3-methylglutaconic aciduria, type VIIA

disease

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Summary

3-methylglutaconic aciduria, type VIIA (MONDO:0859237) is a disease with 1 cohort gene.

At a glance

Cohort genes: 1
ClinVar variants: 12

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	3-methylglutaconic aciduria, type VIIA
Mondo ID	MONDO:0859237
OMIM	619835
DOID	DOID:0081133
UMLS	C5676967
MedGen	1813022
GARD	0026676
Is cancer (heuristic)	no

Data availability: 12 ClinVar variants.

Disease family

Classification path: human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › inborn errors of metabolism › inborn disorder of amino acid and other organic acid metabolism › inborn disorder of amino acid metabolism › inborn organic aciduria › classic organic aciduria › 3-methylglutaconic aciduria › 3-methylglutaconic aciduria, type VIIA

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

12 retrieved; paginated sample, class counts are floors:

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

ClinVar	Variant (HGVS)	Gene	Classification	Review
187786	NM_001258392.3(CLPB):c.1159C>T (p.Arg387Ter)	CLPB	Pathogenic	criteria provided, multiple submitters, no conflicts
187785	NM_001258392.3(CLPB):c.1132A>G (p.Arg378Gly)	LOC126861258	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
869400	NM_001258392.3(CLPB):c.1591C>T (p.Arg531Trp)	CLPB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1010621	NM_001258392.3(CLPB):c.748C>T (p.Arg250Cys)	CLPB	Uncertain significance	criteria provided, multiple submitters, no conflicts
1939221	NM_001258392.3(CLPB):c.428G>A (p.Arg143His)	CLPB	Uncertain significance	criteria provided, multiple submitters, no conflicts
3236439	NM_001258392.3(CLPB):c.374A>G (p.His125Arg)	CLPB	Uncertain significance	criteria provided, single submitter
3376825	NM_001258392.3(CLPB):c.1318C>A (p.Leu440Met)	CLPB	Uncertain significance	criteria provided, single submitter
3377673	NM_001258392.3(CLPB):c.1486+6del	CLPB	Uncertain significance	criteria provided, single submitter
571670	NM_001258392.3(CLPB):c.844A>G (p.Met282Val)	CLPB	Uncertain significance	criteria provided, multiple submitters, no conflicts
573047	NM_001258392.3(CLPB):c.748C>G (p.Arg250Gly)	CLPB	Uncertain significance	criteria provided, multiple submitters, no conflicts
644249	NM_001258392.3(CLPB):c.214G>A (p.Gly72Arg)	CLPB	Uncertain significance	criteria provided, multiple submitters, no conflicts
235218	NM_030813.6(CLPB):c.668G>A (p.Ser223Asn)	CLPB	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CLPB	Orphanet:445038	3-methylglutaconic aciduria-neonatal cataract-neurologic involvement-congenital neutropenia syndrome
CLPB	Orphanet:486	Autosomal dominant severe congenital neutropenia

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
CLPB	HGNC:30664	ENSG00000162129	Q9H078	Mitochondrial disaggregase	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CLPB	Mitochondrial disaggregase	Functions as a regulatory ATPase and participates in secretion/protein trafficking process.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · 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	17.3×	0.058

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CLPB	Scaffold/PPI	no		ClpA/B, Ankyrin_rpt, AAA+_ATPase

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
left testis	1
right testis	1
sperm	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CLPB	205	ubiquitous	marker	sperm, left testis, right testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CLPB	5,095

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CLPB	Q9H078	7

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

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
RIG-I signaling pathway	1	2407.4×	0.002	CLPB
granulocyte differentiation	1	1203.7×	0.002	CLPB
cellular response to heat	1	343.9×	0.004	CLPB
antiviral innate immune response	1	227.7×	0.004	CLPB

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
CLPB	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	CLPB

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)
CLPB	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.

Cohort genes: CLPB