SLC1A4

Chr 2AR

solute carrier family 1 member 4

Also known as: ASCT1, SATT, SPATCCM

NCBI Gene: 6509 ENSG00000115902 UniProt: P43007 OMIM: 600229

The encoded protein is a sodium-dependent neutral amino acid transporter that exchanges amino acids like serine, alanine, and threonine across cell membranes and maintains D-serine homeostasis at synapses. Mutations cause autosomal recessive developmental delay, microcephaly, and intellectual disability with early childhood onset. The gene shows moderate intolerance to loss-of-function variants (LOEUF 0.637) and has an associated GeneReviews entry reflecting its clinical significance.

GeneReviews OMIM ResearchSummary from RefSeq, UniProt

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]

GeneReviews OMIM ResearchGenerating clinical summary…

MultiplemechanismARLOEUF 0.641 OMIM phenotype

Clinical Summary— SLC1A4

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Gene-Disease Validity (ClinGen)

spastic tetraplegia-thin corpus callosum-progressive postnatal microcephaly syndrome · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.30) despite low pLI — interpret in context.

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ClinVar Variants

33 unique Pathogenic / Likely Pathogenic· 118 VUS of 453 total submissions

Explore recent and relevant literature in Research Assistant →

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GeneReview available — SLC1A4

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.64LOEUF

pLI 0.066

Z-score 2.62

OE 0.30 (0.16–0.64)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.73Z-score

OE missense 0.72 (0.65–0.81)

219 obs / 303.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.30 (0.16–0.64)

0≤0.351.4

Missense OE?0.72 (0.65–0.81)

0≤0.61.4

Synonymous OE?0.95

0≤1.21.6

LoF obs/exp: 5 / 16.5Missense obs/exp: 219 / 303.8Syn Z: 0.49

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveSLC1A4-related spastic tetraplegia, thin corpus callosum, and progressive microcephalyOTHERAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.75top 25%

GOF

0.83top 10%

LOF

0.2092th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

453 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic21

Likely Pathogenic12

VUS118

Likely Benign249

Benign32

Conflicting8

Pathogenic

Likely Pathogenic

118

VUS

249

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	16	4	1	0	21
Likely Pathogenic	8	4	0	0	12
VUS	2	113	2	1	118
Likely Benign	0	4	53	192	249
Benign	0	4	21	7	32
Conflicting	—				8
Total	26	129	77	200	440

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

View in ClinVar →

13 pathogenic / likely-pathogenic (of 16) ClinVar copy-number / structural variants overlap SLC1A4 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →