mitochondrial complex I deficiency, nuclear type 28

Summary

mitochondrial complex I deficiency, nuclear type 28 (MONDO:0032632) is a disease caused by NDUFA13 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: NDUFA13 (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	mitochondrial complex I deficiency, nuclear type 28
Mondo ID	MONDO:0032632
OMIM	618249
DOID	DOID:0112095
UMLS	C4748827
MedGen	1648493
GARD	0018376
Is cancer (heuristic)	no

Also known as: MC1DN28

Data availability: 9 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 28

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 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 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

9 retrieved; paginated sample, class counts are floors:

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

ClinVar	Variant (HGVS)	Gene	Classification	Review
983476	NM_015965.7(NDUFA13):c.194del (p.Phe65fs)	NDUFA13	Pathogenic	no assertion criteria provided
983478	NM_015965.7(NDUFA13):c.107T>C (p.Leu36Pro)	NDUFA13	Pathogenic	no assertion criteria provided
2441769	NM_015965.7(NDUFA13):c.44dup (p.Tyr16fs)	LOC130064074	Likely pathogenic	criteria provided, single submitter
2671946	NM_015965.7(NDUFA13):c.94+1G>A	LOC130064074	Likely pathogenic	criteria provided, single submitter
132643	NM_015965.7(NDUFA13):c.170G>A (p.Arg57His)	NDUFA13	Likely pathogenic	criteria provided, multiple submitters, no conflicts
2069279	NM_015965.7(NDUFA13):c.187G>A (p.Glu63Lys)	NDUFA13	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2434082	NM_015965.7(NDUFA13):c.2T>C (p.Met1Thr)	LOC130064074	Uncertain significance	criteria provided, single submitter
2672263	NM_015965.7(NDUFA13):c.433T>C (p.Ter145Gln)	NDUFA13	Uncertain significance	criteria provided, single submitter
3362737	NM_015965.7(NDUFA13):c.310T>C (p.Trp104Arg)	NDUFA13	Uncertain significance	criteria provided, single submitter

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
NDUFA13	Strong	Autosomal recessive	mitochondrial complex I deficiency, nuclear type 28	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
NDUFA13	Orphanet:146	Differentiated thyroid carcinoma

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
NDUFA13	HGNC:17194	ENSG00000186010	Q9P0J0	NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 13	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
NDUFA13	NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 13	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: 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)
NDUFA13	Other/Unknown	no		GRIM-19

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
heart left ventricle	1
right atrium auricular region	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
NDUFA13	134	ubiquitous	marker	apex of heart, heart left ventricle, right atrium auricular region

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
NDUFA13	3,268

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
NDUFA13	Q9P0J0	8

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 6. 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×	0.017	NDUFA13
Mitochondrial protein degradation	1	114.2×	0.017	NDUFA13
Respiratory electron transport	1	95.2×	0.017	NDUFA13
Aerobic respiration and respiratory electron transport	1	88.5×	0.017	NDUFA13
Metabolism of proteins	1	12.4×	0.086	NDUFA13
Metabolism	1	11.6×	0.086	NDUFA13

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
protein insertion into mitochondrial inner membrane	1	1296.3×	0.005	NDUFA13
positive regulation of execution phase of apoptosis	1	842.6×	0.005	NDUFA13
cellular response to interferon-beta	1	526.6×	0.005	NDUFA13
mitochondrial respiratory chain complex I assembly	1	411.0×	0.005	NDUFA13
extrinsic apoptotic signaling pathway	1	306.4×	0.005	NDUFA13
proton motive force-driven mitochondrial ATP synthesis	1	263.3×	0.005	NDUFA13
aerobic respiration	1	247.8×	0.005	NDUFA13
cellular response to retinoic acid	1	234.1×	0.005	NDUFA13
positive regulation of protein catabolic process	1	203.0×	0.005	NDUFA13
negative regulation of DNA-templated transcription	1	31.6×	0.032	NDUFA13

Therapeutics

Drug target analysis

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

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
NDUFA13	1	3

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
ALISERTIB	3	NDUFA13

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
NDUFA13	6	Binding:6

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

1 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.

Compound	Max phase	Cohort target (bioactivity)
ALISERTIB	3	NDUFA13

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	1	NDUFA13
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 0.