GeneBe

AGXT

protein-coding

alanine--glyoxylate aminotransferase

Gene summary

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]

Previous symbols:
  • SPAT

MANE transcript

NM_000030.3

Inheritance

AR

ClinVar variants

P:355U:166B:250

Top phenotype

Hyperoxaluria, primary, type 1

gnomAD constraint

pLI —, LoF o/e 0.66

Max pathogenic AF

—

Genomic locus

chr2:240,868,824-240,880,502

External References & Databases

Ensembl (ENSG00000172482)NCBI Gene (189)OMIM (604285)HGNC:341GenCCUniProt (P21549)AlphaFoldClinVar (AGXT)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~11.7 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

primary hyperoxaluria type 1DEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0009823

Submitter: Natera

primary hyperoxaluria type 1STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0009823

Submitter: Labcorp Genetics (formerly Invitae)

primary hyperoxaluria type 1DEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0009823

Submitter: G2P

primary hyperoxaluria type 1DEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0009823

Submitter: Ambry Genetics

alanine glyoxylate aminotransferase deficiencyDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0100278

Submitter: ClinGen

*AGXT* was first reported in relation to autosomal recessive alanine glyoxylate aminotransferase deficiency in 1991 (Nishiyama K et al., PMID: 2039493). At least 28 variants (e.g. missense, in-frame indel, nonsense, frameshift, etc) have been reported in humans. Evidence supporting this gene-disease relationship includes case-level data, segregation data, and experimental data. Summary of Case Level and Experimental Data: 16.5 points. Variants in this gene have been reported in at least 24 probands in 9 publications (PMIDs: 26383609, 8101040, 30341509, 27915025, 27659337, 2039493, 1349575, 18810341, 16931222). Variants in this gene segregated with disease in 3 additional family members. The gene-disease association is supported by animal models and expression studies. In summary, *AGXT* is definitively associated with autosomal recessive alanine glyoxylate aminotransferase deficiency. This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time.

primary hyperoxaluria type 1STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0009823

Submitter: PanelApp Australia

primary hyperoxaluria type 1DEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0009823

Submitter: Myriad Women's Health

primary hyperoxaluria type 1SUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0009823

Submitter: Orphanet

Clinical Genomic Database (CGD)

Hyperoxaluria, primary, type 1AR

Manifestation: Biochemical; Cardiovascular; Renal

Intervention: Biochemical; Cardiovascular; Renal

Rationale: Fluid intake and medical management (eg, pyridoxine in those who are pyridoxine responsive, potassium/sodium citrate or neutral orthophosphate) can be beneficial to reduce calcium oxalate supersaturation/biosynthesis and reduce stone formation; Organ transplantation (preemptive liver transplantation or liver/kidney transplantation) may be beneficial; Surveillance for renal and related complications (which can include cardiac dysrhythmias) can be beneficial; Dehydration and excessive intake of oxalate-rich foods should be avoided, as well as certain vitamins and medications

Refs: 449695; 6472428; 3974685; 2887776; 2797068; 2189732; 7969325; 1703535; 2039493; 1961759; 9604813; 10586179; 10453743; 10485304; 11562405; 8507692; 11688375; 12543880; 15327387; 16247357; 15855742; 15464418; 15840016; 15849466; 15767715; 16810517; 16916735; 17460142; 17495019; 18359396; 18282470; 18337715; 19935811; 19571789; 19225556; 19132372; 19479957; 20733487; 20016466; 20301460; 20490484; 22547750; 22821680; 22956877; 23439734; 23810941; 24012869Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to AGXT variants in ClinVar

16 Conditions Cataloged
not providedTotal: 620
Primary hyperoxaluria, type ITotal: 522
not specifiedTotal: 60
AGXT-related disorderTotal: 50
Primary hyperoxaluriaTotal: 48
Inborn genetic diseasesTotal: 41
Alanine glyoxylate aminotransferase deficiencyTotal: 6
Kidney stoneTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000030.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
9
clinvar
231
clinvar
1
clinvar
 241
missense
47
clinvar
104
clinvar
154
clinvar
17
clinvar
1
clinvar
 323
nonsense
39
clinvar
15
clinvar
 54
start loss
2
clinvar
1
clinvar
 3
frameshift
59
clinvar
30
clinvar
3
clinvar
 92
splice donor/acceptor (+/-2bp)
30
clinvar
28
clinvar
 58
Total1771781662482771

Highest pathogenic variant AF is 0.00095089513

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 74 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_000030.3RefSeqNP_000021.111MANE Select
ENST00000307503.4EnsemblENSP00000302620.311MANE Select
ENST00000908227.1EnsemblENSP00000578286.19Standard
ENST00000908227.2EnsemblENSP00000578286.19Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Alanine, aspartate and glutamate metabolism - Homo sapiens (human)
  • Peroxisome - Homo sapiens (human)
  • Glycine, serine and threonine metabolism - Homo sapiens (human)
  • Glyoxylate and dicarboxylate metabolism - Homo sapiens (human)
  • Pyruvate Carboxylase Deficiency

Biological Process

  • protein targeting to peroxisome
  • Notch signaling pathway
  • glyoxylate catabolic process
  • glycine biosynthetic process, by transamination of glyoxylate
  • L-cysteine catabolic process

Molecular Function

  • serine-pyruvate transaminase activity
  • signaling receptor binding
  • protein binding
  • alanine-glyoxylate transaminase activity
  • transaminase activity

Cellular Component

  • mitochondrial matrix
  • peroxisome
  • peroxisomal matrix
  • cytosol
  • intracellular membrane-bounded organelle

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000307503
Coding exons
11
Length
12024
Individuals with no LoFs
125702
Homozygous LoFs
0
Heterozygous LoFs
44
Defined
125746
p
0.000175
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense-0.2682632511.050.00001582496
Missense (PolyPhen)11491.9681.2396923
Synonymous-0.6401231141.080.00000788815
Loss of Function1.461421.30.6570.00000108222

Population LoF Frequency

PopulationCAFp-valueStatus
African00.0absent
Latino/Admixed American0.0000580.000058rare
Ashkenazi Jewish00.0absent
East Asian0.000540.00054rare
Finnish00.0absent
European (Non-Finnish)0.000270.00025rare
South Asian0.0000650.000065rare
Other0.000160.00016rare

dbNSFP Gene Annotations

Source: dbNSFP

Disease
DISEASE: Hyperoxaluria primary 1 (HP1) [MIM:259900]: An inborn error of glyoxylate metabolism characterized by increased excretion of oxalate and glycolate, and progressive tissue accumulation of insoluble calcium oxalate. Affected individuals are at risk for nephrolithiasis, nephrocalcinosis and early onset end-stage renal disease. {ECO:0000269|PubMed:10394939, ECO:0000269|PubMed:10453743, ECO:0000269|PubMed:10541294, ECO:0000269|PubMed:10862087, ECO:0000269|PubMed:10960483, ECO:0000269|PubMed:12559847, ECO:0000269|PubMed:12777626, ECO:0000269|PubMed:1301173, ECO:0000269|PubMed:1349575, ECO:0000269|PubMed:15253729, ECO:0000269|PubMed:15849466, ECO:0000269|PubMed:15961946, ECO:0000269|PubMed:15963748, ECO:0000269|PubMed:16971151, ECO:0000269|PubMed:1703535, ECO:0000269|PubMed:17495019, ECO:0000269|PubMed:2039493, ECO:0000269|PubMed:23229545, ECO:0000269|PubMed:24055001, ECO:0000269|PubMed:24934730, ECO:0000269|PubMed:26149463, ECO:0000269|PubMed:8101040, ECO:0000269|PubMed:9192270, ECO:0000269|PubMed:9604803}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec
0.600

Intolerance Scores

LoFtool
0.0556
RVIS EVS
0.64
RVIS percentile EVS
84.1

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
N
Indispensability score
0.266

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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