SLC1A4

Chr 2AR

solute carrier family 1 member 4

Also known as: ASCT1, SATT, SPATCCM

NCBI Gene: 6509ENSG00000115902UniProt: P43007

The protein encoded by this gene is a sodium-dependent neutral amino acid transporter for alanine, serine, cysteine, and threonine. Defects in this gene have been associated with developmental delay, microcephaly, and intellectual disability. [provided by RefSeq, Jan 2017]

Primary Disease Associations & Inheritance

Spastic tetraplegia, thin corpus callosum, and progressive microcephalyMIM #616657
AR
467
ClinVar variants
46
Pathogenic / LP
0.07
pLI score
0
Active trials
Clinical Summary— SLC1A4
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.30) despite low pLI — interpret in context.
📋
ClinVar Variants
46 Pathogenic / Likely Pathogenic· 118 VUS of 467 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.64LOEUF
pLI 0.066
Z-score 2.62
OE 0.30 (0.16–0.64)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.73Z-score
OE missense 0.72 (0.65–0.81)
219 obs / 303.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.30 (0.16–0.64)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.72 (0.65–0.81)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.95
0≤1.21.6
LoF obs/exp: 5 / 16.5Missense obs/exp: 219 / 303.8Syn Z: 0.49

ClinVar Variant Classifications

467 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic30
Likely Pathogenic16
VUS118
Likely Benign249
Benign33
Conflicting8
30
Pathogenic
16
Likely Pathogenic
118
VUS
249
Likely Benign
33
Benign
8
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
12
4
14
0
30
Likely Pathogenic
6
4
6
0
16
VUS
1
110
6
1
118
Likely Benign
0
4
53
192
249
Benign
0
4
22
7
33
Conflicting
—8
Total19126101200454

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

SLC1A4 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

SLC1A4-related spastic tetraplegia, thin corpus callosum, and progressive microcephaly

definitive
ARUndeterminedAbsent Gene Product, Altered Gene Product Structure
Dev. Disorders
G2P ↗
missense variantstop gained NMD triggering

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Spastic tetraplegia, thin corpus callosum, and progressive microcephaly

MIM #616657

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Analysis of a new therapeutic target and construction of a prognostic model for breast cancer based on ferroptosis genes.
Li Q et al.·Comput Biol Med
2023Functional
A new type of blood-brain barrier aminoacidopathy underlies metabolic microcephaly associated with SLC1A4 mutations.
Odeh M et al.·Brain
2024
Dominant-negative variant in SLC1A4 causes an autosomal dominant epilepsy syndrome.
Pujol-Giménez J et al.·Ann Clin Transl Neurol
2023Case report
Novel European SLC1A4 variant: infantile spasms and population ancestry analysis.
Conroy J et al.·J Hum Genet
2016Case report
Serine biosynthesis and transport defects.
El-Hattab AW·Mol Genet Metab
2016Review
A rare cause of microcephaly, thin corpus callosum and refractory epilepsy due to a novel SLC1A4 gene mutation.
Sarigecili E et al.·Clin Neurol Neurosurg
2022
A novel SLC1A4 homozygous mutation causing congenital microcephaly, epileptic encephalopathy and spastic tetraparesis: a video-EEG and tractography - case study.
Pironti E et al.·J Neurogenet
2018Case report
Severe neurodevelopmental disorder with intractable seizures due to a novel SLC1A4 homozygous variant.
Sedláčková L et al.·Eur J Med Genet
2021Case report
A homozygous mutation in SLC1A4 in siblings with severe intellectual disability and microcephaly.
Srour M et al.·Clin Genet
2015Case report
In silico analysis shows slc1a4 as a potential target of hsa-mir-133a for regulating glutamine metabolism in gastric cancer.
Chakraborty A et al.·Int J Biol Macromol
2024
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
DMNQ induces ferroptosis and augments the efficacy of anti-PD-L1 immunotherapy in gastric cancer via the STAT3/SLC1A4 axis to mediate cysteine metabolism reprogramming.
Zhu W et al.·Redox Biol
2026🔓 Open Access
Skullcapflavone II Inhibits SLC1A4-Mediated L-Serine Uptake and Promotes Mitochondrial Damage in Gastric Cancer.
Zhao J et al.·Adv Sci (Weinh)
2025🔓 Open Access
SLC1A4 and Serine Homeostasis: Implications for Neurodevelopmental and Neurodegenerative Disorders.
Elazar D et al.·Int J Mol Sci
2025🔓 Open Access
Human urine stem cells protect against cyclophosphamide-induced premature ovarian failure by inhibiting SLC1A4-mediated outflux of intracellular serine in ovarian granulosa cells.
Gu HC et al.·Cell Mol Biol Lett
2025🔓 Open Access
SLC1A4 Promotes Malignant Transformation of Hepatocellular Carcinoma by Activating the AKT Signaling.
Zheng J et al.·Anal Cell Pathol (Amst)
2025🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools