glutaric acidemia IIa

Summary

glutaric acidemia IIa (MONDO:0700073) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 5

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	glutaric acidemia IIa
Mondo ID	MONDO:0700073
UMLS	C3278154
MedGen	479784
GARD	0026345
Is cancer (heuristic)	no

Also known as: ETFA deficiency · GA2A · glutaric acidemia 2A · multiple acyl-CoA dehydrogenase deficiency caused by mutation in ETFA

Data availability: 5 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by developmental or physiological process › metabolic disease › glutaric aciduria › multiple acyl-CoA dehydrogenase deficiency › glutaric acidemia IIa

Related subtypes (4): multiple acyl-CoA dehydrogenase deficiency, severe neonatal type, multiple acyl-CoA dehydrogenase deficiency, mild type, glutaric acidemia IIb, glutaric acidemia IIc

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:

2 conflicting classifications of pathogenicity, 1 pathogenic/likely pathogenic, 1 pathogenic, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
2593	NM_000126.4(ETFA):c.470T>G (p.Val157Gly)	ETFA	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2594	NM_000126.4(ETFA):c.797C>T (p.Thr266Met)	ETFA	Pathogenic	criteria provided, multiple submitters, no conflicts
2595	NM_000126.4(ETFA):c.346G>A (p.Gly116Arg)	ETFA	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1209001	NM_000126.4(ETFA):c.806TAG[1] (p.Val270del)	ETFA	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2597	NM_000126.4(ETFA):c.963+1del	ETFA	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

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
ETFA	Orphanet:394529	Multiple acyl-CoA dehydrogenase deficiency, severe neonatal type
ETFA	Orphanet:394532	Multiple acyl-CoA dehydrogenase deficiency, mild type

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
ETFA	HGNC:3481	ENSG00000140374	P13804	Electron transfer flavoprotein subunit alpha, mitochondrial	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ETFA	Electron transfer flavoprotein subunit alpha, mitochondrial	Heterodimeric electron transfer flavoprotein that accepts electrons from several mitochondrial dehydrogenases, including acyl-CoA dehydrogenases, glutaryl-CoA and sarcosine dehydrogenase.

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)
ETFA	Other/Unknown	no		ETF_a/FixB, Rossmann-like_a/b/a_fold, ETF_a/b_N

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
jejunal mucosa	1
oocyte	1
secondary oocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ETFA	297	ubiquitous	marker	oocyte, secondary oocyte, jejunal mucosa

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ETFA	3,353

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ETFA	P13804	4

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. 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
Respiratory electron transport	1	95.2×	0.011	ETFA

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
amino acid catabolic process	1	2808.7×	0.001	ETFA
fatty acid beta-oxidation using acyl-CoA dehydrogenase	1	1404.3×	0.001	ETFA
respiratory electron transport chain	1	842.6×	0.001	ETFA

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ETFA	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
ETFA	1	Binding:1

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	ETFA

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)
ETFA	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.