LETM1 leucine zipper and EF-hand containing transmembrane protein 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: LETM1provided by HGNC
Official Full Name: leucine zipper and EF-hand containing transmembrane protein 1provided by HGNC
Primary source: HGNC:HGNC:6556
See related: Ensembl:ENSG00000168924 MIM:604407; AllianceGenome:HGNC:6556
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: KHE; Mdm38; CONDMIM; SLC55A1
Summary: This gene encodes a protein that is localized to the inner mitochondrial membrane. The protein functions to maintain the mitochondrial tubular shapes and is required for normal mitochondrial morphology and cellular viability. Mutations in this gene cause Wolf-Hirschhorn syndrome, a complex malformation syndrome caused by the deletion of parts of the distal short arm of chromosome 4. Related pseudogenes have been identified on chromosomes 8, 15 and 19. [provided by RefSeq, Oct 2009]
Expression: Ubiquitous expression in colon (RPKM 12.1), kidney (RPKM 9.6) and 25 other tissues See more
Orthologs: mouse all
NEW: Try the new Gene table
Try the new Transcript table

Genomic context

Location:: 4p16.3

Exon count:: 15

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	4	NC_000004.12 (1811479..1856156, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	4	NC_060928.1 (1809954..1854630, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	4	NC_000004.11 (1813206..1857883, complement)

Chromosome 4 - NC_000004.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

Go to the top of the page Help

Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

Go to the top of the page Help

See details

Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

Go to the top of the page Help

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Circ_0061140 Contributes to Ovarian Cancer Progression by Targeting miR-761/LETM1 Signaling.
Title: Circ_0061140 Contributes to Ovarian Cancer Progression by Targeting miR-761/LETM1 Signaling.
LETM1 (leucine zipper-EF-hand-containing transmembrane protein 1) silence reduces the proliferation, invasion, migration and angiogenesis in esophageal squamous cell carcinoma via KIF14 (kinesin family member 14).
Title: LETM1 (leucine zipper-EF-hand-containing transmembrane protein 1) silence reduces the proliferation, invasion, migration and angiogenesis in esophageal squamous cell carcinoma via KIF14 (kinesin family member 14).
Suppression of LETM1 inhibits the proliferation and stemness of colorectal cancer cells through reactive oxygen species-induced autophagy.
Title: Suppression of LETM1 inhibits the proliferation and stemness of colorectal cancer cells through reactive oxygen species-induced autophagy.
The leucine zipper EF-hand containing transmembrane protein-1 EF-hand is a tripartite calcium, temperature, and pH sensor.
Title: The leucine zipper EF-hand containing transmembrane protein-1 EF-hand is a tripartite calcium, temperature, and pH sensor.
The mitochondrial inner membrane protein LETM1 modulates cristae organization through its LETM domain.
Title: The mitochondrial inner membrane protein LETM1 modulates cristae organization through its LETM domain.
Wholeexome sequencing identifies a novel mutation of SLC20A2 (c.C1849T) as a possible cause of hereditary multiple exostoses in a Chinese family.
Title: Whole‑exome sequencing identifies a novel mutation of SLC20A2 (c.C1849T) as a possible cause of hereditary multiple exostoses in a Chinese family.
MiR-613 blocked the progression of cervical cancer by targeting LETM1.
Title: MiR-613 blocked the progression of cervical cancer by targeting LETM1.
LETM1 could serve as a potential prognostic biomarker and a therapeutic target for the better clinical management of gastric adenocarcinoma
Title: LETM1 is a potential biomarker that predicts poor prognosis in gastric adenocarcinoma.
LETM1 is a potential prognostic biomarker of lung non-small cell carcinoma.
Title: LETM1 is a potential biomarker of prognosis in lung non-small cell carcinoma.
LETM1 expression was remarkably upregulated in human fetal sagittal sections and colorectal adenocarcinoma tissues. The expression of LETM1 in colorectal adenocarcinoma tissue was correlated with clinical stage, lymph node metastasis, distant metastasis, and microvessel density.
Title: LETM1 is a potential cancer stem-like cell marker and predicts poor prognosis in colorectal adenocarcinoma.

Submit: New GeneRIF Correction See all GeneRIFs (37)

Phenotypes

Go to the top of the page Help

Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
4p partial monosomy syndrome MedGen: C1956097 OMIM: 194190 GeneReviews: Not available	Compare labs
Neurodegeneration, childhood-onset, with multisystem involvement due to mitochondrial dysfunction MedGen: C5774240 OMIM: 620089 GeneReviews: Not available	Compare labs

Copy number response

Description
Copy number response Haploinsufficency No evidence available (Last evaluated 2012-02-03) ClinGen Genome Curation Page Triplosensitivity No evidence available (Last evaluated 2012-02-03) ClinGen Genome Curation Page

Variation

Go to the top of the page Help

See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

Go to the top of the page Help

Protein interactions

Protein	Gene	Interaction	Pubs
Vpr	vpr	A stable-isotope labeling by amino acids in cell culture coupled with mass spectrometry-based proteomics identifies downregulation of leucine zipper-EF-hand containing transmembrane protein 1 (LETM1) expression by HIV-1 Vpr in Vpr transduced macrophages	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

Go to the top of the page Help

Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

Go to the top of the page Help

Markers

RH41928 (e-PCR)
- UniSTS:77928

D1S1425 (e-PCR)
- UniSTS:149621

SHGC-24744 (e-PCR)
- UniSTS:60573

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables calcium ion binding	TAS Traceable Author Statement more info	PubMed
enables calcium:proton antiporter activity	IBA Inferred from Biological aspect of Ancestor more info
enables calcium:proton antiporter activity	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables ribosome binding	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in calcium export from the mitochondrion	IDA Inferred from Direct Assay more info	PubMed
involved_in calcium export from the mitochondrion	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in calcium ion transport	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cristae formation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in inner mitochondrial membrane organization	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in mitochondrial calcium ion homeostasis	IDA Inferred from Direct Assay more info	PubMed
involved_in mitochondrial calcium ion transmembrane transport	IBA Inferred from Biological aspect of Ancestor more info
involved_in mitochondrial calcium ion transmembrane transport	IDA Inferred from Direct Assay more info	PubMed
involved_in mitochondrial calcium ion transmembrane transport	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in mitochondrial potassium ion transmembrane transport	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in mitochondrion organization	IBA Inferred from Biological aspect of Ancestor more info
involved_in negative regulation of mitochondrial calcium ion concentration	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in protein hexamerization	ISS Inferred from Sequence or Structural Similarity more info
involved_in protein homooligomerization	ISS Inferred from Sequence or Structural Similarity more info
involved_in proton transmembrane transport	IEA Inferred from Electronic Annotation more info
involved_in regulation of cellular hyperosmotic salinity response	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
located_in mitochondrial inner membrane	IDA Inferred from Direct Assay more info	PubMed
located_in mitochondrion	HTP more info	PubMed
is_active_in mitochondrion	IBA Inferred from Biological aspect of Ancestor more info
located_in mitochondrion	IDA Inferred from Direct Assay more info
located_in mitochondrion	TAS Traceable Author Statement more info	PubMed

General protein information

Go to the top of the page Help

Preferred Names: mitochondrial proton/calcium exchanger protein

Names: LETM1 and EF-hand domain-containing protein 1, mitochondrial; Mdm38 homolog; electroneutral mitochondrial K(+)/H(+)exchanger; leucine zipper-EF-hand containing transmembrane protein 1

NCBI Reference Sequences (RefSeq)

Go to the top of the page Help

NEW Try the new Transcript table

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_013063.1 RefSeqGene

Range

5092..49769

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_012318.3 → NP_036450.1 mitochondrial proton/calcium exchanger protein precursor

See identical proteins and their annotated locations for NP_036450.1

Status: REVIEWED

Source sequence(s)

AC105448, AF061025

Consensus CDS

CCDS3355.1

UniProtKB/Swiss-Prot

B4DED2, O95202, Q9UF65

Related

ENSP00000305653.2, ENST00000302787.3

Conserved Domains (1) summary

pfam07766
Location:155 → 410

LETM1; LETM1-like protein

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000004.12 Reference GRCh38.p14 Primary Assembly

Range

1811479..1856156 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_006713884.2 → XP_006713947.1 mitochondrial proton/calcium exchanger protein isoform X1

Conserved Domains (1) summary

pfam07766
Location:155 → 410

LETM1; LETM1-like protein
XM_047415673.1 → XP_047271629.1 mitochondrial proton/calcium exchanger protein isoform X2

Alternate T2T-CHM13v2.0

Genomic

NC_060928.1 Alternate T2T-CHM13v2.0

Range

1809954..1854630 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054349978.1 → XP_054205953.1 mitochondrial proton/calcium exchanger protein isoform X1
XM_054349980.1 → XP_054205955.1 mitochondrial proton/calcium exchanger protein isoform X2
XM_054349979.1 → XP_054205954.1 mitochondrial proton/calcium exchanger protein isoform X3