GPT2

Summary

GPT2 (glutamic–pyruvic transaminase 2, HGNC:18062) is a protein-coding gene on chromosome 16q11.2, encoding Alanine aminotransferase 2 (Q8TD30). Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate.

This gene encodes a mitochondrial alanine transaminase, a pyridoxal enzyme that catalyzes the reversible transamination between alanine and 2-oxoglutarate to generate pyruvate and glutamate. Alanine transaminases play roles in gluconeogenesis and amino acid metabolism in many tissues including skeletal muscle, kidney, and liver. Activating transcription factor 4 upregulates this gene under metabolic stress conditions in hepatocyte cell lines. A loss of function mutation in this gene has been associated with developmental encephalopathy. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 84706 — RefSeq curated summary.

At a glance

• Gene–disease (curated): glutamate pyruvate transaminase 2 deficiency (Definitive, ClinGen)
• Clinical variants (ClinVar): 149 total — 8 pathogenic, 8 likely-pathogenic
• Phenotypes (HPO): 37
• MANE Select transcript: NM_133443

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18062
Approved symbol	GPT2
Name	glutamic–pyruvic transaminase 2
Location	16q11.2
Locus type	gene with protein product
Status	Approved
Aliases	ALT2
Ensembl gene	ENSG00000166123
Ensembl biotype	protein_coding
OMIM	138210
Entrez	84706

Gene structure

Transcript identifiers

Ensembl transcripts: 25 — 23 protein_coding, 2 retained_intron

ENST00000340124, ENST00000440783, ENST00000562132, ENST00000562801, ENST00000569193, ENST00000860229, ENST00000860230, ENST00000860231, ENST00000860232, ENST00000860233, ENST00000860234, ENST00000860235, ENST00000860236, ENST00000860237, ENST00000860238, ENST00000860239, ENST00000860240, ENST00000860241, ENST00000860242, ENST00000927697, ENST00000927698, ENST00000927699, ENST00000927700, ENST00000953142, ENST00000953143

RefSeq mRNA: 2 — MANE Select: NM_133443 NM_001142466, NM_133443

CCDS: CCDS10725, CCDS45478

Canonical transcript exons

ENST00000340124 — 12 exons

Exon	Start	End
ENSE00001100034	46900682	46900790
ENSE00001131354	46916628	46916707
ENSE00001131363	46909684	46909927
ENSE00001131371	46906842	46906975
ENSE00001131395	46884362	46884467
ENSE00001165297	46884694	46884958
ENSE00002597269	46928907	46931289
ENSE00003462750	46897648	46897737
ENSE00003489448	46918621	46918757
ENSE00003644019	46922242	46922416
ENSE00003646343	46926925	46927037
ENSE00003647453	46924389	46924544

Expression profiles

Bgee: expression breadth ubiquitous, 237 present calls, max score 97.61.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 18.5648 / max 6512.8984, expressed in 1546 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
153920	8.0048	1472
153923	3.8121	604
153929	1.4049	262
153924	1.2598	306
153922	1.0834	264
153925	0.9460	254
153926	0.8563	236
153927	0.5914	111
207866	0.3800	159
153928	0.2260	79

Top tissues by expression

252 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	97.61	gold quality
body of pancreas	UBERON:0001150	97.50	gold quality
hindlimb stylopod muscle	UBERON:0004252	96.74	gold quality
right lobe of liver	UBERON:0001114	96.02	gold quality
ventricular zone	UBERON:0003053	95.54	gold quality
esophagus mucosa	UBERON:0002469	95.47	gold quality
amygdala	UBERON:0001876	93.84	gold quality
liver	UBERON:0002107	93.53	gold quality
skeletal muscle tissue	UBERON:0001134	93.27	gold quality
esophagus squamous epithelium	UBERON:0006920	93.25	gold quality
vastus lateralis	UBERON:0001379	93.23	gold quality
minor salivary gland	UBERON:0001830	93.09	gold quality
quadriceps femoris	UBERON:0001377	93.05	gold quality
gastrocnemius	UBERON:0001388	92.98	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	92.71	gold quality
body of stomach	UBERON:0001161	92.61	gold quality
caudate nucleus	UBERON:0001873	92.61	gold quality
upper arm skin	UBERON:0004263	92.55	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	92.54	gold quality
nucleus accumbens	UBERON:0001882	92.52	gold quality
putamen	UBERON:0001874	92.45	gold quality
muscle of leg	UBERON:0001383	92.44	gold quality
biceps brachii	UBERON:0001507	92.38	gold quality
saliva-secreting gland	UBERON:0001044	92.30	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	92.28	gold quality
anterior cingulate cortex	UBERON:0009835	92.25	gold quality
skin of abdomen	UBERON:0001416	92.18	gold quality
right frontal lobe	UBERON:0002810	92.08	gold quality
mouth mucosa	UBERON:0003729	91.90	gold quality
pancreas	UBERON:0001264	91.71	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	15.67
E-MTAB-6386	no	171.38

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ATF4, PPARA

miRNA regulators (miRDB)

86 targeting GPT2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-629-3P	99.85	67.99	1875
HSA-MIR-4420	99.82	70.08	1624
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-8080	99.82	67.52	1342
HSA-MIR-181B-2-3P	99.81	70.06	1646

Literature-anchored findings (GeneRIF, showing 20)

• expression of GPT2 especially in muscle and fat, suggests a unique and previously unrecognized role of this gene product in glucose, amino acid, and fatty acid metabolism and homeostasis. (PMID:11863375)
• The biliary IL-6 and TNF-alpha levels were positively correlated with serum DBIL, TBA and gamma-GT levels in infantile hepatitis syndrome subjects. (PMID:17109502)
• Elevation of liver enzymes and hepatic insulin resistance as reflected by fasting insulin occur in the early stages of insulin resistance and highlight the central role of the liver in insulin resistance in the general population. (PMID:17596883)
• A clinical method for selective measurement of ALT1 and 2 in human plasma is described. (PMID:19360321)
• ATF4 silencing prevented the activating effect of histidinol and tunicamycin on ATF4 and ALT2 expression. Our findings point to ALT2 as an enzyme involved in the metabolic adaptation of the cell to stress (PMID:24418603)
• Recessively inherited loss of function GPT2 mutations are a novel cause of intellectual disability. (PMID:25758935)
• The GPT2 gene demonstrates increasing expression in brain in the early postnatal period, and GPT2 protein localizes to mitochondria. Akin to the human phenotype, Gpt2-null mice exhibit reduced brain growth. Through metabolomics and direct isotope tracing experiments, we find a number of metabolic abnormalities associated with loss of Gpt2 (PMID:27601654)
• GPT2 reduced alpha-ketoglutarate level in cells leading to the inhibition of proline hydroxylase 2 (PHD2) activity involved in the regulation of HIF1alpha stability. Accumulation of HIF1alpha, resulting from GPT2-alpha-ketoglutarate-PHD2 axis, constitutively activates sonic hedgehog (Shh) signaling pathway. (PMID:28839461)
• We here describe novel compound heterozygous missense variants, NM_133443:c.[400C>T] and NM_133443:[1435G>A], in the glutamic-pyruvic transaminase 2 (GPT2) gene in a large consanguineous family with two affected siblings diagnosed with microcephaly intellectual disability and developmental delay (IDD). (PMID:29226631)
• Because of the consistent presence of pyramidal tract affection in GPT2 patients, we further suggest that GPT2 mutations should be considered in cases with complex hereditary spastic paraplegia (PMID:29882329)
• GPT2 is an important component of the adaptive metabolic response for glutamine deprivation and indicate that targeting this pathway in combination with Glutaminase inhibition may be an effective therapeutic approach for cancer treatment. (PMID:30765862)
• GPT2-related autosomal recessive intellectual disability represents an important new neurogenetic syndrome involving developmental as well as progressive features, notably motor disabilities (PMID:31471722)
• A novel missense variant in GPT2 causes non-syndromic autosomal recessive intellectual disability in a consanguineous Iranian family. (PMID:31978613)
• Abrogating GPT2 in triple-negative breast cancer inhibits tumor growth and promotes autophagy. (PMID:33368291)
• [The Influence of Glutamic Pyruvate Transaminase 2 to Biological Characteristics of Acute Myeloid Leukemia Cell HL-60]. (PMID:33812407)
• Thyroid hormone regulates glutamine metabolism and anaplerotic fluxes by inducing mitochondrial glutamate aminotransferase GPT2. (PMID:35196498)
• Loss of mitochondrial enzyme GPT2 causes early neurodegeneration in locus coeruleus. (PMID:35908744)
• SPTBN1 abrogates renal clear cell carcinoma progression via glycolysis reprogramming in a GPT2-dependent manner. (PMID:36527113)
• The delta subunit of the GABAA receptor is necessary for the GPT2-promoted breast cancer metastasis. (PMID:36923530)
• Exosomal GPT2 derived from triple-negative breast cancer cells promotes metastasis by activating BTRC. (PMID:37287397)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	gpt2	ENSDARG00000012199
mus_musculus	Gpt2	ENSMUSG00000031700
rattus_norvegicus	Gpt2	ENSRNOG00000059579
drosophila_melanogaster	CG1640	FBGN0030478
drosophila_melanogaster	CG6321	FBGN0036117
caenorhabditis_elegans		WBGENE00009232
caenorhabditis_elegans		WBGENE00010984
caenorhabditis_elegans	C32F10.8	WBGENE00016333

Paralogs (7): AADAT (ENSG00000109576), ACCS (ENSG00000110455), KYAT3 (ENSG00000137944), GPT (ENSG00000167701), KYAT1 (ENSG00000171097), TAT (ENSG00000198650), ACCSL (ENSG00000205126)

Protein

Protein identifiers

Alanine aminotransferase 2 — Q8TD30 (reviewed: Q8TD30)

Alternative names: Glutamate pyruvate transaminase 2, Glutamic–alanine transaminase 2, Glutamic–pyruvic transaminase 2

All UniProt accessions (2): Q8TD30, H3BU54

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate.

Subunit / interactions. Homodimer.

Tissue specificity. Expressed at high levels in muscle, adipose tissue, kidney and brain and at lower levels in the liver and breast.

Disease relevance. Neurodevelopmental disorder with spastic paraplegia and microcephaly (NEDSPM) [MIM:616281] An autosomal recessive syndrome characterized by severe psychomotor developmental delay, dysarthria, walking difficulties, moderately to severely impaired intellectual development, poor or absent speech, and progressive microcephaly. The disease is caused by variants affecting the gene represented in this entry.

Pathway. Amino-acid degradation; L-alanine degradation via transaminase pathway; pyruvate from L-alanine: step 1/1.

Similarity. Belongs to the class-I pyridoxal-phosphate-dependent aminotransferase family. Alanine aminotransferase subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8TD30-1	1	yes
Q8TD30-2	2

RefSeq proteins (2): NP_001135938, NP_597700* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004839	Aminotransferase_I/II_large	Domain
IPR015421	PyrdxlP-dep_Trfase_major	Homologous_superfamily
IPR015422	PyrdxlP-dep_Trfase_small	Homologous_superfamily
IPR015424	PyrdxlP-dep_Trfase	Homologous_superfamily
IPR045088	ALAT1/2-like	Family

Pfam: PF00155

Catalyzed reactions (Rhea), 1 shown:

• L-alanine + 2-oxoglutarate = pyruvate + L-glutamate (RHEA:19453)

UniProt features (55 total): helix 21, strand 14, binding site 6, turn 5, modified residue 4, chain 1, region of interest 1, splice variant 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
3IHJ	X-RAY DIFFRACTION	2.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TD30-F1	91.89	0.89

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (6): 187; 188; 216; 271; 338; 350

Post-translational modifications (4): 505, 512, 341, 415

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-8964540	Alanine metabolism

MSigDB gene sets: 209 (showing top): RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, PEREZ_TP63_TARGETS, GOBP_ALPHA_AMINO_ACID_METABOLIC_PROCESS, BHATI_G2M_ARREST_BY_2METHOXYESTRADIOL_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, SHEPARD_BMYB_MORPHOLINO_DN, GOBP_DICARBOXYLIC_ACID_METABOLIC_PROCESS, ZHAN_MULTIPLE_MYELOMA_CD1_UP, GHO_ATF5_TARGETS_UP, TERAMOTO_OPN_TARGETS_CLUSTER_7, GTGCCTT_MIR506, GOBP_ORGANIC_ACID_CATABOLIC_PROCESS, GOBP_ORGANIC_ACID_METABOLIC_PROCESS

GO Biological Process (4): 2-oxoglutarate metabolic process (GO:0006103), obsolete L-alanine metabolic process (GO:0042851), L-alanine catabolic process (GO:0042853), biosynthetic process (GO:0009058)

GO Molecular Function (4): L-alanine:2-oxoglutarate transaminase activity (GO:0004021), pyridoxal phosphate binding (GO:0030170), transaminase activity (GO:0008483), transferase activity (GO:0016740)

GO Cellular Component (3): mitochondrion (GO:0005739), mitochondrial matrix (GO:0005759), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Metabolism of amino acids and derivatives	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
dicarboxylic acid metabolic process	1
L-amino acid catabolic process	1
proteinogenic amino acid catabolic process	1
metabolic process	1
L-alanine:oxo-acid transaminase activity	1
anion binding	1
vitamin B6 binding	1
transferase activity, transferring nitrogenous groups	1
catalytic activity	1
cytoplasm	1
intracellular membrane-bounded organelle	1
mitochondrion	1
intracellular organelle lumen	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

2754 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GPT2	ALB	P02768	889
GPT2	CRP	P02741	872
GPT2	F2	P00734	843
GPT2	HP	P00737	777
GPT2	AFP	P02771	748
GPT2	GOT1	P17174	734
GPT2	INS	P01308	726
GPT2	F3	P13726	720
GPT2	GOT1L1	Q8NHS2	683
GPT2	GPX8	Q8TED1	676
GPT2	GPX7	Q96SL4	675
GPT2	GOT2	P00505	665
GPT2	IL6	P05231	664
GPT2	GPX5	O75715	653
GPT2	GPX6	P59796	653

IntAct

23 interactions, top by confidence:

A	B	Type	Score
LYRM4	NDUFAB1	psi-mi:“MI:0914”(association)	0.640
GPHA2	PLXNA2	psi-mi:“MI:0914”(association)	0.530
PLA2G10	CHEK1	psi-mi:“MI:0914”(association)	0.530
GPT2	CLPX	psi-mi:“MI:0914”(association)	0.530
SLC10A6	GPT2	psi-mi:“MI:0915”(physical association)	0.400
SIRT4	VWA8	psi-mi:“MI:0914”(association)	0.350
CUL3	PXDNL	psi-mi:“MI:0914”(association)	0.350
THEM4	KIAA0391	psi-mi:“MI:0914”(association)	0.350
NME4	NDUFAB1	psi-mi:“MI:0914”(association)	0.350
USP20		psi-mi:“MI:0914”(association)	0.350
BABAM1	PYCR3	psi-mi:“MI:0914”(association)	0.350
IMMP2L	ANKHD1-EIF4EBP3	psi-mi:“MI:0914”(association)	0.350
THEM5	PRORP	psi-mi:“MI:0914”(association)	0.350
UQCRFS1	VWA8	psi-mi:“MI:0914”(association)	0.350
THEM4	PRORP	psi-mi:“MI:0914”(association)	0.350
THEM5	HARS2	psi-mi:“MI:0914”(association)	0.350
THEM5	GTPBP10	psi-mi:“MI:0914”(association)	0.350
THEM5	OAT	psi-mi:“MI:0914”(association)	0.350

BioGRID (46): GPT2 (Affinity Capture-MS), ADSL (Co-fractionation), AHCY (Co-fractionation), CCBL2 (Co-fractionation), CFL1 (Co-fractionation), GOT1 (Co-fractionation), GPD1L (Co-fractionation), SOD2 (Co-fractionation), GPT2 (Affinity Capture-MS), GPT2 (Affinity Capture-MS), GPT2 (Affinity Capture-MS), GPT2 (Affinity Capture-RNA), GPT2 (Affinity Capture-MS), GPT2 (Affinity Capture-MS), GPT2 (Proximity Label-MS)

ESM2 similar proteins: A0A1J6KGJ9, A0A314KSQ4, A2RU49, A5PJU6, A7M6E7, A7M6E8, B4G0F3, B8BKI7, B9SQI7, C6JS30, E0CSI1, E0CTF3, G1SPE9, O08848, O15228, O22190, O23732, O81829, O82333, P11172, P23599, P31531, P37821, P42700, P46416, Q00379, Q10D00, Q2R483, Q3U1V6, Q4U3P8, Q5R962, Q6GM82, Q6I581, Q6YJI5, Q7TNK6, Q7Z4G4, Q8BGT5, Q8TD30, Q94A08, Q94AH8

Diamond homologs: A2AIG8, A4IFH5, F4I7I0, P13191, P24298, P25409, P34106, P52892, P52893, P52894, Q10334, Q28DB5, Q4WMJ9, Q54MJ7, Q5E9H2, Q6GM82, Q6NYL5, Q8BGT5, Q8QZR5, Q8TD30, Q9LDV4, Q9LR30, Q9S7E9, Q84WZ8, Q9W698, B4U9L1, P04694, Q58CZ9, Q5W6F9, Q8QZR1, Q9FN30, Q96QU6, P27486, Q0CS62, Q3UX83, Q9SAR0, Q4AC99, Q8EXQ7

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
GPT2	“up-regulates quantity”	2-oxoglutarate(2-)	“chemical modification”
GPT2	“down-regulates quantity”	“glutamic acid”	“chemical modification”

Disease & clinical

Clinical variants and AI predictions

ClinVar

149 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	8
Likely pathogenic	8
Uncertain significance	78
Likely benign	25
Benign	9

Top pathogenic / likely-pathogenic (16)

Variant ID	HGVS	Classification
254655	NM_133443.4(GPT2):c.1210C>T (p.Arg404Ter)	Pathogenic
280442	NM_133443.4(GPT2):c.181G>T (p.Glu61Ter)	Pathogenic
3069205	NM_133443.4(GPT2):c.306del (p.Gln103fs)	Pathogenic
522105	NM_133443.4(GPT2):c.70C>T (p.Gln24Ter)	Pathogenic
983537	NM_133443.4(GPT2):c.400C>T (p.Arg134Cys)	Pathogenic
983538	NM_133443.4(GPT2):c.1435G>A (p.Val479Met)	Pathogenic
983539	NM_133443.4(GPT2):c.1432_1433del (p.Val478fs)	Pathogenic
983541	NM_133443.4(GPT2):c.812A>C (p.Asn271Thr)	Pathogenic
1254563	NM_133443.4(GPT2):c.1133dup (p.Val379fs)	Likely pathogenic
187856	NM_133443.4(GPT2):c.459C>G (p.Ser153Arg)	Likely pathogenic
2572428	NM_133443.4(GPT2):c.58del (p.Trp20fs)	Likely pathogenic
2572609	NM_133443.4(GPT2):c.333+2T>G	Likely pathogenic
2572611	NM_133443.4(GPT2):c.924_925del (p.Pro309fs)	Likely pathogenic
3893149	NM_133443.4(GPT2):c.643C>T (p.Gln215Ter)	Likely pathogenic
978392	NM_133443.4(GPT2):c.269del (p.Val90fs)	Likely pathogenic
988735	NM_133443.4(GPT2):c.1177dup (p.Val393fs)	Likely pathogenic

SpliceAI

2862 predictions. Top by Δscore:

Variant	Effect	Δscore
16:46884955:GCGG:G	donor_gain	1.0000
16:46884956:CGGG:C	donor_loss	1.0000
16:46884959:GTG:G	donor_loss	1.0000
16:46897641:T:A	acceptor_gain	1.0000
16:46897643:CCCA:C	acceptor_loss	1.0000
16:46897646:A:AG	acceptor_gain	1.0000
16:46897646:AG:A	acceptor_gain	1.0000
16:46897646:AGG:A	acceptor_gain	1.0000
16:46897646:AGGG:A	acceptor_loss	1.0000
16:46897647:G:A	acceptor_gain	1.0000
16:46897647:G:GA	acceptor_gain	1.0000
16:46897647:GGG:G	acceptor_gain	1.0000
16:46897647:GGGT:G	acceptor_gain	1.0000
16:46897647:GGGTA:G	acceptor_gain	1.0000
16:46897735:CAGGT:C	donor_loss	1.0000
16:46897736:AGGT:A	donor_loss	1.0000
16:46897738:GTG:G	donor_loss	1.0000
16:46897739:T:G	donor_loss	1.0000
16:46906955:G:GT	donor_gain	1.0000
16:46906971:TTTCT:T	donor_gain	1.0000
16:46906976:G:GG	donor_gain	1.0000
16:46916708:GTAAG:G	donor_loss	1.0000
16:46916709:T:A	donor_loss	1.0000
16:46918744:GGC:G	donor_gain	1.0000
16:46918754:GCGA:G	donor_gain	1.0000
16:46918756:GA:G	donor_gain	1.0000
16:46918758:G:GG	donor_gain	1.0000
16:46922231:T:TA	acceptor_gain	1.0000
16:46922412:GCCGA:G	donor_gain	1.0000
16:46922415:GA:G	donor_gain	1.0000

AlphaMissense

3421 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:46906847:T:C	Y150H	1.000
16:46909753:T:C	Y216H	1.000
16:46909920:C:A	N271K	1.000
16:46909920:C:G	N271K	1.000
16:46918743:G:C	K341N	1.000
16:46918743:G:T	K341N	1.000
16:46922253:G:C	R350T	1.000
16:46922253:G:T	R350I	1.000
16:46927006:T:C	F484L	1.000
16:46927008:T:A	F484L	1.000
16:46927008:T:G	F484L	1.000
16:46927037:G:T	R494M	1.000
16:46884899:T:C	Y62H	0.999
16:46897690:G:A	G96R	0.999
16:46897690:G:C	G96R	0.999
16:46897690:G:T	G96W	0.999
16:46897691:G:A	G96E	0.999
16:46906850:A:C	S151R	0.999
16:46906852:T:A	S151R	0.999
16:46906852:T:G	S151R	0.999
16:46906862:G:C	G155R	0.999
16:46906956:G:A	G186E	0.999
16:46906961:A:C	S188R	0.999
16:46906963:T:A	S188R	0.999
16:46906963:T:G	S188R	0.999
16:46909754:A:G	Y216C	0.999
16:46909828:T:A	W241R	0.999
16:46909828:T:C	W241R	0.999
16:46909850:T:A	L248H	0.999
16:46909900:T:C	C265R	0.999

dbSNP variants (sampled 300 via entrez): RS1000008639 (16:46906138 A>G), RS1000048668 (16:46889731 T>C), RS1000084863 (16:46915733 CCACACACA>C,CCA,CCACA,CCACACA,CCACACACACA), RS1000126149 (16:46929954 C>G,T), RS1000231433 (16:46905796 A>G), RS1000255983 (16:46886221 A>G), RS1000267948 (16:46882371 G>A), RS1000284594 (16:46900116 G>A), RS1000294038 (16:46930845 G>A,C), RS1000315788 (16:46890762 C>T), RS1000366845 (16:46893485 C>G,T), RS1000412269 (16:46912205 A>G), RS1000434804 (16:46913126 C>T), RS1000453141 (16:46931294 G>A), RS1000565572 (16:46931570 G>C)

Disease associations

OMIM: gene MIM:138210 | disease phenotypes: MIM:616281, MIM:616282, MIM:261750

GenCC curated gene-disease

Disease	Classification	Inheritance
glutamate pyruvate transaminase 2 deficiency	Definitive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
glutamate pyruvate transaminase 2 deficiency	Definitive	AR

Mondo (5): glutamate pyruvate transaminase 2 deficiency (MONDO:0014567), intellectual disability (MONDO:0001071), hereditary spastic paraplegia 73 (MONDO:0014568), glycogen storage disease IXb (MONDO:0009868), neurodevelopmental disorder (MONDO:0700092)

Orphanet (5): Postnatal microcephaly-infantile hypotonia-spastic diplegia-dysarthria-intellectual disability syndrome (Orphanet:477673), Autosomal dominant spastic paraplegia type 73 (Orphanet:444099), Glycogen storage disease due to liver and muscle phosphorylase kinase deficiency (Orphanet:79240), Rare genetic intellectual disability (Orphanet:183757), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

37 total (30 of 37 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000218	High palate
HP:0000252	Microcephaly
HP:0000286	Epicanthus
HP:0000341	Narrow forehead
HP:0000358	Posteriorly rotated ears
HP:0000369	Low-set ears
HP:0000601	Hypotelorism
HP:0000750	Delayed speech and language development
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001257	Spasticity
HP:0001258	Spastic paraplegia
HP:0001260	Dysarthria
HP:0001263	Global developmental delay
HP:0001276	Hypertonia
HP:0001288	Gait disturbance
HP:0001298	Encephalopathy
HP:0001337	Tremor
HP:0001344	Absent speech
HP:0001347	Hyperreflexia
HP:0001371	Flexion contracture
HP:0001508	Failure to thrive
HP:0002069	Bilateral tonic-clonic seizure
HP:0002079	Hypoplasia of the corpus callosum
HP:0002121	Generalized non-motor (absence) seizure
HP:0002136	Broad-based gait
HP:0002307	Drooling
HP:0002373	Febrile seizure (within the age range of 3 months to 6 years)

GWAS associations

0 associations (top):

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D065886	Neurodevelopmental Disorders	F03.625
C563008	Glycogen Storage Disease IXB (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

80 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases methylation, affects methylation, decreases expression	9
arsenite	affects expression, affects binding, decreases reaction	2
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression, increases expression	2
Copper	affects binding, increases expression	2
Diazinon	increases expression, increases methylation	2
Hydrogen Peroxide	affects expression, increases expression	2
Tetrachlorodibenzodioxin	decreases expression	2
Tunicamycin	increases expression	2
Cyclosporine	increases expression	2
Aflatoxin B1	decreases methylation, affects methylation	2
Cadmium Chloride	increases expression, increases abundance	2
Thapsigargin	increases expression	2
Particulate Matter	increases abundance, increases expression, affects cotreatment	2
aristolochic acid I	decreases expression	1
GSK-J4	decreases expression	1
beta-N-methylamino-L-alanine	affects cotreatment, increases expression	1
tungsten carbide	increases expression, affects cotreatment	1
methylmercuric chloride	increases expression	1
2,4-diaminobutyric acid	affects cotreatment, increases expression	1
pirinixic acid	affects binding, increases activity, increases expression	1
sodium arsenite	increases expression	1
cobaltous chloride	increases expression	1
perfluorooctanoic acid	increases expression	1
ochratoxin A	decreases expression	1
benzo(e)pyrene	affects methylation	1
potassium chromate(VI)	increases expression	1
aflatoxin B2	increases methylation	1
1-nitropyrene	increases expression	1
perfluorooctane sulfonic acid	increases expression	1
CGP 52608	affects binding, increases reaction	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_SQ48	HAP1 GPT2 (-) 1	Cancer cell line	Male
CVCL_SQ49	HAP1 GPT2 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

199 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT03479476	PHASE2/PHASE3	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome
NCT02616796	PHASE1/PHASE2	COMPLETED	Effects of Social Gaze Training on Brain and Behavior in Fragile X Syndrome
NCT06860672	EARLY_PHASE1	RECRUITING	Clinical Trial of the Dual Vector Base Editor for the Treatment of the CHD3-R1025W Mutation
NCT00597948	Not specified	COMPLETED	Healthy Lifestyles for People With Intellectual Disabilities
NCT01087320	Not specified	RECRUITING	Genome Medical Sequencing for Gene Discovery
NCT01652963	Not specified	UNKNOWN	Picture-based Computerised Assessment and Training of Cognitive Behaviour Therapy Skills
NCT01695395	Not specified	COMPLETED	Mental Health Care Provision for Adults With Intellectual Disability and a Mental Disorder
NCT01867554	Not specified	COMPLETED	Research and Characterization of New Genes Involved in Intellectual Disability
NCT01915381	Not specified	COMPLETED	Improving Adherence Healthy Lifestyle With a Smartphone Application Based on Adults With Intellectual Disabilities
NCT01988623	Not specified	COMPLETED	Pivotal Response Treatment for Individuals With Intellectual Disabilities
NCT02099773	Not specified	COMPLETED	Support Staff-client Interactions With Augmentative and Alternative Communication
NCT02136849	Not specified	COMPLETED	Inter-regional Project of the Great Western Exploration Approach for Exome Molecular Causes Severe Intellectual Disability Isolated or Syndromic
NCT02225041	Not specified	COMPLETED	Sedation Strategy and Cognitive Outcome After Critical Illness in Early Childhood
NCT02414438	Not specified	COMPLETED	Establishing the Clinical Utility of First StepDx PLUS and NextStepDx PLUS Study
NCT02451761	Not specified	COMPLETED	Apparently Balanced Chromosomal Translocation/ Next-generation Sequencing/ Intellectual Disability
NCT02461420	Not specified	ACTIVE_NOT_RECRUITING	Mapping the Genotype, Phenotype, and Natural History of Phelan-McDermid Syndrome
NCT02461459	Not specified	ACTIVE_NOT_RECRUITING	Autism Spectrum Disorder (ASD) and Intellectual Disability (ID) Determinants in Tuberous Sclerosis Complex (TSC)
NCT02486081	Not specified	COMPLETED	Development and Application-Smart Football for Movement Evaluation and Training in the Special Education Population
NCT02504502	Not specified	COMPLETED	Enhancing Genomic Laboratory Reports to Enhance Communication and Empower Patients
NCT02513277	Not specified	COMPLETED	Diabetes Screening & Prevention for People With Learning (Intellectual) Disabilities:STOP Diabetes Study
NCT02561754	Not specified	COMPLETED	Weight Management for Adolescents With IDD
NCT02591446	Not specified	COMPLETED	Transcranial Magnetic Stimulation Studies in Autism Spectrum Disorders
NCT02714868	Not specified	COMPLETED	Evaluation of Project TEAM (Teens Making Environmental and Activity Modifications)
NCT02721394	Not specified	UNKNOWN	FCT With Young Children With ID in the UK: A Feasibility Project V.1
NCT02746614	Not specified	COMPLETED	Psychomotor Therapy Effects in Adaptive Behavior and Motor Proficiency in Intellectual Disability
NCT02836405	Not specified	COMPLETED	TMS for the Investigation of Brain Plasticity in Autism Spectrum Disorders