mitochondrial complex III deficiency nuclear type 8

Summary

mitochondrial complex III deficiency nuclear type 8 (MONDO:0014364) is a disease caused by LYRM7 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: LYRM7 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 14

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	mitochondrial complex III deficiency nuclear type 8
Mondo ID	MONDO:0014364
OMIM	615838
DOID	DOID:0080117
UMLS	C4014440
MedGen	862877
GARD	0016018
Is cancer (heuristic)	no

Also known as: LYRM7 mitochondrial complex III deficiency · MC3DN8 · mitochondrial complex III deficiency caused by mutation in LYRM7 · mitochondrial complex III deficiency nuclear type 8 · mitochondrial complex III deficiency, nuclear type 8

Data availability: 14 ClinVar variants · 1 GenCC gene-disease record.

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 8

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 6, mitochondrial complex III deficiency nuclear type 7, 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

14 retrieved; paginated sample, class counts are floors:

5 uncertain significance, 5 pathogenic, 3 likely pathogenic, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1323256	NM_181705.4(LYRM7):c.2T>C (p.Met1Thr)	LYRM7	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
135664	NM_181705.4(LYRM7):c.73G>A (p.Asp25Asn)	LYRM7	Pathogenic	no assertion criteria provided
223134	NM_181705.4(LYRM7):c.244+5dup	LYRM7	Pathogenic	no assertion criteria provided
223135	NM_181705.4(LYRM7):c.190TTA[3] (p.Leu66dup)	LYRM7	Pathogenic	no assertion criteria provided
223136	NM_181705.4(LYRM7):c.214C>T (p.Gln72Ter)	LYRM7	Pathogenic	no assertion criteria provided
223137	NM_181705.4(LYRM7):c.37del (p.Thr13fs)	LYRM7	Pathogenic	criteria provided, multiple submitters, no conflicts
1712258	NM_181705.4(LYRM7):c.309del (p.Lys103fs)	LYRM7	Likely pathogenic	criteria provided, single submitter
3776779	NM_181705.4(LYRM7):c.19-3C>G	LYRM7	Likely pathogenic	criteria provided, single submitter
638440	NM_181705.4(LYRM7):c.214C>G (p.Gln72Glu)	LYRM7	Likely pathogenic	criteria provided, single submitter
1027904	NM_181705.4(LYRM7):c.264C>A (p.Asp88Glu)	LYRM7	Uncertain significance	criteria provided, multiple submitters, no conflicts
1687220	NM_181705.4(LYRM7):c.120C>A (p.Phe40Leu)	LYRM7	Uncertain significance	criteria provided, single submitter
1904336	NM_181705.4(LYRM7):c.142TCT[1] (p.Ser49del)	LYRM7	Uncertain significance	criteria provided, multiple submitters, no conflicts
2689385	NM_181705.4(LYRM7):c.128A>G (p.Asn43Ser)	LYRM7	Uncertain significance	criteria provided, single submitter
870569	NM_181705.4(LYRM7):c.244+6T>G	LYRM7	Uncertain significance	no assertion criteria provided

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
LYRM7	Strong	Autosomal recessive	mitochondrial complex III deficiency nuclear type 8	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
LYRM7	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
LYRM7	HGNC:28072	ENSG00000186687	Q5U5X0	Complex III assembly factor LYRM7	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
LYRM7	Complex III assembly factor LYRM7	Assembly factor required for Rieske Fe-S protein UQCRFS1 incorporation into the cytochrome b-c1 (CIII) complex.

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)
LYRM7	Other/Unknown	no		Complex1_LYR_dom, Complex1_LYR_LYRM7, MZM1/LYRM7

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
deltoid	1
left ventricle myocardium	1
vastus lateralis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
LYRM7	254	ubiquitous	marker	left ventricle myocardium, vastus lateralis, deltoid

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
LYRM7	1,740

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
LYRM7	Q5U5X0	91.70

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 III assembly	1	439.2×	0.009	LYRM7
Respiratory electron transport	1	95.2×	0.015	LYRM7
Aerobic respiration and respiratory electron transport	1	88.5×	0.015	LYRM7
Metabolism	1	11.6×	0.086	LYRM7

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
mitochondrial respiratory chain complex III assembly	1	1203.7×	0.002	LYRM7
cellular respiration	1	432.1×	0.002	LYRM7

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
LYRM7	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	LYRM7

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)
LYRM7	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.