GPT2

glutamic--pyruvic transaminase 2

Basic information

Region (hg38): 16:46884362-46931289

Links

ENSG00000166123 ∙ NCBI:84706 ∙ OMIM:138210 ∙ HGNC:18062 ∙ Uniprot:Q8TD30 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• glutamate pyruvate transaminase 2 deficiency (Limited), mode of inheritance: AR
• glutamate pyruvate transaminase 2 deficiency (Supportive), mode of inheritance: AR
• glutamate pyruvate transaminase 2 deficiency (Strong), mode of inheritance: AR
• glutamate pyruvate transaminase 2 deficiency (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neurodevelopmental disorder with spastic paraplegia and/or microcephaly	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Neurologic	25758935

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GPT2 gene.

• Glutamate pyruvate transaminase 2 deficiency (3 variants)
• not provided (2 variants)
• Inborn genetic diseases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GPT2 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				19	7	26
missense		1	45	3	1	50
nonsense	3	1				4
start loss						0
frameshift	1	4				5
inframe indel			1			1
splice donor/acceptor (+/-2bp)		1				1
splice region			5	2	1	8
non coding						0
Total	4	7	46	22	8

Highest pathogenic variant AF is 0.0000131

Variants in GPT2

This is a list of pathogenic ClinVar variants found in the GPT2 region.

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

Position	Type	Phenotype	Significance	ClinVar
16-46884747-G-T		Inborn genetic diseases	Uncertain significance (Nov 01, 2021)
16-46884753-G-A		Inborn genetic diseases	Uncertain significance (Jan 24, 2025)
16-46884772-CT-C		Glutamate pyruvate transaminase 2 deficiency	Likely pathogenic (-)
16-46884780-G-A		Inborn genetic diseases	Uncertain significance (Sep 29, 2023)
16-46884785-C-T		Inborn genetic diseases • Glutamate pyruvate transaminase 2 deficiency	Pathogenic (Nov 03, 2017)
16-46884804-A-C		Inborn genetic diseases	Uncertain significance (Nov 12, 2020)
16-46884805-G-C		Inborn genetic diseases	Uncertain significance (Mar 25, 2024)
16-46884809-T-G		Inborn genetic diseases	Uncertain significance (Oct 12, 2021)
16-46884878-C-T		Inborn genetic diseases	Uncertain significance (Oct 28, 2024)
16-46884896-G-T			Pathogenic (Oct 13, 2016)
16-46884932-G-A		Glutamate pyruvate transaminase 2 deficiency	Uncertain significance (Nov 11, 2023)
16-46884938-A-ATCGAGC			Uncertain significance (Jun 18, 2021)
16-46884947-G-C		Inborn genetic diseases	Uncertain significance (Oct 26, 2021)
16-46897670-A-G		Aggressive behavior;Frequent falls;Intellectual disability, mild;Delayed speech and language development	Uncertain significance (-)
16-46897672-GT-G		Rare genetic intellectual disability	Likely pathogenic (-)
16-46897678-C-T		Glutamate pyruvate transaminase 2 deficiency	Likely pathogenic (Oct 08, 2021)
16-46897690-G-A		Intellectual disability	Conflicting classifications of pathogenicity (Sep 07, 2022)
16-46897692-G-A			Likely benign (Feb 01, 2024)
16-46897706-TG-T		Glutamate pyruvate transaminase 2 deficiency	Pathogenic (Jan 24, 2024)
16-46897732-C-T		Glutamate pyruvate transaminase 2 deficiency • Inborn genetic diseases • GPT2-related neurodevelopmental disorder	Uncertain significance (Jan 03, 2025)
16-46897739-T-G		Glutamate pyruvate transaminase 2 deficiency	Likely pathogenic (May 17, 2023)
16-46900679-C-T		Intellectual disability	Likely benign (Jul 01, 2024)
16-46900691-C-T		GPT2-related disorder	Benign (Dec 31, 2019)
16-46900719-G-C		Glutamate pyruvate transaminase 2 deficiency • Inborn genetic diseases	Uncertain significance (Feb 15, 2025)
16-46900723-C-T		GPT2-related disorder	Likely benign (Jan 27, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GPT2	protein_coding	protein_coding	ENST00000340124	11	46920

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000340	0.998	125715	0	32	125747	0.000127

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.88	216	309	0.700	0.0000180	3401
Missense in Polyphen		69	126.67	0.54472		1339
Synonymous	0.573	122	130	0.936	0.00000834	1043
Loss of Function	2.69	10	24.3	0.412	0.00000120	279

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000271	0.000271
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.000287	0.000277
European (Non-Finnish)	0.0000177	0.0000176
Middle Eastern	0.000109	0.000109
South Asian	0.000432	0.000425
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. {ECO:0000269|PubMed:11863375}.
• Pathway: Alanine, aspartate and glutamate metabolism - Homo sapiens (human);Arginine biosynthesis - Homo sapiens (human);Glucose-Alanine Cycle;Amino Acid metabolism;Alanine Aspartate Asparagine metabolism;Glutamate Glutamine metabolism;Metabolism of amino acids and derivatives;Glycolysis Gluconeogenesis;Metabolism;alanine biosynthesis/degradation;Amino acid synthesis and interconversion (transamination) (Consensus)

Recessive Scores

• pRec: 0.757

Intolerance Scores

• loftool: 0.243
• rvis_EVS: -0.43
• rvis_percentile_EVS: 25.37

Haploinsufficiency Scores

• pHI: 0.188
• hipred: Y
• hipred_score: 0.639
• ghis: 0.493

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.777

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Gpt2
• Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); cellular phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: 2-oxoglutarate metabolic process;cellular amino acid biosynthetic process;L-alanine metabolic process;L-alanine catabolic process
• Cellular component: mitochondrial matrix
• Molecular function: L-alanine:2-oxoglutarate aminotransferase activity;pyridoxal phosphate binding