SLC46A3

Chr 13

solute carrier family 46 member 3

Also known as: FKSG16

NCBI Gene: 283537ENSG00000139508UniProt: Q7Z3Q1OMIM: 616764

SLC46A3 encodes a lysosomal transporter that moves steroid conjugates, bile acids, and other small molecules from lysosomes to the cytoplasm, and also plays roles in copper homeostasis and innate immune signaling. Mutations cause autosomal recessive developmental and epileptic encephalopathy with onset in infancy or early childhood. The gene is not highly constrained against loss-of-function variants.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 1.18
Clinical Summary— SLC46A3
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
33 unique Pathogenic / Likely Pathogenic· 73 VUS of 114 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.18LOEUF
pLI 0.000
Z-score 0.96
OE 0.77 (0.51–1.18)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.49Z-score
OE missense 0.91 (0.82–1.02)
224 obs / 245.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.77 (0.51–1.18)
0≤0.351.4
Missense OE0.91 (0.82–1.02)
0≤0.61.4
Synonymous OE0.84
0≤1.21.6
LoF obs/exp: 15 / 19.6Missense obs/exp: 224 / 245.4Syn Z: 1.18
DN
0.74top 25%
GOF
0.6443th %ile
LOF
0.2191th %ile

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

DNprediction above median
GOFprediction 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

114 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic30
Likely Pathogenic3
VUS73
Likely Benign3
30
Pathogenic
3
Likely Pathogenic
73
VUS
3
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
30
0
30
Likely Pathogenic
0
0
3
0
3
VUS
0
66
7
0
73
Likely Benign
0
2
0
1
3
Benign
0
0
0
0
0
Total068401109

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

View in ClinVar →

Protein Context — Lollipop Plot

SLC46A3 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 3 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Macrolide and Ketolide Antibiotics Inhibit the Cytotoxic Effect of Trastuzumab Emtansine in HER2-Positive Breast Cancer Cells: Implication of a Potential Drug-ADC Interaction in Cancer Chemotherapy.
Kiyomiya K et al.·Mol Pharm
2023
Characterization of T-DM1-resistant breast cancer cells.
Sauveur J et al.·Pharmacol Res Perspect
2020
SLC46A3 as a Potential Predictive Biomarker for Antibody-Drug Conjugates Bearing Noncleavable Linked Maytansinoid and Pyrrolobenzodiazepine Warheads.
Kinneer K et al.·Clin Cancer Res
2018
Massively parallel pooled screening reveals genomic determinants of nanoparticle delivery.
Boehnke N et al.·Science
2022
Transcriptomic profiling of hepatic tissues for drug metabolism genes in nonalcoholic fatty liver disease: A study of human and animals.
Chen L et al.·Front Endocrinol (Lausanne)
2023
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Exploring flavonoids as potent SLC46A3 inhibitors: Insights from the structural characteristics of flavonoid-SLC46A3 interactions.
Tomabechi R et al.·Biochem Pharmacol
2025
Identification of 5-Carboxyfluorescein as a Probe Substrate of SLC46A3 and Its Application in a Fluorescence-Based In Vitro Assay Evaluating the Interaction with SLC46A3.
Tomabechi R et al.·Mol Pharm
2023
SLC46A3 is a lysosomal proton-coupled steroid conjugate and bile acid transporter involved in transport of active catabolites of T-DM1.
Tomabechi R et al.·PNAS Nexus
2022Open Access
Lysosomal SLC46A3 modulates hepatic cytosolic copper homeostasis.
Kim JH et al.·Nat Commun
2021Open Access
Increased expression of SLC46A3 to oppose the progression of hepatocellular carcinoma and its effect on sorafenib therapy.
Zhao Q et al.·Biomed Pharmacother
2019
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients