TMEM70 transmembrane protein 70 [Homo sapiens (human)] - Gene

Summary

Official Symbol: TMEM70provided by HGNC
Official Full Name: transmembrane protein 70provided by HGNC
Primary source: HGNC:HGNC:26050
See related: Ensembl:ENSG00000175606 MIM:612418
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: MC5DN2
Summary: This gene likely encodes a mitochondrial membrane protein. The encoded protein may play a role in biogenesis of mitochondrial ATP synthase. Mutations in this gene have been associated with neonatal mitochondrial encephalocardiomyopathy due to ATP synthase deficiency. Alternatively spliced transcript variants have been described. [provided by RefSeq, Feb 2010]
Expression: Ubiquitous expression in adrenal (RPKM 9.0), testis (RPKM 8.5) and 25 other tissues See more
Orthologs: mouse all

Genomic context

Location:: 8q21.11

Exon count:: 4

Annotation release	Status	Assembly	Chr	Location
109.20200815	current	GRCh38.p13 (GCF_000001405.39)	8	NC_000008.11 (73976195..73982783)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	8	NC_000008.10 (74888377..74895018)

Chromosome 8 - NC_000008.11 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
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?

TMEM70 functions in the assembly of complexes I and V.
Title: TMEM70 functions in the assembly of complexes I and V.
cause of hyperammonemia in TMEM70 deficiency was previously assumed to be related to carbamoyl phosphate synthase 1 deficiency, but our finding of hypercitrullinemia rules out this possibility. We thus propose a different etiology for the hyperammonemia seen in these patients
Title: TMEM70 deficiency: Novel mutation and hypercitrullinemia during metabolic decompensation.
Chinese family with dual LQT1 and HCM phenotypes associated with tetrad heterozygous mutations in KCNQ1, MYH7, MYLK2, and TMEM70 mutations.
Title: Dual LQT1 and HCM phenotypes associated with tetrad heterozygous mutations in KCNQ1, MYH7, MYLK2, and TMEM70 genes in a three-generation Chinese family.
In summary, TMEM70 mutations can cause distinct ultrastructural mitochondrial degeneration and almost complete deficiency of ATP synthase but are still amenable to treatment.
Title: ATP synthase deficiency due to TMEM70 mutation leads to ultrastructural mitochondrial degeneration and is amenable to treatment.
TMEM70 deficiency is a panethnic, multisystemic disease with variable outcome depending mainly on adequate management of hyperammonaemic crises in the neonatal period and early childhood.
Title: TMEM70 deficiency: long-term outcome of 48 patients.
Pulmonary hypertension has rarely been reported in mitochondrial disorders and, so far, it has been described in association with TMEM70 deficiency only in one patient
Title: Persistent pulmonary arterial hypertension in the newborn (PPHN): a frequent manifestation of TMEM70 defective patients.
These data indicate that the biological function of TMEM70 in the ATP synthase biogenesis may be mediated through interaction with other protein(s).
Title: Mitochondrial membrane assembly of TMEM70 protein.
this study suggests that mutant TMEM70 associates in high molecular weight complexes (470-550 kDa) when expressed in Hela cells and exerts a direct action in ATP synthase biogenesis and assembly, mediating the incorporation of F1 moieties.
Title: TMEM70: a mutational hot spot in nuclear ATP synthase deficiency with a pivotal role in complex V biogenesis.
Fibroblasts from 10 patients with TMEM70 317-2A>G homozygous mutation showed a significant 82-89% decrease of ATP synthase and 50-162% increase of respiratory chain complex IV and 22-53% increase of complex III.
Title: Compensatory upregulation of respiratory chain complexes III and IV in isolated deficiency of ATP synthase due to TMEM70 mutation.
The authors report a fragmented mitochondrial network and swollen and irregularly shaped mitochondria with partial to complete loss of the cristae in fibroblasts of a patient with a novel TMEM70 gene deletion.
Title: Restoration of complex V deficiency caused by a novel deletion in the human TMEM70 gene normalizes mitochondrial morphology.

Submit: New GeneRIF Correction See all GeneRIFs (20)

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
Nuclearly-encoded mitochondrial complex V (ATP synthase) deficiency 2 MedGen: C3279699 OMIM: 614052 GeneReviews: Not available	Compare labs

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)

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

D8S2076 (e-PCR)
- UniSTS:23465

WI-15063 (e-PCR)
- UniSTS:60852

Homology

Homologs of the TMEM70 gene: The TMEM70 gene is conserved in Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, fruit fly, mosquito, and frog.
Orthologs from Annotation Pipeline: 339 organisms have orthologs with human gene TMEM70
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
molecular_function	ND No biological Data available more info
protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
mitochondrial proton-transporting ATP synthase complex assembly	IBA Inferred from Biological aspect of Ancestor more info	PubMed
mitochondrial proton-transporting ATP synthase complex assembly	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
integral component of mitochondrial membrane	IBA Inferred from Biological aspect of Ancestor more info	PubMed
integral component of mitochondrial membrane	IDA Inferred from Direct Assay more info	PubMed
mitochondrial inner membrane	IEA Inferred from Electronic Annotation more info
mitochondrion	IDA Inferred from Direct Assay more info
nucleoplasm	IDA Inferred from Direct Assay more info

General protein information

Go to the top of the page Help

Preferred Names: transmembrane protein 70, mitochondrial

NCBI Reference Sequences (RefSeq)

Go to the top of the page Help

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_016618.1 RefSeqGene

Range

5001..11642

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001040613.3 → NP_001035703.1 transmembrane protein 70, mitochondrial isoform b

Status: REVIEWED

Description

Transcript Variant: This variant (2) uses an alternate splice site in the 3' coding region, which results in a frameshift, compared to variant 1. It encodes isoform b, which has a shorter and distinct C-terminus, compared to isoform a.

Source sequence(s)

BC002748, BF439499, BM984431, DB483583

Consensus CDS

CCDS47876.1

UniProtKB/Swiss-Prot

Q9BUB7

Related

ENSP00000429467.1, ENST00000517439.1
NM_017866.6 → NP_060336.3 transmembrane protein 70, mitochondrial isoform a

See identical proteins and their annotated locations for NP_060336.3

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the shortest transcript and encodes the longer isoform (a).

Source sequence(s)

BC002748, BM984431, DB483583

Consensus CDS

CCDS6215.1

UniProtKB/Swiss-Prot

Q9BUB7

Related

ENSP00000312599.5, ENST00000312184.6

Conserved Domains (1) summary

pfam06979
Location:108 → 232

TMEM70; Assembly, mitochondrial proton-transport ATP synth complex

RNA

NR_033334.2 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (3) contains an alternate internal exon, compared to variant 1. This variant is represented as non-coding because use of the supported translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

BC002748, BM984431, BU542365, DB483583