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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 15 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
SLC1A4
solute carrier family 1 member 4
Chromosome 2 Β· 2p14
NCBI Gene: 6509Ensembl: ENSG00000115902.12HGNC: HGNC:10942UniProt: P43007
68PubMed Papers
21Diseases
0Drugs
32Pathogenic Variants
FUNCTIONAL ROLE
Transporter
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
L-cystine transmembrane transporter activityL-cystine transportchloride channel activityprotein bindingspastic tetraplegia-thin corpus callosum-progressive postnatal microcephaly syndromegenetic disordermacular telangiectasia type 2Intellectual disability
✦AI Summary

SLC1A4 encodes a sodium-coupled neutral amino acid transporter that plays a critical role in brain serine homeostasis and neurodevelopment. The protein functions as an obligatory amino acid exchanger at the blood-brain barrier, facilitating L-serine transport from blood into the brain 1. SLC1A4 transports various neutral amino acids including L-serine, D-serine, L-alanine, and L-threonine in a bidirectional manner coupled to sodium influx. In the brain, SLC1A4 is essential for maintaining adequate L-serine levels required for protein synthesis, sphingolipid metabolism, and D-serine production for NMDA receptor function 2. The transporter also contributes to cellular redox balance through serine metabolism pathways 34. Pathogenic mutations in SLC1A4 cause a severe neurodevelopmental disorder characterized by microcephaly, spastic tetraplegia, thin corpus callosum, and refractory epilepsy 51. The disease mechanism involves impaired L-serine transport across the blood-brain barrier, leading to decreased brain serine content, accumulation of cytotoxic sphingolipids, and neurodegeneration 1. Early L-serine supplementation has shown therapeutic potential in mouse models, suggesting possible treatment approaches for SLC1A4-related disorders 1.

Sources cited
1
SLC1A4 functions as L-serine transporter at blood-brain barrier and causes microcephaly when mutated
PMID: 38662784
2
SLC1A4 transports L-serine and D-serine isomers important for neurotransmission
PMID: 40076728
3
SLC1A4 mutations cause microcephaly, spastic tetraplegia, and refractory epilepsy
PMID: 35605507
4
SLC1A4 mediates L-serine uptake affecting cellular redox balance
PMID: 40971730
5
SLC1A4 regulates intracellular serine levels through serine efflux
PMID: 39972244
Disease Associationsβ“˜21
spastic tetraplegia-thin corpus callosum-progressive postnatal microcephaly syndromeOpen Targets
0.80Strong
genetic disorderOpen Targets
0.47Moderate
macular telangiectasia type 2Open Targets
0.41Moderate
Intellectual disabilityOpen Targets
0.37Weak
coronary artery calcificationOpen Targets
0.31Weak
ovarian dysfunctionOpen Targets
0.27Weak
liver diseaseOpen Targets
0.27Weak
lacrimal apparatus diseaseOpen Targets
0.25Weak
eye diseaseOpen Targets
0.19Weak
Alzheimer diseaseOpen Targets
0.19Weak
skin diseaseOpen Targets
0.17Weak
Abruptio PlacentaeOpen Targets
0.16Weak
psoriasisOpen Targets
0.16Weak
microcephalyOpen Targets
0.12Weak
hepatocellular carcinomaOpen Targets
0.09Suggestive
cardiac arrhythmiaOpen Targets
0.06Suggestive
liver neoplasmOpen Targets
0.06Suggestive
MODYOpen Targets
0.05Suggestive
chronic hepatitisOpen Targets
0.05Suggestive
schizophreniaOpen Targets
0.05Suggestive
Spastic tetraplegia, thin corpus callosum, and progressive microcephalyUniProt
Pathogenic Variants32
NM_003038.5(SLC1A4):c.766G>A (p.Glu256Lys)Pathogenic
Spastic tetraplegia-thin corpus callosum-progressive postnatal microcephaly syndrome|not provided|Inborn genetic diseases
β˜…β˜…β˜†β˜†2025β†’ Residue 256
NM_003038.5(SLC1A4):c.1369C>T (p.Arg457Trp)Pathogenic
Spastic tetraplegia-thin corpus callosum-progressive postnatal microcephaly syndrome|not provided|Inborn genetic diseases|SLC1A4-related spastic tetraplegia-thin corpus callosum-progressive postnatal microcephaly syndrome
β˜…β˜…β˜†β˜†2025β†’ Residue 457
NM_003038.5(SLC1A4):c.964C>T (p.Arg322Ter)Pathogenic
Spastic tetraplegia-thin corpus callosum-progressive postnatal microcephaly syndrome|not provided
β˜…β˜…β˜†β˜†2024β†’ Residue 322
NM_003038.5(SLC1A4):c.1364+1G>TPathogenic
not provided
β˜…β˜†β˜†β˜†2026
NM_003038.5(SLC1A4):c.234_237dup (p.Glu80fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 80
NM_003038.5(SLC1A4):c.807_810del (p.Pro270fs)Likely pathogenic
Spastic tetraplegia-thin corpus callosum-progressive postnatal microcephaly syndrome
β˜…β˜†β˜†β˜†2024β†’ Residue 270
NM_003038.5(SLC1A4):c.950_953del (p.Tyr317fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2023β†’ Residue 317
NM_003038.5(SLC1A4):c.514dup (p.Leu172fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2023β†’ Residue 172
NM_003038.5(SLC1A4):c.971dup (p.Asn324fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2023β†’ Residue 324
NM_003038.5(SLC1A4):c.913del (p.His305fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2023β†’ Residue 305
NM_003038.5(SLC1A4):c.1229+1G>CLikely pathogenic
not provided
β˜…β˜†β˜†β˜†2023
NM_003038.5(SLC1A4):c.1123del (p.Ala375fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2023β†’ Residue 375
NM_003038.5(SLC1A4):c.1229+1G>ALikely pathogenic
not provided
β˜…β˜†β˜†β˜†2023
NM_003038.5(SLC1A4):c.170_192del (p.Gly57fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2023β†’ Residue 57
NM_003038.5(SLC1A4):c.801G>A (p.Trp267Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2023β†’ Residue 267
NM_003038.5(SLC1A4):c.951_954del (p.Ile316_Tyr317insTer)Pathogenic
not provided
β˜…β˜†β˜†β˜†2023β†’ Residue 316
NM_003038.5(SLC1A4):c.925G>T (p.Gly309Ter)Likely pathogenic
Spastic tetraplegia-thin corpus callosum-progressive postnatal microcephaly syndrome
β˜…β˜†β˜†β˜†2023β†’ Residue 309
NM_003038.5(SLC1A4):c.634-1G>CLikely pathogenic
SLC1A4-related disorder
β˜…β˜†β˜†β˜†2023
NM_003038.5(SLC1A4):c.404T>A (p.Leu135Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2022β†’ Residue 135
NM_003038.5(SLC1A4):c.805_808dup (p.Pro270fs)Likely pathogenic
Spastic tetraplegia-thin corpus callosum-progressive postnatal microcephaly syndrome
β˜…β˜†β˜†β˜†2022β†’ Residue 270
View on ClinVar β†—
Related Genes
ERVW-1Protein interaction98%SLC7A1Protein interaction75%SLC3A2Protein interaction73%SLC1A5Shared pathway32%SLC1A3Shared pathway25%SLC1A2Shared pathway24%
Tissue Expression6 tissues
Brain
100%
Bone Marrow
63%
Ovary
34%
Heart
25%
Liver
23%
Lung
14%
Gene Interaction Network
Click a node to explore
SLC1A4ERVW-1SLC7A1SLC3A2SLC1A5SLC1A3SLC1A2
PROTEIN STRUCTURE
Preparing viewer…
PDB7P4I Β· 4.20 Γ… Β· EM
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.80LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.53 [0.36–0.80]
RankingsWhere SLC1A4 stands among ~20K protein-coding genes
  • #6,949of 20,598
    Most Researched68
  • #1,758of 5,498
    Most Pathogenic Variants32
  • #6,581of 17,882
    Most Constrained (LOEUF)0.80
Genes detectedSLC1A4
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
NAT10-mediated mRNA N
PMID: 39506072
Nat Cell Biol Β· 2024
1.00
2
Hypoxia-induced cysteine metabolism reprogramming is crucial for the tumorigenesis of colorectal cancer.
PMID: 39079386
Redox Biol Β· 2024
0.90
3
SLC1A4 and Serine Homeostasis: Implications for Neurodevelopmental and Neurodegenerative Disorders.
PMID: 40076728
Int J Mol Sci Β· 2025
0.80
4
Analysis of a new therapeutic target and construction of a prognostic model for breast cancer based on ferroptosis genes.
PMID: 37643511
Comput Biol Med Β· 2023
0.70
5
Skullcapflavone II Inhibits SLC1A4-Mediated L-Serine Uptake and Promotes Mitochondrial Damage in Gastric Cancer.
PMID: 40971730
Adv Sci (Weinh) Β· 2025
0.60