IDI2

Summary

IDI2 (isopentenyl-diphosphate delta isomerase 2, HGNC:23487) is a protein-coding gene on chromosome 10p15.3, encoding Isopentenyl-diphosphate delta-isomerase 2 (Q9BXS1). Catalyzes the 1,3-allylic rearrangement of the homoallylic substrate isopentenyl (IPP) to its highly electrophilic allylic isomer, dimethylallyl diphosphate (DMAPP).

The protein encoded by this gene catalyzes the conversion of isopentenyl diphosphate to dimethylallyl diphosphate, which is a precursor for the synthesis of cholesterol and other isoprenoids. This gene, which is a product of an ancestral gene duplication event, encodes a protein that may be involved in the aggregation of alpha-synuclein in the cerebral cortex of patients with Lewy body disease. In addition, segmental copy number gains in this locus have been associated with sporadic amyotrophic lateral sclerosis.

Source: NCBI Gene 91734 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 30 total — 1 pathogenic
• MANE Select transcript: NM_033261

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23487
Approved symbol	IDI2
Name	isopentenyl-diphosphate delta isomerase 2
Location	10p15.3
Locus type	gene with protein product
Status	Approved
Aliases	IPPI2
Ensembl gene	ENSG00000148377
Ensembl biotype	protein_coding
OMIM	615389
Entrez	91734

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000277517, ENST00000955306

RefSeq mRNA: 1 — MANE Select: NM_033261 NM_033261

CCDS: CCDS7055

Canonical transcript exons

ENST00000277517 — 5 exons

Exon	Start	End
ENSE00000984873	1022683	1022775
ENSE00000984874	1020767	1020897
ENSE00000998522	1025816	1025859
ENSE00000998523	1018910	1019834
ENSE00001388610	1024582	1024744

Expression profiles

Bgee: expression breadth broad, 84 present calls, max score 97.85.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.5711 / max 488.0224, expressed in 19 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
107871	0.5711	19

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
hindlimb stylopod muscle	UBERON:0004252	97.85	gold quality
gastrocnemius	UBERON:0001388	97.45	gold quality
vastus lateralis	UBERON:0001379	96.22	gold quality
quadriceps femoris	UBERON:0001377	96.15	gold quality
skeletal muscle organ	UBERON:0014892	95.34	gold quality
muscle of leg	UBERON:0001383	95.30	gold quality
skeletal muscle tissue	UBERON:0001134	95.24	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	94.90	gold quality
biceps brachii	UBERON:0001507	94.70	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	94.23	gold quality
deltoid	UBERON:0001476	93.75	gold quality
muscle tissue	UBERON:0002385	88.13	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.00	gold quality
oocyte	CL:0000023	65.28	gold quality
oviduct epithelium	UBERON:0004804	64.80	silver quality
myocardium	UBERON:0002349	60.00	gold quality
trabecular bone tissue	UBERON:0002483	59.81	silver quality
heart right ventricle	UBERON:0002080	58.44	gold quality
jejunum	UBERON:0002115	57.29	gold quality
body of tongue	UBERON:0011876	56.70	gold quality
tongue	UBERON:0001723	56.40	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	56.00	gold quality
superior surface of tongue	UBERON:0007371	54.99	gold quality
decidua	UBERON:0002450	54.70	gold quality
vena cava	UBERON:0004087	54.27	gold quality
lateral nuclear group of thalamus	UBERON:0002736	54.13	gold quality
nasal cavity epithelium	UBERON:0005384	53.95	gold quality
germinal epithelium of ovary	UBERON:0001304	53.67	gold quality
sperm	CL:0000019	53.60	gold quality
pharyngeal mucosa	UBERON:0000355	53.54	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.22

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

39 targeting IDI2, 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-4673	100.00	66.64	1490
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-8062	99.88	68.43	995
HSA-MIR-520F-3P	99.82	71.32	1216
HSA-MIR-3681-5P	99.82	66.88	387
HSA-MIR-8076	99.78	68.52	1170
HSA-MIR-3913-5P	99.78	67.26	968
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-5093	99.67	69.26	2291
HSA-MIR-6849-5P	99.64	66.00	352
HSA-MIR-425-5P	99.59	67.67	900
HSA-MIR-105-5P	99.54	69.24	2060
HSA-MIR-7853-5P	99.54	69.30	2055
HSA-MIR-3122	99.50	66.33	821
HSA-MIR-5584-5P	99.49	68.22	2814
HSA-MIR-12131	99.48	68.72	1673
HSA-MIR-12132	99.47	68.90	1341
HSA-MIR-1911-3P	99.15	66.17	528
HSA-MIR-146A-3P	99.13	68.99	1881
HSA-MIR-4795-5P	99.11	66.90	876
HSA-MIR-5583-3P	99.06	65.68	1018
HSA-MIR-10524-5P	99.05	66.08	963
HSA-MIR-511-5P	98.97	70.94	2268
HSA-MIR-4711-3P	98.97	66.87	1020
HSA-MIR-1261	98.62	68.10	896
HSA-MIR-4317	98.49	67.09	987

Literature-anchored findings (GeneRIF, showing 4)

• IDI2 is expressed at high levels only in skeletal muscle, where it may be involved in the specialized production of isoprenyl diphosphates for the posttranslational modification of proteins. (PMID:14629038)
• Enzyme kinetic analysis; both isozymes IDI1 and IDI2 are localized to the peroxisome by a PTS1-dependent pathway; data suggest that IDI2 is regulated independently from IDI1, by a mechanism that may involve PPARalpha (PMID:17202134)
• Within the 40-kb region on 10p15.3 subtelomere, which harbours two genes encoding isopentenyl diphosphate isomerase 1 (IDI1) and IDI2, there was found a segmental copy-number gain in a large proportion of sporadic amyotrophic lateral sclerosis patients. (PMID:20955688)
• The present findings suggest that IDI1 and IDI2 may be associated with the production of cholesterol metabolites in neurons, leading to alpha-synuclein aggregation during the process of Lewy body formation. (PMID:25950736)

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
danio_rerio	idi1	ENSDARG00000019976
mus_musculus	Idi2l	ENSMUSG00000021148
mus_musculus	Idi2	ENSMUSG00000033520
rattus_norvegicus		ENSRNOG00000073631
rattus_norvegicus		ENSRNOG00000078548
rattus_norvegicus		ENSRNOG00000080401
rattus_norvegicus		ENSRNOG00000085059
drosophila_melanogaster	Idi	FBGN0038876
caenorhabditis_elegans		WBGENE00019460

Paralogs (1): IDI1 (ENSG00000067064)

Protein

Protein identifiers

Isopentenyl-diphosphate delta-isomerase 2 — Q9BXS1 (reviewed: Q9BXS1)

Alternative names: Isopentenyl pyrophosphate isomerase 2

All UniProt accessions (1): Q9BXS1

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the 1,3-allylic rearrangement of the homoallylic substrate isopentenyl (IPP) to its highly electrophilic allylic isomer, dimethylallyl diphosphate (DMAPP).

Subcellular location. Peroxisome.

Tissue specificity. Muscle-specific expression.

Cofactor. Binds 1 Mg(2+) ion per subunit.

Pathway. Isoprenoid biosynthesis; dimethylallyl diphosphate biosynthesis; dimethylallyl diphosphate from isopentenyl diphosphate: step 1/1.

Similarity. Belongs to the IPP isomerase type 1 family.

RefSeq proteins (1): NP_150286* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000086	NUDIX_hydrolase_dom	Domain
IPR011876	IsopentenylPP_isomerase_typ1	Family
IPR015797	NUDIX_hydrolase-like_dom_sf	Homologous_superfamily

Pfam: PF00293

Catalyzed reactions (Rhea), 1 shown:

• isopentenyl diphosphate = dimethylallyl diphosphate (RHEA:23284)

UniProt features (38 total): helix 13, strand 9, binding site 8, turn 3, active site 2, chain 1, domain 1, short sequence motif 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2PNY	X-RAY DIFFRACTION	1.81

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BXS1-F1	95.85	0.92

Functional residue map

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

Catalytic / active sites (2): 86; 148

Ligand- & substrate-binding residues (8): 87; 146; 148; 36; 40; 51; 70; 74

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-9969896	Lanosterol biosynthesis
R-HSA-191273	Cholesterol biosynthesis

MSigDB gene sets: 66 (showing top): GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_PHOSPHOLIPID_BIOSYNTHETIC_PROCESS, GOBP_SMALL_MOLECULE_BIOSYNTHETIC_PROCESS, GOBP_STEROID_BIOSYNTHETIC_PROCESS, KEGG_TERPENOID_BACKBONE_BIOSYNTHESIS, GOBP_LIPID_METABOLIC_PROCESS, GOBP_LIPID_BIOSYNTHETIC_PROCESS, GOBP_STEROL_BIOSYNTHETIC_PROCESS, GOBP_ISOPRENOID_BIOSYNTHETIC_PROCESS, REACTOME_CHOLESTEROL_BIOSYNTHESIS, GOBP_ALCOHOL_BIOSYNTHETIC_PROCESS, GOBP_ISOPRENOID_METABOLIC_PROCESS, chr10p15

GO Biological Process (10): cholesterol biosynthetic process (GO:0006695), isoprenoid biosynthetic process (GO:0008299), isopentenyl diphosphate biosynthetic process (GO:0009240), isopentenyl diphosphate metabolic process (GO:0046490), dimethylallyl diphosphate biosynthetic process (GO:0050992), lipid metabolic process (GO:0006629), steroid biosynthetic process (GO:0006694), steroid metabolic process (GO:0008202), cholesterol metabolic process (GO:0008203), sterol biosynthetic process (GO:0016126)

GO Molecular Function (5): isopentenyl-diphosphate delta-isomerase activity (GO:0004452), metal ion binding (GO:0046872), protein binding (GO:0005515), isomerase activity (GO:0016853), intramolecular oxidoreductase activity (GO:0016860)

GO Cellular Component (3): cytoplasm (GO:0005737), peroxisome (GO:0005777), cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Cholesterol biosynthesis	1
Metabolism of steroids	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
lipid biosynthetic process	2
phospholipid biosynthetic process	2
sterol metabolic process	2
cellular anatomical structure	2
cholesterol metabolic process	1
sterol biosynthetic process	1
secondary alcohol biosynthetic process	1
isoprenoid metabolic process	1
isoprenoid biosynthetic process	1
isopentenyl diphosphate metabolic process	1
phospholipid metabolic process	1
dimethylallyl diphosphate metabolic process	1
primary metabolic process	1
steroid metabolic process	1
lipid metabolic process	1
secondary alcohol metabolic process	1
steroid biosynthetic process	1
intramolecular oxidoreductase activity, transposing C=C bonds	1
cation binding	1
binding	1
catalytic activity	1
isomerase activity	1
intracellular anatomical structure	1
microbody	1
cytoplasm	1

Protein interactions and networks

STRING

768 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IDI2	MVD	P53602	804
IDI2	GGPS1	O95749	802
IDI2	MVK	Q03426	771
IDI2	PMVK	Q15126	760
IDI2	FDPS	P14324	742
IDI2	FDFT1	P37268	724
IDI2	SQLE	Q14534	710
IDI2	HMGCR	P04035	709
IDI2	HMGCS1	Q01581	687
IDI2	ACAT2	Q9BWD1	682
IDI2	ACAT1	P24752	660
IDI2	LSS	P48449	643
IDI2	HMGCS2	P54868	628
IDI2	DHCR7	Q9UBM7	609
IDI2	SC5D	O75845	581

IntAct

13 interactions, top by confidence:

A	B	Type	Score
LDB1	IDI2	psi-mi:“MI:0915”(physical association)	0.670
RNF114	IDI2	psi-mi:“MI:0915”(physical association)	0.400
IDI2	LMX1B	psi-mi:“MI:0914”(association)	0.350
RNF114	USO1	psi-mi:“MI:0914”(association)	0.350
RABL2B	RASEF	psi-mi:“MI:0914”(association)	0.350
FMC1	DNM1L	psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
RABL2B	CEP43	psi-mi:“MI:0914”(association)	0.350
BCL6	CACNA1A	psi-mi:“MI:0914”(association)	0.350
IDI2	LDB1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (33): LDB1 (Affinity Capture-MS), ISL2 (Affinity Capture-MS), SSBP2 (Affinity Capture-MS), SSBP4 (Affinity Capture-MS), SSBP3 (Affinity Capture-MS), LMO4 (Affinity Capture-MS), LMX1B (Affinity Capture-MS), FAM76B (Affinity Capture-MS), TRIM27 (Affinity Capture-MS), IDI2 (Affinity Capture-MS), IDI2 (Affinity Capture-MS), SSBP3 (Affinity Capture-MS), LDB1 (Affinity Capture-MS), SSBP2 (Affinity Capture-MS), SSBP4 (Affinity Capture-MS)

ESM2 similar proteins: A0A1D8PLI2, A8XXC0, B5F9P6, I1RZ92, O42641, O42939, O74234, O74429, O94632, P0DKY8, P14743, P15496, P30418, P32377, P38635, P40506, P41888, P43075, P47173, P53128, P53164, P78820, P91148, P91309, Q01976, Q09297, Q09512, Q10132, Q17607, Q4WM52, Q54J08, Q54QA6, Q54QE4, Q54YQ9, Q553B6, Q55EL3, Q5E7U8, Q5PQ50, Q6BJF4, Q6C7G2

Diamond homologs: A0A1D8PLI2, A0A7C9FSB8, A1T5G2, A4FK76, A8GDW2, A9AST0, A9MRI5, B1VTW2, B5F9P6, I1RZ92, O35586, O35760, O42641, O48964, O48965, P15496, P58044, Q0RBQ7, Q10132, Q13907, Q1LZ95, Q38929, Q39471, Q39472, Q39664, Q42553, Q4R4W5, Q4WM52, Q5E7U8, Q5NWG5, Q5R8R6, Q5YYB6, Q6A5Z1, Q6D3F5, Q7N0A6, Q82MJ7, Q8BFZ6, Q9BXS1, Q9NH02, Q9X7Q6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	22
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
815309	GRCh37/hg19 10p15.3-15.1(chr10:100026-4433206)x3	Pathogenic

SpliceAI

757 predictions. Top by Δscore:

Variant	Effect	Δscore
10:1020644:T:TA	donor_gain	0.9900
10:1024576:GGCTA:G	donor_loss	0.9900
10:1024577:GCTA:G	donor_loss	0.9900
10:1024578:CTA:C	donor_loss	0.9900
10:1024579:TA:T	donor_loss	0.9900
10:1024580:ACCTT:A	donor_loss	0.9900
10:1024581:CCT:C	donor_loss	0.9900
10:1024612:T:TA	donor_gain	0.9900
10:1025812:TAAC:T	donor_loss	0.9900
10:1025815:CCT:C	donor_gain	0.9900
10:1025815:CCTCT:C	donor_gain	0.9900
10:1020651:T:TA	donor_gain	0.9800
10:1020664:T:TA	donor_gain	0.9800
10:1022594:TGAG:T	donor_gain	0.9800
10:1022773:GCCC:G	acceptor_loss	0.9800
10:1022776:C:CA	acceptor_loss	0.9800
10:1022776:C:CC	acceptor_gain	0.9800
10:1022777:T:A	acceptor_loss	0.9800
10:1025814:A:AC	donor_gain	0.9800
10:1025815:C:CC	donor_gain	0.9800
10:1020648:T:TA	donor_gain	0.9700
10:1022676:GACT:G	donor_loss	0.9700
10:1022677:ACTC:A	donor_loss	0.9700
10:1022678:CT:C	donor_loss	0.9700
10:1022679:T:TG	donor_loss	0.9700
10:1022680:C:CA	donor_loss	0.9700
10:1022681:A:AA	donor_loss	0.9700
10:1022771:CAGCC:C	acceptor_gain	0.9700
10:1022774:CC:C	acceptor_gain	0.9700
10:1022775:CC:C	acceptor_gain	0.9700

AlphaMissense

1500 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:1022687:A:C	F77L	0.987
10:1022687:A:T	F77L	0.987
10:1022689:A:G	F77L	0.987
10:1022756:G:C	F54L	0.984
10:1022756:G:T	F54L	0.984
10:1022758:A:G	F54L	0.984
10:1024616:C:A	K36N	0.964
10:1024616:C:G	K36N	0.964
10:1024607:G:C	C39W	0.960
10:1020872:G:C	S87R	0.959
10:1020872:G:T	S87R	0.959
10:1020874:T:G	S87R	0.959
10:1020810:G:T	A108D	0.958
10:1022696:T:A	K74N	0.957
10:1022696:T:G	K74N	0.957
10:1022697:T:A	K74I	0.951
10:1020869:G:C	H88Q	0.949
10:1020869:G:T	H88Q	0.949
10:1022741:A:C	F59L	0.947
10:1022741:A:T	F59L	0.947
10:1022743:A:G	F59L	0.947
10:1019589:A:C	F204L	0.944
10:1019589:A:T	F204L	0.944
10:1019591:A:G	F204L	0.944
10:1019576:A:G	W209R	0.942
10:1019576:A:T	W209R	0.942
10:1022753:G:C	S55R	0.942
10:1022753:G:T	S55R	0.942
10:1022755:T:G	S55R	0.942
10:1019579:A:G	W208R	0.941

dbSNP variants (sampled 300 via entrez): RS1000424885 (10:1024700 C>A), RS1000701932 (10:1020231 T>C), RS1000887371 (10:1024708 G>C,T), RS1000926596 (10:1023789 A>G), RS1000978949 (10:1023524 T>C), RS1000983414 (10:1024964 G>C), RS1000988728 (10:1023197 C>G,T), RS1001120628 (10:1020390 C>T), RS1001432645 (10:1025194 G>A), RS1001956853 (10:1024173 A>G), RS1002257816 (10:1019810 T>C,G), RS1002525757 (10:1026237 G>C), RS1002671500 (10:1022062 A>G), RS1003134964 (10:1022172 T>C,G), RS1003496752 (10:1018666 G>C)

Disease associations

OMIM: gene MIM:615389 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST007876_58	Estimated glomerular filtration rate	6.000000e-24

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — Lanosterol biosynthesis pathway

CTD chemical–gene interactions

8 total (human), top 8 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Aflatoxin B1	decreases methylation, increases methylation	2
aflatoxin B2	decreases methylation	1
jinfukang	affects cotreatment, decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Cisplatin	affects cotreatment, decreases expression	1
Estradiol	increases expression	1
Smoke	decreases expression, increases abundance	1
Urethane	decreases expression	1

Clinical trials (associated diseases)

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