IDH1

isocitrate dehydrogenase (NADP(+)) 1, the group of Isocitrate dehydrogenases

Basic information

Region (hg38): 2:208236228-208266074

Links

ENSG00000138413 ∙ NCBI:3417 ∙ OMIM:147700 ∙ HGNC:5382 ∙ Uniprot:O75874 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the IDH1 gene.

• Inborn genetic diseases (337 variants)
• not provided (31 variants)
• not specified (9 variants)
• Enchondromatosis (3 variants)
• Acute myeloid leukemia (3 variants)
• Transitional cell carcinoma of the bladder (2 variants)
• Glioblastoma (2 variants)
• Multiple myeloma (2 variants)
• Hepatocellular carcinoma (2 variants)
• Glioma susceptibility 1 (2 variants)
• Lung adenocarcinoma (2 variants)
• Myelodysplastic syndrome (2 variants)
• Neoplasm of brain (2 variants)
• Neoplasm of the large intestine (2 variants)
• Astrocytoma (2 variants)
• Prostate adenocarcinoma (2 variants)
• Medulloblastoma (2 variants)
• Brainstem glioma (2 variants)
• Adenoid cystic carcinoma (2 variants)
• Breast neoplasm (2 variants)
• Malignant melanoma of skin (2 variants)
• Metaphyseal chondromatosis with D-2-hydroxyglutaric aciduria (1 variants)
• Diffuse pediatric-type high-grade glioma, H3-wildtype and IDH-wildtype (1 variants)
• Enchondromatosis;Maffucci syndrome (1 variants)
• Metaphyseal chondromatosis (1 variants)
• Maffucci syndrome (1 variants)
• Glioblastoma multiforme, somatic (1 variants)
• Paroxysmal extreme pain disorder (1 variants)
• Diffuse midline glioma, H3 K27-altered (1 variants)
• Oligodendroglioma (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the IDH1 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				136	1	137
missense		4	197	5	3	209
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				3	4	7
non coding					13	13
Total	0	4	197	141	17

Highest pathogenic variant AF is 0.000309

Variants in IDH1

This is a list of pathogenic ClinVar variants found in the IDH1 region.

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

Position	Type	Phenotype	Significance	ClinVar
2-208237088-G-C		not specified	Likely benign (Feb 12, 2022)
2-208237091-C-T		not specified	Likely benign (Apr 12, 2020)
2-208237101-T-C		not specified	Uncertain significance (Feb 21, 2022)
2-208237101-T-G		not specified	Uncertain significance (Dec 23, 2023)
2-208237104-A-T		not specified	Uncertain significance (Jun 29, 2021)
2-208237106-C-T		not specified	Likely benign (Jun 03, 2020)
2-208237117-C-T		not specified	Uncertain significance (Jun 17, 2023)
2-208237118-T-C		not specified	Likely benign (Jun 20, 2022)
2-208237119-C-T		not specified	Uncertain significance (May 12, 2022)
2-208237128-T-C		not specified	Uncertain significance (Jan 17, 2024)
2-208237132-T-A		not specified	Uncertain significance (May 01, 2022)
2-208237132-T-C		not specified	Uncertain significance (Mar 02, 2024)
2-208237143-G-A		not specified	Uncertain significance (Nov 15, 2022)
2-208237145-A-T		not specified	Uncertain significance (Jan 31, 2024)
2-208237146-T-C		not specified	Uncertain significance (Feb 25, 2024)
2-208237148-C-A		not specified	Uncertain significance (Jul 18, 2023)
2-208237153-A-G		not specified	Uncertain significance (Aug 10, 2021)
2-208237162-G-A		not specified	Uncertain significance (Dec 12, 2022)
2-208237162-G-T		not specified	Uncertain significance (Jan 17, 2024)
2-208237166-C-T		not specified	Likely benign (May 12, 2023)
2-208237169-A-G		not specified	Likely benign (Aug 07, 2022)
2-208237174-C-T			Benign (May 29, 2018)
2-208237393-A-ACT			Benign (Jun 19, 2021)
2-208238771-G-A			Benign (Jun 19, 2021)
2-208239072-T-C		not specified	Uncertain significance (Nov 18, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
IDH1	protein_coding	protein_coding	ENST00000415913	8	29848

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.62e-12	0.0737	125703	0	45	125748	0.000179

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.604	207	233	0.889	0.0000124	2754
Missense in Polyphen		87	106.08	0.82011		1272
Synonymous	0.873	72	82.1	0.877	0.00000486	757
Loss of Function	0.404	19	21.0	0.905	0.00000109	248

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000492	0.000481
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.000217	0.000217
Finnish	0.00	0.00
European (Non-Finnish)	0.000178	0.000176
Middle Eastern	0.000217	0.000217
South Asian	0.000294	0.000294
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Disease: 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:19117336, ECO:0000269|PubMed:19935646}. Note=The gene represented in this entry is involved in disease pathogenesis. Mutations affecting Arg-132 are tissue-specific, and suggest that this residue plays a unique role in the development of high-grade gliomas. Mutations of Arg-132 to Cys, His, Leu or Ser abolish magnesium binding and abolish the conversion of isocitrate to alpha-ketoglutarate. Instead, alpha-ketoglutarate is converted to R(-)-2-hydroxyglutarate. Elevated levels of R(-)-2- hydroxyglutarate are correlated with an elevated risk of malignant brain tumors. {ECO:0000269|PubMed:19935646}.; DISEASE: Note=Genetic variations are associated with cartilaginous tumors such as enchondroma or chondrosarcoma. Mutations of Arg-132 to Cys, Gly or His abolish the conversion of isocitrate to alpha- ketoglutarate. Instead, alpha-ketoglutarate is converted to R(-)- 2-hydroxyglutarate. {ECO:0000269|PubMed:26161668}.
• Pathway: Citrate cycle (TCA cycle) - Homo sapiens (human);Central carbon metabolism in cancer - Homo sapiens (human);Glutathione metabolism - Homo sapiens (human);Peroxisome - Homo sapiens (human);Warburg Effect;The oncogenic action of Succinate;The oncogenic action of Fumarate;The oncogenic action of 2-hydroxyglutarate;The oncogenic action of L-2-hydroxyglutarate in Hydroxygluaricaciduria;The oncogenic action of D-2-hydroxyglutarate in Hydroxygluaricaciduria ;Glutathione metabolism;miR-targeted genes in epithelium - TarBase;miR-targeted genes in leukocytes - TarBase;miR-targeted genes in lymphocytes - TarBase;miR-targeted genes in squamous cell - TarBase;TCA Cycle and Deficiency of Pyruvate Dehydrogenase complex (PDHc);Amino Acid metabolism;Neutrophil degranulation;Disease;Metabolism of proteins;Innate Immune System;Immune System;Metabolism;Peroxisomal protein import;NADPH regeneration;Abnormal conversion of 2-oxoglutarate to 2-hydroxyglutarate;Diseases of metabolism;Metabolism of cofactors;Metabolism of vitamins and cofactors;TCA cycle (Consensus)

Recessive Scores

• pRec: 0.416

Intolerance Scores

• loftool: 0.568
• rvis_EVS: 0.02
• rvis_percentile_EVS: 55.45

Haploinsufficiency Scores

• pHI: 0.864
• hipred: Y
• hipred_score: 0.507
• ghis: 0.456

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.915

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Idh1
• Phenotype: homeostasis/metabolism phenotype; growth/size/body region phenotype; respiratory system phenotype; immune system phenotype; skeleton phenotype; hematopoietic system phenotype; 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)

Zebrafish Information Network

• Gene name: idh1
• Affected structure: whole organism
• Phenotype tag: abnormal
• Phenotype quality: has fewer parts of type

Gene ontology

• Biological process: glyoxylate cycle;tricarboxylic acid cycle;isocitrate metabolic process;2-oxoglutarate metabolic process;protein targeting to peroxisome;NADP metabolic process;NADPH regeneration;glutathione metabolic process;response to oxidative stress;female gonad development;neutrophil degranulation;response to steroid hormone;regulation of phospholipid catabolic process;regulation of phospholipid biosynthetic process
• Cellular component: extracellular region;cytoplasm;mitochondrion;peroxisome;peroxisomal matrix;cytosol;secretory granule lumen;extracellular exosome;tertiary granule lumen;ficolin-1-rich granule lumen
• Molecular function: magnesium ion binding;isocitrate dehydrogenase (NADP+) activity;signaling receptor binding;identical protein binding;protein homodimerization activity;cadherin binding;NADP binding;NAD binding;(R)-2-hydroxyglutarate dehydrogenase activity