mitochondrial complex I deficiency, nuclear type 11

Summary

mitochondrial complex I deficiency, nuclear type 11 (MONDO:0032617) is a disease caused by NDUFAF1 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: NDUFAF1 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 13

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	mitochondrial complex I deficiency, nuclear type 11
Mondo ID	MONDO:0032617
OMIM	618234
DOID	DOID:0112089
UMLS	C4748769
MedGen	1648356
GARD	0016321
Is cancer (heuristic)	no

Also known as: MC1DN11

Data availability: 13 ClinVar variants · 3 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 11

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 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

13 retrieved; paginated sample, class counts are floors:

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

ClinVar	Variant (HGVS)	Gene	Classification	Review
30622	NM_016013.4(NDUFAF1):c.619A>C (p.Thr207Pro)	NDUFAF1	Pathogenic	no assertion criteria provided
30624	NM_016013.4(NDUFAF1):c.631C>T (p.Arg211Cys)	NDUFAF1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1029422	NM_016013.4(NDUFAF1):c.512C>T (p.Ala171Val)	NDUFAF1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1213729	NM_016013.4(NDUFAF1):c.457A>G (p.Lys153Glu)	NDUFAF1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1362095	NM_016013.4(NDUFAF1):c.199G>A (p.Val67Ile)	NDUFAF1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1701002	NM_016013.4(NDUFAF1):c.259A>G (p.Arg87Gly)	NDUFAF1	Uncertain significance	criteria provided, multiple submitters, no conflicts
2434084	NM_016013.4(NDUFAF1):c.624_625del (p.Tyr209fs)	NDUFAF1	Uncertain significance	criteria provided, multiple submitters, no conflicts
30623	NM_016013.4(NDUFAF1):c.758A>G (p.Lys253Arg)	NDUFAF1	Uncertain significance	criteria provided, single submitter
30625	NM_016013.4(NDUFAF1):c.733G>A (p.Gly245Arg)	NDUFAF1	Uncertain significance	criteria provided, multiple submitters, no conflicts
129688	NM_016013.4(NDUFAF1):c.26G>A (p.Arg9His)	NDUFAF1	Benign	criteria provided, multiple submitters, no conflicts
129689	NM_016013.4(NDUFAF1):c.92G>T (p.Arg31Leu)	NDUFAF1	Benign	criteria provided, multiple submitters, no conflicts
138454	NM_016013.4(NDUFAF1):c.526G>A (p.Glu176Lys)	NDUFAF1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
138455	NM_016013.4(NDUFAF1):c.558A>G (p.Ile186Met)	NDUFAF1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · 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
NDUFAF1	Strong	Autosomal recessive	mitochondrial complex I deficiency, nuclear type 11	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
NDUFAF1	Orphanet:2609	Isolated complex I deficiency

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
NDUFAF1	HGNC:18828	ENSG00000137806	Q9Y375	Complex I intermediate-associated protein 30, mitochondrial	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
NDUFAF1	Complex I intermediate-associated protein 30, mitochondrial	As part of the MCIA complex, involved in the assembly of the mitochondrial complex I.

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)
NDUFAF1	Other/Unknown	no		Galactose-bd-like_sf, NADH-UbQ_OxRdtase-assoc_prot30, NDUFAF1

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
apex of heart	1
gastrocnemius	1
right adrenal gland	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
NDUFAF1	281	ubiquitous	marker	apex of heart, gastrocnemius, right adrenal gland

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
NDUFAF1	1,716

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
NDUFAF1	Q9Y375	73.37

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. 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×	0.006	NDUFAF1

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
chaperone-mediated protein complex assembly	1	702.2×	0.004	NDUFAF1
mitochondrial respiratory chain complex I assembly	1	411.0×	0.004	NDUFAF1
mitochondrial electron transport, NADH to ubiquinone	1	358.6×	0.004	NDUFAF1
protein-containing complex assembly	1	113.9×	0.009	NDUFAF1

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
NDUFAF1	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
NDUFAF1	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	1	NDUFAF1

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)
NDUFAF1	4	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.