LETM2

Chr 8

leucine zipper and EF-hand containing transmembrane protein 2

Also known as: SLC55A2

NCBI Gene: 137994 ENSG00000165046 UniProt: Q2VYF4 OMIM: 620380

Predicted to enable transmembrane transporter activity. Predicted to be involved in mitochondrial calcium ion transmembrane transport and mitochondrion organization. Located in mitochondrion. [provided by Alliance of Genome Resources, Jul 2025]

OMIM Research

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.54

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.54LOEUF

pLI 0.000

Z-score -0.50

OE 1.11 (0.81–1.54)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.06Z-score

OE missense 1.01 (0.91–1.13)

228 obs / 225.4 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.11 (0.81–1.54)

0≤0.351.4

Missense OE?1.01 (0.91–1.13)

0≤0.61.4

Synonymous OE?0.95

0≤1.21.6

LoF obs/exp: 26 / 23.4Missense obs/exp: 228 / 225.4Syn Z: 0.35

Background carrier burden — how many people carry a rare variant somewhere in LETM2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 84

612 rare PASS variants

Rare truncating (LoF)

1 in 380

137 rare PASS variants

Rare synonymous (reference)

1 in 290

215 rare PASS variants

Rare missense and truncating variants are carried at similar rates in LETM2; 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 120	1 in 850
South Asian	~43k	1 in 100	1 in 700
Remaining (unassigned)	~30k	1 in 60	1 in 860
European (Finnish)	~27k	1 in 450	1 in 4,400
Admixed American	~22k	1 in 59	1 in 410
African / African American	~21k	1 in 65	1 in 560
East Asian	~20k	1 in 90	1 in 460
Ashkenazi Jewish	~13k	1 in 700	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 75	1 in 360

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): 7 of 10 coding exons well covered in gnomAD exomes; exons 2, 4, 9 marginal. Genomes: all 10.? see exons ↓