mitochondrial complex III deficiency nuclear type 6

Summary

mitochondrial complex III deficiency nuclear type 6 (MONDO:0014194) is a disease caused by CYC1 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: CYC1 (GenCC Definitive)
• 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 III deficiency nuclear type 6
Mondo ID	MONDO:0014194
OMIM	615453
DOID	DOID:0080115
UMLS	C3809553
MedGen	815883
GARD	0015970
Is cancer (heuristic)	no

Also known as: CYC1 mitochondrial complex III deficiency · MC3DN6 · mitochondrial complex III deficiency caused by mutation in CYC1 · mitochondrial complex III deficiency, nuclear type 6

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 III deficiency › mitochondrial complex III deficiency, nuclear type › mitochondrial complex III deficiency nuclear type 6

Related subtypes (10): mitochondrial complex III deficiency nuclear type 1, mitochondrial complex III deficiency nuclear type 2, mitochondrial complex III deficiency nuclear type 3, mitochondrial complex III deficiency nuclear type 4, mitochondrial complex III deficiency nuclear type 5, mitochondrial complex III deficiency nuclear type 7, mitochondrial complex III deficiency nuclear type 8, mitochondrial complex III deficiency nuclear type 9, mitochondrial complex III deficiency, nuclear type 10, mitochondrial complex III deficiency, nuclear type 11

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

ClinVar	Variant (HGVS)	Gene	Classification	Review
66019	NM_001916.5(CYC1):c.288G>T (p.Trp96Cys)	CYC1	Pathogenic	no assertion criteria provided
66020	NM_001916.5(CYC1):c.643C>T (p.Leu215Phe)	CYC1	Pathogenic	criteria provided, single submitter
1900186	NM_001916.5(CYC1):c.11C>T (p.Ala4Val)	CYC1	Uncertain significance	criteria provided, multiple submitters, no conflicts
3001473	NM_001916.5(CYC1):c.854G>A (p.Arg285Gln)	CYC1	Uncertain significance	criteria provided, multiple submitters, no conflicts
870566	NM_001916.5(CYC1):c.949C>T (p.Arg317Trp)	CYC1	Uncertain significance	no assertion criteria provided
1255439	NM_001916.5(CYC1):c.226A>G (p.Met76Val)	CYC1	Benign	criteria provided, multiple submitters, no conflicts
1255440	NM_001916.5(CYC1):c.772+19_772+20del	CYC1	Benign	criteria provided, multiple submitters, no conflicts
379959	NM_001916.5(CYC1):c.99T>G (p.Arg33=)	CYC1	Benign	criteria provided, multiple submitters, no conflicts
389380	NM_001916.5(CYC1):c.873+7G>A	CYC1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · 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
CYC1	Definitive	Autosomal recessive	mitochondrial complex III deficiency nuclear type 6	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CYC1	Orphanet:1460	Isolated complex III 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
CYC1	HGNC:2579	ENSG00000179091	P08574	Cytochrome c1, heme protein, mitochondrial	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CYC1	Cytochrome c1, heme protein, mitochondrial	Component of the ubiquinol-cytochrome c oxidoreductase, a multisubunit transmembrane complex that is part of the mitochondrial electron transport chain which drives oxidative phosphorylation.

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)
CYC1	Other/Unknown	no		Cyt_c1, Cyt_c1_TM_anchor_C, Cyt_c-like_dom_sf

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
cardiac ventricle	1
heart left ventricle	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CYC1	284	ubiquitous	marker	apex of heart, heart left ventricle, cardiac ventricle

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CYC1	3,199

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CYC1	P08574	5

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. 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 III assembly	1	439.2×	0.007	CYC1
Mitochondrial protein import	1	167.9×	0.009	CYC1
Respiratory electron transport	1	95.2×	0.011	CYC1

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
response to glucagon	1	1685.2×	0.001	CYC1
mitochondrial electron transport, ubiquinol to cytochrome c	1	1296.3×	0.001	CYC1
cellular respiration	1	432.1×	0.002	CYC1

Therapeutics

Drug target analysis

Approved (phase 4): 1 · 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).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
CYC1	GILTERITINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CYC1	1	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
GILTERITINIB	4	CYC1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
CYC1	2	Binding:2

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)
GILTERITINIB	4	CYC1

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	CYC1
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	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.