ISOC2

Summary

ISOC2 (isochorismatase domain containing 2, HGNC:26278) is a protein-coding gene on chromosome 19q13.42, encoding Isochorismatase domain-containing protein 2 (Q96AB3).

Involved in protein destabilization. Located in cytoplasm and nucleus.

Source: NCBI Gene 79763 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 65 total
• MANE Select transcript: NM_001136201

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26278
Approved symbol	ISOC2
Name	isochorismatase domain containing 2
Location	19q13.42
Locus type	gene with protein product
Status	Approved
Aliases	FLJ23469
Ensembl gene	ENSG00000063241
Ensembl biotype	protein_coding
OMIM	612928
Entrez	79763

Gene structure

Transcript identifiers

Ensembl transcripts: 28 — 25 protein_coding, 3 retained_intron

ENST00000085068, ENST00000425675, ENST00000438389, ENST00000587226, ENST00000589080, ENST00000589108, ENST00000590921, ENST00000591718, ENST00000910867, ENST00000910868, ENST00000910869, ENST00000910870, ENST00000910871, ENST00000910872, ENST00000910873, ENST00000910874, ENST00000910875, ENST00000910876, ENST00000910877, ENST00000927670, ENST00000927671, ENST00000927672, ENST00000927673, ENST00000927674, ENST00000927675, ENST00000927676, ENST00000927677, ENST00000941413

RefSeq mRNA: 3 — MANE Select: NM_001136201 NM_001136201, NM_001136202, NM_024710

CCDS: CCDS12925, CCDS46194, CCDS46195

Canonical transcript exons

ENST00000425675 — 6 exons

Exon	Start	End
ENSE00000579329	55454989	55455106
ENSE00000876746	55455636	55455845
ENSE00001791614	55455260	55455330
ENSE00002779860	55452985	55453388
ENSE00002868304	55461512	55461642
ENSE00003554978	55456349	55456489

Expression profiles

Bgee: expression breadth ubiquitous, 219 present calls, max score 98.43.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 59.3515 / max 342.3522, expressed in 1817 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
182823	59.3515	1817

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	98.43	gold quality
mucosa of transverse colon	UBERON:0004991	96.91	gold quality
apex of heart	UBERON:0002098	96.11	gold quality
hindlimb stylopod muscle	UBERON:0004252	95.93	gold quality
right atrium auricular region	UBERON:0006631	95.30	gold quality
metanephros cortex	UBERON:0010533	94.91	gold quality
muscle layer of sigmoid colon	UBERON:0035805	94.85	gold quality
transverse colon	UBERON:0001157	94.78	gold quality
left testis	UBERON:0004533	94.76	gold quality
right adrenal gland	UBERON:0001233	94.66	gold quality
adenohypophysis	UBERON:0002196	94.52	gold quality
right adrenal gland cortex	UBERON:0035827	94.51	gold quality
right testis	UBERON:0004534	94.45	gold quality
lower esophagus mucosa	UBERON:0035834	94.39	gold quality
gastrocnemius	UBERON:0001388	94.21	gold quality
left adrenal gland	UBERON:0001234	93.96	gold quality
left adrenal gland cortex	UBERON:0035825	93.90	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	93.85	gold quality
cardiac atrium	UBERON:0002081	93.65	gold quality
muscle of leg	UBERON:0001383	93.60	gold quality
liver	UBERON:0002107	93.51	gold quality
lower esophagus	UBERON:0013473	93.04	gold quality
lower esophagus muscularis layer	UBERON:0035833	93.03	gold quality
adult mammalian kidney	UBERON:0000082	92.94	gold quality
body of stomach	UBERON:0001161	92.94	gold quality
heart left ventricle	UBERON:0002084	92.88	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	92.78	gold quality
omental fat pad	UBERON:0010414	92.71	gold quality
peritoneum	UBERON:0002358	92.64	gold quality
right lobe of thyroid gland	UBERON:0001119	92.63	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-8271	yes	8.95
E-ANND-3	yes	5.51

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

9 targeting ISOC2, 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-4713-3P	100.00	65.92	505
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-6887-3P	99.66	67.83	1778
HSA-MIR-6887-5P	98.56	68.49	1295
HSA-MIR-6795-5P	98.52	68.51	1277
HSA-MIR-4691-3P	98.11	66.83	1204
HSA-MIR-450B-3P	97.56	66.12	512
HSA-MIR-769-3P	97.06	64.83	464
HSA-MIR-7108-3P	94.37	64.79	183

Literature-anchored findings (GeneRIF, showing 1)

• ISOC2 is a novel functional protein, which is able to bind and co-localize with a tumor suppressor gene p16(INK4a). (PMID:17658461)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	isoc2	ENSDARG00000013371
mus_musculus	Isoc2b	ENSMUSG00000052605
mus_musculus	Isoc2a	ENSMUSG00000086784
rattus_norvegicus	Isoc2b	ENSRNOG00000016829
rattus_norvegicus	Isoc2a	ENSRNOG00000050348
caenorhabditis_elegans		WBGENE00009436

Paralogs (1): ISOC1 (ENSG00000066583)

Protein

Protein identifiers

Isochorismatase domain-containing protein 2 — Q96AB3 (reviewed: Q96AB3)

All UniProt accessions (3): Q96AB3, K7EKW4, K7ENV7

UniProt curated annotations — full annotation on UniProt →

Subunit / interactions. Interacts with CDKN2A.

Subcellular location. Cytoplasm. Nucleus.

Similarity. Belongs to the isochorismatase family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q96AB3-1	1	yes
Q96AB3-2	2
Q96AB3-3	3

RefSeq proteins (3): NP_001129673, NP_001129674, NP_078986 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000868	Isochorismatase-like_dom	Domain
IPR036380	Isochorismatase-like_sf	Homologous_superfamily
IPR050993	Isochorismatase_domain	Family

Pfam: PF00857

UniProt features (5 total): modified residue 2, splice variant 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96AB3-F1	95.00	0.91

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 (2): 7, 202

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 76 (showing top): BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOBP_PROTEIN_DESTABILIZATION, GOBP_REGULATION_OF_PROTEIN_STABILITY, DOUGLAS_BMI1_TARGETS_UP, ISRE_01, STEIN_ESRRA_TARGETS_UP, HIRSCH_CELLULAR_TRANSFORMATION_SIGNATURE_DN, LU_EZH2_TARGETS_UP, WAKABAYASHI_ADIPOGENESIS_PPARG_RXRA_BOUND_8D, SHEDDEN_LUNG_CANCER_GOOD_SURVIVAL_A12, WANG_MLL_TARGETS, MYC_UP.V1_UP, MTOR_UP.N4.V1_UP, EIF4E_UP, RPS14_DN.V1_DN

GO Biological Process (1): protein destabilization (GO:0031648)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (3): nucleus (GO:0005634), cytoplasm (GO:0005737), mitochondrion (GO:0005739)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular membrane-bounded organelle	2
regulation of protein stability	1
binding	1
intracellular anatomical structure	1
cellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

1720 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ISOC2	CDKN2A	P42771	700
ISOC2	IZUMO2	Q6UXV1	574
ISOC2	ZNF579	Q8NAF0	564
ISOC2	TMEM86B	Q8N661	537
ISOC2	FIZ1	Q96SL8	504
ISOC2	NAT14	Q8WUY8	495
ISOC2	NIT2	Q9NQR4	487
ISOC2	RASIP1	Q5U651	465
ISOC2	TIMM21	Q9BVV7	451
ISOC2	PPP6R1	Q9UPN7	449
ISOC2	PI4KA	P42356	437
ISOC2	SLCO6A1	Q86UG4	430
ISOC2	MYL9	P24844	419
ISOC2	TRIR	Q9BQ61	409
ISOC2	GMPS	P49915	407

IntAct

17 interactions, top by confidence:

A	B	Type	Score
TGFBRAP1	ACVR1	psi-mi:“MI:0914”(association)	0.730
TMEM184A	SLC33A1	psi-mi:“MI:0914”(association)	0.530
MRAP2	PODXL	psi-mi:“MI:0914”(association)	0.530
ISOC2	ISOC2	psi-mi:“MI:0915”(physical association)	0.370
HSCB	RBP5	psi-mi:“MI:0914”(association)	0.350
NME4	PMPCB	psi-mi:“MI:0914”(association)	0.350
ISOC2	GTPBP1	psi-mi:“MI:0914”(association)	0.350
UPK1A	A2ML1	psi-mi:“MI:0914”(association)	0.350
BHLHA15	RNASEH1	psi-mi:“MI:0914”(association)	0.350
VASH1	PGAM2	psi-mi:“MI:0914”(association)	0.350
ISOC2	DNLZ	psi-mi:“MI:0914”(association)	0.350
CLDN3	ISOC2	psi-mi:“MI:0914”(association)	0.350
FECH	POTEF	psi-mi:“MI:0914”(association)	0.350
sseF	SNAP23	psi-mi:“MI:2364”(proximity)	0.270
LSM8	ISOC2	psi-mi:“MI:0915”(physical association)	0.000
PDK2	ISOC2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (94): ISOC2 (Two-hybrid), ISOC2 (Affinity Capture-RNA), ISOC2 (Affinity Capture-RNA), ISOC2 (Affinity Capture-RNA), ISOC2 (Affinity Capture-MS), FH (Co-fractionation), CALML3 (Two-hybrid), ISOC2 (Affinity Capture-MS), ISOC2 (Affinity Capture-MS), ALAD (Affinity Capture-MS), NIT1 (Affinity Capture-MS), TGFBRAP1 (Affinity Capture-MS), PUSL1 (Affinity Capture-MS), DNLZ (Affinity Capture-MS), SELO (Affinity Capture-MS)

ESM2 similar proteins: A0JME6, A6QLY4, B5X0W9, F6HDM2, G4YEI5, O49472, P08030, P09556, P13995, P35914, P47956, P47957, P54886, P54889, P85094, Q01637, Q08C33, Q0P5C2, Q32KX0, Q32LQ3, Q3T099, Q43153, Q4R826, Q54NZ6, Q54NZ8, Q5M8W9, Q5PQ71, Q5R4M8, Q5R9E1, Q5RC03, Q5U3Z3, Q5ZKA5, Q68FS1, Q6DF67, Q6I7R3, Q6NY77, Q8HXZ6, Q8K009, Q8LG77, Q8TB37

Diamond homologs: A0JME6, A6QLY4, B5X0W9, G4YEI5, P85094, Q08C33, Q0IHU5, Q32KX0, Q4R826, Q54NZ6, Q54NZ8, Q54RC7, Q54RF0, Q5PQ71, Q5PQA5, Q5RC03, Q5U3Z3, Q6DF67, Q6I7R3, Q91V64, Q96AB3, Q96CN7, Q9DCC7, P21367

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	55
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

703 predictions. Top by Δscore:

Variant	Effect	Δscore
19:55454983:CATTA:C	donor_loss	1.0000
19:55454985:TTAC:T	donor_loss	1.0000
19:55454986:TA:T	donor_loss	1.0000
19:55454987:ACCT:A	donor_gain	1.0000
19:55454988:C:G	donor_loss	1.0000
19:55454988:CCTC:C	donor_gain	1.0000
19:55454990:T:TA	donor_gain	1.0000
19:55455103:CTGG:C	acceptor_gain	1.0000
19:55455104:TGG:T	acceptor_gain	1.0000
19:55455105:GG:G	acceptor_gain	1.0000
19:55455107:C:CC	acceptor_gain	1.0000
19:55455107:C:CG	acceptor_loss	1.0000
19:55455109:G:C	acceptor_gain	1.0000
19:55455113:G:C	acceptor_gain	1.0000
19:55455113:G:GC	acceptor_gain	1.0000
19:55455256:TCAC:T	donor_loss	1.0000
19:55455257:CA:C	donor_loss	1.0000
19:55455258:A:C	donor_loss	1.0000
19:55455331:C:CC	acceptor_gain	1.0000
19:55455630:TCTCA:T	donor_loss	1.0000
19:55455631:CTCAC:C	donor_loss	1.0000
19:55455632:TCAC:T	donor_loss	1.0000
19:55455633:CACCA:C	donor_loss	1.0000
19:55455634:A:AC	donor_gain	1.0000
19:55455634:ACCA:A	donor_loss	1.0000
19:55455635:C:CA	donor_loss	1.0000
19:55455635:C:CC	donor_gain	1.0000
19:55455652:G:A	donor_gain	1.0000
19:55455848:G:C	acceptor_gain	1.0000
19:55455852:CAG:C	acceptor_gain	1.0000

AlphaMissense

1309 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:55454995:G:C	F177L	0.993
19:55454995:G:T	F177L	0.993
19:55454997:A:G	F177L	0.993
19:55455738:C:A	K82N	0.992
19:55455738:C:G	K82N	0.992
19:55456415:C:A	Q24H	0.992
19:55456415:C:G	Q24H	0.992
19:55456422:T:A	D22V	0.988
19:55456422:T:G	D22A	0.987
19:55455726:G:C	S86R	0.986
19:55455726:G:T	S86R	0.986
19:55455728:T:G	S86R	0.986
19:55455729:G:C	F85L	0.985
19:55455729:G:T	F85L	0.985
19:55455731:A:G	F85L	0.985
19:55455043:G:C	S161R	0.983
19:55455043:G:T	S161R	0.983
19:55455045:T:G	S161R	0.983
19:55456406:G:C	F27L	0.983
19:55456406:G:T	F27L	0.983
19:55456408:A:G	F27L	0.983
19:55456421:G:C	D22E	0.983
19:55456421:G:T	D22E	0.983
19:55455273:A:G	C136R	0.982
19:55455279:C:G	D134H	0.981
19:55455665:A:G	C107R	0.981
19:55455314:A:G	L122P	0.980
19:55456425:C:T	C21Y	0.979
19:55455095:C:G	R144P	0.977
19:55455023:A:G	L168P	0.976

dbSNP variants (sampled 300 via entrez): RS1000052871 (19:55458072 GAAAA>G), RS1000224962 (19:55452955 G>A,T), RS1000250804 (19:55463153 T>C,G), RS1000273000 (19:55462995 GA>G), RS1000303057 (19:55463479 G>A), RS1001116350 (19:55453495 T>A,C), RS1001681377 (19:55458704 T>A,C), RS1001696730 (19:55459313 T>G), RS1001734161 (19:55453194 G>A,C,T), RS1001857769 (19:55462666 T>A), RS1001979371 (19:55453839 AAAATAAAT>A,AAAAT,AAAATAAATAAAT), RS1002425152 (19:55457344 C>G), RS1002643528 (19:55456184 C>T), RS1003345142 (19:55454834 G>T), RS1003369169 (19:55460617 C>T)

Disease associations

OMIM: gene MIM:612928 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	3
Benzo(a)pyrene	decreases expression, increases methylation	3
bisphenol A	decreases expression, increases expression	2
entinostat	affects cotreatment, increases expression	2
Acetaminophen	decreases expression	2
Valproic Acid	affects expression, increases expression	2
arsenite	affects binding, increases reaction	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
benzo(e)pyrene	increases methylation	1
cupric chloride	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
corosolic acid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
Resveratrol	decreases expression, affects cotreatment	1
Sunitinib	decreases expression	1
Fulvestrant	increases methylation	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Ivermectin	decreases expression	1
Manganese	affects cotreatment, increases abundance, increases expression	1
Methapyrilene	increases methylation	1
Methylcholanthrene	affects binding, increases reaction	1
Plant Extracts	affects cotreatment, decreases expression	1
Dronabinol	decreases expression	1
Thiram	decreases expression	1
Tunicamycin	increases expression	1
Urethane	decreases expression	1
Cyclosporine	decreases expression	1
Aflatoxin B1	increases methylation	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_ST11	HAP1 ISOC2 (-) 1	Cancer cell line	Male
CVCL_XP87	HAP1 ISOC2 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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