Curated summary · agent-written · kb/genes/curated/hgnc_26050.md

All 12 claims checked against the KB draft

TMEM70 across dismech

TMEM70 (transmembrane protein 70) is named by 1 disorder entry.

Normal function

ai-gene-review gives TMEM70's core molecular functions as mitochondrial proton-transporting ATP synthase complex binding; and protein-macromolecule adaptor activity: an inner-membrane scaffold for assembly of the Fo c-ring, not a subunit or catalyst of ATP synthase.

Causative record

The one entry naming TMEM70 types it as causative: Mitochondrial Complex V (ATP Synthase) Deficiency, Nuclear Type 2, with variant origin germline. The gene sits on the node Loss of TMEM70 Ancillary Biogenesis Factor Function, annotated with mitochondrial proton-transporting ATP synthase complex assembly.

Where the layers agree and disagree

The ai-gene-review core functions list no biological process, so the two layers share 0 GO process terms by exact identifier; the KB's assembly process is the process those scaffold functions serve. ClinGen classifies TMEM70 for 1 disease, mitochondrial disease, a lumped grouping with no matching dismech entry.

Underlined values are claims re-computed from the knowledge base each time this page is built. The tables below are the source of truth.

Normal function · from ai-gene-review (Q9BUB7, commit 79fe13b38970) · AI-generated, not KB evidence

TMEM70 is a scaffold protein of the inner mitochondrial membrane that plays a critical role in the biogenesis of mitochondrial ATP synthase (Complex V). It facilitates the membrane insertion and oligomer formation of the subunit c (ATP5MC1) into the c8-ring, which is the membrane sector of the enzyme's rotor. TMEM70 forms oligomeric scaffolds within mitochondrial cristae that promote in situ assembly of the ATP synthase proton channel. TMEM70 deficiency causes severe ATP synthase deficiency and neonatal mitochondrial encephalocardiomyopathy. TMEM70 also has a secondary role in the stability of Complex I membrane-bound subassemblies through interaction with the MCIA complex.

TMEM70 acts as a scaffold/adaptor protein that brings together subunit c molecules during c8-ring assembly. It forms oligomeric complexes that interact with subunit c and promote its membrane insertion and oligomerization. UniProt describes TMEM70 as a "Scaffold protein that participates in the c-ring assembly of mitochondrial ATP synthase" (PMID:32275929, PMID:31652072, PMID:33359711).

molecular function: protein-macromolecule adaptor activity

TMEM70 directly binds to ATP synthase subunit c (ATP5MC1/ATP5MC3) during the assembly process. This interaction is essential for facilitating c-ring formation and membrane insertion. Multiple studies have demonstrated direct interaction between TMEM70 and subunit c using immunoprecipitation and mass spectrometry (PMID:31652072, PMID:33359711, PMID:33753518).

molecular function: mitochondrial proton-transporting ATP synthase complex binding

In the knowledge base · computed from kb/ at build time

Disorders

Relationship is the entry's genetic[].relationship_type. untyped means the entry has a genetic record for the gene but does not type it; its free-text association is shown instead.

Disorder	Relationship	Where the gene appears
Mitochondrial Complex V (ATP Synthase) Deficiency, Nuclear Type 2	causative germline	mechanism: Loss of TMEM70 Ancillary Biogenesis Factor Function

ClinGen gene–disease validity · snapshot 2026-10-03 · matched to entries by MONDO

An entry matches when ClinGen's MONDO disease is the entry's own disease term, a subtype term, or an exact-match mapping. An amber status marks an entry ClinGen supports the gene for (Definitive, Strong or Moderate) whose own record does not type it. A Limited, Disputed or Refuted tier on such an entry is not a gap.

ClinGen disease	MOI	Classification	dismech entry
mitochondrial disease MONDO:0044970	AR	Definitive 2022-06-16	no dismech entry