Combined oxidative phosphorylation deficiency 53

Summary

Combined oxidative phosphorylation deficiency 53 (MONDO:0030378) is a disease caused by C2orf69 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: C2orf69 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 10

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	combined oxidative phosphorylation deficiency 53
Mondo ID	MONDO:0030378
OMIM	619423
DOID	DOID:0070426
UMLS	C5543631
MedGen	1779083
GARD	0025556
Is cancer (heuristic)	no

Also known as: combined oxidative phosphorylation deficiency due to C2orf69 deficiency · COXPD53

Data availability: 10 ClinVar variants · 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by developmental or physiological process › metabolic disease › developmental anomaly of metabolic origin › inborn mitochondrial metabolism disorder › mitochondrial oxidative phosphorylation disorder › combined oxidative phosphorylation deficiency › combined oxidative phosphorylation deficiency 53

Related subtypes (57): severe X-linked mitochondrial encephalomyopathy, hepatoencephalopathy due to combined oxidative phosphorylation defect type 1, combined oxidative phosphorylation defect type 2, fatal mitochondrial disease due to combined oxidative phosphorylation defect type 3, combined oxidative phosphorylation defect type 4, hypotonia with lactic acidemia and hyperammonemia, combined oxidative phosphorylation defect type 7, combined oxidative phosphorylation defect type 8, combined oxidative phosphorylation defect type 9, mitochondrial hypertrophic cardiomyopathy with lactic acidosis due to MTO1 deficiency, combined oxidative phosphorylation defect type 11, leukoencephalopathy-thalamus and brainstem anomalies-high lactate syndrome, combined oxidative phosphorylation defect type 13, combined oxidative phosphorylation defect type 14, combined oxidative phosphorylation defect type 15, infantile hypertrophic cardiomyopathy due to MRPL44 deficiency, combined oxidative phosphorylation defect type 17, growth and developmental delay-hypotonia-vision impairment-lactic acidosis syndrome, combined oxidative phosphorylation deficiency 19, combined oxidative phosphorylation defect type 20, combined oxidative phosphorylation defect type 21, mitochondrial proton-transporting ATP synthase complex deficiency, combined oxidative phosphorylation defect type 23, combined oxidative phosphorylation defect type 24, combined oxidative phosphorylation defect type 25, combined oxidative phosphorylation defect type 26, combined oxidative phosphorylation defect type 27, combined oxidative phosphorylation deficiency 28, combined oxidative phosphorylation deficiency 29, combined oxidative phosphorylation defect type 30, lethal left ventricular non-compaction-seizures-hypotonia-cataract-developmental delay syndrome, combined oxidative phosphorylation deficiency 40, combined oxidative phosphorylation deficiency 41, combined oxidative phosphorylation deficiency 42, combined oxidative phosphorylation deficiency 43, combined oxidative phosphorylation deficiency 44, combined oxidative phosphorylation deficiency 52, combined oxidative phosphorylation deficiency 54, combined oxidative phosphorylation deficiency 37, combined oxidative phosphorylation deficiency 38, combined oxidative phosphorylation deficiency 39, combined oxidative phosphorylation deficiency 45, combined oxidative phosphorylation deficiency 46, combined oxidative phosphorylation deficiency 47, combined oxidative phosphorylation deficiency 48, combined oxidative phosphorylation deficiency 51, combined oxidative phosphorylation deficiency 32, combined oxidative phosphorylation deficiency 33, combined oxidative phosphorylation deficiency 34, combined oxidative phosphorylation deficiency 35, combined oxidative phosphorylation deficiency 36, combined oxidative phosphorylation deficiency 55, combined oxidative phosphorylation deficiency 56, combined oxidative phosphorylation deficiency 57, combined oxidative phosphorylation deficiency 58, combined oxidative phosphorylation deficiency 59, combined oxidative phosphorylation deficiency 60

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

10 retrieved; paginated sample, class counts are floors:

6 pathogenic, 2 uncertain significance, 1 likely pathogenic, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1177454	NM_153689.6(C2orf69):c.843_847del (p.Lys282fs)	C2orf69	Pathogenic	no assertion criteria provided
1177455	NM_153689.6(C2orf69):c.280del (p.Glu94fs)	C2orf69	Pathogenic	no assertion criteria provided
1177456	NM_153689.6(C2orf69):c.588_592del (p.Asn196fs)	C2orf69	Pathogenic	no assertion criteria provided
1177457	NM_153689.6(C2orf69):c.311_313del (p.Leu104_Tyr105delinsHis)	C2orf69	Pathogenic	no assertion criteria provided
1177458	NM_153689.6(C2orf69):c.909_925del (p.Ser304fs)	C2orf69	Pathogenic	no assertion criteria provided
1177459	NM_153689.6(C2orf69):c.929G>A (p.Trp310Ter)	C2orf69	Pathogenic	no assertion criteria provided
870947	NM_153689.6(C2orf69):c.298del (p.Gln100fs)	C2orf69	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2446879	NM_153689.6(C2orf69):c.187_191dup (p.Asp64fs)	C2orf69	Likely pathogenic	criteria provided, single submitter
3383370	NM_153689.6(C2orf69):c.439A>T (p.Ile147Phe)	C2orf69	Uncertain significance	criteria provided, single submitter
3893019	NM_153689.6(C2orf69):c.3G>T (p.Met1Ile)	C2orf69	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 1 · Orphanet: 0 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
C2orf69	Strong	Autosomal recessive	combined oxidative phosphorylation deficiency 53

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
C2orf69	HGNC:26799	ENSG00000178074	Q8N8R5	Mitochondrial protein C2orf69	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
C2orf69	Mitochondrial protein C2orf69	May play a role in the respiratory chain.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
C2orf69	Other/Unknown	no		C2orf69_mit

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
Brodmann (1909) area 23	1
Brodmann (1909) area 46	1
sperm	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
C2orf69	255	ubiquitous	marker	sperm, Brodmann (1909) area 46, Brodmann (1909) area 23

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
C2orf69	524

Structural data

PDB: 0 · AlphaFold-only: 1 · No structure: 0

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
C2orf69	Q8N8R5	79.05

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
oxidative phosphorylation	1	1404.3×	7e-04	C2orf69

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
C2orf69	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	C2orf69

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
C2orf69	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.