TMEM70

transmembrane protein 70, the group of Mitochondrial respiratory chain complex assembly factors

Basic information

Region (hg38): 8:73972437-73982783

Links

ENSG00000175606 ∙ NCBI:54968 ∙ OMIM:612418 ∙ HGNC:26050 ∙ Uniprot:Q9BUB7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• mitochondrial complex V (ATP synthase) deficiency, nuclear type 2 (Supportive), mode of inheritance: AR
• mitochondrial disease (Definitive), mode of inheritance: AR
• mitochondrial complex V (ATP synthase) deficiency, nuclear type 2 (Strong), mode of inheritance: AR
• mitochondrial complex V (ATP synthase) deficiency, nuclear type 2 (Definitive), mode of inheritance: AR
• mitochondrial complex V (ATP synthase) deficiency, nuclear type 2 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Mitochondrial complex V (ATP synthase) deficiency, nuclear type 2	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Biochemical; Cardiovascular; Craniofacial; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic; Ophthalmologic	18953340; 21147908; 24485043

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TMEM70 gene.

• Mitochondrial_complex_V_(ATP_synthase)_deficiency,_nuclear_type_2 (289 variants)
• Inborn_genetic_diseases (41 variants)
• not_provided (38 variants)
• not_specified (18 variants)
• TMEM70-related_disorder (5 variants)
• Autosomal_recessive_disease (2 variants)
• Neurodevelopmental_disorder (1 variants)
• Mitochondrial_proton-transporting_ATP_synthase_complex_deficiency (1 variants)
• See_cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TMEM70 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000017866.6. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	89		91
missense		3	130	12	2	147
nonsense	5	1	3			9
start loss		1	1			2
frameshift	13	11	3			27
splice donor/acceptor (+/-2bp)	1	5	1			7
Total	19	21	140	101	2

Highest pathogenic variant AF is 0.00012886901

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TMEM70	protein_coding	protein_coding	ENST00000312184	3	10347

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
		125709	0	35	125744	0.000139

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.129	139	143	0.970	0.00000724	1652
Missense in Polyphen		33	41.227	0.80046		496
Synonymous	-0.552	65	59.6	1.09	0.00000297	547
Loss of Function	1.75	4	9.95	0.402	6.48e-7	98

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000289	0.000289
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.000139	0.000139
European (Non-Finnish)	0.000150	0.000149
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000653	0.0000653
Other	0.000328	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in biogenesis of mitochondrial ATP synthase. {ECO:0000269|PubMed:18953340, ECO:0000269|PubMed:20937241}.
• Disease: DISEASE: Mitochondrial complex V deficiency, nuclear 2 (MC5DN2) [MIM:614052]: A mitochondrial disorder with heterogeneous clinical manifestations including dysmorphic features, psychomotor retardation, hypotonia, growth retardation, cardiomyopathy, enlarged liver, hypoplastic kidneys and elevated lactate levels in urine, plasma and cerebrospinal fluid. {ECO:0000269|PubMed:18953340, ECO:0000269|PubMed:22986587}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.0543

Intolerance Scores

• loftool: 0.696
• rvis_EVS: 1.06
• rvis_percentile_EVS: 91.51

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.131

Gene Damage Prediction

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

Gene ontology

• Biological process: mitochondrial proton-transporting ATP synthase complex assembly
• Cellular component: nucleoplasm;mitochondrion;mitochondrial inner membrane;integral component of mitochondrial membrane
• Molecular function: molecular_function