AGXT

Chr 2AR

alanine--glyoxylate aminotransferase

Also known as: AGT, AGT1, AGXT1, PH1, SPAT, SPT, Ser-PyrAT, TLH6

NCBI Gene: 189 ENSG00000172482 UniProt: P21549 OMIM: 604285

The protein is a peroxisomal aminotransferase that catalyzes the transamination of glyoxylate to glycine, contributing to glyoxylate detoxification in the liver. Mutations cause primary hyperoxaluria type 1, an autosomal recessive disorder that leads to excessive oxalate production and can result in kidney stones, nephrocalcinosis, and progressive kidney disease. This gene is not constrained against loss-of-function variants, and some disease-causing mutations are known to alter the protein's subcellular targeting.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene is expressed only in the liver and the encoded protein is localized mostly in the peroxisomes, where it is involved in glyoxylate detoxification. Mutations in this gene, some of which alter subcellular targetting, have been associated with type I primary hyperoxaluria. [provided by RefSeq, Jul 2008]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 1.031 OMIM phenotype

Clinical Summary— AGXT

🧬

Gene-Disease Validity (ClinGen)

alanine glyoxylate aminotransferase deficiency · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡

Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

📋

ClinVar Variants

353 unique Pathogenic / Likely Pathogenic· 196 VUS of 1043 total submissions

💊

Clinical Trials

6 active or recruiting trials — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

📖

GeneReview available — AGXT

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.03LOEUF

pLI 0.000

Z-score 1.46

OE 0.66 (0.43–1.03)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.27Z-score

OE missense 1.05 (0.95–1.16)

263 obs / 251.1 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.66 (0.43–1.03)

0≤0.351.4

Missense OE?1.05 (0.95–1.16)

0≤0.61.4

Synonymous OE?1.08

0≤1.21.6

LoF obs/exp: 14 / 21.3Missense obs/exp: 263 / 251.1Syn Z: -0.64

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveAGXT-related hyperoxaluria, primaryLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.74top 25%

GOF

0.5759th %ile

LOF

0.3164th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

1043 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic188

Likely Pathogenic165

VUS196

Likely Benign402

Benign48

Conflicting42

188

Pathogenic

165

Likely Pathogenic

196

VUS

402

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	122	51	15	0	188
Likely Pathogenic	69	94	2	0	165
VUS	2	148	36	10	196
Likely Benign	0	12	169	221	402
Benign	0	2	43	3	48
Conflicting	—				42
Total	193	307	265	234	1,041

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

104 pathogenic / likely-pathogenic (of 119) ClinVar copy-number / structural variants overlap AGXT — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →