IDH3A

isocitrate dehydrogenase (NAD(+)) 3 catalytic subunit alpha, the group of Isocitrate dehydrogenases

Basic information

Region (hg38): 15:78131497-78171945

Links

ENSG00000166411 ∙ NCBI:3419 ∙ OMIM:601149 ∙ HGNC:5384 ∙ Uniprot:P50213 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• retinitis pigmentosa 90 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Retinitis pigmentosa 90	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	Ophthalmologic	28412069; 30058936; 31012789

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the IDH3A gene.

• not provided (240 variants)
• Inborn genetic diseases (9 variants)
• Retinitis pigmentosa 90 (8 variants)
• Retinitis pigmentosa (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the IDH3A 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			2	49	6	57
missense	1		81	3		85
nonsense	3		1			4
start loss			1			1
frameshift	3					3
inframe indel						0
splice donor/acceptor (+/-2bp)		5				5
splice region			11	16	3	30
non coding			3	39	14	56
Total	7	5	88	91	20

Highest pathogenic variant AF is 0.0000526

Variants in IDH3A

This is a list of pathogenic ClinVar variants found in the IDH3A region.

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

Position	Type	Phenotype	Significance	ClinVar
15-78149232-C-G			Benign (May 12, 2021)
15-78149405-T-C			Uncertain significance (Jan 17, 2022)
15-78149411-G-T			Uncertain significance (Oct 01, 2022)
15-78149413-C-T			Uncertain significance (Feb 23, 2022)
15-78149414-C-T			Uncertain significance (Jun 09, 2023)
15-78149415-C-G			Likely benign (Jun 23, 2023)
15-78149416-G-T		not specified	Uncertain significance (Oct 17, 2022)
15-78149420-G-A			Pathogenic (Oct 22, 2021)
15-78149423-T-C			Uncertain significance (Apr 28, 2022)
15-78149424-C-T			Likely benign (Sep 17, 2021)
15-78149427-T-C			Benign (Feb 01, 2024)
15-78149429-A-G		not specified	Uncertain significance (Jan 09, 2024)
15-78149432-T-C			Likely pathogenic (Nov 29, 2022)
15-78149435-G-A			Uncertain significance (Jun 13, 2023)
15-78149436-C-CGCTGGCAGGCCGGCGTGTGGCAG			Likely benign (Mar 23, 2021)
15-78149438-CT-GG			Likely benign (Jun 15, 2023)
15-78149439-T-TGGCAGGCCGGCGTGTGGCAGGCA			Likely benign (Apr 09, 2023)
15-78149441-G-T			Likely benign (Mar 04, 2023)
15-78149443-A-G			Likely benign (Oct 06, 2023)
15-78149444-G-T			Likely benign (Jul 12, 2022)
15-78149446-C-A			Likely benign (May 05, 2023)
15-78149449-G-T			Likely benign (Aug 08, 2022)
15-78149450-C-G			Likely benign (Oct 29, 2022)
15-78149544-T-G			Benign (May 12, 2021)
15-78155203-A-G			Likely benign (Aug 31, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
IDH3A	protein_coding	protein_coding	ENST00000299518	11	40452

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.157	0.842	125736	0	12	125748	0.0000477

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.59	115	224	0.514	0.0000129	2404
Missense in Polyphen		46	108.92	0.42232		1102
Synonymous	-0.220	83	80.5	1.03	0.00000494	701
Loss of Function	2.99	5	19.1	0.262	9.57e-7	229

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.000185	0.000185
European (Non-Finnish)	0.0000440	0.0000439
Middle Eastern	0.000109	0.000109
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalytic subunit of the enzyme which catalyzes the decarboxylation of isocitrate (ICT) into alpha-ketoglutarate. The heterodimer composed of the alpha (IDH3A) and beta (IDH3B) subunits and the heterodimer composed of the alpha (IDH3A) and gamma (IDH3G) subunits, have considerable basal activity but the full activity of the heterotetramer (containing two subunits of IDH3A, one of IDH3B and one of IDH3G) requires the assembly and cooperative function of both heterodimers. {ECO:0000269|PubMed:28139779}.
• Pathway: Citrate cycle (TCA cycle) - Homo sapiens (human);Warburg Effect;The oncogenic action of Succinate;The oncogenic action of Fumarate;Pyruvate dehydrogenase deficiency (E3);Pyruvate dehydrogenase deficiency (E2);2-ketoglutarate dehydrogenase complex deficiency;Mitochondrial complex II deficiency;Fumarase deficiency;Congenital lactic acidosis;Citric Acid Cycle;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 ;TCA Cycle and Deficiency of Pyruvate Dehydrogenase complex (PDHc);TCA Cycle;Citrate 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;TCA cycle;superpathway of conversion of glucose to acetyl CoA and entry into the TCA cycle (Consensus)

Recessive Scores

• pRec: 0.448

Intolerance Scores

• loftool: 0.500
• rvis_EVS: -0.01
• rvis_percentile_EVS: 53.51

Haploinsufficiency Scores

• pHI: 0.210
• hipred: Y
• hipred_score: 0.707
• ghis: 0.576

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.502

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Idh3a
• Phenotype: vision/eye phenotype

Gene ontology

• Biological process: carbohydrate metabolic process;tricarboxylic acid cycle
• Cellular component: nucleus;mitochondrion;mitochondrial matrix;myelin sheath
• Molecular function: magnesium ion binding;isocitrate dehydrogenase (NAD+) activity;NAD binding