IDH3G

Summary

IDH3G (isocitrate dehydrogenase (NAD(+)) 3 non-catalytic subunit gamma, HGNC:5386) is a protein-coding gene on chromosome Xq28, encoding Isocitrate dehydrogenase [NAD] subunit gamma, mitochondrial (P51553). Regulatory subunit which plays a role in the allosteric regulation 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 gamma subunit of one isozyme of NAD(+)-dependent isocitrate dehydrogenase. This gene is a candidate gene for periventricular heterotopia. Several alternatively spliced transcript variants of this gene have been described, but only some of their full length natures have been determined.

Source: NCBI Gene 3421 — RefSeq curated summary.

At a glance

• Gene–disease (curated): retinitis pigmentosa (Limited, GenCC)
• Clinical variants (ClinVar): 110 total — 3 pathogenic
• Phenotypes (HPO): 14
• MANE Select transcript: NM_004135

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5386
Approved symbol	IDH3G
Name	isocitrate dehydrogenase (NAD(+)) 3 non-catalytic subunit gamma
Location	Xq28
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000067829
Ensembl biotype	protein_coding
OMIM	300089
Entrez	3421

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 19 protein_coding, 4 protein_coding_CDS_not_defined

ENST00000217901, ENST00000370092, ENST00000370093, ENST00000427365, ENST00000444338, ENST00000444450, ENST00000454076, ENST00000461215, ENST00000491235, ENST00000495356, ENST00000497043, ENST00000854366, ENST00000854367, ENST00000918597, ENST00000958648, ENST00000958649, ENST00000958650, ENST00000958651, ENST00000958652, ENST00000958653, ENST00000958654, ENST00000958655, ENST00000958656

RefSeq mRNA: 2 — MANE Select: NM_004135 NM_004135, NM_174869

CCDS: CCDS14730, CCDS44019

Canonical transcript exons

ENST00000217901 — 13 exons

Exon	Start	End
ENSE00000677981	153786355	153786449
ENSE00001936970	153785768	153785973
ENSE00001957990	153794246	153794375
ENSE00003463871	153787823	153787955
ENSE00003504709	153789712	153789824
ENSE00003508844	153787464	153787597
ENSE00003519867	153790564	153790575
ENSE00003556866	153788075	153788135
ENSE00003604601	153790810	153790851
ENSE00003684698	153786212	153786272
ENSE00003690050	153790195	153790292
ENSE00003785199	153787051	153787153
ENSE00003790147	153786801	153786947

Expression profiles

Bgee: expression breadth ubiquitous, 299 present calls, max score 97.51.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 93.3599 / max 326.1704, expressed in 1824 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
200906	52.1069	1820
200905	41.0934	1817
200907	0.1436	29
200904	0.0159	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	97.51	gold quality
cerebellar hemisphere	UBERON:0002245	97.19	gold quality
cerebellar cortex	UBERON:0002129	97.15	gold quality
mucosa of stomach	UBERON:0001199	97.14	gold quality
mucosa of transverse colon	UBERON:0004991	97.04	gold quality
apex of heart	UBERON:0002098	97.01	gold quality
right atrium auricular region	UBERON:0006631	96.99	gold quality
left adrenal gland	UBERON:0001234	96.83	gold quality
right adrenal gland	UBERON:0001233	96.82	gold quality
left adrenal gland cortex	UBERON:0035825	96.78	gold quality
right adrenal gland cortex	UBERON:0035827	96.76	gold quality
hindlimb stylopod muscle	UBERON:0004252	96.72	gold quality
right frontal lobe	UBERON:0002810	96.68	gold quality
heart left ventricle	UBERON:0002084	96.65	gold quality
cerebellum	UBERON:0002037	96.63	gold quality
granulocyte	CL:0000094	96.61	gold quality
transverse colon	UBERON:0001157	96.57	gold quality
gastrocnemius	UBERON:0001388	96.55	gold quality
cardiac ventricle	UBERON:0002082	96.55	gold quality
cardiac atrium	UBERON:0002081	96.49	gold quality
popliteal artery	UBERON:0002250	96.47	gold quality
tibial artery	UBERON:0007610	96.47	gold quality
small intestine Peyer’s patch	UBERON:0003454	96.40	gold quality
nucleus accumbens	UBERON:0001882	96.34	gold quality
metanephros cortex	UBERON:0010533	96.34	gold quality
aorta	UBERON:0000947	96.31	gold quality
adrenal cortex	UBERON:0001235	96.29	gold quality
left uterine tube	UBERON:0001303	96.22	gold quality
thoracic aorta	UBERON:0001515	96.17	gold quality
ascending aorta	UBERON:0001496	96.16	gold quality

Single-cell (SCXA)

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

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

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

12 targeting IDH3G, 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-4481	100.00	66.42	1669
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-18A-5P	99.29	71.05	806
HSA-MIR-18B-5P	99.29	71.05	806
HSA-MIR-4735-3P	99.14	69.85	777
HSA-MIR-6506-5P	99.04	65.66	1386
HSA-MIR-6760-5P	98.87	66.73	1515
HSA-MIR-3135B	98.61	65.33	1470
HSA-MIR-619-5P	98.57	64.97	1988
HSA-MIR-4664-5P	98.17	65.07	1020
HSA-MIR-4314	97.50	67.30	1369
HSA-MIR-342-5P	97.25	64.10	817

Literature-anchored findings (GeneRIF, showing 2)

• active sites of the human NAD-IDH are shared between alpha and gamma subunits and between alpha and beta subunits (PMID:16737955)
• Aspartate-190 is a determinant of IDH gamma subunit affinity for the manganese (MnII) ion, as well as for nicotinamide-adenine dinucleotide (NAD), but is not directly required for the catalytic reaction. (PMID:17432878)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	idh3g	ENSDARG00000023648
mus_musculus	Idh3g	ENSMUSG00000002010
rattus_norvegicus	Idh3g	ENSRNOG00000055572
drosophila_melanogaster	CG7755	FBGN0034105
drosophila_melanogaster	Idh3g	FBGN0039358
caenorhabditis_elegans		WBGENE00009440
caenorhabditis_elegans	idhg-2	WBGENE00016266

Paralogs (2): IDH3B (ENSG00000101365), IDH3A (ENSG00000166411)

Protein

Protein identifiers

Isocitrate dehydrogenase [NAD] subunit gamma, mitochondrial — P51553 (reviewed: P51553)

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

All UniProt accessions (6): P51553, E7EQB8, E9PF84, G5E9Q7, H0Y5Q7, H7C1W2

UniProt curated annotations — full annotation on UniProt →

Function. Regulatory subunit which plays a role in the allosteric regulation 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. Photoreceptor inner segment.

Disease relevance. Retinitis pigmentosa 99 (RP99) [MIM:301148] An X-linked recessive form of retinitis pigmentosa, 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. The disease may be 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.

Cofactor. Divalent metal cations; Mn(2+) or Mg(2+). Activity higher in presence of Mn(2+) than of Mg(2+). Binds 1 Mg(2+) or Mn(2+) ion per subunit.

Similarity. Belongs to the isocitrate and isopropylmalate dehydrogenases family.

Isoforms (2)

UniProt ID	Names	Canonical?
P51553-1	1	yes
P51553-2	2

RefSeq proteins (2): NP_004126, NP_777358 (=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 (67 total): mutagenesis site 16, strand 16, helix 14, binding site 9, sequence variant 4, turn 4, transit peptide 1, chain 1, splice variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

12 structures.

PDB	Method	Resolution (Å)
6L59	X-RAY DIFFRACTION	2.25
6L57	X-RAY DIFFRACTION	2.3
5GRI	X-RAY DIFFRACTION	2.31
5YVT	X-RAY DIFFRACTION	2.4
5GRF	X-RAY DIFFRACTION	2.5
8GRH	X-RAY DIFFRACTION	2.51
5GRE	X-RAY DIFFRACTION	2.65
8GRG	X-RAY DIFFRACTION	2.7
5GRL	X-RAY DIFFRACTION	2.79
5GRH	X-RAY DIFFRACTION	2.8
7CE3	X-RAY DIFFRACTION	3.47
8GS5	X-RAY DIFFRACTION	4.49

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P51553-F1	89.04	0.81

Functional residue map

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

Ligand- & substrate-binding residues (9): 324; 120; 133; 136; 167; 254; 254; 312; 313

Mutagenesis-validated functional residues (16):

Position	Phenotype
117	no effect on the activation of the heterodimer composed of idh3a and idh3g subunits by citrate.
120	significantly impairs the activation of the heterodimer composed of idh3a and idh3g subunits by citrate.
130	no significant effect on the activation of the heterodimer composed of idh3a and idh3g subunits by citrate.
133	significantly impairs the activation of the heterodimer composed of idh3a and idh3g subunits by citrate.
136	significantly impairs the activation of the heterodimer composed of idh3a and idh3g subunits by citrate.
167	significantly impairs the activation of the heterodimer composed of idh3a and idh3g subunits by citrate.
173	no effect on the activation of the heterodimer composed of idh3a and idh3g subunits by citrate and adp.
174	significantly impairs the activation of the heterodimer composed of idh3a and idh3g subunits by citrate.
190	complete loss of the activation of the heterotetramer and the heterodimer composed of idh3a and idh3g subunits by citrat
229	significantly impairs the activation of the heterodimer composed of idh3a and idh3g subunits by citrate and adp.
276	significantly impairs the activation of the heterodimer composed of idh3a and idh3g subunits by citrate and adp.
311	significantly impairs the activation of the heterodimer composed of idh3a and idh3g subunits by citrate.
312	significantly impairs the activation of the heterodimer composed of idh3a and idh3g subunits by adp.
313	significantly impairs the activation of the heterodimer composed of idh3a and idh3g subunits by adp.
315	no significant effect on the activation of the heterodimer composed of idh3a and idh3g subunits by adp.
324	complete loss of the activation of the heterodimer composed of idh3a and idh3g subunits by adp.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-1268020	Mitochondrial protein import
R-HSA-71403	Citric acid cycle (TCA cycle)

MSigDB gene sets: 166 (showing top): STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, AAGCCAT_MIR135A_MIR135B, MORF_HDAC1, MORF_HDAC2, CCATCCA_MIR432, GOBP_GENERATION_OF_PRECURSOR_METABOLITES_AND_ENERGY, MARTINEZ_RB1_TARGETS_UP, WATANABE_RECTAL_CANCER_RADIOTHERAPY_RESPONSIVE_UP, MORF_RAB6A, GOBP_TRICARBOXYLIC_ACID_METABOLIC_PROCESS, WTGAAAT_UNKNOWN, MORF_BUB3, GOBP_CARBOHYDRATE_METABOLIC_PROCESS, GOBP_ORGANIC_ACID_METABOLIC_PROCESS, GCM_NF2

GO Biological Process (3): carbohydrate metabolic process (GO:0005975), tricarboxylic acid cycle (GO:0006099), isocitrate metabolic process (GO:0006102)

GO Molecular Function (8): magnesium ion binding (GO:0000287), isocitrate dehydrogenase (NAD+) activity (GO:0004449), ATP binding (GO:0005524), NAD binding (GO:0051287), nucleotide binding (GO:0000166), protein binding (GO:0005515), oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor (GO:0016616), metal ion binding (GO:0046872)

GO Cellular Component (5): photoreceptor inner segment (GO:0001917), nucleolus (GO:0005730), mitochondrion (GO:0005739), mitochondrial matrix (GO:0005759), isocitrate dehydrogenase complex (NAD+) (GO:0045242)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Protein localization	1
Aerobic respiration and respiratory electron transport	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
primary metabolic process	2
aerobic respiration	1
tricarboxylic acid metabolic process	1
secondary alcohol metabolic process	1
metal ion binding	1
isocitrate dehydrogenase [NAD(P)+] activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
adenyl nucleotide binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
oxidoreductase activity, acting on CH-OH group of donors	1
cation binding	1
cellular anatomical structure	1
nuclear lumen	1
intracellular membraneless organelle	1
cytoplasm	1
intracellular membrane-bounded organelle	1
mitochondrion	1
intracellular organelle lumen	1
tricarboxylic acid cycle heteromeric enzyme complex	1
oxidoreductase complex	1

Protein interactions and networks

STRING

2640 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IDH3G	IDH3A	P50213	967
IDH3G	IDH2	P48735	951
IDH3G	IDH1	O75874	924
IDH3G	IDH3B	O43837	919
IDH3G	SSR4	P51571	825
IDH3G	PDHB	P11177	741
IDH3G	MDH2	P40926	713
IDH3G	OGDH	Q02218	700
IDH3G	SUCLG1	P53597	688
IDH3G	ACO2	Q99798	670
IDH3G	SUCLA2	Q9P2R7	660
IDH3G	CS	O75390	616
IDH3G	NNT	Q13423	612
IDH3G	OGDHL	Q9ULD0	604
IDH3G	PKM	P14618	597

IntAct

60 interactions, top by confidence:

A	B	Type	Score
IDH3A	IDH3G	psi-mi:“MI:0407”(direct interaction)	0.820
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
HSPD1	NUDT19	psi-mi:“MI:0914”(association)	0.710
IDH3A	IDH3B	psi-mi:“MI:0915”(physical association)	0.690
IDH3A	IDH3B	psi-mi:“MI:0914”(association)	0.690
IDH3G	HSPD1	psi-mi:“MI:0915”(physical association)	0.640
	IDH3A	psi-mi:“MI:0407”(direct interaction)	0.610
BPNT1	GTPBP10	psi-mi:“MI:0914”(association)	0.530
LPAR1	TMEM223	psi-mi:“MI:0914”(association)	0.530
MBIP	TADA2A	psi-mi:“MI:0914”(association)	0.530
	IDH3A	psi-mi:“MI:0407”(direct interaction)	0.440
	IDH3B	psi-mi:“MI:0915”(physical association)	0.400
MYC	ILVBL	psi-mi:“MI:0914”(association)	0.350
KSR1	FAM168B	psi-mi:“MI:0914”(association)	0.350
ORF26	ATP1B1	psi-mi:“MI:0914”(association)	0.350
LRRK2		psi-mi:“MI:0914”(association)	0.350
IDH3B	DBT	psi-mi:“MI:0914”(association)	0.350
NDUFA4	NUDT19	psi-mi:“MI:0914”(association)	0.350
NDUFS3	ACOT7	psi-mi:“MI:0914”(association)	0.350
CIAO1	SOX1	psi-mi:“MI:0914”(association)	0.350
MALSU1	VWA8	psi-mi:“MI:0914”(association)	0.350
PTH2R	METTL15	psi-mi:“MI:0914”(association)	0.350
RPL35A	SMCHD1	psi-mi:“MI:0914”(association)	0.350

BioGRID (94): IDH3G (Affinity Capture-MS), IDH3G (Affinity Capture-MS), ACO2 (Co-fractionation), IDH1 (Co-fractionation), IDH3A (Co-fractionation), IDH3G (Co-fractionation), IDH3G (Co-fractionation), KPNA2 (Co-fractionation), IDH3G (Affinity Capture-MS), IDH3G (Affinity Capture-MS), IDH3G (Affinity Capture-MS), IDH3G (Affinity Capture-MS), IDH3G (Affinity Capture-MS), HSPD1 (Affinity Capture-MS), IDH3G (Affinity Capture-MS)

ESM2 similar proteins: A1A4J1, A2E9H3, A2EF58, C4QXA5, O42938, O61068, O83146, O94200, O94201, P00511, P08237, P12382, P16862, P17858, P30835, P47857, P47858, P47859, P47860, P51553, P52034, P52784, P59680, P78985, Q01813, Q03216, Q0IIG5, Q27483, Q27665, Q27705, Q27778, Q2HYU2, Q2RNU4, Q4W9B8, Q5R636, Q5R7V5, Q5RAG9, Q60HD9, Q867C9, Q8TGA0

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
IDH3G	“form complex”	IDH	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	0
Uncertain significance	28
Likely benign	3
Benign	1

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
3897910	NM_004135.4(IDH3G):c.325C>G (p.Arg109Gly)	Pathogenic
3897911	NM_004135.4(IDH3G):c.1129C>T (p.Gln377Ter)	Pathogenic
987741	Single allele	Pathogenic

SpliceAI

2634 predictions. Top by Δscore:

Variant	Effect	Δscore
X:153786347:CCACT:C	donor_loss	1.0000
X:153786348:CACTC:C	donor_loss	1.0000
X:153786349:ACTCA:A	donor_loss	1.0000
X:153786351:TCAC:T	donor_loss	1.0000
X:153786352:CACTT:C	donor_loss	1.0000
X:153786353:A:AC	donor_gain	1.0000
X:153786353:A:C	donor_loss	1.0000
X:153786354:C:CC	donor_gain	1.0000
X:153786354:CT:C	donor_gain	1.0000
X:153786354:CTT:C	donor_gain	1.0000
X:153786354:CTTG:C	donor_gain	1.0000
X:153786354:CTTGA:C	donor_gain	1.0000
X:153786445:GTAGC:G	acceptor_gain	1.0000
X:153786446:TAGC:T	acceptor_gain	1.0000
X:153786447:AGC:A	acceptor_gain	1.0000
X:153786447:AGCC:A	acceptor_loss	1.0000
X:153786448:GC:G	acceptor_gain	1.0000
X:153786449:CC:C	acceptor_gain	1.0000
X:153786449:CCTG:C	acceptor_loss	1.0000
X:153786450:C:CC	acceptor_gain	1.0000
X:153786451:T:A	acceptor_loss	1.0000
X:153786459:C:CT	acceptor_gain	1.0000
X:153786460:A:T	acceptor_gain	1.0000
X:153786785:TGC:T	donor_gain	1.0000
X:153786795:ACTCA:A	donor_loss	1.0000
X:153786797:TCA:T	donor_loss	1.0000
X:153786798:CACT:C	donor_loss	1.0000
X:153786799:A:AC	donor_gain	1.0000
X:153786799:ACTGT:A	donor_loss	1.0000
X:153786800:C:CA	donor_gain	1.0000

AlphaMissense

2598 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:153786442:C:A	R311M	1.000
X:153786807:A:C	F306L	1.000
X:153786807:A:T	F306L	1.000
X:153786809:A:G	F306L	1.000
X:153786895:C:T	G277D	1.000
X:153787067:T:A	D254V	1.000
X:153787475:C:A	K221N	1.000
X:153787475:C:G	K221N	1.000
X:153787843:A:G	Y174H	1.000
X:153787856:G:C	N169K	1.000
X:153787856:G:T	N169K	1.000
X:153789712:C:G	G116R	1.000
X:153789713:C:A	K115N	1.000
X:153789713:C:G	K115N	1.000
X:153790243:C:T	G62E	1.000
X:153790244:C:A	G62W	1.000
X:153786358:A:G	L339P	0.999
X:153786367:A:G	L336P	0.999
X:153786367:A:T	L336Q	0.999
X:153786370:A:C	M335R	0.999
X:153786378:G:C	S332R	0.999
X:153786378:G:T	S332R	0.999
X:153786380:T:G	S332R	0.999
X:153786402:G:C	N324K	0.999
X:153786402:G:T	N324K	0.999
X:153786406:G:T	A323D	0.999
X:153786441:C:A	R311S	0.999
X:153786441:C:G	R311S	0.999
X:153786442:C:G	R311T	0.999
X:153786805:T:A	E307V	0.999

dbSNP variants (sampled 300 via entrez): RS1000061564 (X:153786012 G>A), RS1000114958 (X:153785760 G>A,T), RS1001972850 (X:153790962 G>A,T), RS1002300712 (X:153791421 A>G), RS1002542494 (X:153796209 C>T), RS1002631891 (X:153787690 C>A), RS1004042473 (X:153789374 T>C,G), RS1005928264 (X:153788600 G>A), RS1006455913 (X:153796218 C>T), RS1006747489 (X:153792922 A>G), RS1007233517 (X:153792503 C>A), RS1007821461 (X:153794355 C>A,T), RS1008163661 (X:153794663 T>C), RS1008499868 (X:153790703 G>A,C), RS1009972424 (X:153785733 T>G)

Disease associations

OMIM: gene MIM:300089 | disease phenotypes: MIM:301148, MIM:603513, MIM:612900, MIM:300934

GenCC curated gene-disease

Disease	Classification	Inheritance
retinitis pigmentosa	Limited	X-linked

Mondo (4): retinitis pigmentosa 99 (MONDO:0978291), spastic quadriplegic cerebral palsy (MONDO:0016215), SSR4-congenital disorder of glycosylation (MONDO:0010490), retinitis pigmentosa (MONDO:0019200)

Orphanet (2): Inherited congenital spastic tetraplegia (Orphanet:210141), SSR4-CDG (Orphanet:370927)

HPO phenotypes

14 total (14 of 14 shown, HPO-id order):

HPO	Term
HP:0000543	Optic disc pallor
HP:0000662	Nyctalopia
HP:0001133	Constriction of peripheral visual field
HP:0001419	X-linked recessive inheritance
HP:0007722	Retinal pigment epithelial atrophy
HP:0007737	Spicular pigmentation of the retina
HP:0008043	Focal retinal arteriolar constriction
HP:0011003	High myopia
HP:0011462	Young adult onset
HP:0025159	Hypoautofluorescent retinal lesion
HP:0030529	Ring scotoma
HP:0030629	Perifoveal ring of hyperautofluorescence
HP:0032037	Mildly reduced visual acuity
HP:0034362	Dull foveal reflex

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D012174	Retinitis Pigmentosa	C11.270.684; C11.768.585.658.500; C16.320.290.684

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	2
Valproic Acid	decreases expression, affects cotreatment, increases expression	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
bisphenol F	increases expression	1
moringin	affects cotreatment, increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
beta-lapachone	decreases expression	1
ochratoxin A	decreases expression	1
benzo(e)pyrene	increases methylation	1
potassium chromate(VI)	decreases expression	1
bisphenol B	increases expression	1
abrine	increases expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	decreases expression	1
bisphenol S	increases expression	1
(+)-JQ1 compound	decreases expression	1
Sunitinib	decreases expression	1
Benzo(a)pyrene	increases methylation, affects methylation	1
Cannabidiol	affects cotreatment, increases expression	1
Citrinin	increases expression	1
Diazinon	increases methylation	1
Gold	affects binding, increases expression	1
Hydralazine	affects cotreatment, increases expression	1
Isoniazid	increases expression, decreases expression	1
Ivermectin	decreases expression	1
Manganese	affects binding	1
Methapyrilene	increases methylation	1
Phenobarbital	affects expression	1
Polyethyleneimine	affects binding, increases expression	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B2Z8	Abcam HEK293T IDH3G KO	Transformed cell line	Female

Clinical trials (associated diseases)

236 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)
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
NCT01068561	PHASE1	COMPLETED	Autologous Bone Marrow-Derived Stem Cells Transplantation For Retinitis Pigmentosa