mitochondrial complex I deficiency, nuclear type 7

Summary

mitochondrial complex I deficiency, nuclear type 7 (MONDO:0032612) is a disease caused by NDUFV2 (GenCC Strong), with 2 cohort genes.

At a glance

• Causal gene: NDUFV2 (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 23

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	mitochondrial complex I deficiency, nuclear type 7
Mondo ID	MONDO:0032612
OMIM	618229
DOID	DOID:0112092
UMLS	C4748760
MedGen	1648484
GARD	0016317
Is cancer (heuristic)	no

Also known as: MC1DN7

Data availability: 23 ClinVar variants · 4 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 7

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 36, 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 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

23 retrieved; paginated sample, class counts are floors:

10 uncertain significance, 3 benign, 3 likely pathogenic, 2 pathogenic/likely pathogenic, 2 pathogenic, 2 conflicting classifications of pathogenicity, 1 not provided

ClinVar	Variant (HGVS)	Gene	Classification	Review
1194462	NM_021074.5(NDUFV2):c.62_63del (p.His21fs)	NDUFV2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1705393	NM_021074.5(NDUFV2):c.547G>A (p.Ala183Thr)	NDUFV2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
279920	NM_021074.5(NDUFV2):c.120+5_120+8del	NDUFV2	Pathogenic	criteria provided, multiple submitters, no conflicts
4689201	NM_021074.5(NDUFV2):c.206del (p.Asn69fs)	NDUFV2	Pathogenic	criteria provided, single submitter
1704593	NC_000018.9:g.(9124982_9126828)_(9126906_9134183)del	NDUFV2	Likely pathogenic	criteria provided, single submitter
3256772	NM_021074.5(NDUFV2):c.346G>C (p.Ala116Pro)	NDUFV2	Likely pathogenic	no assertion criteria provided
3780012	NM_021074.5(NDUFV2):c.587del (p.Asp195_Leu196insTer)	NDUFV2	Likely pathogenic	criteria provided, single submitter
327876	NM_021074.5(NDUFV2):c.17C>G (p.Ala6Gly)	LOC130062145	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
617494	NM_021074.5(NDUFV2):c.669_670insG (p.Ser224fs)	NDUFV2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1033973	NM_021074.5(NDUFV2):c.427C>T (p.Arg143Ter)	NDUFV2	Uncertain significance	no assertion criteria provided
1180489	NM_021074.5(NDUFV2):c.580G>A (p.Glu194Lys)	NDUFV2	Uncertain significance	no assertion criteria provided
1332721	NM_021074.5(NDUFV2):c.548C>T (p.Ala183Val)	NDUFV2	Uncertain significance	criteria provided, single submitter
214867	NM_021074.5(NDUFV2):c.553A>G (p.Met185Val)	NDUFV2	Uncertain significance	criteria provided, multiple submitters, no conflicts
2434096	NM_021074.5(NDUFV2):c.579+1G>A	NDUFV2	Uncertain significance	criteria provided, single submitter
2434097	NM_021074.5(NDUFV2):c.121-3T>C	NDUFV2	Uncertain significance	criteria provided, single submitter
290426	NM_021074.5(NDUFV2):c.428G>A (p.Arg143Gln)	NDUFV2	Uncertain significance	criteria provided, multiple submitters, no conflicts
3062026	NM_021074.5(NDUFV2):c.656+8T>A	NDUFV2	Uncertain significance	criteria provided, single submitter
3891815	NM_021074.5(NDUFV2):c.242C>T (p.Pro81Leu)	NDUFV2	Uncertain significance	criteria provided, single submitter
4293306	NM_021074.5(NDUFV2):c.551C>T (p.Pro184Leu)	NDUFV2	Uncertain significance	criteria provided, single submitter
129703	NM_021074.5(NDUFV2):c.201A>T (p.Val67=)	NDUFV2	Benign	criteria provided, multiple submitters, no conflicts
9054	NM_021074.5(NDUFV2):c.86T>C (p.Val29Ala)	NDUFV2	Benign	criteria provided, multiple submitters, no conflicts
214864	NM_021074.5(NDUFV2):c.301-3del	NDUFV2-AS1	Benign	criteria provided, multiple submitters, no conflicts
4279938	GRCh37/hg19 18p11.22(chr18:9119472-9119588)x1	NDUFV2	not provided	no classification provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · Orphanet: 2 · 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
NDUFV2	Strong	Autosomal recessive	mitochondrial complex I deficiency, nuclear type 7	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
NDUFV2	Orphanet:139447	Progressive cavitating leukoencephalopathy
NDUFV2	Orphanet:2609	Isolated complex I deficiency

Cohort genes → proteins

2 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
NDUFV2	HGNC:7717	ENSG00000178127	P19404	NADH dehydrogenase [ubiquinone] flavoprotein 2, mitochondrial	gencc,clinvar
NDUFV2-AS1	HGNC:50826	ENSG00000266053		NDUFV2 antisense RNA 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
NDUFV2	NADH dehydrogenase [ubiquinone] flavoprotein 2, mitochondrial	Core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) which catalyzes electron transfer from NADH through the respiratory chain, using ubiquinone as an electron acceptor.

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)
NDUFV2	Other/Unknown	no		NuoE-like, Thioredoxin-like_sf, NuoE_N
NDUFV2-AS1	Other/Unknown	no

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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
apex of heart	1
gastrocnemius	1
hindlimb stylopod muscle	1
left testis	1
right testis	1
sperm	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
NDUFV2	137	ubiquitous	marker	apex of heart, gastrocnemius, hindlimb stylopod muscle
NDUFV2-AS1	186	broad	yes	sperm, left testis, right testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
NDUFV2	3,918
NDUFV2-AS1	0

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
NDUFV2	P19404	7

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. 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×	0.015	NDUFV2
Respiratory electron transport	1	95.2×	0.015	NDUFV2
Aerobic respiration and respiratory electron transport	1	88.5×	0.015	NDUFV2
Metabolism	1	11.6×	0.086	NDUFV2

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
cardiac muscle tissue development	1	887.0×	0.005	NDUFV2
mitochondrial electron transport, NADH to ubiquinone	1	358.6×	0.005	NDUFV2
proton motive force-driven mitochondrial ATP synthesis	1	263.3×	0.005	NDUFV2
aerobic respiration	1	247.8×	0.005	NDUFV2
nervous system development	1	45.9×	0.022	NDUFV2

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
NDUFV2	0	0
NDUFV2-AS1	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
NDUFV2	5	Binding:5

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	NDUFV2, NDUFV2-AS1

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)
NDUFV2	5	—
NDUFV2-AS1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.