Alanine glyoxylate aminotransferase deficiency

Summary

Alanine glyoxylate aminotransferase deficiency (MONDO:0100278) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 6

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	alanine glyoxylate aminotransferase deficiency
Mondo ID	MONDO:0100278
GARD	0026120
Is cancer (heuristic)	no

Also known as: AGXT defect · AGXT deficiency · alanine glyoxylate aminotransferase deficiency

Data availability: 6 ClinVar variants.

Disease family

An umbrella term covering 1 Mondo subtype.

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › inborn errors of metabolism › peroxisomal disease › peroxisomal single enzyme/protein defect › disorder of glyoxylate metabolism › alanine glyoxylate aminotransferase deficiency

Subtypes (1): primary hyperoxaluria type 1

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

6 retrieved; paginated sample, class counts are floors:

4 conflicting classifications of pathogenicity, 1 pathogenic, 1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
140583	NM_000030.3(AGXT):c.33dup (p.Lys12fs)	AGXT	Pathogenic	criteria provided, multiple submitters, no conflicts
198982	NM_000030.3(AGXT):c.866G>A (p.Arg289His)	AGXT	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
204018	NM_000030.3(AGXT):c.32C>A (p.Pro11His)	AGXT	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
204060	NM_000030.3(AGXT):c.1142G>A (p.Arg381Lys)	AGXT	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
204194	NM_000030.3(AGXT):c.662_664del (p.Ser221del)	AGXT	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2069242	NM_000030.3(AGXT):c.31C>T (p.Pro11Ser)	AGXT	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
AGXT	Orphanet:93598	Primary hyperoxaluria type 1

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
AGXT	HGNC:341	ENSG00000172482	P21549	Alanine–glyoxylate aminotransferase	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
AGXT	Alanine–glyoxylate aminotransferase	Peroxisomal aminotransferase that catalyzes the transamination of glyoxylate to glycine and contributes to the glyoxylate detoxification.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Enzyme (other)	1	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
AGXT	Enzyme (other)	yes	2.6.1.44	Aminotrans_V_dom, PyrdxlP-dep_Trfase_major, PyrdxlP-dep_Trfase_small

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
endometrium epithelium	1
liver	1
right lobe of liver	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
AGXT	125	tissue_specific	marker	right lobe of liver, liver, endometrium epithelium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
AGXT	2,648

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
AGXT	P21549	17

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 5. 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
Glyoxylate metabolism and glycine degradation	1	761.3×	0.007	AGXT
Protein localization	1	190.3×	0.010	AGXT
Peroxisomal protein import	1	173.0×	0.010	AGXT
Metabolism of amino acids and derivatives	1	67.6×	0.018	AGXT
Metabolism	1	11.6×	0.086	AGXT

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
obsolete glycine biosynthetic process, by transamination of glyoxylate	1	5617.3×	4e-04	AGXT
oxalic acid secretion	1	5617.3×	4e-04	AGXT
glyoxylate catabolic process	1	4213.0×	4e-04	AGXT
L-cysteine catabolic process	1	4213.0×	4e-04	AGXT
L-alanine catabolic process	1	4213.0×	4e-04	AGXT
glyoxylate metabolic process	1	2808.7×	5e-04	AGXT
L-serine metabolic process	1	1685.2×	7e-04	AGXT
Notch signaling pathway	1	141.6×	0.007	AGXT

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
AGXT	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
AGXT	8	Binding:8

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
AGXT	2.6.1.44, 2.6.1.51	alanine-glyoxylate transaminase, serine-pyruvate transaminase

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	1	AGXT
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

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)
AGXT	8	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.