ISOC1

Summary

ISOC1 (isochorismatase domain containing 1, HGNC:24254) is a protein-coding gene on chromosome 5q23.3, encoding Isochorismatase domain-containing protein 1 (Q96CN7).

Predicted to be located in peroxisome. Predicted to be active in cytoplasm.

Source: NCBI Gene 51015 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 60 total
• Druggable target: yes
• MANE Select transcript: NM_016048

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24254
Approved symbol	ISOC1
Name	isochorismatase domain containing 1
Location	5q23.3
Locus type	gene with protein product
Status	Approved
Aliases	CGI-111
Ensembl gene	ENSG00000066583
Ensembl biotype	protein_coding
OMIM	620805
Entrez	51015

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 7 protein_coding

ENST00000173527, ENST00000514194, ENST00000868047, ENST00000868048, ENST00000868049, ENST00000918282, ENST00000954509

RefSeq mRNA: 1 — MANE Select: NM_016048 NM_016048

CCDS: CCDS43357

Canonical transcript exons

ENST00000173527 — 5 exons

Exon	Start	End
ENSE00000425755	129104956	129105075
ENSE00000538475	129106946	129107062
ENSE00000822450	129105185	129105388
ENSE00001232283	129112855	129114028
ENSE00001232288	129094749	129095075

Expression profiles

Bgee: expression breadth ubiquitous, 284 present calls, max score 98.59.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 16.7467 / max 219.7108, expressed in 1793 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
58372	16.3139	1793
58371	0.4329	239

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	98.59	gold quality
oocyte	CL:0000023	97.69	gold quality
germinal epithelium of ovary	UBERON:0001304	96.90	gold quality
left ventricle myocardium	UBERON:0006566	96.47	gold quality
myocardium	UBERON:0002349	96.33	gold quality
esophagus squamous epithelium	UBERON:0006920	96.26	gold quality
jejunal mucosa	UBERON:0000399	96.04	gold quality
upper leg skin	UBERON:0004262	95.99	gold quality
cardiac muscle of right atrium	UBERON:0003379	95.87	gold quality
heart right ventricle	UBERON:0002080	95.50	gold quality
epithelium of esophagus	UBERON:0001976	95.09	gold quality
adult organism	UBERON:0007023	95.08	gold quality
hair follicle	UBERON:0002073	94.92	gold quality
vena cava	UBERON:0004087	94.28	gold quality
liver	UBERON:0002107	94.11	gold quality
right lobe of liver	UBERON:0001114	93.96	gold quality
cardiac atrium	UBERON:0002081	93.85	gold quality
squamous epithelium	UBERON:0006914	93.69	gold quality
right atrium auricular region	UBERON:0006631	93.62	gold quality
cardiac ventricle	UBERON:0002082	93.55	gold quality
heart left ventricle	UBERON:0002084	93.50	gold quality
skin of hip	UBERON:0001554	93.09	gold quality
mammalian vulva	UBERON:0000997	92.83	gold quality
jejunum	UBERON:0002115	92.63	gold quality
heart	UBERON:0000948	92.56	gold quality
epithelium of nasopharynx	UBERON:0001951	92.39	gold quality
nasopharynx	UBERON:0001728	92.37	gold quality
nephron tubule	UBERON:0001231	92.28	gold quality
mucosa of sigmoid colon	UBERON:0004993	92.24	gold quality
colonic mucosa	UBERON:0000317	91.63	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.87
E-GEOD-100618	no	266.76

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

86 targeting ISOC1, 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-1277-5P	100.00	73.95	5056
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488
HSA-MIR-548D-5P	99.94	71.23	3502

Literature-anchored findings (GeneRIF, showing 3)

• Knockdown of ISOC1 inhibits the proliferation and migration and induces the apoptosis of colon cancer cells through the AKT/GSK-3beta pathway. (PMID:31740942)
• ISOC1 promotes the proliferation of gastric cancer cells by positively regulating CDK19. (PMID:33275227)
• Functional Analysis of Immune Signature Genes in Th1* Memory Cells Links ISOC1 and Pyrimidine Metabolism to IFN-gamma and IL-17 Production. (PMID:33547171)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	isoc1	ENSDARG00000060069
mus_musculus	Isoc1	ENSMUSG00000024601
rattus_norvegicus	Isoc1	ENSRNOG00000019711
drosophila_melanogaster	CG3663	FBGN0035044
drosophila_melanogaster	CG11333	FBGN0039850

Paralogs (1): ISOC2 (ENSG00000063241)

Protein

Protein identifiers

Isochorismatase domain-containing protein 1 — Q96CN7 (reviewed: Q96CN7)

All UniProt accessions (2): Q96CN7, D6RGE2

UniProt curated annotations — full annotation on UniProt →

Similarity. Belongs to the isochorismatase family.

RefSeq proteins (1): NP_057132* (*=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 (3 total): modified residue 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96CN7-F1	90.34	0.80

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): 160, 279

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 165 (showing top): RRAGTTGT_UNKNOWN, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GCM_ZNF198, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, RODWELL_AGING_KIDNEY_NO_BLOOD_DN, WEI_MYCN_TARGETS_WITH_E_BOX, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_1, MORI_SMALL_PRE_BII_LYMPHOCYTE_DN, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_DN, TIEN_INTESTINE_PROBIOTICS_24HR_UP, BRACHAT_RESPONSE_TO_CISPLATIN, BREDEMEYER_RAG_SIGNALING_NOT_VIA_ATM_UP, AMIT_SERUM_RESPONSE_120_MCF10A, HUANG_DASATINIB_RESISTANCE_DN

GO Biological Process (0):

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

GO Cellular Component (2): cytoplasm (GO:0005737), peroxisome (GO:0005777)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	1
intracellular anatomical structure	1
cellular anatomical structure	1
microbody	1

Protein interactions and networks

STRING

1738 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ISOC1	RASGEF1C	Q8N431	500
ISOC1	MINAR2	P59773	479
ISOC1	BLVRB	P30043	475
ISOC1	DNAJB5	O75953	472
ISOC1	LIX1	Q8N485	459
ISOC1	PLCH1	Q4KWH8	456
ISOC1	EIF4B	P23588	444
ISOC1	PRAMEF20	Q5VT98	440
ISOC1	MATN2	O00339	432
ISOC1	PEX3	P56589	422
ISOC1	NIT2	Q9NQR4	417
ISOC1	PEX11B	O96011	409
ISOC1	PECR	Q9BY49	404
ISOC1	SAMD12	Q8N8I0	400
ISOC1	SAAL1	Q96ER3	398

IntAct

34 interactions, top by confidence:

A	B	Type	Score
ATG13	ULK1	psi-mi:“MI:2364”(proximity)	0.940
CALCOCO1	ISOC1	psi-mi:“MI:0915”(physical association)	0.560
ISOC1	CALCOCO1	psi-mi:“MI:0915”(physical association)	0.560
VTN	HAT1	psi-mi:“MI:0914”(association)	0.530
ISOC1	ARHGAP8	psi-mi:“MI:0915”(physical association)	0.400
CFTR	ISOC1	psi-mi:“MI:0915”(physical association)	0.370
JUN	TPM3	psi-mi:“MI:0914”(association)	0.350
VTN	HAT1	psi-mi:“MI:0914”(association)	0.350
ZDHHC5	HACD3	psi-mi:“MI:0914”(association)	0.350
DDHD1	PYGM	psi-mi:“MI:0914”(association)	0.350
ISOC1	PRKCA	psi-mi:“MI:0914”(association)	0.350
VENTX	UBA6	psi-mi:“MI:0914”(association)	0.350
VSIG1	RIMOC1	psi-mi:“MI:0914”(association)	0.350
CEP290	ARPC3	psi-mi:“MI:2364”(proximity)	0.270
CEP135	CCDC66	psi-mi:“MI:2364”(proximity)	0.270
SASS6	DVL2	psi-mi:“MI:2364”(proximity)	0.270
EVC2	PGRMC2	psi-mi:“MI:2364”(proximity)	0.270
NIN	ARPC3	psi-mi:“MI:2364”(proximity)	0.270
CAT	VWA8	psi-mi:“MI:2364”(proximity)	0.270
ATG3	PPP2R5C	psi-mi:“MI:2364”(proximity)	0.270
ATG9A	GPR89A	psi-mi:“MI:2364”(proximity)	0.270
ULK2	UBR5	psi-mi:“MI:2364”(proximity)	0.270
CDH5	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
ZMYM3	TAF4	psi-mi:“MI:2364”(proximity)	0.270
ISOC1	pilQ	psi-mi:“MI:0915”(physical association)	0.000
ISOC1	smC	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (88): CALCOCO1 (Two-hybrid), LACTB2 (Co-fractionation), MTHFD1L (Co-fractionation), UMPS (Co-fractionation), ISOC1 (Affinity Capture-MS), ISOC1 (Proximity Label-MS), ISOC1 (Proximity Label-MS), ISOC1 (Proximity Label-MS), ISOC1 (Proximity Label-MS), ISOC1 (Proximity Label-MS), ARHGAP8 (Affinity Capture-MS), ISOC1 (Affinity Capture-MS), ISOC1 (Affinity Capture-MS), ISOC1 (Affinity Capture-MS), ISOC1 (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.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 43 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.

GO biological processes:

GO term	Partners	Fold	FDR
mitophagy	5	43.0×	2e-05
autophagosome assembly	5	30.4×	7e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	50
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

705 predictions. Top by Δscore:

Variant	Effect	Δscore
5:129105183:A:AG	acceptor_gain	1.0000
5:129105183:AGTT:A	acceptor_gain	1.0000
5:129105184:G:GA	acceptor_gain	1.0000
5:129105184:GTT:G	acceptor_gain	1.0000
5:129105184:GTTG:G	acceptor_gain	1.0000
5:129105386:GAA:G	donor_gain	1.0000
5:129105389:G:GG	donor_gain	1.0000
5:129106943:TAGAC:T	acceptor_loss	1.0000
5:129106944:A:AG	acceptor_gain	1.0000
5:129106945:G:GG	acceptor_gain	1.0000
5:129106945:GA:G	acceptor_gain	1.0000
5:129106945:GAC:G	acceptor_gain	1.0000
5:129106945:GACTC:G	acceptor_gain	1.0000
5:129107047:G:GT	donor_gain	1.0000
5:129107060:GAGGT:G	donor_loss	1.0000
5:129107061:AGGTA:A	donor_loss	1.0000
5:129107062:GGTAA:G	donor_loss	1.0000
5:129107063:GTA:G	donor_loss	1.0000
5:129107064:T:G	donor_loss	1.0000
5:129095003:G:GG	donor_gain	0.9900
5:129095074:AG:A	donor_loss	0.9900
5:129095075:GG:G	donor_loss	0.9900
5:129095076:G:A	donor_loss	0.9900
5:129095077:T:A	donor_loss	0.9900
5:129104954:A:AG	acceptor_gain	0.9900
5:129104955:G:GG	acceptor_gain	0.9900
5:129105017:A:T	donor_gain	0.9900
5:129105071:GATTG:G	donor_gain	0.9900
5:129105072:A:G	donor_gain	0.9900
5:129105182:CAGT:C	acceptor_loss	0.9900

AlphaMissense

1916 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:129105005:G:A	C120Y	1.000
5:129105006:T:G	C120W	1.000
5:129105008:A:C	D121A	1.000
5:129105008:A:G	D121G	1.000
5:129105008:A:T	D121V	1.000
5:129105015:G:C	Q123H	1.000
5:129105015:G:T	Q123H	1.000
5:129105023:T:C	F126S	1.000
5:129105243:G:A	G163D	1.000
5:129105249:G:A	G165E	1.000
5:129105301:G:C	K182N	1.000
5:129105301:G:T	K182N	1.000
5:129105308:T:C	F185L	1.000
5:129105310:T:A	F185L	1.000
5:129105310:T:G	F185L	1.000
5:129105380:G:A	G209R	1.000
5:129105380:G:C	G209R	1.000
5:129105381:G:A	G209E	1.000
5:129105387:A:T	E211V	1.000
5:129106955:T:C	C215R	1.000
5:129106956:G:A	C215Y	1.000
5:129106957:C:G	C215W	1.000
5:129107046:G:T	R245M	1.000
5:129112936:T:C	F278L	1.000
5:129112938:C:A	F278L	1.000
5:129112938:C:G	F278L	1.000
5:129105004:T:C	C120R	0.999
5:129105007:G:C	D121H	0.999
5:129105007:G:T	D121Y	0.999
5:129105009:T:A	D121E	0.999

dbSNP variants (sampled 300 via entrez): RS1000047959 (5:129103332 A>G), RS1000287691 (5:129103620 T>A), RS1000328820 (5:129109606 G>A), RS1000364658 (5:129097615 A>G), RS1000544292 (5:129107948 T>C), RS1000660384 (5:129108281 C>A,T), RS1000979253 (5:129114090 A>T), RS1001217385 (5:129101587 C>T), RS1001322906 (5:129110833 A>G), RS1001642119 (5:129098842 A>C,G), RS1001941244 (5:129094451 G>A), RS1001995036 (5:129094256 C>T), RS1002220186 (5:129106484 C>A), RS1002262990 (5:129100159 C>G), RS1002297660 (5:129100424 T>A)

Disease associations

OMIM: gene MIM:620805 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST005580_275	Intraocular pressure	7.000000e-10
GCST005580_85	Intraocular pressure	3.000000e-11
GCST008156_107	Hip circumference adjusted for BMI	2.000000e-06
GCST008159_29	Waist-to-hip ratio adjusted for BMI	7.000000e-06
GCST008162_26	Hip circumference	4.000000e-06

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004695	intraocular pressure measurement
EFO:0008039	BMI-adjusted hip circumference
EFO:0007788	BMI-adjusted waist-hip ratio

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5724662 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Cyclosporine	decreases expression	3
bisphenol A	decreases expression, increases expression	2
Tretinoin	decreases expression	2
Valproic Acid	decreases methylation, increases expression	2
Cadmium Chloride	decreases expression	2
decabromobiphenyl ether	decreases expression	1
mono-(2-ethylhexyl)phthalate	increases expression	1
sodium arsenite	affects cotreatment, increases abundance, increases expression	1
cobaltous chloride	decreases expression	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	increases reaction, affects binding	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
bisphenol S	increases expression	1
LDN 193189	affects cotreatment, increases expression	1
bisphenol AF	increases expression	1
Sunitinib	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	increases expression, affects cotreatment, increases abundance	1
Dexamethasone	increases expression	1
Diethylhexyl Phthalate	decreases expression	1
Doxorubicin	decreases expression	1
Ivermectin	decreases expression	1
Manganese	increases abundance, increases expression, affects cotreatment	1
Progesterone	decreases expression	1

ChEMBL screening assays

6 unique, capped per target: 6 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5697733	Binding	Inhibition of ISOC1 (unknown origin) assessed as fold change at 10 uM incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia. — Nature

Clinical trials (associated diseases)

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