Glutaric acidemia type 3

Summary

Glutaric acidemia type 3 (MONDO:0009283) is a disease caused by SUGCT (GenCC Strong), with 2 cohort genes.

At a glance

• Prevalence: Unknown (Worldwide)
• Causal gene: SUGCT (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 11
• Phenotypes (HPO): 13

Clinical features

Signs & symptoms

Clinical features (HPO)

13 HPO clinical features (Orphanet curated; top 13 by frequency):

HPO ID	Term	Frequency
HP:0003150	Glutaric aciduria	Obligate (100%)
HP:0011021	Abnormality of circulating enzyme level	Very frequent (80-99%)
HP:0000960	Sacral dimple	Occasional (5-29%)
HP:0001254	Lethargy	Occasional (5-29%)
HP:0001263	Global developmental delay	Occasional (5-29%)
HP:0001328	Specific learning disability	Occasional (5-29%)
HP:0001508	Failure to thrive	Occasional (5-29%)
HP:0001993	Ketoacidosis	Occasional (5-29%)
HP:0002500	Abnormal cerebral white matter morphology	Occasional (5-29%)
HP:0002518	Abnormal periventricular white matter morphology	Occasional (5-29%)
HP:0002919	Ketonuria	Occasional (5-29%)
HP:0003530	Glutaric acidemia	Occasional (5-29%)
HP:0100710	Impulsivity	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	glutaric acidemia type 3
Mondo ID	MONDO:0009283
MeSH	C562818
OMIM	231690
Orphanet	35706
DOID	DOID:0112246
SNOMED CT	238070003
UMLS	C0342873
MedGen	87464
GARD	0012469
Is cancer (heuristic)	no

Also known as: GA III · GA3 · glutaric acidemia type 3 · glutaric acidemia type III · glutaric aciduria (disease) caused by mutation in SUGCT · glutaric aciduria type 3 · glutaric aciduria type III · glutaryl-CoA oxidase deficiency · SUGCT glutaric aciduria (disease)

Data availability: 11 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by developmental or physiological process › metabolic disease › glutaric aciduria › glutaric acidemia type 3

Related subtypes (2): glutaryl-CoA dehydrogenase deficiency, multiple acyl-CoA dehydrogenase deficiency

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

11 retrieved; paginated sample, class counts are floors:

4 uncertain significance, 3 conflicting classifications of pathogenicity, 2 pathogenic, 2 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
3390921	NC_000015.10:g.76211811_76230784del	ETFA	Pathogenic	criteria provided, single submitter
1850	NM_001193313.2(SUGCT):c.514C>T (p.Arg172Ter)	SUGCT	Pathogenic	criteria provided, single submitter
2581584	NM_001193313.2(SUGCT):c.313-1G>C	SUGCT	Likely pathogenic	criteria provided, single submitter
4845907	NM_001193313.2(SUGCT):c.1014G>A (p.Trp338Ter)	SUGCT	Likely pathogenic	criteria provided, single submitter
1849	NM_001193313.2(SUGCT):c.985C>T (p.Arg329Trp)	SUGCT	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1851	NM_001193313.2(SUGCT):c.301C>T (p.Arg101Ter)	SUGCT	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3780683	NM_001193313.2(SUGCT):c.265del (p.Val89fs)	SUGCT	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3323560	NM_001193313.2(SUGCT):c.1204C>G (p.Pro402Ala)	SUGCT	Uncertain significance	criteria provided, multiple submitters, no conflicts
3323561	NM_001193313.2(SUGCT):c.1202C>G (p.Pro401Arg)	SUGCT	Uncertain significance	criteria provided, multiple submitters, no conflicts
3892582	NM_001193313.2(SUGCT):c.1205C>T (p.Pro402Leu)	SUGCT	Uncertain significance	criteria provided, single submitter
634624	NM_001193313.2(SUGCT):c.1090-65315C>T	SUGCT	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 3 · 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
SUGCT	Strong	Autosomal recessive	glutaric acidemia type 3	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SUGCT	Orphanet:35706	Glutaric acidemia type 3
ETFA	Orphanet:394529	Multiple acyl-CoA dehydrogenase deficiency, severe neonatal type
ETFA	Orphanet:394532	Multiple acyl-CoA dehydrogenase deficiency, mild type

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SUGCT	HGNC:16001	ENSG00000175600	Q9HAC7	Succinyl-CoA:glutarate CoA-transferase	gencc,clinvar
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)
SUGCT	Succinyl-CoA:glutarate CoA-transferase	Coenzyme A (CoA) transferase that reversibly catalyzes the transfer of a CoA moiety from a dicarboxyl-CoA to a dicarboxylate in a metabolite recycling process.
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: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5

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
Enzyme (other)	1	6.0×	0.320
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SUGCT	Enzyme (other)	yes	2.8.3.13	CoA-Trfase_fam_III, CoA-Trfase_III_dom_1_sf, CoA-Trfase_III_dom3_sf
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.

2 cohort genes 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
oocyte	2
right adrenal gland cortex	1
right coronary artery	1
jejunal mucosa	1
secondary oocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SUGCT	191	ubiquitous	marker	right adrenal gland cortex, oocyte, right coronary artery
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
SUGCT	1,164

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ETFA	P13804	4
SUGCT	Q9HAC7	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. Enrichment computed across 2 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: 2

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SUGCT	0	0
ETFA	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
ETFA	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
SUGCT	2.8.3.13	succinate-hydroxymethylglutarate CoA-transferase

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; 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	1	SUGCT
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	ETFA

Undrugged target profiles

2 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
SUGCT	0	—
ETFA	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.