IDH3B

isocitrate dehydrogenase (NAD(+)) 3 non-catalytic subunit beta, the group of Isocitrate dehydrogenases

Basic information

Region (hg38): 20:2658393-2664219

Links

ENSG00000101365 ∙ NCBI:3420 ∙ OMIM:604526 ∙ HGNC:5385 ∙ Uniprot:O43837 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• retinitis pigmentosa (Supportive), mode of inheritance: AD
• retinitis pigmentosa 46 (Strong), mode of inheritance: AR
• retinitis pigmentosa 46 (Strong), mode of inheritance: AR
• IDH3B-related retinopathy (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Retinitis pigmentosa 46	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	18806796

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the IDH3B gene.

• not provided (4 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the IDH3B 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			4	52	2	58
missense			121	2		123
nonsense	2		2			4
start loss			1			1
frameshift	2		3			5
inframe indel			4			4
splice donor/acceptor (+/-2bp)		1	6			7
splice region			13	9	1	23
non coding			5	38	10	53
Total	4	1	146	92	12

Highest pathogenic variant AF is 0.0000526

Variants in IDH3B

This is a list of pathogenic ClinVar variants found in the IDH3B region.

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

Position	Type	Phenotype	Significance	ClinVar
20-2658498-A-G		Retinitis pigmentosa	Uncertain significance (Jan 13, 2018)
20-2658516-T-C		Retinitis pigmentosa	Benign/Likely benign (May 12, 2021)
20-2658527-G-T		IDH3B-related disorder	Likely benign (Feb 22, 2019)
20-2658539-T-C		Retinitis pigmentosa	Uncertain significance (Jan 13, 2018)
20-2658548-A-G		Retinitis pigmentosa	Uncertain significance (Jan 12, 2018)
20-2658574-T-C		Retinitis pigmentosa	Uncertain significance (Jan 12, 2018)
20-2658612-C-T		Retinitis pigmentosa	Uncertain significance (Jan 12, 2018)
20-2658751-C-T			Likely benign (Feb 20, 2023)
20-2658754-G-A			Likely benign (Oct 18, 2021)
20-2658755-C-G			Uncertain significance (Mar 10, 2020)
20-2658758-C-T			Uncertain significance (Nov 05, 2019)
20-2658762-T-C			Uncertain significance (Jul 21, 2021)
20-2658763-A-G			Likely benign (Jul 17, 2023)
20-2658764-G-C		Retinitis pigmentosa	Uncertain significance (Oct 26, 2020)
20-2658766-C-T			Benign (Dec 11, 2023)
20-2658777-C-T		Retinitis pigmentosa	Conflicting classifications of pathogenicity (Jan 06, 2024)
20-2658778-G-A			Likely benign (Nov 13, 2023)
20-2658778-G-C			Uncertain significance (Aug 15, 2022)
20-2658783-C-G		not specified	Uncertain significance (May 31, 2023)
20-2658787-CTT-C			Uncertain significance (Jul 04, 2022)
20-2658788-TTGA-T		Retinitis Pigmentosa, Recessive • Retinal dystrophy • Retinitis pigmentosa 46	Uncertain significance (Aug 25, 2022)
20-2658790-G-A			Likely benign (Apr 22, 2022)
20-2658792-T-C			Uncertain significance (Jul 24, 2022)
20-2658798-C-T			Uncertain significance (Nov 08, 2022)
20-2658799-G-A			Likely benign (Aug 10, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
IDH3B	protein_coding	protein_coding	ENST00000380843	12	5825

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.99e-11	0.155	125682	0	66	125748	0.000262

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.419	200	217	0.920	0.0000129	2523
Missense in Polyphen		73	95.987	0.76052		1149
Synonymous	-0.459	89	83.7	1.06	0.00000508	758
Loss of Function	0.628	18	21.1	0.852	0.00000117	244

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000297	0.000297
Ashkenazi Jewish	0.000198	0.000198
East Asian	0.000217	0.000217
Finnish	0.000231	0.000231
European (Non-Finnish)	0.000326	0.000325
Middle Eastern	0.000217	0.000217
South Asian	0.000164	0.000163
Other	0.000815	0.000815

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Plays a structural role to facilitate the assembly and ensure the full activity of the enzyme catalyzing 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}.
• Disease: DISEASE: Retinitis pigmentosa 46 (RP46) [MIM:612572]: A retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well. {ECO:0000269|PubMed:18806796}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• 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;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: 0.236

Intolerance Scores

• loftool: 0.902
• rvis_EVS: -0.4
• rvis_percentile_EVS: 26.73

Haploinsufficiency Scores

• pHI: 0.379
• hipred: N
• hipred_score: 0.439
• ghis: 0.589

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.842

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Idh3b

Gene ontology

• Biological process: tricarboxylic acid cycle;isocitrate metabolic process;electron transport chain
• Cellular component: nucleus;mitochondrion;mitochondrial matrix
• Molecular function: magnesium ion binding;isocitrate dehydrogenase (NAD+) activity;electron transfer activity;NAD binding