LETM2

protein-coding

leucine zipper and EF-hand containing transmembrane protein 2, the group of Solute carrier family 55, LETM mitochondrial cation/proton exchangers|EF-hand domain containing

Gene summary

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]

MANE transcript

NM_001286819.2

Inheritance

—

ClinVar variants

U:68B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 1.11

Max pathogenic AF

—

Genomic locus

chr8:38,386,207-38,409,527

External References & Databases

Ensembl (ENSG00000165046)

Transcript & Mutation Effects

hg38 • Region Span ~23.3 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to LETM2 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 65

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001286819.2. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous						0
missense			65 clinvar	2 clinvar		67
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	0	68	2	0	70

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 38 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001286819.2	RefSeq	NP_001273748.1	10	MANE Select
ENST00000379957.9	Ensembl	ENSP00000369291.4	10	MANE Select
NM_001199659.3	RefSeq	NP_001186588.1	9	Standard
NM_001199660.3	RefSeq	NP_001186589.1	8	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Molecular Function

ribosome binding

Cellular Component

mitochondrial inner membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000523983
Coding exons: 9
Length: 23321
Individuals with no LoFs: 125278
Homozygous LoFs: 6
Heterozygous LoFs: 464
Defined: 125748
p: 0.00187

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.0617	228	225	1.01	0.0000113	2871
Missense (PolyPhen)		49	46.869	1.0455		668
Synonymous	0.347	84	88.1	0.953	0.00000465	874
Loss of Function	-0.501	26	23.4	1.11	0.00000136	272

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0037	0.0037	notable
Latino/Admixed American	0.00099	0.00098	rare
Ashkenazi Jewish	0.0023	0.0023	notable
East Asian	0.0014	0.0014	notable
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00056	0.00055	rare
South Asian	0.0086	0.0084	notable
Other	0.0015	0.0015	notable

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.0742

Intolerance Scores

LoFtool: 0.561
RVIS EVS: 1.08
RVIS percentile EVS: 91.81

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.00678

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium