mitochondrial complex I deficiency, nuclear type 17

Summary

mitochondrial complex I deficiency, nuclear type 17 (MONDO:0032622) is a disease caused by NDUFAF6 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: NDUFAF6 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 39

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	mitochondrial complex I deficiency, nuclear type 17
Mondo ID	MONDO:0032622
OMIM	618239
DOID	DOID:0112078
UMLS	C4748786
MedGen	1648418
GARD	0018372
Is cancer (heuristic)	no

Also known as: MC1DN17

Data availability: 39 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 17

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 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 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

39 retrieved; paginated sample, class counts are floors:

11 uncertain significance, 8 pathogenic, 6 conflicting classifications of pathogenicity, 5 likely pathogenic, 3 pathogenic/likely pathogenic, 3 benign, 3 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1064539	NM_152416.4(NDUFAF6):c.420+2_420+3insTA	NDUFAF6	Pathogenic	no assertion criteria provided
1064697	NM_152416.4(NDUFAF6):c.485del (p.Asn162fs)	NDUFAF6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
372255	NM_152416.4(NDUFAF6):c.805C>G (p.His269Asp)	NDUFAF6	Pathogenic	no assertion criteria provided
372256	NM_152416.4(NDUFAF6):c.226T>C (p.Ser76Pro)	NDUFAF6	Pathogenic	no assertion criteria provided
372258	NM_152416.4(NDUFAF6):c.206A>T (p.Asp69Val)	NDUFAF6	Pathogenic	no assertion criteria provided
372259	NM_152416.4(NDUFAF6):c.820A>G (p.Arg274Gly)	NDUFAF6	Pathogenic	no assertion criteria provided
503873	NM_152416.4(NDUFAF6):c.559_563del (p.Tyr187fs)	NDUFAF6	Pathogenic	criteria provided, multiple submitters, no conflicts
547	NM_152416.4(NDUFAF6):c.296A>G (p.Gln99Arg)	NDUFAF6	Pathogenic	no assertion criteria provided
929495	NM_152416.4(NDUFAF6):c.420+784C>T	NDUFAF6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
929496	NM_152416.4(NDUFAF6):c.555_559del (p.Tyr187fs)	NDUFAF6	Pathogenic	no assertion criteria provided
972921	NM_152416.4(NDUFAF6):c.337C>T (p.Arg113Ter)	NDUFAF6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1029199	NM_152416.4(NDUFAF6):c.420+1_420+2dup	NDUFAF6	Likely pathogenic	criteria provided, single submitter
3767217	NM_152416.4(NDUFAF6):c.536A>G (p.Glu179Gly)	NDUFAF6	Likely pathogenic	criteria provided, single submitter
3775662	NM_152416.4(NDUFAF6):c.198-2A>C	NDUFAF6	Likely pathogenic	criteria provided, single submitter
430873	NM_152416.4(NDUFAF6):c.328G>T (p.Gly110Ter)	NDUFAF6	Likely pathogenic	criteria provided, multiple submitters, no conflicts
4813841	NM_152416.4(NDUFAF6):c.322del (p.Thr108fs)	NDUFAF6	Likely pathogenic	criteria provided, single submitter
1905568	NM_152416.4(NDUFAF6):c.967del (p.Tyr323fs)	NDUFAF6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
214212	NM_152416.4(NDUFAF6):c.371T>C (p.Ile124Thr)	NDUFAF6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
214215	NM_152416.4(NDUFAF6):c.233_242dup (p.Glu82fs)	NDUFAF6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2507351	NM_152416.4(NDUFAF6):c.694C>A (p.Pro232Thr)	NDUFAF6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
284262	NM_152416.4(NDUFAF6):c.715-3C>A	NDUFAF6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
372254	NM_152416.4(NDUFAF6):c.532G>C (p.Ala178Pro)	NDUFAF6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1988700	NM_152416.4(NDUFAF6):c.82G>C (p.Gly28Arg)	LOC113788297	Uncertain significance	criteria provided, multiple submitters, no conflicts
4292574	NM_152416.4(NDUFAF6):c.61_81dup (p.Leu27_Gly28insCysCysArgArgProProLeu)	LOC113788297	Uncertain significance	criteria provided, single submitter
1333393	NM_152416.4(NDUFAF6):c.266C>T (p.Ala89Val)	NDUFAF6	Uncertain significance	criteria provided, single submitter
2413146	NM_152416.4(NDUFAF6):c.634G>A (p.Gly212Ser)	NDUFAF6	Uncertain significance	criteria provided, single submitter
2413147	NM_152416.4(NDUFAF6):c.907C>T (p.Arg303Ter)	NDUFAF6	Uncertain significance	criteria provided, single submitter
2444196	NM_152416.4(NDUFAF6):c.655G>C (p.Ala219Pro)	NDUFAF6	Uncertain significance	criteria provided, single submitter
2664869	NM_152416.4(NDUFAF6):c.239C>T (p.Pro80Leu)	NDUFAF6	Uncertain significance	criteria provided, single submitter
3775908	NM_152416.4(NDUFAF6):c.620T>C (p.Ile207Thr)	NDUFAF6	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 1 · 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
NDUFAF6	Strong	Autosomal recessive	mitochondrial complex I deficiency, nuclear type 17	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
NDUFAF6	Orphanet:3337	Primary Fanconi renotubular syndrome

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
NDUFAF6	HGNC:28625	ENSG00000156170	Q330K2	NADH dehydrogenase (ubiquinone) complex I, assembly factor 6	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
NDUFAF6	NADH dehydrogenase (ubiquinone) complex I, assembly factor 6	Involved in the assembly of mitochondrial NADH:ubiquinone oxidoreductase complex (complex I) at early stages.

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)
NDUFAF6	Other/Unknown	no		Squ/phyt_synthse, Isoprenoid_synthase_dom_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
deltoid	1
right uterine tube	1
tibialis anterior	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
NDUFAF6	242	ubiquitous	marker	right uterine tube, tibialis anterior, deltoid

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
NDUFAF6	1,990

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
NDUFAF6	Q330K2	87.70

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. 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
Complex I biogenesis	1	165.5×	0.015	NDUFAF6
Respiratory electron transport	1	95.2×	0.015	NDUFAF6
Aerobic respiration and respiratory electron transport	1	88.5×	0.015	NDUFAF6
Metabolism	1	11.6×	0.086	NDUFAF6

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
mitochondrial respiratory chain complex I assembly	1	411.0×	0.002	NDUFAF6

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
NDUFAF6	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	NDUFAF6

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)
NDUFAF6	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.