mitochondrial complex IV deficiency, nuclear type 8

Summary

mitochondrial complex IV deficiency, nuclear type 8 (MONDO:0033638) is a disease caused by TACO1 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: TACO1 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 51

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	mitochondrial complex IV deficiency, nuclear type 8
Mondo ID	MONDO:0033638
OMIM	619052
DOID	DOID:0070495
UMLS	C5436689
MedGen	1765544
GARD	0016407
Is cancer (heuristic)	no

Also known as: MC4DN8 · mitochondrial complex IV deficiency, nuclear type 8

Data availability: 51 ClinVar variants · 4 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 IV deficiency, nuclear-type › mitochondrial complex IV deficiency, nuclear type 8

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 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 IV deficiency, nuclear type 24, 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

51 retrieved; paginated sample, class counts are floors:

35 uncertain significance, 8 likely pathogenic, 4 likely benign, 1 conflicting classifications of pathogenicity, 1 pathogenic/likely pathogenic, 1 benign/likely benign, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
2443079	NM_016360.4(TACO1):c.280+1G>C	TACO1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
982266	NM_016360.4(TACO1):c.421C>T (p.Arg141Ter)	TACO1	Pathogenic	criteria provided, multiple submitters, no conflicts
3064510	NM_016360.4(TACO1):c.255_258del (p.Leu84_Cys85insTer)	TACO1	Likely pathogenic	criteria provided, single submitter
3582593	NM_016360.4(TACO1):c.75_76delinsC (p.Arg25fs)	TACO1	Likely pathogenic	criteria provided, single submitter
3582601	NM_016360.4(TACO1):c.280G>T (p.Glu94Ter)	TACO1	Likely pathogenic	criteria provided, single submitter
3582610	NM_016360.4(TACO1):c.428del (p.Pro143fs)	TACO1	Likely pathogenic	criteria provided, single submitter
3582613	NM_016360.4(TACO1):c.516-1G>A	TACO1	Likely pathogenic	criteria provided, single submitter
3582617	NM_016360.4(TACO1):c.775G>T (p.Glu259Ter)	TACO1	Likely pathogenic	criteria provided, single submitter
411	NM_016360.4(TACO1):c.472dup (p.His158fs)	TACO1	Likely pathogenic	criteria provided, single submitter
818073	NM_016360.4(TACO1):c.97del (p.Arg33fs)	TACO1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1443668	NM_016360.4(TACO1):c.73A>G (p.Arg25Gly)	TACO1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1029447	NM_016360.4(TACO1):c.476A>G (p.Lys159Arg)	TACO1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1380080	NM_016360.4(TACO1):c.847C>G (p.Leu283Val)	TACO1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1394869	NM_016360.4(TACO1):c.685G>A (p.Val229Ile)	TACO1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1514943	NM_016360.4(TACO1):c.448A>G (p.Ile150Val)	TACO1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1929101	NM_016360.4(TACO1):c.452A>G (p.Glu151Gly)	TACO1	Uncertain significance	criteria provided, multiple submitters, no conflicts
2067109	NM_016360.4(TACO1):c.180C>A (p.His60Gln)	TACO1	Uncertain significance	criteria provided, multiple submitters, no conflicts
2141926	NM_016360.4(TACO1):c.424G>A (p.Gly142Ser)	TACO1	Uncertain significance	criteria provided, multiple submitters, no conflicts
2146498	NM_016360.4(TACO1):c.265C>T (p.Arg89Cys)	TACO1	Uncertain significance	criteria provided, multiple submitters, no conflicts
2160160	NM_016360.4(TACO1):c.613C>T (p.Arg205Cys)	TACO1	Uncertain significance	criteria provided, multiple submitters, no conflicts
2436926	NM_016360.4(TACO1):c.814G>A (p.Asp272Asn)	TACO1	Uncertain significance	criteria provided, single submitter
2436927	NM_016360.4(TACO1):c.693+4A>G	TACO1	Uncertain significance	criteria provided, single submitter
2550462	NM_016360.4(TACO1):c.422G>A (p.Arg141Gln)	TACO1	Uncertain significance	criteria provided, multiple submitters, no conflicts
324445	NM_016360.4(TACO1):c.511A>C (p.Asn171His)	TACO1	Uncertain significance	criteria provided, multiple submitters, no conflicts
3582594	NM_016360.4(TACO1):c.76G>A (p.Ala26Thr)	TACO1	Uncertain significance	criteria provided, single submitter
3582595	NM_016360.4(TACO1):c.98G>T (p.Arg33Leu)	TACO1	Uncertain significance	criteria provided, single submitter
3582596	NM_016360.4(TACO1):c.112G>A (p.Glu38Lys)	TACO1	Uncertain significance	criteria provided, single submitter
3582597	NM_016360.4(TACO1):c.152A>G (p.His51Arg)	TACO1	Uncertain significance	criteria provided, single submitter
3582598	NM_016360.4(TACO1):c.163G>A (p.Ala55Thr)	TACO1	Uncertain significance	criteria provided, single submitter
3582599	NM_016360.4(TACO1):c.264C>T (p.Ile88=)	TACO1	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · Orphanet: 0 · 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
TACO1	Strong	Autosomal recessive	mitochondrial complex IV deficiency, nuclear type 8	6

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
TACO1	HGNC:24316	ENSG00000136463	Q9BSH4	Translational activator of cytochrome c oxidase 1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TACO1	Translational activator of cytochrome c oxidase 1	Acts as a translational activator of mitochondrially-encoded cytochrome c oxidase 1.

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)
TACO1	Other/Unknown	no		Transcrip_reg_TACO1-like, Integrase-like_N, Transcrip_reg_TACO1-like_dom3

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
mucosa of transverse colon	1
right lobe of liver	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TACO1	265	ubiquitous	marker	apex of heart, mucosa of transverse colon, right lobe of liver

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TACO1	2,209

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TACO1	Q9BSH4	7

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 IV assembly	1	228.4×	0.015	TACO1
Respiratory electron transport	1	95.2×	0.015	TACO1
Aerobic respiration and respiratory electron transport	1	88.5×	0.015	TACO1
Metabolism	1	11.6×	0.086	TACO1

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
motor learning	1	2407.4×	6e-04	TACO1
regulation of mitochondrial translation	1	2407.4×	6e-04	TACO1
mitochondrial respiratory chain complex IV assembly	1	624.1×	0.002	TACO1

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
TACO1	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	TACO1

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)
TACO1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.