SLC7A5

Chr 16

solute carrier family 7 member 5

Also known as: 4F2LC, CD98, D16S469E, E16, LAT1, MPE16

NCBI Gene: 8140 ENSG00000103257 UniProt: Q01650 OMIM: 600182

This gene encodes a large neutral amino acid transporter that forms a heterodimer with SLC3A2 to facilitate sodium-independent transport of essential amino acids including phenylalanine, tyrosine, leucine, and tryptophan across cell membranes, particularly at the blood-brain barrier. Mutations cause autosomal recessive autism spectrum disorder with intellectual disability, though the specific neurological phenotypes and age of onset associated with SLC7A5 deficiency require further clinical characterization. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.514), suggesting some tolerance to haploinsufficiency.

GeneReviews OMIM ResearchSummary from RefSeq, UniProt

Enables L-amino acid transmembrane transporter activity and secondary active transmembrane transporter activity. Involved in carboxylic acid transport; thyroid hormone transport; and xenobiotic transport. Located in several cellular components, including apical plasma membrane; cytosol; and microvillus membrane. Part of amino acid transport complex. Implicated in cholangiocarcinoma; colon cancer; hepatocellular carcinoma; and lung squamous cell carcinoma. Biomarker of esophagitis; gastrointestinal system cancer (multiple); malignant astrocytoma (multiple); and respiratory system cancer (multiple). [provided by Alliance of Genome Resources, Apr 2025]

GeneReviews OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 0.51

Clinical Summary— SLC7A5

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Gene-Disease Validity (ClinGen)

complex neurodevelopmental disorder · ARModerate

Moderate evidence — consider for supplementary testing

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.24) despite low pLI — interpret in context.

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ClinVar Variants

70 VUS of 103 total submissions

Explore recent and relevant literature in Research Assistant →

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GeneReview available — SLC7A5

Authoritative clinical overview · Recommended first read

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.51LOEUF

pLI 0.235

Z-score 3.17

OE 0.24 (0.13–0.51)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.65Z-score

OE missense 0.73 (0.65–0.82)

215 obs / 294.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.24 (0.13–0.51)

0≤0.351.4

Missense OE?0.73 (0.65–0.82)

0≤0.61.4

Synonymous OE?1.47

0≤1.21.6

LoF obs/exp: 5 / 20.4Missense obs/exp: 215 / 294.7Syn Z: -4.42

This gene — mechanism propensity

0.79top 25%

GOF

0.84top 5%

LOF

0.2092th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

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

ClinVar Variant Classifications

103 submitted variants in ClinVar

ClinVar

Classification Summary

VUS70

Likely Benign11

Benign11

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	69	1	0	70
Likely Benign	3	4	4	11
Benign	3	2	6	11
Total	75	7	10	92

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

View in ClinVar →

53 pathogenic / likely-pathogenic (of 79) ClinVar copy-number / structural variants overlap SLC7A5 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →