SLC7A5

Chr 16

solute carrier family 7 member 5

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

NCBI Gene: 8140 ENSG00000103257 UniProt: Q01650

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]

Active trials

Pathogenic / LP

164

ClinVar variants

Pubs (1 yr)

1.6

Missense Z

0.51

LOEUF

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

51 Pathogenic / Likely Pathogenic· 90 VUS of 164 total submissions

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GeneReview available — SLC7A5

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

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.

0.51LOEUF

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?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.

1.65Z-score

OE missense 0.73 (0.65–0.82)

215 obs / 294.7 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.0.24 (0.13–0.51)

0≤0.351.4

Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.73 (0.65–0.82)

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.1.47

0≤1.21.6

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

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.