mitochondrial complex I deficiency, nuclear type 36

Summary

mitochondrial complex I deficiency, nuclear type 36 (MONDO:0030902) is a disease with 2 cohort genes.

At a glance

• Cohort genes: 2
• ClinVar variants: 2

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	mitochondrial complex I deficiency, nuclear type 36
Mondo ID	MONDO:0030902
OMIM	619170
UMLS	C5436935
MedGen	1773965
GARD	0016431
Is cancer (heuristic)	no

Also known as: MC1DN36 · mitochondrial complex 1 deficiency, nuclear type 36 · mitochondrial complex I deficiency, nuclear type 36

Data availability: 2 ClinVar variants · 2 GenCC gene-disease records.

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 › mitochondrial respiratory chain complex deficiency › mitochondrial complex I deficiency › mitochondrial complex I deficiency, nuclear type › mitochondrial complex I deficiency, nuclear type 36

Related subtypes (36): mitochondrial complex I deficiency, nuclear type 12, mitochondrial complex I deficiency, nuclear type 30, Leber hereditary optic neuropathy, autosomal recessive, mitochondrial complex I deficiency, nuclear type 37, mitochondrial complex I deficiency, nuclear type 2, mitochondrial complex I deficiency, nuclear type 3, mitochondrial complex I deficiency, nuclear type 4, mitochondrial complex I deficiency, nuclear type 5, mitochondrial complex I deficiency, nuclear type 6, mitochondrial complex I deficiency, nuclear type 7, mitochondrial complex I deficiency, nuclear type 8, mitochondrial complex I deficiency, nuclear type 9, mitochondrial complex I deficiency, nuclear type 10, mitochondrial complex I deficiency, nuclear type 11, mitochondrial complex I deficiency, nuclear type 13, mitochondrial complex I deficiency, nuclear type 14, mitochondrial complex I deficiency, nuclear type 15, mitochondrial complex I deficiency, nuclear type 16, mitochondrial complex I deficiency, nuclear type 17, mitochondrial complex I deficiency, nuclear type 18, mitochondrial complex I deficiency, nuclear type 19, mitochondrial complex I deficiency, nuclear type 21, mitochondrial complex I deficiency, nuclear type 22, mitochondrial complex I deficiency, nuclear type 23, mitochondrial complex I deficiency, nuclear type 24, mitochondrial complex I deficiency, nuclear type 25, mitochondrial complex I deficiency, nuclear type 26, mitochondrial complex I deficiency, nuclear type 27, mitochondrial complex I deficiency, nuclear type 28, mitochondrial complex I deficiency, nuclear type 29, mitochondrial complex I deficiency, nuclear type 31, mitochondrial complex I deficiency, nuclear type 32, mitochondrial complex I deficiency, nuclear type 33, mitochondrial complex I deficiency, nuclear type 34, mitochondrial complex I deficiency, nuclear type 1, mitochondrial complex I deficiency, nuclear type 39

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

2 retrieved; paginated sample, class counts are floors:

2 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
813295	NM_004549.6(NDUFC2):c.173A>T (p.His58Leu)	NDUFC2-KCTD14	Pathogenic	criteria provided, single submitter
813296	NM_004549.6(NDUFC2):c.346_*7del (p.His116fs)	NDUFC2-KCTD14	Pathogenic	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
NDUFC2	Moderate	Autosomal recessive	mitochondrial complex I deficiency, nuclear type 36	2

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
NDUFC2	HGNC:7706	ENSG00000151366	O95298	NADH dehydrogenase [ubiquinone] 1 subunit C2	gencc
NDUFC2-KCTD14	HGNC:42956	ENSG00000259112	E9PQ53	NADH dehydrogenase [ubiquinone] 1 subunit C2, isoform 2	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
NDUFC2	NADH dehydrogenase [ubiquinone] 1 subunit C2	Accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), that is believed not to be involved in catalysis but required for the complex assembly.
NDUFC2-KCTD14	NADH dehydrogenase [ubiquinone] 1 subunit C2, isoform 2	Accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), that is believed not to be involved in catalysis.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · 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	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
NDUFC2	Other/Unknown	no		NDUC2
NDUFC2-KCTD14	Other/Unknown	no		NDUC2

Expression context

Cohort genes with no expression data: 0.

2 cohort genes 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
left adrenal gland	1
left adrenal gland cortex	1
right adrenal gland	1
hindlimb stylopod muscle	1
male germ line stem cell (sensu Vertebrata) in testis	1
primordial germ cell in gonad	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
NDUFC2	268	ubiquitous	marker	right adrenal gland, left adrenal gland, left adrenal gland cortex
NDUFC2-KCTD14	133	ubiquitous	marker	male germ line stem cell (sensu Vertebrata) in testis, hindlimb stylopod muscle, primordial germ cell in gonad

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
NDUFC2	1,639
NDUFC2-KCTD14	5

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
NDUFC2	O95298	7

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
NDUFC2-KCTD14	E9PQ53	84.85

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 7. Enrichment computed across 2 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
Complex I biogenesis	1	165.5×	0.026	NDUFC2
Respiratory electron transport	1	95.2×	0.026	NDUFC2
Aerobic respiration and respiratory electron transport	1	88.5×	0.026	NDUFC2
Innate Immune System	1	25.5×	0.061	NDUFC2
Neutrophil degranulation	1	23.1×	0.061	NDUFC2
Immune System	1	13.0×	0.086	NDUFC2
Metabolism	1	11.6×	0.086	NDUFC2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
mitochondrial electron transport, NADH to ubiquinone	2	358.6×	6e-05	NDUFC2-KCTD14, NDUFC2
positive regulation of mitochondrial membrane potential	1	1053.2×	0.004	NDUFC2
positive regulation of ATP biosynthetic process	1	601.9×	0.004	NDUFC2
negative regulation of reactive oxygen species biosynthetic process	1	495.6×	0.004	NDUFC2
negative regulation of non-canonical NF-kappaB signal transduction	1	255.3×	0.006	NDUFC2
mitochondrial respiratory chain complex I assembly	1	205.5×	0.006	NDUFC2
proton motive force-driven mitochondrial ATP synthesis	1	131.7×	0.008	NDUFC2
aerobic respiration	1	123.9×	0.008	NDUFC2

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
NDUFC2	0	0
NDUFC2-KCTD14	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
NDUFC2	4	Binding:4

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	2	NDUFC2, NDUFC2-KCTD14

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
NDUFC2	4	—
NDUFC2-KCTD14	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.