mitochondrial complex I deficiency, nuclear type 24

Summary

mitochondrial complex I deficiency, nuclear type 24 (MONDO:0032628) is a disease with 2 cohort genes.

At a glance

• Cohort genes: 2
• ClinVar variants: 8

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	mitochondrial complex I deficiency, nuclear type 24
Mondo ID	MONDO:0032628
OMIM	618245
DOID	DOID:0112079
UMLS	C4748803
MedGen	1648364
GARD	0016328
Is cancer (heuristic)	no

Also known as: MC1DN24

Data availability: 8 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 24

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 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

8 retrieved; paginated sample, class counts are floors:

3 uncertain significance, 2 benign, 1 likely benign, 1 benign/likely benign, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
65455	NM_005005.3(NDUFB9):c.191T>C (p.Leu64Pro)	NDUFB9	Pathogenic	no assertion criteria provided
1185599	NM_005005.3(NDUFB9):c.431C>T (p.Thr144Met)	NDUFB9	Uncertain significance	criteria provided, single submitter
3891814	NM_005005.3(NDUFB9):c.479A>G (p.Glu160Gly)	NDUFB9	Uncertain significance	criteria provided, single submitter
427000	NM_005005.3(NDUFB9):c.294+5G>T	NDUFB9	Uncertain significance	criteria provided, multiple submitters, no conflicts
802438	NC_000008.11:g.124557903G>A	MTSS1	Benign	criteria provided, multiple submitters, no conflicts
802439	NC_000008.11:g.124567749C>T	MTSS1	Benign	criteria provided, multiple submitters, no conflicts
1318387	NM_005005.3(NDUFB9):c.-51A>G	NDUFB9	Likely benign	criteria provided, multiple submitters, no conflicts
138472	NM_005005.3(NDUFB9):c.24C>T (p.Pro8=)	NDUFB9	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
NDUFB9	Moderate	Autosomal recessive	mitochondrial complex I deficiency, nuclear type 24	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
NDUFB9	Orphanet:2609	Isolated complex I deficiency

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
NDUFB9	HGNC:7704	ENSG00000147684	Q9Y6M9	NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 9	gencc,clinvar
MTSS1	HGNC:20443	ENSG00000170873	O43312	Protein MTSS 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
NDUFB9	NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 9	Accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), that is believed to be not involved in catalysis.
MTSS1	Protein MTSS 1	May be related to cancer progression or tumor metastasis in a variety of organ sites, most likely through an interaction with the actin cytoskeleton.

Protein-family classification

Druggable: 0 · Difficult: 1 · 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
Scaffold/PPI	1	8.6×	0.225
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
NDUFB9	Other/Unknown	no		Complex1_LYR_dom, NDUFB9, Complex1_LYR_NDUFB9_LYRM3
MTSS1	Scaffold/PPI	no		WH2_dom, I-BAR_dom, AH/BAR_dom_sf

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
cardiac muscle of right atrium	1
kidney epithelium	1
left ventricle myocardium	1
metanephric glomerulus	1
pigmented layer of retina	1
renal glomerulus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
NDUFB9	255	ubiquitous	marker	left ventricle myocardium, cardiac muscle of right atrium, kidney epithelium
MTSS1	294	ubiquitous	marker	pigmented layer of retina, renal glomerulus, metanephric glomerulus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
NDUFB9	3,165
MTSS1	1,628

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
NDUFB9	Q9Y6M9	7
MTSS1	O43312	1

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	NDUFB9
Respiratory electron transport	1	95.2×	0.015	NDUFB9
Aerobic respiration and respiratory electron transport	1	88.5×	0.015	NDUFB9
Metabolism	1	11.6×	0.086	NDUFB9

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
nephron tubule epithelial cell differentiation	1	4213.0×	0.002	MTSS1
glomerulus morphogenesis	1	2808.7×	0.002	MTSS1
microspike assembly	1	2106.5×	0.002	MTSS1
adherens junction maintenance	1	2106.5×	0.002	MTSS1
renal tubule morphogenesis	1	2106.5×	0.002	MTSS1
epithelial cell proliferation involved in renal tubule morphogenesis	1	1685.2×	0.002	MTSS1
cellular response to fluid shear stress	1	648.1×	0.004	MTSS1
positive regulation of actin filament bundle assembly	1	601.9×	0.004	MTSS1
plasma membrane organization	1	443.5×	0.004	MTSS1
mitochondrial electron transport, NADH to ubiquinone	1	179.3×	0.009	NDUFB9
negative regulation of epithelial cell proliferation	1	145.3×	0.011	MTSS1
proton motive force-driven mitochondrial ATP synthesis	1	131.7×	0.011	NDUFB9
aerobic respiration	1	123.9×	0.011	NDUFB9
cell surface receptor protein tyrosine kinase signaling pathway	1	86.9×	0.014	MTSS1
sensory perception of sound	1	50.5×	0.022	NDUFB9
actin cytoskeleton organization	1	39.6×	0.027	MTSS1
cell adhesion	1	18.7×	0.053	MTSS1

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
NDUFB9	0	0
MTSS1	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
NDUFB9	5	Binding:5

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; 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	NDUFB9, MTSS1

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)
NDUFB9	5	—
MTSS1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.