2 with measured affinity, of 4 total; 2 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149433: Binding affinity to human SLC7A1 incubated for 45 mins by Kinobead based pull down assay	kd	1.6750	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149433: Binding affinity to human SLC7A1 incubated for 45 mins by Kinobead based pull down assay	kd	4.0595	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases methylation, affects cotreatment, increases expression	6
bisphenol A	affects expression, decreases expression, decreases methylation, increases expression	5
sodium arsenite	increases abundance, increases expression	5
methylmercuric chloride	increases expression, affects cotreatment	4
Cyclosporine	increases expression	4
perfluorooctane sulfonic acid	increases expression	3
Benzo(a)pyrene	decreases expression, increases expression, increases methylation	3
cobaltous chloride	decreases expression, increases expression	2
Arsenic	increases abundance, increases expression	2
Cisplatin	increases expression, decreases expression	2
Tetrachlorodibenzodioxin	affects expression, decreases expression	2
Tretinoin	decreases expression	2
Tunicamycin	increases expression	2
Aflatoxin B1	increases expression, increases methylation	2
Cadmium Chloride	decreases reaction, increases abundance, increases palmitoylation, decreases expression	2
Thapsigargin	increases expression	2
Particulate Matter	increases abundance, increases expression, affects cotreatment	2
aristolochic acid I	decreases expression	1
TL8-506	affects cotreatment, increases expression	1
dicrotophos	increases expression	1
tremortin	increases expression	1
chloroacetaldehyde	decreases expression	1
alpha phellandrene	decreases expression	1
triphenyl phosphate	affects expression	1
trichostatin A	affects expression	1
arsenite	decreases reaction, affects binding	1
2-amino-9H-pyrido(2,3-b)indole	increases expression	1
2-bromopalmitate	decreases reaction, increases abundance, increases palmitoylation	1
zinc chromate	decreases expression, increases abundance	1
benzo(e)pyrene	increases methylation	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652475	Binding	Binding affinity to human SLC7A1 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

5 cell lines: 4 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B3HK	Abcam HEK293T SLC7A1 KO	Transformed cell line	Female
CVCL_D4QE	HCT116-SLC7A1-KO-c3	Cancer cell line	Male
CVCL_D4QF	HCT116-SLC7A1-KO-c5	Cancer cell line	Male
CVCL_TP08	HAP1 SLC7A1 (-) 1	Cancer cell line	Male
CVCL_TP09	HAP1 SLC7A1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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