GOT1

protein-coding

glutamic-oxaloacetic transaminase 1

Gene summary

Glutamic-oxaloacetic transaminase is a pyridoxal phosphate-dependent enzyme which exists in cytoplasmic and mitochondrial forms, GOT1 and GOT2, respectively. GOT plays a role in amino acid metabolism and the urea and tricarboxylic acid cycles. The two enzymes are homodimeric and show close homology. [provided by RefSeq, Jul 2008]

MANE transcript

NM_002079.3

Inheritance

—

ClinVar variants

U:55B:4

Top phenotype

GOT1-related disorder

gnomAD constraint

pLI —, LoF o/e 0.39

Max pathogenic AF

—

Genomic locus

chr10:99,396,870-99,430,624

External References & Databases

Ensembl (ENSG00000120053)

Transcript & Mutation Effects

hg38 • Region Span ~33.8 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to GOT1 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 46

not providedTotal: 3

GOT1-related disorderTotal: 3

ASPARTATE AMINOTRANSFERASE, SERUM LEVEL OF, QUANTITATIVE TRAIT LOCUS 1Total: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002079.3. 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.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			3 clinvar	1 clinvar		4
missense			46 clinvar	2 clinvar	1 clinvar	49
nonsense						0
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			5 clinvar			5
Total	0	0	55	3	1	59

Highest pathogenic variant AF is 0.00033460648

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 33 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_002079.3	RefSeq	NP_002070.1	9	MANE Select
ENST00000370508.7	Ensembl	ENSP00000359539.5	9	MANE Select
ENST00000894926.1	Ensembl	ENSP00000564985.1	9	Standard
ENST00000894926.2	Ensembl	ENSP00000564985.1	9	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Alanine, aspartate and glutamate metabolism - Homo sapiens (human)
Arginine and proline metabolism - Homo sapiens (human)
Phenylalanine metabolism - Homo sapiens (human)
Phenylalanine, tyrosine and tryptophan biosynthesis - Homo sapiens (human)
Cysteine and methionine metabolism - Homo sapiens (human)

Biological Process

gluconeogenesis
2-oxoglutarate metabolic process
oxaloacetate metabolic process
glycerol biosynthetic process
aspartate metabolic process

Molecular Function

L-aspartate:2-oxoglutarate aminotransferase activity
phosphatidylserine decarboxylase activity
pyridoxal phosphate binding
carboxylic acid binding
L-cysteine:2-oxoglutarate aminotransferase activity

Cellular Component

nucleus
nucleoplasm
cytoplasm
lysosome
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000370508
Coding exons: 9
Length: 33755
Individuals with no LoFs: 125727
Homozygous LoFs: 0
Heterozygous LoFs: 21
Defined: 125748
p: 0.0000835

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.95	158	244	0.649	0.0000137	2691
Missense (PolyPhen)		65	108.82	0.59732		1171
Synonymous	0.806	82	91.8	0.893	0.00000507	838
Loss of Function	2.73	9	23.2	0.389	0.00000141	230

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00018	0.00018	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00011	0.00011	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00011	0.00011	rare
South Asian	0.000065	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Biosynthesis of L-glutamate from L-aspartate or L- cysteine. Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system. Acts as a scavenger of glutamate in brain neuroprotection. The aspartate aminotransferase activity is involved in hepatic glucose synthesis during development and in adipocyte glyceroneogenesis. Using L-cysteine as substrate, regulates levels of mercaptopyruvate, an important source of hydrogen sulfide. Mercaptopyruvate is converted into H(2)S via the action of 3- mercaptopyruvate sulfurtransferase (3MST). Hydrogen sulfide is an important synaptic modulator and neuroprotectant in the brain. {ECO:0000269|PubMed:16039064}.;

Recessive Scores

pRec: 0.599

Intolerance Scores

LoFtool: 0.383
RVIS EVS: -0.58
RVIS percentile EVS: 18.44

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.976

Gene Damage Prediction

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