LETMD1

protein-coding

LETM1 domain containing 1, the group of Solute carrier family 55, LETM mitochondrial cation/proton exchangers

Gene summary

This gene encodes a mitochondrial outer membrane protein. It has a potential role in tumorigenesis, which may result from negative regulation of the p53 tumor suppressor gene. Alternatively spliced transcript variants have been noted for this gene. [provided by RefSeq, Aug 2011]

MANE transcript

NM_015416.5

Inheritance

—

ClinVar variants

U:57B:4

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.3

Max pathogenic AF

—

Genomic locus

chr12:51,047,962-51,060,424

External References & Databases

Ensembl (ENSG00000050426)

Transcript & Mutation Effects

hg38 • Region Span ~12.5 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 LETMD1 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 54

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_015416.5. 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			51 clinvar	4 clinvar		55
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			6 clinvar			6
Total	0	0	57	4	0	61

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 141 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_015416.5	RefSeq	NP_056231.3	9	MANE Select
ENST00000262055.9	Ensembl	ENSP00000262055.4	9	MANE Select
NM_001243689.2	RefSeq	NP_001230618.1	9	Standard
NM_001300765.2	RefSeq	NP_001287694.1	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Molecular Function

protein binding
ribosome binding

Cellular Component

nucleoplasm
mitochondrion
mitochondrial outer membrane
mitochondrial inner membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000418425
Coding exons: 9
Length: 12463
Individuals with no LoFs: 125717
Homozygous LoFs: 0
Heterozygous LoFs: 30
Defined: 125747
p: 0.000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.543	193	215	0.896	0.0000119	2408
Missense (PolyPhen)		41	53.426	0.76742		608
Synonymous	-1.07	89	77.0	1.16	0.00000381	752
Loss of Function	2.91	6	20.1	0.299	9.19e-7	231

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.00035	0.00032	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00016	0.00016	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000098	0.000097	rare
South Asian	0.000099	0.000098	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Involved in tumorigenesis and may function as a negative regulator of the p53/TP53. {ECO:0000269|PubMed:12879013}.;

Recessive Scores

pRec: 0.0774

Intolerance Scores

LoFtool: 0.568
RVIS EVS: 0.26
RVIS percentile EVS: 70.26

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.907

Gene Damage Prediction

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