IDH2

isocitrate dehydrogenase (NADP(+)) 2, the group of Isocitrate dehydrogenases

Basic information

Region (hg38): 15:90083045-90102477

Links

ENSG00000182054

∙ NCBI:3418 ∙ OMIM:147650 ∙ HGNC:5383 ∙ Uniprot:P48735 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

d-2-hydroxyglutaric aciduria 2 (Strong), mode of inheritance: AD
D-2-hydroxyglutaric aciduria (Supportive), mode of inheritance: AD
mitochondrial disease (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
D-2-hydroxyglutaric aciduria 2	AD	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	Biochemical; Cardiovascular; Craniofacial; Neurologic	20847235

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the IDH2 gene.

D-2-hydroxyglutaric_aciduria_2 (180 variants)
not_provided (56 variants)
Inborn_genetic_diseases (26 variants)
not_specified (22 variants)
IDH2-related_disorder (7 variants)
Acute_myocardial_infarction (4 variants)
Enchondromatosis (2 variants)
Cleft_palate (2 variants)
Teratoma (1 variants)
Lymphatic_malformation (1 variants)
Vascular_malformation (1 variants)
Mitochondrial_disease (1 variants)
Maffucci_syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the IDH2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000002168.4. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			3 clinvar	46 clinvar	9 clinvar	58
missense	2 clinvar	4 clinvar	120 clinvar	9 clinvar		135
nonsense			2 clinvar			2
start loss						0
frameshift			3 clinvar			3
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	2	4	130	55	9

Highest pathogenic variant AF is 0.0000439968

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
IDH2	protein_coding	protein_coding	ENST00000330062	11	19460

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.883	0.117	125738	0	10	125748	0.0000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.34	191	251	0.762	0.0000163	2965
Missense in Polyphen		82	137.29	0.59729		1522
Synonymous	-2.17	131	103	1.27	0.00000748	868
Loss of Function	3.54	3	20.2	0.149	8.95e-7	261

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000578	0.0000578
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.0000464	0.0000462
European (Non-Finnish)	0.0000528	0.0000527
Middle Eastern	0.0000544	0.0000544
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

Function: FUNCTION: Plays a role in intermediary metabolism and energy production. It may tightly associate or interact with the pyruvate dehydrogenase complex.;
Disease: DISEASE: D-2-hydroxyglutaric aciduria 2 (D2HGA2) [MIM:613657]: A neurometabolic disorder causing developmental delay, epilepsy, hypotonia, and dysmorphic features. Both a mild and a severe phenotype exist. The severe phenotype is homogeneous and is characterized by early infantile-onset epileptic encephalopathy and cardiomyopathy. The mild phenotype has a more variable clinical presentation. Diagnosis is based on the presence of an excess of D-2-hydroxyglutaric acid in the urine. {ECO:0000269|PubMed:20847235}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Glioma (GLM) [MIM:137800]: Gliomas are benign or malignant central nervous system neoplasms derived from glial cells. They comprise astrocytomas and glioblastoma multiforme that are derived from astrocytes, oligodendrogliomas derived from oligodendrocytes and ependymomas derived from ependymocytes. {ECO:0000269|PubMed:19228619, ECO:0000269|PubMed:25495392}. Note=The gene represented in this entry is involved in disease pathogenesis.; DISEASE: Note=enetic variations are associated with cartilaginous tumors such as enchondroma or chondrosarcoma. {ECO:0000269|PubMed:26161668}.;
Pathway: Citrate cycle (TCA cycle) - Homo sapiens (human);Glutathione metabolism - Homo sapiens (human);Peroxisome - Homo sapiens (human);The oncogenic action of Succinate;The oncogenic action of Fumarate;Glutaminolysis and Cancer;The oncogenic action of 2-hydroxyglutarate;The oncogenic action of L-2-hydroxyglutarate in Hydroxygluaricaciduria;The oncogenic action of D-2-hydroxyglutarate in Hydroxygluaricaciduria ;fig-met-1-last-solution;TCA Cycle;Citric acid cycle (TCA cycle);Pyruvate metabolism and Citric Acid (TCA) cycle;The citric acid (TCA) cycle and respiratory electron transport;Metabolism;TCA cycle;Transcriptional activation of mitochondrial biogenesis;Mitochondrial biogenesis;Organelle biogenesis and maintenance (Consensus)

Recessive Scores

pRec: 0.811

Intolerance Scores

loftool: 0.307
rvis_EVS: -0.38
rvis_percentile_EVS: 27.88

Haploinsufficiency Scores

pHI: 0.333
hipred: Y
hipred_score: 0.685
ghis: 0.536

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: S
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.943

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Idh2
Phenotype: cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); neoplasm;

Gene ontology

Biological process: carbohydrate metabolic process;glyoxylate cycle;tricarboxylic acid cycle;isocitrate metabolic process;2-oxoglutarate metabolic process;NADP metabolic process;NADP biosynthetic process;negative regulation of glial cell proliferation;negative regulation of glial cell migration;negative regulation of matrix metallopeptidase secretion
Cellular component: mitochondrion;mitochondrial matrix;peroxisome;cytosol;extracellular exosome
Molecular function: magnesium ion binding;isocitrate dehydrogenase (NADP+) activity;protein homodimerization activity;NAD binding