SLC46A3

Chr 13

solute carrier family 46 member 3

Also known as: FKSG16

NCBI Gene: 283537 ENSG00000139508 UniProt: Q7Z3Q1

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.

ResearchSummary from RefSeq, UniProt

The protein encoded by this gene is a member of a transmembrane protein family that transports small molecules across membranes. The encoded protein has been found in lysosomal membranes, where it can transport catabolites from the lysosomes to the cytoplasm. This protein has been shown to be an effective transporter of the cytotoxic drug maytansine, which is used in antibody-based targeting of cancer cells. [provided by RefSeq, Dec 2016]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.18

LOEUF

Multiple*

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

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 OE?0.77 (0.51–1.18)

0≤0.351.4

Missense OE?0.91 (0.82–1.02)

0≤0.61.4

Synonymous OE?0.84

0≤1.21.6

LoF obs/exp: 15 / 19.6Missense obs/exp: 224 / 245.4Syn Z: 1.18

Background carrier burden — how many people carry a rare variant somewhere in SLC46A3?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 110

548 rare PASS variants

Rare truncating (LoF)

1 in 470

102 rare PASS variants

Rare synonymous (reference)

1 in 270

197 rare PASS variants

Rare missense and truncating variants are carried at similar rates in SLC46A3; this gene does not show strong loss-of-function constraint by this measure. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 200	1 in 450
South Asian	~43k	1 in 96	1 in 380
Remaining (unassigned)	~30k	1 in 99	1 in 490
European (Finnish)	~27k	1 in 560	1 in 2,200
Admixed American	~22k	1 in 85	1 in 480
African / African American	~21k	1 in 73	1 in 860
East Asian	~20k	1 in 100	1 in 690
Ashkenazi Jewish	~13k	1 in 2,200	1 in 1,300
Middle Eastern	~2,884	1 in 66	1 in 480

Each group is summed over the variants that are rare in that group. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 5 coding exons well covered in gnomAD exomes and genomes.? see exons ↓