mitochondrial complex IV deficiency, nuclear type 24

Summary

mitochondrial complex IV deficiency, nuclear type 24 (MONDO:0980755) is a disease with 3 cohort genes.

At a glance

• Cohort genes: 3
• ClinVar variants: 5

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	mitochondrial complex IV deficiency, nuclear type 24
Mondo ID	MONDO:0980755
OMIM	621431
Is cancer (heuristic)	no

Data availability: 5 ClinVar variants.

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 IV deficiency, nuclear-type › mitochondrial complex IV deficiency, nuclear type 24

Related subtypes (21): pancreatic insufficiency-anemia-hyperostosis syndrome, mitochondrial complex IV deficiency, nuclear type 3, mitochondrial complex IV deficiency, nuclear type 4, mitochondrial complex IV deficiency, nuclear type 7, mitochondrial complex IV deficiency, nuclear type 8, mitochondrial complex IV deficiency, nuclear type 10, mitochondrial complex IV deficiency, nuclear type 11, mitochondrial complex IV deficiency, nuclear type 12, mitochondrial complex IV deficiency, nuclear type 14, mitochondrial complex IV deficiency, nuclear type 15, mitochondrial complex IV deficiency, nuclear type 16, mitochondrial complex IV deficiency, nuclear type 17, mitochondrial complex IV deficiency, nuclear type 18, mitochondrial complex IV deficiency, nuclear type 19, mitochondrial complex IV deficiency, nuclear type 20, mitochondrial complex IV deficiency, nuclear type 21, mitochondrial complex IV deficiency, nuclear type 1, mitochondrial complex IV deficiency, nuclear type 22, mitochondrial complex IV deficiency, nuclear type 23, COX deficiency, benign infantile mitochondrial myopathy, mitochondrial complex 4 deficiency, nuclear type 25

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

5 retrieved; paginated sample, class counts are floors:

5 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
3899914	NM_021826.5(FASTKD5):c.1210C>T (p.Arg404Cys)	FASTKD5	Pathogenic	no assertion criteria provided
3899913	NM_021826.5(FASTKD5):c.1901T>C (p.Leu634Pro)	UBOX5	Pathogenic	no assertion criteria provided
3899912	NM_021826.5(FASTKD5):c.1716dup (p.Pro573fs)	UBOX5-AS1	Pathogenic	no assertion criteria provided
3899915	NM_021826.5(FASTKD5):c.374A>G (p.Tyr125Cys)	UBOX5-AS1	Pathogenic	no assertion criteria provided
3899916	NM_021826.5(FASTKD5):c.2028_2029del (p.Ala678fs)	UBOX5-AS1	Pathogenic	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 0 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Cohort genes → proteins

3 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
UBOX5	HGNC:17777	ENSG00000185019	O94941	RING finger protein 37	clinvar
FASTKD5	HGNC:25790	ENSG00000215251	Q7L8L6	FAST kinase domain-containing protein 5, mitochondrial	clinvar
UBOX5-AS1	HGNC:44111	ENSG00000235958		UBOX5 antisense RNA 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
UBOX5	RING finger protein 37	May have a ubiquitin-protein ligase activity acting as an E3 ubiquitin-protein ligase or as a ubiquitin-ubiquitin ligase promoting elongation of ubiquitin chains on substrates.
FASTKD5	FAST kinase domain-containing protein 5, mitochondrial	Plays an important role in the processing of non-canonical mitochondrial mRNA precursors.

Protein-family classification

Druggable: 1 · Difficult: 1 · Unknown: 1 · Druggable fraction: 0.33

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
Kinase	1	9.2×	0.313
Transcription factor	1	2.8×	0.482
Other/Unknown	1	0.6×	0.914

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
UBOX5	Transcription factor	no		Znf_RING, Ubox_domain, Znf_RING/FYVE/PHD
FASTKD5	Kinase	yes		FAST_Leu-rich, FAST_2, RAP
UBOX5-AS1	Other/Unknown	no

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)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
diaphragm	1
olfactory bulb	1
type B pancreatic cell	1
gastrocnemius	1
muscle of leg	1
muscle organ	1
male germ line stem cell (sensu Vertebrata) in testis	1
primordial germ cell in gonad	1
sural nerve	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
UBOX5	222	ubiquitous	marker	olfactory bulb, type B pancreatic cell, diaphragm
FASTKD5	264	ubiquitous	yes	gastrocnemius, muscle of leg, muscle organ
UBOX5-AS1	132		marker	male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad, sural nerve

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
UBOX5	1,354
FASTKD5	914
UBOX5-AS1	0

Structural data

PDB: 0 · AlphaFold-only: 2 · No structure: 1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
FASTKD5	Q7L8L6	79.38
UBOX5	O94941	71.33

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 5. Enrichment computed across 3 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
FASTK family proteins regulate processing and stability of mitochondrial RNAs	1	1427.5×	0.004	FASTKD5
Class I MHC mediated antigen processing & presentation	1	35.0×	0.071	UBOX5
Antigen processing: Ubiquitination & Proteasome degradation	1	18.6×	0.082	UBOX5
Adaptive Immune System	1	14.9×	0.082	UBOX5
Immune System	1	6.5×	0.148	UBOX5

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
mitochondrial RNA processing	1	1404.3×	0.002	FASTKD5
regulation of mitochondrial mRNA stability	1	1203.7×	0.002	FASTKD5
protein polyubiquitination	1	57.7×	0.023	UBOX5
mRNA processing	1	39.4×	0.025	FASTKD5

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 3 evidence-associated genes (33%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
UBOX5	0	0
FASTKD5	0	0
UBOX5-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
FASTKD5	1	Binding:1

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	1	FASTKD5
E	Difficult family or no structure, no drug	2	UBOX5, UBOX5-AS1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
UBOX5	0	—
FASTKD5	1	—
UBOX5-AS1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.