Combined oxidative phosphorylation deficiency 33

disease

On this page

Also known as COXPD33

Summary

Combined oxidative phosphorylation deficiency 33 (MONDO:0054677) is a disease caused by C1QBP (GenCC Strong), with 1 cohort gene.

At a glance

Causal gene: C1QBP (GenCC Strong)
Cohort genes: 1
ClinVar variants: 9

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	combined oxidative phosphorylation deficiency 33
Mondo ID	MONDO:0054677
OMIM	617713
DOID	DOID:0111495
NCIT	C174440
UMLS	C4540209
MedGen	1623699
GARD	0025959
Is cancer (heuristic)	no

Also known as: combined oxidative phosphorylation deficiency 33 · COXPD33

Data availability: 9 ClinVar variants · 2 GenCC gene-disease records · 1 cell line.

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 33

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

9 retrieved; paginated sample, class counts are floors:

3 uncertain significance, 3 pathogenic, 2 conflicting classifications of pathogenicity, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
441242	NM_001212.4(C1QBP):c.612C>G (p.Phe204Leu)	C1QBP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
441243	NM_001212.4(C1QBP):c.824T>C (p.Leu275Pro)	C1QBP	Pathogenic	no assertion criteria provided
441244	NM_001212.4(C1QBP):c.739G>T (p.Gly247Trp)	C1QBP	Pathogenic	no assertion criteria provided
441245	NM_001212.4(C1QBP):c.823C>T (p.Leu275Phe)	C1QBP	Pathogenic	no assertion criteria provided
2439614	NM_001212.4(C1QBP):c.576+2T>A	C1QBP	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
441246	NM_001212.4(C1QBP):c.562_564del (p.Tyr188del)	C1QBP	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2439613	NM_001212.4(C1QBP):c.478-7T>G	C1QBP	Uncertain significance	criteria provided, single submitter
4086218	NM_001212.4(C1QBP):c.757G>A (p.Ala253Thr)	C1QBP	Uncertain significance	criteria provided, single submitter
441241	NM_001212.4(C1QBP):c.557G>C (p.Cys186Ser)	C1QBP	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 2 · 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
C1QBP	Strong	Autosomal recessive	combined oxidative phosphorylation deficiency 33	2

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
C1QBP	HGNC:1243	ENSG00000108561	Q07021	Complement component 1 Q subcomponent-binding protein, mitochondrial	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
C1QBP	Complement component 1 Q subcomponent-binding protein, mitochondrial	Multifunctional and multicompartmental protein involved in inflammation and infection processes, ribosome biogenesis, protein synthesis in mitochondria, regulation of apoptosis, transcriptional regulation and pre-mRNA splicing.

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)
C1QBP	Other/Unknown	no		MAM33, MAM33_sf

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
mucosa of transverse colon	1
rectum	1
right adrenal gland	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
C1QBP	288	ubiquitous	marker	mucosa of transverse colon, right adrenal gland, rectum

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
C1QBP	4,534

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
C1QBP	Q07021	4

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 19. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways 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.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Defective Intrinsic Pathway for Apoptosis Due to p14ARF Loss of Function	1	5710.0×	0.003	C1QBP
R-HSA-140837	1	1427.5×	0.004	C1QBP
Regulation of FXIIa and plasma kallikrein activity	1	1142.0×	0.004	C1QBP
R-HSA-140877	1	951.7×	0.004	C1QBP
Apoptotic factor-mediated response	1	878.5×	0.004	C1QBP
Defective Intrinsic Pathway for Apoptosis	1	761.3×	0.004	C1QBP
Diseases of programmed cell death	1	634.4×	0.004	C1QBP
Intrinsic Pathway for Apoptosis	1	292.8×	0.008	C1QBP
FXIIa activates plasma kallikrein-kinin system	1	173.0×	0.011	C1QBP
Apoptosis	1	167.9×	0.011	C1QBP
Programmed Cell Death	1	146.4×	0.011	C1QBP
RHOC GTPase cycle	1	146.4×	0.011	C1QBP
RHOA GTPase cycle	1	74.6×	0.020	C1QBP
RHO GTPase cycle	1	60.1×	0.023	C1QBP
Hemostasis	1	36.0×	0.033	C1QBP
Signaling by Rho GTPases	1	34.2×	0.033	C1QBP
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1	33.5×	0.033	C1QBP
Disease	1	13.1×	0.081	C1QBP
Signal Transduction	1	10.2×	0.098	C1QBP

GO biological processes by enrichment

GO term	Cohort genes	Fold	FDR	Sample cohort genes
negative regulation of MDA-5 signaling pathway	1	4213.0×	0.002	C1QBP
mitochondrial RNA catabolic process	1	2808.7×	0.002	C1QBP
cytosolic ribosome assembly	1	2407.4×	0.002	C1QBP
positive regulation of trophoblast cell migration	1	2407.4×	0.002	C1QBP
regulation of complement activation	1	2106.5×	0.002	C1QBP
negative regulation of RIG-I signaling pathway	1	2106.5×	0.002	C1QBP
positive regulation of dendritic cell chemotaxis	1	2106.5×	0.002	C1QBP
negative regulation of defense response to virus	1	1296.3×	0.003	C1QBP
positive regulation of mitochondrial translation	1	1123.5×	0.003	C1QBP
negative regulation of interleukin-12 production	1	1053.2×	0.003	C1QBP
negative regulation of mRNA splicing, via spliceosome	1	766.0×	0.003	C1QBP
positive regulation of neutrophil chemotaxis	1	648.1×	0.003	C1QBP
negative regulation of double-strand break repair via homologous recombination	1	624.1×	0.003	C1QBP
complement activation, classical pathway	1	543.6×	0.004	C1QBP
negative regulation of type II interferon production	1	383.0×	0.005	C1QBP
positive regulation of substrate adhesion-dependent cell spreading	1	374.5×	0.005	C1QBP
positive regulation of cell adhesion	1	271.8×	0.006	C1QBP
phosphatidylinositol 3-kinase/protein kinase B signal transduction	1	210.7×	0.007	C1QBP
RNA splicing	1	88.2×	0.016	C1QBP
mRNA processing	1	78.8×	0.016	C1QBP
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	1	78.4×	0.016	C1QBP
positive regulation of apoptotic process	1	56.7×	0.022	C1QBP
DNA damage response	1	53.5×	0.022	C1QBP
immune response	1	47.1×	0.024	C1QBP
innate immune response	1	33.6×	0.032	C1QBP
apoptotic process	1	28.7×	0.036	C1QBP
negative regulation of transcription by RNA polymerase II	1	17.7×	0.056	C1QBP

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
C1QBP	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
C1QBP	1	Binding:1

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	C1QBP

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)
C1QBP	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.

Cohort genes: C1QBP