IDH3B

Summary

IDH3B (isocitrate dehydrogenase (NAD(+)) 3 non-catalytic subunit beta, HGNC:5385) is a protein-coding gene on chromosome 20p13, encoding Isocitrate dehydrogenase [NAD] subunit beta, mitochondrial (O43837). 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.

Isocitrate dehydrogenases catalyze the oxidative decarboxylation of isocitrate to 2-oxoglutarate. These enzymes belong to two distinct subclasses, one of which utilizes NAD(+) as the electron acceptor and the other NADP(+). Five isocitrate dehydrogenases have been reported: three NAD(+)-dependent isocitrate dehydrogenases, which localize to the mitochondrial matrix, and two NADP(+)-dependent isocitrate dehydrogenases, one of which is mitochondrial and the other predominantly cytosolic. NAD(+)-dependent isocitrate dehydrogenases catalyze the allosterically regulated rate-limiting step of the tricarboxylic acid cycle. Each isozyme is a heterotetramer that is composed of two alpha subunits, one beta subunit, and one gamma subunit. The protein encoded by this gene is the beta subunit of one isozyme of NAD(+)-dependent isocitrate dehydrogenase. Multiple alternatively spliced transcript variants encoding different isoforms have been described for this gene.

Source: NCBI Gene 3420 — RefSeq curated summary.

At a glance

• Gene–disease (curated): retinitis pigmentosa 46 (Strong, GenCC) — +2 more curated relationships
• Clinical variants (ClinVar): 366 total — 8 pathogenic, 13 likely-pathogenic
• Phenotypes (HPO): 36
• Druggable target: yes
• MANE Select transcript: NM_006899

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5385
Approved symbol	IDH3B
Name	isocitrate dehydrogenase (NAD(+)) 3 non-catalytic subunit beta
Location	20p13
Locus type	gene with protein product
Status	Approved
Aliases	RP46
Ensembl gene	ENSG00000101365
Ensembl biotype	protein_coding
OMIM	604526
Entrez	3420

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 7 protein_coding, 6 retained_intron, 2 nonsense_mediated_decay

ENST00000380843, ENST00000380851, ENST00000462967, ENST00000466494, ENST00000466999, ENST00000474315, ENST00000477689, ENST00000479376, ENST00000488299, ENST00000491065, ENST00000492240, ENST00000613370, ENST00000864850, ENST00000935364, ENST00000963243

RefSeq mRNA: 4 — MANE Select: NM_006899 NM_001258384, NM_001330763, NM_006899, NM_174855

CCDS: CCDS13031, CCDS13032, CCDS74696, CCDS82594

Canonical transcript exons

ENST00000380843 — 12 exons

Exon	Start	End
ENSE00003458517	2663446	2663566
ENSE00003513033	2663925	2664005
ENSE00003558317	2660909	2660969
ENSE00003571490	2659699	2659793
ENSE00003581008	2663660	2663758
ENSE00003607007	2658395	2658837
ENSE00003649420	2660030	2660176
ENSE00003652731	2660263	2660365
ENSE00003694571	2659525	2659585
ENSE00003720244	2660697	2660829
ENSE00003731232	2660457	2660590
ENSE00003846515	2664153	2664216

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 98.56.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 52.0150 / max 243.7578, expressed in 1827 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
186098	52.0150	1827

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	98.56	gold quality
heart left ventricle	UBERON:0002084	98.43	gold quality
cardiac ventricle	UBERON:0002082	98.40	gold quality
right hemisphere of cerebellum	UBERON:0014890	98.40	gold quality
cerebellar hemisphere	UBERON:0002245	98.32	gold quality
cerebellar cortex	UBERON:0002129	98.29	gold quality
mucosa of transverse colon	UBERON:0004991	98.12	gold quality
right atrium auricular region	UBERON:0006631	98.12	gold quality
transverse colon	UBERON:0001157	98.05	gold quality
cardiac atrium	UBERON:0002081	98.01	gold quality
metanephros cortex	UBERON:0010533	98.00	gold quality
heart	UBERON:0000948	97.99	gold quality
small intestine Peyer’s patch	UBERON:0003454	97.97	gold quality
granulocyte	CL:0000094	97.91	gold quality
left ovary	UBERON:0002119	97.84	gold quality
cerebellum	UBERON:0002037	97.83	gold quality
left ventricle myocardium	UBERON:0006566	97.82	gold quality
right lobe of thyroid gland	UBERON:0001119	97.81	gold quality
muscle layer of sigmoid colon	UBERON:0035805	97.81	gold quality
vastus lateralis	UBERON:0001379	97.79	gold quality
heart right ventricle	UBERON:0002080	97.78	gold quality
gastrocnemius	UBERON:0001388	97.75	gold quality
quadriceps femoris	UBERON:0001377	97.74	gold quality
hindlimb stylopod muscle	UBERON:0004252	97.72	gold quality
body of uterus	UBERON:0009853	97.72	gold quality
body of stomach	UBERON:0001161	97.67	gold quality
right ovary	UBERON:0002118	97.65	gold quality
lower esophagus	UBERON:0013473	97.65	gold quality
lower esophagus muscularis layer	UBERON:0035833	97.65	gold quality
muscle of leg	UBERON:0001383	97.64	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-100618	no	922.90
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

15 targeting IDH3B, 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-4533	100.00	69.48	2758
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-4428	99.73	66.41	1733
HSA-MIR-4690-5P	99.65	66.24	813
HSA-MIR-940	99.37	66.14	2064
HSA-MIR-6808-5P	99.31	66.23	2150
HSA-MIR-6893-5P	99.31	66.25	2119
HSA-MIR-4742-5P	98.89	68.41	1542
HSA-MIR-558	97.50	67.16	977
HSA-MIR-212-5P	96.83	67.43	950
HSA-MIR-3189-3P	96.80	66.34	896
HSA-MIR-1268A	87.06	61.46	145
HSA-MIR-1268B	87.06	61.46	145

Literature-anchored findings (GeneRIF, showing 12)

• In the presence of USP47, MAPK would be stabilized as USP47 acts to deubiquitinate MAPK, thus counteracting the direct ubiquitination of MAPK by POE/UBR4 activity. (PMID:27552662)
• A Key Role for the Ubiquitin Ligase UBR4 in Myofiber Hypertrophy in Drosophila and Mice. (PMID:31365869)
• Antagonistic control of myofiber size and muscle protein quality control by the ubiquitin ligase UBR4 during aging. (PMID:33658508)
• IDPm activity appears to be modulated through enzymatic glutathionylation and deglutathionylation during oxidative stress (PMID:15653693)
• active sites of the human NAD-IDH are shared between alpha and gamma subunits and between alpha and beta subunits (PMID:16737955)
• Asp192 is needed for optimal affinity of IDH beta subunit for nicotinamide-adenine dinucleotide (NAD) substrate, but is not critical for catalysis. (PMID:17432878)
• Homozygous for loss-of-function mutations in IDH3B is associated with retinitis pigmentosa. (PMID:18806796)
• The point mutations of isocitrate dehydrogenase are essentially unique to gliomas. (PMID:19498431)
• Human NAD-dependent isocitrate dehydrogenase (IDH) is a heterotetrameric mitochondrial enzyme with 2alpha:1beta:1gamma subunit ratio subunits shich share 40-52% identity in amino acid sequence. (PMID:20435888)
• High IDH3B expression is associated with esophageal squamous cell carcinoma. (PMID:31053633)
• Polymorphism on chromosome 20p13 near the IDH3B gene is associated with uterine prolapse. (PMID:32619879)
• A positive feedback inhibition of isocitrate dehydrogenase 3beta on paired-box gene 6 promotes Alzheimer-like pathology. (PMID:38679634)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	idh3b	ENSDARG00000044753
mus_musculus	Idh3b	ENSMUSG00000027406
rattus_norvegicus	Idh3b	ENSRNOG00000007316
drosophila_melanogaster	Idh3b	FBGN0038922
caenorhabditis_elegans		WBGENE00007993

Paralogs (2): IDH3G (ENSG00000067829), IDH3A (ENSG00000166411)

Protein

Protein identifiers

Isocitrate dehydrogenase [NAD] subunit beta, mitochondrial — O43837 (reviewed: O43837)

Alternative names: Isocitric dehydrogenase subunit beta, NAD(+)-specific ICDH subunit beta

All UniProt accessions (5): O43837, A0A087WZN1, A0A087X2E5, A0A0D9SET9, A0A0D9SG66

UniProt curated annotations — full annotation on UniProt →

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.

Subunit / interactions. Heterooligomer of subunits alpha (IDH3A), beta (IDH3B), and gamma (IDH3G) in the apparent ratio of 2:1:1. The heterodimer containing one IDH3A and one IDH3B subunit and the heterodimer containing one IDH3A and one IDH3G subunit assemble into a heterotetramer (which contains two subunits of IDH3A, one of IDH3B and one of IDH3G) and further into the heterooctamer.

Subcellular location. Mitochondrion.

Disease relevance. 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. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. The heterotetramer and the heterodimer composed of IDH3A and IDH3G subunits can be allosterically activated by citrate (CIT) or/and ADP, and the two activators can act independently or synergistically. The heterodimer composed of IDH3A and IDH3B subunits cannot be allosterically regulated and the allosteric regulation of the heterotetramer is through the IDH3G subunit and not the IDH3B subunit. The IDH3G subunit contains the allosteric site which consists of a CIT-binding site and an ADP-binding site, and the binding of CIT and ADP causes conformational changes at the allosteric site which are transmitted to the active site in the catalytic subunit (IDH3A) through a cascade of conformational changes at the heterodimer interface, leading to stabilization of the isocitrate-binding at the active site and thus activation of the enzyme. ATP can activate the heterotetramer and the heterodimer composed of IDH3A and IDH3G subunits at low concentrations but inhibits their activities at high concentrations, whereas ATP exhibits only inhibitory effect on the heterodimer composed of IDH3A and IDH3B subunits.

Similarity. Belongs to the isocitrate and isopropylmalate dehydrogenases family.

Isoforms (3)

UniProt ID	Names	Canonical?
O43837-1	B	yes
O43837-2	A
O43837-3	C

RefSeq proteins (4): NP_001245313, NP_001317692, NP_008830, NP_777280 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004434	Isocitrate_DH_NAD	Family
IPR019818	IsoCit/isopropylmalate_DH_CS	Conserved_site
IPR024084	IsoPropMal-DH-like_dom	Domain

Pfam: PF00180

Enzyme classification (BRENDA):

• EC 1.1.1.41 — isocitrate dehydrogenase (NAD+) (BRENDA: 54 organisms, 76 substrates, 122 inhibitors, 162 Km, 90 kcat entries)

Substrate kinetics (BRENDA)

8 substrates with measured Km, best-characterized 8. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
NAD+	0.004–20.65	60
ISOCITRATE	0.009–41	37
NADP+	0.0082–8.2	27
D-ISOCITRATE	0.09–62.2	20
DL-ISOCITRATE	0.002–0.385	6
D,L-ISOCITRATE	0.03–0.45	3
MN2+	0.22–0.39	2
HOMOISOCITRATE	0.0183	1

UniProt features (46 total): strand 15, helix 15, turn 4, sequence variant 4, sequence conflict 3, splice variant 2, transit peptide 1, chain 1, modified residue 1

Structure

Experimental structures (PDB)

9 structures.

PDB	Method	Resolution (Å)
8GRD	X-RAY DIFFRACTION	2.7
8GRU	X-RAY DIFFRACTION	2.85
8GRB	X-RAY DIFFRACTION	2.85
6KDE	X-RAY DIFFRACTION	3
6KDY	X-RAY DIFFRACTION	3.02
6KDF	X-RAY DIFFRACTION	3.05
6KE3	X-RAY DIFFRACTION	3.31
7CE3	X-RAY DIFFRACTION	3.47
8GS5	X-RAY DIFFRACTION	4.49

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O43837-F1	88.28	0.79

Functional residue map

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

Post-translational modifications (1): 199

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-71403	Citric acid cycle (TCA cycle)

MSigDB gene sets: 231 (showing top): MODULE_93, MODULE_151, ENK_UV_RESPONSE_KERATINOCYTE_UP, MORF_UBE2I, PUJANA_CHEK2_PCC_NETWORK, GOBP_GENERATION_OF_PRECURSOR_METABOLITES_AND_ENERGY, MORF_RAF1, MCBRYAN_PUBERTAL_BREAST_4_5WK_DN, MORF_CTBP1, GOBP_TRICARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_ORGANIC_ACID_METABOLIC_PROCESS, MORF_AATF, PUJANA_BRCA_CENTERED_NETWORK, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_CH_OH_GROUP_OF_DONORS, ULE_SPLICING_VIA_NOVA2

GO Biological Process (2): tricarboxylic acid cycle (GO:0006099), isocitrate metabolic process (GO:0006102)

GO Molecular Function (6): magnesium ion binding (GO:0000287), isocitrate dehydrogenase (NAD+) activity (GO:0004449), electron transfer activity (GO:0009055), NAD binding (GO:0051287), protein binding (GO:0005515), oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor (GO:0016616)

GO Cellular Component (4): nucleus (GO:0005634), mitochondrion (GO:0005739), mitochondrial matrix (GO:0005759), isocitrate dehydrogenase complex (NAD+) (GO:0045242)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Aerobic respiration and respiratory electron transport	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular membrane-bounded organelle	2
aerobic respiration	1
primary metabolic process	1
tricarboxylic acid metabolic process	1
secondary alcohol metabolic process	1
metal ion binding	1
isocitrate dehydrogenase [NAD(P)+] activity	1
molecular_function	1
adenyl nucleotide binding	1
binding	1
oxidoreductase activity, acting on CH-OH group of donors	1
cytoplasm	1
mitochondrion	1
intracellular organelle lumen	1
tricarboxylic acid cycle heteromeric enzyme complex	1
oxidoreductase complex	1

Protein interactions and networks

STRING

2974 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IDH3B	IDH3A	P50213	933
IDH3B	IDH3G	P51553	919
IDH3B	IDH2	P48735	903
IDH3B	NNT	Q13423	808
IDH3B	PRCD	Q00LT1	781
IDH3B	ZNF513	Q8N8E2	749
IDH3B	IMPG2	Q9BZV3	733
IDH3B	CERKL	Q49MI3	726
IDH3B	PDE6G	P18545	725
IDH3B	MDH2	P40926	722
IDH3B	PCARE	A6NGG8	719
IDH3B	EYS	Q5T1H1	718
IDH3B	OGDH	Q02218	712
IDH3B	ACO2	Q99798	708
IDH3B	FSCN2	O14926	708
IDH3B	IDH1	O75874	708

IntAct

92 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
LPAR1	TMEM223	psi-mi:“MI:0914”(association)	0.530
rep	NKRF	psi-mi:“MI:0914”(association)	0.500
IDH3B	MAPK6	psi-mi:“MI:0915”(physical association)	0.370
OTUB1		psi-mi:“MI:0914”(association)	0.350
OTUB1	EPM2A	psi-mi:“MI:0914”(association)	0.350
JUN	TPM3	psi-mi:“MI:0914”(association)	0.350
MYC	ILVBL	psi-mi:“MI:0914”(association)	0.350
HSCB	RBP5	psi-mi:“MI:0914”(association)	0.350
APBB1	SSPOP	psi-mi:“MI:0914”(association)	0.350
Prdm16	ESYT2	psi-mi:“MI:0914”(association)	0.350
Mecom	ESYT2	psi-mi:“MI:0914”(association)	0.350
BCL2L14		psi-mi:“MI:0914”(association)	0.350
IRF2	VWA8	psi-mi:“MI:0914”(association)	0.350
NT5C3A	VWA8	psi-mi:“MI:0914”(association)	0.350
TNFRSF10A	NAP1L4	psi-mi:“MI:0914”(association)	0.350
PA	ESYT2	psi-mi:“MI:0914”(association)	0.350
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350
ITM2B	ILVBL	psi-mi:“MI:0914”(association)	0.350
CARTPT	MEIS1	psi-mi:“MI:0914”(association)	0.350
IDH3B	DCX	psi-mi:“MI:0914”(association)	0.350
GPD1	IDH3B	psi-mi:“MI:0914”(association)	0.350
IDH3A	IDH3B	psi-mi:“MI:0914”(association)	0.350
GDF3	IDH3B	psi-mi:“MI:0914”(association)	0.350

BioGRID (139): IDH3B (Affinity Capture-RNA), IDH3B (Affinity Capture-RNA), IDH3B (Affinity Capture-MS), IDH3B (Affinity Capture-MS), IDH3B (Affinity Capture-MS), IDH3G (Affinity Capture-MS), DBT (Affinity Capture-MS), IDH3B (Affinity Capture-MS), CASP3 (Co-fractionation), IDH1 (Co-fractionation), IDH3B (Co-fractionation), IDH3B (Affinity Capture-MS), IDH3B (Proximity Label-MS), IDH3B (Proximity Label-MS), IDH3B (Proximity Label-MS)

ESM2 similar proteins: A2RRV9, A4FV58, A4QN59, A7SDA8, A8PGQ3, A8WH18, A8XZU0, B0WU52, B3N018, B3NKH7, B4GXC8, B4IMH3, B4ISL0, B4JBE6, B4KFU7, B4LQR5, B4MUM8, B4NSS7, B5DK31, B6K2N0, O43837, O77784, P29696, P37223, P41565, P51553, P70404, Q16ML2, Q28479, Q2YDU6, Q58CP0, Q5BK18, Q5RBT4, Q5RF36, Q68FX0, Q6CFR3, Q6DE00, Q6DHP6, Q6GP25, Q6ING7

Diamond homologs: A0PPY6, A4QDP9, A8L554, B0RIP4, B1VZ57, B2HIH1, B3DTF8, B7GUI8, C1B2M3, C3PFX5, C4LJH3, C5C2I9, D4GYE8, O13302, O13696, O14104, O27441, O29610, O29627, O43837, O59394, O67480, O77784, O81796, O86504, O94229, O94230, P05645, P12010, P24098, P28241, P28834, P29696, P33197, P40495, P41019, P41560, P41563, P41564, P41565

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
IDH3B	“form complex”	IDH	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 117 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Anchoring of the basal body to the plasma membrane	8	10.9×	4e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	8
Likely pathogenic	13
Uncertain significance	171
Likely benign	129
Benign	16

Top pathogenic / likely-pathogenic (21)

Variant ID	HGVS	Classification
1409852	NM_006899.5(IDH3B):c.128_138del (p.Val43fs)	Pathogenic
1513710	NM_006899.5(IDH3B):c.490C>T (p.Arg164Ter)	Pathogenic
1516744	NM_006899.5(IDH3B):c.184G>T (p.Glu62Ter)	Pathogenic
2135942	NM_006899.5(IDH3B):c.691C>T (p.Gln231Ter)	Pathogenic
2817124	NC_000020.11:g.2663759del	Pathogenic
4693955	NM_006899.5(IDH3B):c.115C>T (p.Gln39Ter)	Pathogenic
4702478	NM_006899.5(IDH3B):c.937C>T (p.Gln313Ter)	Pathogenic
5505	NM_006899.5(IDH3B):c.589del (p.Ile197fs)	Pathogenic
1396201	NM_006899.5(IDH3B):c.36+1G>A	Likely pathogenic
1512058	NM_006899.5(IDH3B):c.768+2T>G	Likely pathogenic
1974298	NM_006899.5(IDH3B):c.117+1G>T	Likely pathogenic
2082408	NM_006899.5(IDH3B):c.1010+1G>A	Likely pathogenic
2119719	NM_006899.5(IDH3B):c.532-2A>G	Likely pathogenic
3587148	NM_006899.5(IDH3B):c.918_924del (p.Ala307fs)	Likely pathogenic
3587149	NM_006899.5(IDH3B):c.700_703del (p.Glu234fs)	Likely pathogenic
3587150	NM_006899.5(IDH3B):c.667A>T (p.Lys223Ter)	Likely pathogenic
3587153	NM_006899.5(IDH3B):c.107C>A (p.Ser36Ter)	Likely pathogenic
3663424	NM_006899.5(IDH3B):c.531+1G>C	Likely pathogenic
632372	NM_006899.5(IDH3B):c.768+1G>T	Likely pathogenic
636036	NM_006899.5(IDH3B):c.59del (p.Pro20fs)	Likely pathogenic
844301	NM_006899.5(IDH3B):c.37-1G>A	Likely pathogenic

SpliceAI

1819 predictions. Top by Δscore:

Variant	Effect	Δscore
20:2658753:AGCTC:A	donor_gain	1.0000
20:2658757:C:CA	donor_gain	1.0000
20:2658861:C:CT	acceptor_gain	1.0000
20:2658862:G:C	acceptor_gain	1.0000
20:2659520:CTCA:C	donor_loss	1.0000
20:2659521:TCA:T	donor_loss	1.0000
20:2659522:CA:C	donor_loss	1.0000
20:2659524:C:CT	donor_loss	1.0000
20:2659581:CAAGA:C	acceptor_gain	1.0000
20:2659582:AAGA:A	acceptor_gain	1.0000
20:2659583:AGA:A	acceptor_gain	1.0000
20:2659584:GA:G	acceptor_gain	1.0000
20:2659586:C:A	acceptor_loss	1.0000
20:2659586:C:CC	acceptor_gain	1.0000
20:2659588:G:C	acceptor_gain	1.0000
20:2659592:A:AC	acceptor_gain	1.0000
20:2659592:A:C	acceptor_gain	1.0000
20:2659594:A:C	acceptor_gain	1.0000
20:2659697:A:AC	donor_gain	1.0000
20:2659698:C:CC	donor_gain	1.0000
20:2659701:A:AC	donor_gain	1.0000
20:2659702:A:C	donor_gain	1.0000
20:2659790:CACC:C	acceptor_gain	1.0000
20:2659792:CC:C	acceptor_gain	1.0000
20:2659793:CC:C	acceptor_gain	1.0000
20:2660173:CCAG:C	acceptor_gain	1.0000
20:2660174:CAGC:C	acceptor_gain	1.0000
20:2660371:C:CT	acceptor_gain	1.0000
20:2660455:A:AC	donor_gain	1.0000
20:2660456:C:CC	donor_gain	1.0000

AlphaMissense

2528 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:2659746:A:C	N321K	0.999
20:2659746:A:T	N321K	0.999
20:2660036:A:C	F303L	0.999
20:2660036:A:T	F303L	0.999
20:2660038:A:G	F303L	0.999
20:2660125:C:A	G274W	0.999
20:2660175:A:G	L257P	0.999
20:2660279:T:A	D251V	0.999
20:2660468:C:A	K218N	0.999
20:2660468:C:G	K218N	0.999
20:2660475:A:T	V216D	0.999
20:2660484:A:T	V213D	0.999
20:2660508:G:T	A205D	0.999
20:2660520:G:T	A201D	0.999
20:2660737:C:G	R164P	0.999
20:2660809:G:T	A140D	0.999
20:2663709:C:T	G56E	0.999
20:2658782:A:T	V376D	0.998
20:2659711:A:G	L333P	0.998
20:2659744:G:T	P322H	0.998
20:2659750:G:T	A320D	0.998
20:2660124:C:A	G274V	0.998
20:2660124:C:T	G274E	0.998
20:2660132:A:C	N271K	0.998
20:2660132:A:T	N271K	0.998
20:2660269:G:C	C254W	0.998
20:2660279:T:G	D251A	0.998
20:2660280:C:G	D251H	0.998
20:2660478:G:T	A215D	0.998
20:2660509:C:G	A205P	0.998

dbSNP variants (sampled 300 via entrez): RS1000377665 (20:2663833 G>A,C), RS1000398688 (20:2662243 T>C), RS1000768464 (20:2663810 G>A,T), RS1001138607 (20:2663627 G>A,C), RS1002224395 (20:2658623 C>A,G,T), RS1002227566 (20:2659017 G>A), RS1002316285 (20:2664986 C>T), RS1002386823 (20:2664573 C>G), RS1002533526 (20:2659924 T>C,G), RS1002829527 (20:2665002 G>A), RS1002845297 (20:2661010 C>A,G,T), RS1003286915 (20:2661399 T>A,C), RS1003725630 (20:2666189 T>G), RS1003846415 (20:2666118 C>T), RS1004003453 (20:2665926 A>C)

Disease associations

OMIM: gene MIM:604526 | disease phenotypes: MIM:612572, MIM:268000

GenCC curated gene-disease

Disease	Classification	Inheritance
retinitis pigmentosa 46	Strong	Autosomal recessive
retinitis pigmentosa	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
IDH3B-related retinopathy	Moderate	AR

Mondo (4): inherited retinal dystrophy (MONDO:0019118), retinitis pigmentosa 46 (MONDO:0012943), optic atrophy (MONDO:0003608), retinitis pigmentosa (MONDO:0019200)

Orphanet (2): OBSOLETE: Inherited retinal disorder (Orphanet:71862), Retinitis pigmentosa (Orphanet:791)

HPO phenotypes

36 total (30 of 36 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000405	Conductive hearing impairment
HP:0000407	Sensorineural hearing impairment
HP:0000501	Glaucoma
HP:0000505	Visual impairment
HP:0000510	Rod-cone dystrophy
HP:0000512	Abnormal electroretinogram
HP:0000543	Optic disc pallor
HP:0000546	Retinal degeneration
HP:0000551	Color vision defect
HP:0000563	Keratoconus
HP:0000580	Pigmentary retinopathy
HP:0000602	Ophthalmoplegia
HP:0000613	Photophobia
HP:0000618	Blindness
HP:0000639	Nystagmus
HP:0000648	Optic atrophy
HP:0000654	Decreased light- and dark-adapted electroretinogram amplitude
HP:0000662	Nyctalopia
HP:0000842	Hyperinsulinemia
HP:0001105	Retinal atrophy
HP:0001133	Constriction of peripheral visual field
HP:0007663	Reduced visual acuity
HP:0007675	Progressive night blindness
HP:0007703	Abnormal retinal pigmentation
HP:0007737	Spicular pigmentation of the retina
HP:0007787	Posterior subcapsular cataract
HP:0007843	Attenuation of retinal blood vessels
HP:0007994	Peripheral visual field loss
HP:0008046	Abnormal retinal vascular morphology

GWAS associations

0 associations (top):

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D009896	Optic Atrophy	C10.292.700.225; C11.640.451
D058499	Retinal Dystrophies	C11.768.585.658
D012174	Retinitis Pigmentosa	C11.270.684; C11.768.585.658.500; C16.320.290.684
C567249	Retinitis Pigmentosa 46 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066460 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, decreases expression, increases expression	3
perfluorooctanoic acid	increases expression, decreases expression	2
Acetaminophen	decreases expression	2
aristolochic acid I	increases expression	1
bisphenol F	increases expression	1
triphenyl phosphate	affects expression	1
decabromobiphenyl ether	affects expression	1
sodium arsenite	increases expression	1
ochratoxin A	decreases expression	1
acipimox	decreases expression	1
nickel sulfate	decreases expression	1
perfluorooctane sulfonic acid	decreases expression	1
perfluoro-n-nonanoic acid	decreases expression	1
K 7174	decreases expression	1
perfluorohexanesulfonic acid	decreases expression	1
nutlin 3	affects cotreatment, increases secretion	1
bisphenol B	increases expression	1
bisphenol AF	increases expression	1
Sunitinib	increases expression	1
Benzo(a)pyrene	increases methylation, affects methylation	1
Dactinomycin	affects cotreatment, increases secretion	1
Ivermectin	decreases expression	1
Lead	decreases expression	1
Fenofibrate	increases expression	1
Quercetin	decreases expression	1
Rotenone	decreases expression	1
Selenium	increases expression	1
Smoke	decreases expression	1
T-2 Toxin	increases expression	1
Vitamin E	increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651614	Binding	Binding affinity to human IDH3B incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00717080	PHASE4	COMPLETED	The Role of Capsular Tension Ring (CTR) in Anterior Capsular Contraction
NCT00000114	PHASE3	COMPLETED	Randomized Trial of Vitamin A and Vitamin E Supplementation for Retinitis Pigmentosa
NCT00000116	PHASE3	COMPLETED	Randomized Trial of DHA for Retinitis Pigmentosa Patients Receiving Vitamin A
NCT00346333	PHASE3	COMPLETED	Clinical Trial of Lutein for Patients With Retinitis Pigmentosa Receiving Vitamin A
NCT01786395	PHASE3	TERMINATED	Phase III Efficacy and Safety Clinical Study of UF-021 for Treatment of Retinitis Pigmentosa
NCT04224207	PHASE3	COMPLETED	Management of Retinitis Pigmentosa by Mesenchymal Stem Cells by Wharton’s Jelly Derived Mesenchymal Stem Cells
NCT04636853	PHASE3	COMPLETED	CB-PRP in Retinitis Pigmentosa and Dry Age-related Macular Degeneration
NCT05537220	PHASE3	ACTIVE_NOT_RECRUITING	Oral N-acetylcysteine for Retinitis Pigmentosa
NCT05800301	PHASE3	COMPLETED	Management of Retinitis Pigmentosa Via Combination of Wharton’s Jelly-derived Mesenchymal Stem Cells and Magnovision
NCT05926583	PHASE3	ACTIVE_NOT_RECRUITING	A Study of AAV5-hRKp.RPGR for the Treatment of Japanese Participants With X-linked Retinitis Pigmentosa
NCT06388200	PHASE3	ACTIVE_NOT_RECRUITING	A Phase 3 Study Of OCU400 Gene Therapy for the Treatment Of Retinitis Pigmentosa
NCT07082855	PHASE3	NOT_YET_RECRUITING	A Multicenter, Randomized, Double-Blind, Controlled Clinical Study of Minocycline for the Treatment of Retinitis Pigmentosa
NCT07290530	PHASE3	NOT_YET_RECRUITING	24-Month Trial of NPI-001 for the Preservation of Photoreceptors in Retinitis Pigmentosa Associated With Usher Syndrome
NCT00100230	PHASE2	COMPLETED	DHA and X-Linked Retinitis Pigmentosa
NCT00447980	PHASE2	COMPLETED	A Study of Encapsulated Cell Technology (ECT) Implant for Participants With Early Stage Retinitis Pigmentosa
NCT00447993	PHASE2	COMPLETED	A Study of Encapsulated Cell Technology (ECT) Implant for Patients With Late Stage Retinitis Pigmentosa
NCT01233609	PHASE2	COMPLETED	Trial of Oral Valproic Acid for Retinitis Pigmentosa
NCT01399515	PHASE2	COMPLETED	Efficacy and Safety of Oral Valproic Acid for Retinitis Pigmentosa
NCT01530659	PHASE2	COMPLETED	Retinal Imaging in CNTF -Releasing Encapsulated Cell Implant Treated Patients for Early-stage Retinitis Pigmentosa
NCT01560715	PHASE2	COMPLETED	Autologous Bone Marrow-Derived Stem Cells Transplantation For Retinitis Pigmentosa
NCT02609165	PHASE2	COMPLETED	Nerve Growth Factor Eye Drops Treatment in Patients With Retinitis Pigmentosa and Cystoid Macular Edema
NCT02661711	PHASE2	COMPLETED	Aflibercept for Macular Oedema With Underlying Retinitis Pigmentosa (AMOUR) Study
NCT02804360	PHASE2	UNKNOWN	Intravitreal Dexamethasone Implant in Retinitis Pigmentosa-related Macular Edema- a Retrospective Study
NCT02837640	PHASE2	UNKNOWN	Studying a Potential Protective Effect of L-Dopa on Retinitis Pigmentosa
NCT03073733	PHASE2	COMPLETED	Safety and Efficacy of Intravitreal Injection of Human Retinal Progenitor Cells in Adults With Retinitis Pigmentosa
NCT04068207	PHASE2	COMPLETED	Minocycline Treatment in Retinitis Pigmentosa
NCT04356716	PHASE2	COMPLETED	Sildenafil for Treatment of Choroidal Ischemia
NCT04604899	PHASE2	COMPLETED	Safety of Repeat Intravitreal Injection of Human Retinal Progenitor Cells (jCell) in Adult Subjects With Retinitis Pigmentosa
NCT04763369	PHASE2	UNKNOWN	Investigation of Therapeutic Efficacy and Safety of UMSCs for the Management of Retinitis Pigmentosa (RP)
NCT04864496	PHASE2	UNKNOWN	Effects of Treatment With N- Acetylcysteine on Visual Outcomes in Patients With Retinitis Pigmentosa
NCT04945772	PHASE2	COMPLETED	Efficacy and Safety of MCO-010 Optogenetic Therapy in Adults With Retinitis Pigmentosa [RESTORE]
NCT05085964	PHASE2	TERMINATED	An Open-Label Extension Study to Evaluate Safety & Tolerability of QR-421a in Subjects With Retinitis Pigmentosa
NCT05392179	PHASE2	COMPLETED	A Study in Subjects With Retinitis Pigmentosa
NCT06627179	PHASE2	RECRUITING	Study to Evaluate Ultevursen in Subjects With Retinitis Pigmentosa (RP) Due to Mutations in Exon 13 of the USH2A Gene
NCT06628947	PHASE2	RECRUITING	A Phase II Study of Intravitreal KIO-301 in Patients With Late-stage Retinitis Pigmentosa
NCT06912633	PHASE2	RECRUITING	Safety of a Single, Intravitreal Injection of 6.0M jCell (Famzeretcel) in Retinitis Pigmentosa (RP)
NCT03763227	PHASE2	COMPLETED	Intravitreal Ranibizumab (Lucentis®) in the Treatment of Non-leaking Macular Cysts in Retinal Dystrophy
NCT00063765	PHASE1	COMPLETED	Evaluation of Safety of Ciliary Neurotrophic Factor Implants in the Eye
NCT00065455	PHASE1	COMPLETED	Investigating the Effect of Vitamin A Supplementation on Retinitis Pigmentosa
NCT00458575	PHASE1	TERMINATED	A Study to Evaluate the Safety of CNTO 2476 in Patients With Advanced Retinitis Pigmentosa