Inborn disorder of amino acid metabolism

Summary

Inborn disorder of amino acid metabolism (MONDO:0004736) is a disease (an umbrella term covering 33 Mondo subtypes) with 1 GWAS associations across 4 studies and 6 clinical trials. Top therapeutic interventions include phenylbutanoic acid, ataluren, and sodium benzoate. A subtype of inborn disorder of amino acid and other organic acid metabolism — broader associated-gene and molecular evidence is on the parent page (see Disease family below).

At a glance

• Umbrella term: 33 Mondo subtypes
• GWAS associations: 1
• Clinical trials: 6

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	inborn disorder of amino acid metabolism
Mondo ID	MONDO:0004736
MeSH	D000592
DOID	DOID:9252
NCIT	C97090
SNOMED CT	42930003
UMLS	C5886841
MedGen	1857273
GARD	0006770
Is cancer (heuristic)	no

Also known as: amino acid metabolism, inborn errors · inborn amino acid metabolism disorder · inborn cellular amino acid metabolic process disorder · inborn error of amino acid metabolism · inborn error of cellular amino acid metabolic process · inherited amino acid metabolic disorder · rare inborn error of cellular amino acid metabolic process

Data availability: 1 GWAS association (4 studies).

Disease family

An umbrella term covering 33 Mondo subtypes.

Classification path: disease › 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

Related subtypes (12): pyruvate metabolism disorder, inborn disorder of lysine and hydroxylysine metabolism, disorder of glutamine metabolism, disorder of beta and omega amino acid metabolism, disorder of melanin metabolism, inborn disorder of bile acid synthesis, inborn disorder of methionine cycle and sulfur amino acid metabolism, inborn disorder of ornithine or proline metabolism, inborn disorder of serine family metabolism, inborn disorder of the gamma-glutamyl cycle, inborn error of biotin metabolism, inherited fatty acid metabolism disorder

Subtypes (33): disorder of methionine catabolism, inborn serine deficiency, cerebral creatine deficiency syndrome, inborn organic aciduria, gamma-amino butyric acid metabolism disorder, homocystinuria, urea cycle disorder, adenylosuccinate lyase deficiency, systemic primary carnitine deficiency disease, cystathioninuria, hyperlysinemia, Brunner syndrome, glycine encephalopathy, aminoacylase 1 deficiency, adenine phosphoribosyltransferase deficiency, hyperphenylalaninemia due to tetrahydrobiopterin deficiency, inborn disorder of tryptophan metabolism, inborn disorder of proline metabolism, inborn disorder of ornithine metabolism, inborn disorder of amino acid transport, inborn disorder of histidine metabolism, inborn disorder of phenylalanine and tyrosine metabolism, inborn disorder of branched-chain amino acid metabolism, arakawa syndrome 2, 2-methylacetoacetyl CoA thiolase deficiency, albinism, hyperphenylalaninemia due to DNAJC12 deficiency, inborn disorder of the metabolism of sulfur-containing amino acids and hydrogen sulfide, inborn disorder of glycine and serine metabolism, inborn disorder of ornithine, proline and hydroxyproline metabolism, inborn disorder of glutamate/glutamine and aspartate/asparagine metabolism, hyperglycinemia, transient neonatal, tetrahydrobiopterin (BH4)-deficient hyperphenylalaninemia

Genetics & variants

GWAS landscape

1 GWAS associations across 4 studies. Top hits map to 2 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs560463877	7e-12	ZCCHC10, AFF4-DT	C	1.8

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90477374	Verma A	2024	2,368	444,815	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90477373	Verma A	2024	632	120,109	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90479917	Verma A	2024	632	120,109	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90481616	Verma A	2024	362	58,763	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	0
Tier 2: splice/UTR	0
Tier 3: regulatory	0
Tier 4: intronic/intergenic	1

MAF distribution

Bucket	Variants
common (>=0.05)	0
low_freq (0.01-0.05)	0
rare (<0.01)	1
unknown	0

Functional consequences

Consequence	Count
intron_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs560463877	5	133004465	C>T	0.001	intron_variant	ZCCHC10, AFF4-DT	7e-12	Tier 4: intronic/intergenic

Genes & proteins

No associated-gene cohort resolved for this disease. Atlas builds the molecular and therapeutic sections — associated genes, protein families, druggability, pathways, interactions, and drug associations — by aggregating over a disease’s associated genes (resolved via GWAS / GenCC / ClinVar / CIViC), and none resolved here. This is expected for antibody-mediated, autoimmune, or otherwise non-gene-defined conditions; the curated evidence for this disease is its clinical features, GWAS susceptibility, and clinical trials (above).

Function

No pathway enrichment — requires an associated-gene cohort.

Therapeutics

Drugs indicated for this disease

2 approved. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Carglumic Acid	Approved (phase 4)
Eladocagene Exuparvovec	Approved (phase 4)

Clinical trials & evidence

Clinical trials

Clinical trials: 6.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	3
Not specified	2
PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00004767	PHASE2	COMPLETED	Phase II Study of Sodium Phenylbutyrate, Sodium Benzoate, Sodium Phenylacetate, and Dietary Intervention for Urea Cycle Disorders
NCT00345605	PHASE2	COMPLETED	Arginine and Buphenyl in Patients With Argininosuccinic Aciduria (ASA), a Urea Cycle Disorder
NCT01141075	PHASE2	TERMINATED	Ataluren for Nonsense Mutation Methylmalonic Acidemia
NCT00004307	PHASE1	UNKNOWN	Study of Treatment and Metabolism in Patients With Urea Cycle Disorders
NCT00237315	Not specified	RECRUITING	Longitudinal Study of Urea Cycle Disorders
NCT06337864	Not specified	RECRUITING	Effect of Large Neutral Amino Acids in Adults With Classical Phenylketonuria

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
PHENYLBUTANOIC ACID	4	4
ATALUREN	4	1
SODIUM BENZOATE	4	1
SODIUM PHENYLACETATE	4	1
ARGININE	3	1