SLC7A4

Summary

SLC7A4 (solute carrier family 7 member 4, HGNC:11062) is a protein-coding gene on chromosome 22q11.21, encoding Cationic amino acid transporter 4 (O43246). Involved in the transport of the cationic amino acids (arginine, lysine and ornithine).

Predicted to enable amino acid transmembrane transporter activity. Predicted to be involved in amino acid transport. Predicted to be located in membrane. Predicted to be active in plasma membrane.

Source: NCBI Gene 6545 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 138 total — 1 pathogenic
• MANE Select transcript: NM_004173

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11062
Approved symbol	SLC7A4
Name	solute carrier family 7 member 4
Location	22q11.21
Locus type	gene with protein product
Status	Approved
Aliases	HCAT3, CAT-4
Ensembl gene	ENSG00000099960
Ensembl biotype	protein_coding
OMIM	603752
Entrez	6545

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 6 protein_coding

ENST00000382932, ENST00000403586, ENST00000426145, ENST00000909291, ENST00000909292, ENST00000909293

RefSeq mRNA: 1 — MANE Select: NM_004173 NM_004173

CCDS: CCDS33608

Canonical transcript exons

ENST00000382932 — 5 exons

Exon	Start	End
ENSE00000651015	21029336	21029444
ENSE00000651016	21029711	21030351
ENSE00001493914	21030831	21031852
ENSE00001493915	21032531	21032561
ENSE00001551492	21028718	21029230

Expression profiles

Bgee: expression breadth ubiquitous, 150 present calls, max score 84.13.

FANTOM5 (CAGE): breadth broad, TPM avg 0.6203 / max 126.1695, expressed in 215 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
193226	0.5517	207
193228	0.0370	18
193227	0.0224	9
193229	0.0092	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	84.13	gold quality
right testis	UBERON:0004534	80.53	gold quality
left testis	UBERON:0004533	80.10	gold quality
testis	UBERON:0000473	78.09	gold quality
prefrontal cortex	UBERON:0000451	75.28	gold quality
right hemisphere of cerebellum	UBERON:0014890	71.94	gold quality
cerebellar hemisphere	UBERON:0002245	71.72	gold quality
cerebellar cortex	UBERON:0002129	71.57	gold quality
esophagus mucosa	UBERON:0002469	71.12	gold quality
right adrenal gland	UBERON:0001233	70.80	gold quality
right adrenal gland cortex	UBERON:0035827	70.73	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	70.13	gold quality
right frontal lobe	UBERON:0002810	70.10	gold quality
cerebellum	UBERON:0002037	69.53	gold quality
frontal cortex	UBERON:0001870	69.48	gold quality
left adrenal gland cortex	UBERON:0035825	69.12	gold quality
left adrenal gland	UBERON:0001234	69.02	gold quality
hypothalamus	UBERON:0001898	68.81	gold quality
Brodmann (1909) area 9	UBERON:0013540	68.77	gold quality
placenta	UBERON:0001987	68.66	gold quality
pituitary gland	UBERON:0000007	68.51	gold quality
tibialis anterior	UBERON:0001385	68.32	silver quality
adenohypophysis	UBERON:0002196	68.22	gold quality
neocortex	UBERON:0001950	67.90	gold quality
cingulate cortex	UBERON:0003027	67.65	gold quality
adrenal cortex	UBERON:0001235	67.43	gold quality
anterior cingulate cortex	UBERON:0009835	67.34	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	66.82	gold quality
adrenal gland	UBERON:0002369	65.78	gold quality
right coronary artery	UBERON:0001625	65.61	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-8060	no	202.46
E-ANND-3	no	1.73

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

9 targeting SLC7A4, 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-4795-3P	100.00	74.62	4024
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-3187-5P	98.36	65.74	1776
HSA-MIR-1285-3P	97.72	67.02	1932
HSA-MIR-5189-5P	97.72	66.96	1814
HSA-MIR-493-3P	97.50	66.44	731
HSA-MIR-612	97.26	65.95	1597
HSA-MIR-6860	97.21	66.31	1656

Literature-anchored findings (GeneRIF, showing 4)

• analysis of the genomic organization (PMID:11665818)
• expression in cell membrane is not sufficient for amino acid transport (SOLUTE CARRIER SLC7A4) (PMID:12049641)
• ZAP-70 reactivity using a T-cell marker as a control allows to identify the majority of patients with an unmutated Ig VH genotype. (PMID:17051526)
• These results suggest a heterogeneous immunophenotype and genotype for c-myc/Ig DLBCL, with CD10(-)/BCL6(+)/MUM1(-) cases the most frequent. (PMID:18460403)

Cross-species orthologs

14 orthologs

Organism	Symbol	Gene ID
danio_rerio	slc7a4	ENSDARG00000068286
mus_musculus	Slc7a4	ENSMUSG00000022756
rattus_norvegicus	Slc7a4	ENSRNOG00000001874
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), SLC7A6 (ENSG00000103064), SLC7A5 (ENSG00000103257), SLC7A10 (ENSG00000130876), SLC7A1 (ENSG00000139514), SLC7A11 (ENSG00000151012), SLC7A7 (ENSG00000155465), SLC7A13 (ENSG00000164893), SLC7A3 (ENSG00000165349)

Protein

Protein identifiers

Cationic amino acid transporter 4 — O43246 (reviewed: O43246)

Alternative names: Solute carrier family 7 member 4

All UniProt accessions (2): O43246, C9JM63

UniProt curated annotations — full annotation on UniProt →

Function. Involved in the transport of the cationic amino acids (arginine, lysine and ornithine).

Subcellular location. Membrane.

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_004164* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002293	AA/rel_permease1	Family
IPR029485	CAT_C	Domain

Pfam: PF13520, PF13906

UniProt features (25 total): transmembrane region 13, glycosylation site 5, sequence variant 3, modified residue 2, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O43246-F1	80.89	0.43

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (2): 422, 427

Glycosylation sites (5): 151, 195, 221, 500, 601

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 66 (showing top): GOBP_AMINO_ACID_TRANSMEMBRANE_TRANSPORT, MODULE_379, GOBP_AMINO_ACID_TRANSPORT, GOBP_BASIC_AMINO_ACID_TRANSPORT, MODULE_88, MODULE_242, MODULE_38, GOBP_TRANSMEMBRANE_TRANSPORT, MODULE_104, MODULE_55, MODULE_13, GOMF_AMINO_ACID_TRANSMEMBRANE_TRANSPORTER_ACTIVITY, GSE13762_CTRL_VS_125_VITAMIND_DAY12_DC_DN, GOMF_TRANSPORTER_ACTIVITY, MODULE_181

GO Biological Process (4): amino acid transport (GO:0006865), amino acid transmembrane transport (GO:0003333), transmembrane transport (GO:0055085), basic amino acid transmembrane transport (GO:1990822)

GO Molecular Function (3): amino acid transmembrane transporter activity (GO:0015171), basic amino acid transmembrane transporter activity (GO:0015174), transmembrane transporter activity (GO:0022857)

GO Cellular Component (2): plasma membrane (GO:0005886), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transport	2
transmembrane transport	2
amino acid transmembrane transport	2
amino acid transport	1
cellular process	1
basic amino acid transport	1
transmembrane transporter activity	1
amino acid transmembrane transporter activity	1
basic amino acid transmembrane transport	1
transporter activity	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

978 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC7A4	COQ7	Q99807	723
SLC7A4	THAP7	Q9BT49	637
SLC7A4	AIFM3	Q96NN9	564
SLC7A4	PI4KA	P42356	528
SLC7A4	SLC43A2	Q8N370	520
SLC7A4	SLC15A4	Q8N697	471
SLC7A4	SLC38A7	Q9NVC3	461
SLC7A4	SLC38A11	Q08AI6	452
SLC7A4	PPIL4	Q8WUA2	450
SLC7A4	P2RX6	O15547	450
SLC7A4	SLC1A4	P43007	449
SLC7A4	KLHL22	Q53GT1	446
SLC7A4	MED15	Q96RN5	443
SLC7A4	SLC38A2	Q96QD8	430
SLC7A4	SLC3A1	Q07837	428
SLC7A4	SLC7A3	Q8WY07	428

IntAct

4 interactions, top by confidence:

A	B	Type	Score
ERBB2	SLC7A4	psi-mi:“MI:0915”(physical association)	0.370
SLC7A14	ESYT2	psi-mi:“MI:0914”(association)	0.350
SLC7A4	ESYT2	psi-mi:“MI:0914”(association)	0.350

BioGRID (107): SLC7A4 (Two-hybrid), SLC7A4 (Affinity Capture-MS), ABCB1 (Affinity Capture-MS), ABCG2 (Affinity Capture-MS), ACBD3 (Affinity Capture-MS), ADPGK (Affinity Capture-MS), AGK (Affinity Capture-MS), AGPAT3 (Affinity Capture-MS), ALG1 (Affinity Capture-MS), ALG11 (Affinity Capture-MS), ANKLE2 (Affinity Capture-MS), ARL6IP5 (Affinity Capture-MS), ATP11B (Affinity Capture-MS), ATP11C (Affinity Capture-MS), ATP1B3 (Affinity Capture-MS)

ESM2 similar proteins: A0A1B0GTI8, A0A2Z2U4G9, A0A494BA31, A5D6W6, A6NC51, A6NDP7, A6NFC5, A6NH21, A6NJY4, A8WCG0, B0BNG2, B1AQL3, E9Q9H8, O43246, P43219, P48546, Q1HG43, Q1HG44, Q2KIG8, Q32L10, Q497B3, Q49LS0, Q49LS7, Q4VV71, Q53RY4, Q58CW5, Q5REM8, Q5XK03, Q658P3, Q6PEY1, Q6UW68, Q80SU6, Q8C0T0, Q8K177, Q8K4R8, Q8K4V2, Q8N130, Q8VE49, Q91XE8, Q923Z0

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, P37103, P0AA47, P0AA48, P76037, A1L3M3, D3ZMM8, O34739

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	120
Likely benign	12
Benign	2

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
929350	GRCh37/hg19 22q11.21(chr22:18844632-21797812)x1	Pathogenic

SpliceAI

724 predictions. Top by Δscore:

Variant	Effect	Δscore
22:21030349:TGG:T	acceptor_gain	1.0000
22:21029334:A:AC	donor_gain	0.9900
22:21029334:AC:A	donor_gain	0.9900
22:21029335:C:CC	donor_gain	0.9900
22:21029335:CC:C	donor_gain	0.9900
22:21029335:CCCAT:C	donor_gain	0.9900
22:21030347:CATGG:C	acceptor_gain	0.9900
22:21030350:GG:G	acceptor_gain	0.9900
22:21030352:C:CC	acceptor_gain	0.9900
22:21030825:TCTCA:T	donor_loss	0.9900
22:21030826:CTCAC:C	donor_loss	0.9900
22:21030827:TCA:T	donor_loss	0.9900
22:21030828:CAC:C	donor_loss	0.9900
22:21030829:A:AC	donor_gain	0.9900
22:21030829:A:AT	donor_loss	0.9900
22:21030830:C:CC	donor_gain	0.9900
22:21030830:CCG:C	donor_gain	0.9900
22:21029331:CT:C	donor_loss	0.9800
22:21029332:T:TA	donor_loss	0.9800
22:21029333:C:CG	donor_loss	0.9800
22:21029335:C:A	donor_loss	0.9800
22:21030088:T:TA	donor_gain	0.9800
22:21030348:ATGG:A	acceptor_gain	0.9800
22:21030351:GC:G	acceptor_loss	0.9800
22:21030352:C:T	acceptor_loss	0.9800
22:21030353:T:A	acceptor_loss	0.9800
22:21030358:C:CT	acceptor_gain	0.9800
22:21031853:CTG:C	acceptor_gain	0.9800
22:21032526:CCCA:C	donor_loss	0.9800
22:21032527:CCA:C	donor_loss	0.9800

AlphaMissense

4064 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:21031060:G:C	F251L	0.995
22:21031060:G:T	F251L	0.995
22:21031062:A:G	F251L	0.995
22:21031069:G:C	F248L	0.991
22:21031069:G:T	F248L	0.991
22:21031071:A:G	F248L	0.991
22:21029412:G:C	S552R	0.985
22:21029412:G:T	S552R	0.985
22:21029414:T:G	S552R	0.985
22:21029762:G:C	S524R	0.985
22:21029762:G:T	S524R	0.985
22:21029764:T:G	S524R	0.985
22:21030110:A:C	S408R	0.984
22:21030110:A:T	S408R	0.984
22:21030112:T:G	S408R	0.984
22:21031081:G:C	C244W	0.984
22:21031176:C:G	G213R	0.983
22:21030092:G:C	F414L	0.981
22:21030092:G:T	F414L	0.981
22:21030094:A:G	F414L	0.981
22:21031465:G:C	F116L	0.981
22:21031465:G:T	F116L	0.981
22:21031467:A:G	F116L	0.981
22:21031688:A:G	L42P	0.981
22:21031580:G:T	A78D	0.980
22:21031001:G:T	A271D	0.979
22:21031061:A:G	F251S	0.978
22:21031455:A:G	W120R	0.978
22:21031455:A:T	W120R	0.978
22:21031149:A:G	W222R	0.977

dbSNP variants (sampled 300 via entrez): RS1000016479 (22:21034170 A>C), RS1000843144 (22:21029393 G>A), RS1000874126 (22:21029175 C>T), RS1001300489 (22:21028271 A>G), RS1001820635 (22:21033207 C>T), RS1002086309 (22:21033046 T>C), RS1002560710 (22:21032293 A>G), RS1003220774 (22:21032817 C>T), RS1003298335 (22:21031887 G>A), RS1003973093 (22:21032521 T>G), RS1004005710 (22:21032332 C>T), RS1005019688 (22:21029141 A>G), RS1005173985 (22:21034558 C>T), RS1005302526 (22:21034151 T>A), RS1005358607 (22:21030617 A>C)

Disease associations

OMIM: gene MIM:603752 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: transporter — SLC7 family

CTD chemical–gene interactions

19 total (human), top 19 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	decreases expression, increases abundance	2
Estradiol	affects cotreatment, decreases expression	2
aristolochic acid I	increases expression	1
FR900359	affects phosphorylation	1
2,5,2’,5’-tetrachlorobiphenyl	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Benzo(a)pyrene	decreases methylation	1
Lead	affects expression	1
Phthalic Acids	increases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Progesterone	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Triclosan	decreases expression	1
Valproic Acid	increases methylation	1
Mifepristone	decreases expression	1
Aflatoxin B1	decreases methylation	1
Cadmium Chloride	increases expression	1
Lactic Acid	decreases expression	1
Particulate Matter	decreases expression, increases abundance	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D4WB	LS180-SLC7A4-KO-c3	Cancer cell line	Female
CVCL_D4WC	LS180-SLC7A4-KO-c4	Cancer cell line	Female

Clinical trials (associated diseases)

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