AGXT

alanine--glyoxylate aminotransferase

Basic information

Region (hg38): 2:240868823-240880502

Previous symbols: [ "SPAT" ]

Links

ENSG00000172482 ∙ NCBI:189 ∙ OMIM:604285 ∙ HGNC:341 ∙ Uniprot:P21549 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• primary hyperoxaluria type 1 (Definitive), mode of inheritance: AR
• primary hyperoxaluria type 1 (Definitive), mode of inheritance: AR
• primary hyperoxaluria type 1 (Supportive), mode of inheritance: AR
• primary hyperoxaluria type 1 (Strong), mode of inheritance: AR
• primary hyperoxaluria type 1 (Definitive), mode of inheritance: AR
• alanine glyoxylate aminotransferase deficiency (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hyperoxaluria, primary, type 1	AR	Biochemical; Cardiovascular; Renal	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	Biochemical; Cardiovascular; Renal	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; 24012869

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the AGXT gene.

• not provided (513 variants)
• Primary hyperoxaluria, type I (353 variants)
• Primary hyperoxaluria (34 variants)
• not specified (29 variants)
• Inborn genetic diseases (13 variants)
• AGXT-related condition (4 variants)
• - (3 variants)
• Nephrocalcinosis;Nephrolithiasis (2 variants)
• Abnormality of metabolism/homeostasis (1 variants)
• Nephrotic syndrome (1 variants)
• See cases (1 variants)
• Nephrolithiasis;Nephrocalcinosis (1 variants)
• Hyperoxaluria (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the AGXT gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				179	3	182
missense	19	73	60	10	2	164
nonsense	18	18				36
start loss	1	1				2
frameshift	36	28	1			65
inframe indel	2	5	5			12
splice donor/acceptor (+/-2bp)	15	20				35
splice region		2	6	32		40
non coding			10	67	38	115
Total	91	145	76	256	43

Highest pathogenic variant AF is 0.000145

Variants in AGXT

This is a list of pathogenic ClinVar variants found in the AGXT region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
2-240868842-C-G		Primary hyperoxaluria, type I	Likely benign (Apr 27, 2017)
2-240868843-G-A		Primary hyperoxaluria, type I	Benign/Likely benign (Apr 09, 2020)
2-240868852-G-A		Primary hyperoxaluria, type I	Uncertain significance (Jan 12, 2018)
2-240868860-C-T		AGXT-related disorder	Likely benign (Nov 19, 2019)
2-240868867-T-C		Primary hyperoxaluria, type I	Pathogenic/Likely pathogenic (Jan 29, 2024)
2-240868867-TG-AT		Primary hyperoxaluria, type I	Pathogenic (Sep 06, 2023)
2-240868868-G-T		Primary hyperoxaluria, type I	Pathogenic (Nov 27, 2014)
2-240868874-T-A			Likely benign (Oct 17, 2022)
2-240868880-G-A			Likely benign (Nov 22, 2023)
2-240868886-G-C			Likely benign (Aug 19, 2023)
2-240868886-G-T			Likely benign (Jul 13, 2023)
2-240868887-G-C		Primary hyperoxaluria, type I • not specified	Uncertain significance (Mar 27, 2024)
2-240868888-TG-AT		Primary hyperoxaluria, type I	Likely pathogenic (Oct 27, 2023)
2-240868890-AC-A		Primary hyperoxaluria, type I • Primary hyperoxaluria • AGXT-related disorder	Pathogenic/Likely pathogenic (Dec 26, 2023)
2-240868890-ACC-A		Primary hyperoxaluria, type I	Pathogenic (Nov 27, 2014)
2-240868890-A-AC		Primary hyperoxaluria, type I • Primary hyperoxaluria • Nephrotic syndrome • AGXT-related disorder • Alanine glyoxylate aminotransferase deficiency	Pathogenic (Jan 24, 2024)
2-240868891-C-A		Primary hyperoxaluria, type I • not specified	Benign/Likely benign (Apr 01, 2024)
2-240868891-C-CA			Pathogenic (Jun 15, 2021)
2-240868892-C-A		Primary hyperoxaluria, type I	Likely benign (Jan 25, 2024)
2-240868892-C-G		Primary hyperoxaluria, type I	Likely benign (Jan 31, 2024)
2-240868892-C-T			Likely benign (Sep 06, 2023)
2-240868893-C-G		Primary hyperoxaluria, type I	Uncertain significance (Feb 13, 2016)
2-240868893-C-T		Primary hyperoxaluria, type I	Pathogenic (Nov 27, 2014)
2-240868893-CC-A		Primary hyperoxaluria, type I	Pathogenic (Oct 27, 2023)
2-240868896-C-G		Primary hyperoxaluria, type I	Uncertain significance (Apr 26, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
AGXT	protein_coding	protein_coding	ENST00000307503	11	12024

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.23e-7	0.814	125702	0	44	125746	0.000175

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.268	263	251	1.05	0.0000158	2496
Missense in Polyphen		114	91.968	1.2396		923
Synonymous	-0.640	123	114	1.08	0.00000788	815
Loss of Function	1.46	14	21.3	0.657	0.00000108	222

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000579	0.0000579
Ashkenazi Jewish	0.00	0.00
East Asian	0.000544	0.000544
Finnish	0.00	0.00
European (Non-Finnish)	0.000267	0.000255
Middle Eastern	0.000544	0.000544
South Asian	0.0000653	0.0000653
Other	0.000164	0.000163

dbNSFP

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.
• Pathway: 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;Primary Hyperoxaluria Type I;3-Phosphoglycerate dehydrogenase deficiency;Lactic Acidemia;Non Ketotic Hyperglycinemia;Glycine and Serine Metabolism;Alanine Metabolism;Dimethylglycine Dehydrogenase Deficiency;Hyperglycinemia, non-ketotic;Dimethylglycine Dehydrogenase Deficiency;Sarcosinemia;Dihydropyrimidine Dehydrogenase Deficiency (DHPD);Alanine and aspartate metabolism;Alanine Aspartate Asparagine metabolism;Metabolism of proteins;Metabolism of amino acids and derivatives;glycine biosynthesis;Glycolysis Gluconeogenesis;Glycine Serine metabolism;Metabolism;Peroxisomal protein import;Glyoxylate metabolism and glycine degradation;Glycine, serine, alanine and threonine metabolism (Consensus)

Recessive Scores

• pRec: 0.600

Intolerance Scores

• loftool: 0.0556
• rvis_EVS: 0.64
• rvis_percentile_EVS: 84.1

Haploinsufficiency Scores

• pHI: 0.593
• hipred: Y
• hipred_score: 0.502
• ghis: 0.646

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.266

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Agxt
• Phenotype: homeostasis/metabolism phenotype; renal/urinary system phenotype

Gene ontology

• Biological process: protein targeting to peroxisome;Notch signaling pathway;glyoxylate catabolic process;glycine biosynthetic process, by transamination of glyoxylate;L-cysteine catabolic process;cellular nitrogen compound metabolic process;L-alanine catabolic process;pyruvate biosynthetic process;glyoxylate metabolic process;oxalic acid secretion;response to glucocorticoid;response to cAMP
• Cellular component: mitochondrial matrix;peroxisome;peroxisomal matrix;cytosol;intracellular membrane-bounded organelle
• Molecular function: serine-pyruvate transaminase activity;signaling receptor binding;protein binding;alanine-glyoxylate transaminase activity;transaminase activity;amino acid binding;pyridoxal phosphate binding;identical protein binding;protein homodimerization activity;protein self-association