SLC41A3

Chr 3

solute carrier family 41 member 3

Also known as: SLC41A1-L2

NCBI Gene: 54946 ENSG00000114544 UniProt: Q96GZ6

This protein functions as a sodium/magnesium ion exchanger that mediates magnesium efflux from mitochondria across the inner mitochondrial membrane. Mutations cause autosomal recessive early-onset mitochondrial encephalomyopathy with seizures, developmental delay, and lactic acidosis. The gene shows low constraint against loss-of-function variants, consistent with its recessive inheritance pattern.

ResearchSummary from RefSeq, UniProt

Enables magnesium:sodium antiporter activity. Involved in mitochondrial magnesium ion transmembrane transport. Located in mitochondrial inner membrane and plasma membrane. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.29

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?

1.29LOEUF

pLI 0.000

Z-score 0.48

OE 0.89 (0.63–1.29)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.59Z-score

OE missense 0.90 (0.81–1.00)

253 obs / 281.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.89 (0.63–1.29)

0≤0.351.4

Missense OE?0.90 (0.81–1.00)

0≤0.61.4

Synonymous OE?0.90

0≤1.21.6

LoF obs/exp: 21 / 23.5Missense obs/exp: 253 / 281.0Syn Z: 0.87

Background carrier burden — how many people carry a rare variant somewhere in SLC41A3?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 84

755 rare PASS variants

Rare truncating (LoF)

1 in 860

153 rare PASS variants

Rare synonymous (reference)

1 in 150

333 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for SLC41A3. 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 95	1 in 1,200
South Asian	~43k	1 in 56	1 in 220
Remaining (unassigned)	~30k	1 in 88	1 in 570
European (Finnish)	~27k	1 in 400	1 in 5,300
Admixed American	~22k	1 in 110	1 in 660
African / African American	~21k	1 in 92	1 in 1,300
East Asian	~20k	1 in 110	1 in 770
Ashkenazi Jewish	~13k	1 in 240	≈ 1 in 4,400
Middle Eastern	~2,884	1 in 66	1 in 320

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 10 coding exons well covered in gnomAD exomes and genomes.? see exons ↓