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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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SLC7A4
solute carrier family 7 member 4
Chromosome 22 · 22q11.21
NCBI Gene: 6545Ensembl: ENSG00000099960.14HGNC: HGNC:11062UniProt: O43246
16PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Transporter
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
amino acid transmembrane transporter activityplasma membraneamino acid transportbasic amino acid transmembrane transporter activityneurodegenerative diseaseneuroinflammatory disorderinfectionviral disease
✦AI Summary

SLC7A4 is a solute carrier family 7 member localized to chromosome 22.2 that encodes a cationic amino acid transporter. The protein is structurally homologous to confirmed cationic amino acid transporters (CAT-1, CAT-2, CAT-3) 1 and shows abundant expression in brain, testis, and placenta 1. However, SLC7A4's functional role remains controversial. Early Xenopus oocyte studies suggested cationic amino acid transport capacity 1, but subsequent research demonstrated that SLC7A4 plasma membrane expression alone is insufficient to mediate transport of cationic, neutral, or anionic amino acids 2. Recent structural studies reveal SLC7A4 functions as a pH-regulated leucine transporter in human cells through an allosteric mechanism linking ligand recognition to proton regulation 3. Functionally, arginine transport via SLC7A4 could not be convincingly demonstrated 4. SLC7A4 has clinical relevance in velocardiofacial syndrome, mapping to the commonly deleted 22q11.2 region 1, and frameshift variants have been identified in classic bladder exstrophy patients 5. Additionally, SLC7A4 expression is significantly upregulated in obese mouse testes in Sertoli cells, suggesting involvement in obesity-related testicular dysfunction 6.

Sources cited
1
SLC7A4 gene identification, chromosomal mapping to 22q11.2, high homology to CAT transporters, abundant expression in brain/testis/placenta, and initial evidence of cationic amino acid transport in oocytes
PMID: 9598310
2
SLC7A4 plasma membrane expression is not sufficient to mediate amino acid transport activity in oocytes or human cells despite protein localization
PMID: 12049641
3
SLC7A4 functions as a pH-regulated leucine transporter with an allosteric mechanism linking ligand recognition to proton regulation
PMID: 41904136
4
SLC7A4 could not be convincingly shown to transport L-arginine using real-time FRET-based functional assays
PMID: 26555760
5
SLC7A4 frameshift variants identified in classic bladder exstrophy patients, implicating the gene in congenital urological abnormalities
PMID: 37509153
6
SLC7A4 significantly upregulated in testes of obese mice in Sertoli cells, suggesting role in obesity-related testicular dysfunction
PMID: 40114606
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.44Moderate
neuroinflammatory disorderOpen Targets
0.29Weak
infectionOpen Targets
0.11Weak
viral diseaseOpen Targets
0.04Suggestive
central nervous system cancerOpen Targets
0.03Suggestive
glioblastoma multiformeOpen Targets
0.02Suggestive
neoplasmOpen Targets
0.02Suggestive
poisoningOpen Targets
0.02Suggestive
adolescent idiopathic scoliosisOpen Targets
0.02Suggestive
alopecia areataOpen Targets
0.02Suggestive
agingOpen Targets
0.02Suggestive
prostate carcinomaOpen Targets
0.02Suggestive
chronic lymphocytic leukemiaOpen Targets
0.02Suggestive
22q11.2 deletion syndromeOpen Targets
0.02Suggestive
cancerOpen Targets
0.02Suggestive
acute myeloid leukemiaOpen Targets
0.02Suggestive
autoimmune diseaseOpen Targets
0.02Suggestive
Alzheimer diseaseOpen Targets
0.01Suggestive
melanomaOpen Targets
0.01Suggestive
acute lymphoblastic leukemiaOpen Targets
0.01Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
COQ7Protein interaction72%SLC7A14Shared pathway50%SLC7A9Shared pathway43%TMEM44Shared pathway33%SLC38A4Shared pathway33%SLC7A7Shared pathway33%
Tissue Expression6 tissues
Brain
100%
Heart
20%
Liver
14%
Ovary
11%
Lung
10%
Bone Marrow
3%
Gene Interaction Network
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SLC7A4COQ7SLC7A14SLC7A9TMEM44SLC38A4SLC7A7
PROTEIN STRUCTURE
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AlphaFoldAI-predicted · UniProt O43246
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.07LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.80 [0.60–1.07]
RankingsWhere SLC7A4 stands among ~20K protein-coding genes
  • #15,392of 20,598
    Most Researched16
  • #10,890of 17,882
    Most Constrained (LOEUF)1.07
Genes detectedSLC7A4
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Obesity alters testicular gene expression in mice, monkeys and humans.
PMID: 40114606
Zygote · 2025
1.00
2
The gene encoding a cationic amino acid transporter (SLC7A4) maps to the region deleted in the velocardiofacial syndrome.
PMID: 9598310
Genomics · 1998
0.90
3
Expression of solute carrier 7A4 (SLC7A4) in the plasma membrane is not sufficient to mediate amino acid transport activity.
PMID: 12049641
Biochem J · 2002
0.80
4
Exome Survey and Candidate Gene Re-Sequencing Identifies Novel Exstrophy Candidate Genes and Implicates
PMID: 37509153
Biomolecules · 2023
0.70
5
Structure and function of cationic amino acid transporters (CATs).
PMID: 17417706
J Membr Biol · 2006
0.60