AGXT2

protein-coding

alanine--glyoxylate aminotransferase 2

Gene summary

The protein encoded by this gene is a class III pyridoxal-phosphate-dependent mitochondrial aminotransferase. It catalyzes the conversion of glyoxylate to glycine using L-alanine as the amino donor. It is an important regulator of methylarginines and is involved in the control of blood pressure in kidney. Polymorphisms in this gene affect methylarginine and beta-aminoisobutyrate metabolism, and are associated with carotid atherosclerosis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2015]

MANE transcript

NM_031900.4

Inheritance

ClinVar variants

U:76B:11

Top phenotype

Beta-aminoisobutyric aciduria

gnomAD constraint

pLI —, LoF o/e 1.29

Max pathogenic AF

—

Genomic locus

chr5:34,998,101-35,048,135

External References & Databases

Ensembl (ENSG00000113492)

Transcript & Mutation Effects

hg38 • Region Span ~50.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

Clinical Genomic Database (CGD)

Beta-aminoisobutyric aciduriaAR

Manifestation: Biochemical

Intervention: General

Rationale: The clinical significance is unclear

Refs: 21572414

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to AGXT2 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 76

not providedTotal: 9

AGXT2-related conditionTotal: 1

Beta-aminoisobutyric acid, urinary excretion ofTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_031900.4. 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.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				6 clinvar	1 clinvar	7
missense			72 clinvar		3 clinvar	75
nonsense			1 clinvar			1
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			2 clinvar	1 clinvar		3
Total	0	0	76	7	4	87

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 42 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_031900.4	RefSeq	NP_114106.1	14	MANE Select
ENST00000231420.11	Ensembl	ENSP00000231420.6	14	MANE Select
NM_001306173.2	RefSeq	NP_001293102.1	12	Standard
NM_001438050.1	RefSeq	NP_001424979.1	12	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Alanine, aspartate and glutamate metabolism - Homo sapiens (human)
Cysteine and methionine metabolism - Homo sapiens (human)
Glycine, serine and threonine metabolism - Homo sapiens (human)
Valine, leucine and isoleucine degradation - Homo sapiens (human)
One carbon metabolism and related pathways

Biological Process

glyoxylate catabolic process
glycine biosynthetic process, by transamination of glyoxylate
L-alanine catabolic process, by transamination
positive regulation of nitric oxide biosynthetic process
glyoxylate metabolic process

Molecular Function

alanine-glyoxylate transaminase activity
pyridoxal phosphate binding
(R)-3-amino-2-methylpropionate-pyruvate transaminase activity

Cellular Component

mitochondrion
mitochondrial matrix

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000231420
Coding exons: 14
Length: 49993
Individuals with no LoFs: 125600
Homozygous LoFs: 0
Heterozygous LoFs: 148
Defined: 125748
p: 0.000589

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.661	315	284	1.11	0.0000155	3362
Missense (PolyPhen)		110	92.657	1.1872		1161
Synonymous	-1.07	114	100	1.14	0.00000557	984
Loss of Function	-1.45	37	28.7	1.29	0.00000165	315

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0021	0.0021	notable
Latino/Admixed American	0.00046	0.00046	rare
Ashkenazi Jewish	0.00030	0.00030	rare
East Asian	0.00033	0.00033	rare
Finnish	0.00018	0.00018	rare
European (Non-Finnish)	0.00039	0.00039	rare
South Asian	0.0012	0.0012	notable
Other	0.00065	0.00065	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Can metabolize asymmetric dimethylarginine (ADMA) via transamination to alpha-keto-delta-(NN-dimethylguanidino) valeric acid (DMGV). ADMA is a potent inhibitor of nitric-oxide (NO) synthase, and this activity provides mechanism through which the kidney regulates blood pressure. {ECO:0000269|PubMed:20018850, ECO:0000269|PubMed:23023372, ECO:0000269|PubMed:24586340}.;

Recessive Scores

pRec: 0.184

Intolerance Scores

LoFtool: 0.339
RVIS EVS: 0.89
RVIS percentile EVS: 89.27

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.337

Gene Damage Prediction

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