INO80B

Summary

INO80B (INO80 complex subunit B, HGNC:13324) is a protein-coding gene on chromosome 2p13.1, encoding INO80 complex subunit B (Q9C086). Induces growth and cell cycle arrests at the G1 phase of the cell cycle. It is a selective cancer dependency (DepMap: 37.3% of cell lines).

This gene encodes a subunit of an ATP-dependent chromatin remodeling complex, INO80, which plays a role in DNA and nucleosome-activated ATPase activity and ATP-dependent nucleosome sliding. Readthrough transcription of this gene into the neighboring downstream gene, which encodes WW domain-binding protein 1, generates a non-coding transcript.

Source: NCBI Gene 83444 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 46 total
• Cancer dependency (DepMap): dependent in 37.3% of screened cell lines
• MANE Select transcript: NM_031288

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13324
Approved symbol	INO80B
Name	INO80 complex subunit B
Location	2p13.1
Locus type	gene with protein product
Status	Approved
Aliases	HMGIYL4, PAPA-1, hIes2, PAP-1BP, IES2
Ensembl gene	ENSG00000115274
Ensembl biotype	protein_coding
OMIM	616456
Entrez	83444

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 4 protein_coding, 2 protein_coding_CDS_not_defined, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000233331, ENST00000409493, ENST00000409917, ENST00000431187, ENST00000455562, ENST00000469849, ENST00000471577, ENST00000473618, ENST00000494986

RefSeq mRNA: 1 — MANE Select: NM_031288 NM_031288

CCDS: CCDS1942

Canonical transcript exons

ENST00000233331 — 5 exons

Exon	Start	End
ENSE00001517080	74457334	74457944
ENSE00001794168	74455087	74455174
ENSE00003721161	74456103	74456272
ENSE00003726673	74455406	74455598
ENSE00003727264	74455818	74455936

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 98.18.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 60.0004 / max 650.0383, expressed in 1822 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
21024	60.0004	1822

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	98.18	gold quality
right uterine tube	UBERON:0001302	95.36	gold quality
left ovary	UBERON:0002119	94.64	gold quality
pituitary gland	UBERON:0000007	94.61	gold quality
ovary	UBERON:0000992	93.91	gold quality
fundus of stomach	UBERON:0001160	93.56	gold quality
adenohypophysis	UBERON:0002196	93.54	gold quality
thyroid gland	UBERON:0002046	93.43	gold quality
left lobe of thyroid gland	UBERON:0001120	93.41	gold quality
right ovary	UBERON:0002118	93.39	gold quality
skin of abdomen	UBERON:0001416	93.23	gold quality
zone of skin	UBERON:0000014	93.08	gold quality
skin of leg	UBERON:0001511	93.02	gold quality
prostate gland	UBERON:0002367	92.96	gold quality
mucosa of stomach	UBERON:0001199	92.88	gold quality
right hemisphere of cerebellum	UBERON:0014890	92.83	gold quality
right lobe of thyroid gland	UBERON:0001119	92.68	gold quality
endocervix	UBERON:0000458	92.67	gold quality
left adrenal gland cortex	UBERON:0035825	92.44	gold quality
body of uterus	UBERON:0009853	92.38	gold quality
body of stomach	UBERON:0001161	92.37	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	92.34	gold quality
minor salivary gland	UBERON:0001830	92.23	gold quality
ectocervix	UBERON:0012249	92.22	gold quality
saliva-secreting gland	UBERON:0001044	92.21	gold quality
fallopian tube	UBERON:0003889	92.20	gold quality
vagina	UBERON:0000996	92.12	gold quality
right adrenal gland cortex	UBERON:0035827	92.10	gold quality
descending thoracic aorta	UBERON:0002345	92.08	gold quality
body of pancreas	UBERON:0001150	92.02	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.84
E-MTAB-7606	no	179.16

Regulation

Is transcription factor: no

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 37.3% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 1)

• pathway-guided genome-wide meta-analysis and mutational analysis identified INO80B gene is a susceptibility gene for pre-eclampsia. (PMID:25143393)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	ino80b	ENSDARG00000062749
mus_musculus	Ino80b	ENSMUSG00000030034
rattus_norvegicus	Ino80b	ENSRNOG00000008873

Protein

Protein identifiers

INO80 complex subunit B — Q9C086 (reviewed: Q9C086)

Alternative names: High mobility group AT-hook 1-like 4, IES2 homolog, PAP-1-associated protein 1, Zinc finger HIT domain-containing protein 4

All UniProt accessions (5): B8ZZ93, B8ZZH7, C9JKY0, Q9C086, H7C171

UniProt curated annotations — full annotation on UniProt →

Function. Induces growth and cell cycle arrests at the G1 phase of the cell cycle. Proposed core component of the chromatin remodeling INO80 complex which is involved in transcriptional regulation, DNA replication and probably DNA repair.

Subunit / interactions. Component of the chromatin remodeling INO80 complex; specifically part of a complex module associated with the helicase ATP-binding and the helicase C-terminal domain of INO80. Interacts with RP9.

Subcellular location. Nucleus. Nucleolus.

RefSeq proteins (1): NP_112578* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006880	INO80B_C	Domain
IPR007529	Znf_HIT	Domain
IPR029523	INO80B/Ies2	Family

Pfam: PF04438, PF04795

UniProt features (15 total): modified residue 5, region of interest 4, chain 1, zinc finger region 1, sequence variant 1, sequence conflict 1, coiled-coil region 1, compositionally biased region 1

Structure

Experimental structures (PDB)

8 structures.

PDB	Method	Resolution (Å)
7ZI4	ELECTRON MICROSCOPY	3.2
9GE5	ELECTRON MICROSCOPY	3.35
9GCG	ELECTRON MICROSCOPY	3.43
9GEV	ELECTRON MICROSCOPY	3.47
9GFB	ELECTRON MICROSCOPY	3.55
9GF6	ELECTRON MICROSCOPY	3.8
9GFM	ELECTRON MICROSCOPY	3.8
6HTS	ELECTRON MICROSCOPY	4.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9C086-F1	66.22	0.17

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 (5): 127, 130, 132, 97, 99

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-5689603	UCH proteinases
R-HSA-5696394	DNA Damage Recognition in GG-NER
R-HSA-392499	Metabolism of proteins
R-HSA-5688426	Deubiquitination
R-HSA-5696398	Nucleotide Excision Repair
R-HSA-5696399	Global Genome Nucleotide Excision Repair (GG-NER)
R-HSA-597592	Post-translational protein modification
R-HSA-73894	DNA Repair

MSigDB gene sets: 151 (showing top): GOBP_CHROMOSOME_ORGANIZATION, MODULE_255, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, MODULE_317, GOBP_TELOMERE_ORGANIZATION, GOBP_POSITIVE_REGULATION_OF_ORGANELLE_ORGANIZATION, GOBP_REGULATION_OF_DNA_REPAIR, GOBP_REGULATION_OF_TELOMERE_MAINTENANCE, GOBP_REGULATION_OF_CELL_CYCLE, GOBP_REGULATION_OF_RESPONSE_TO_STRESS, GOBP_DNA_STRAND_ELONGATION, GOBP_DNA_DAMAGE_RESPONSE, GOBP_POSITIVE_REGULATION_OF_DNA_REPAIR, GOBP_POSITIVE_REGULATION_OF_TELOMERE_MAINTENANCE, GOBP_POSITIVE_REGULATION_OF_CHROMOSOME_ORGANIZATION

GO Biological Process (14): telomere maintenance (GO:0000723), regulation of DNA replication (GO:0006275), DNA repair (GO:0006281), regulation of DNA repair (GO:0006282), DNA recombination (GO:0006310), chromatin remodeling (GO:0006338), regulation of chromosome organization (GO:0033044), positive regulation of DNA repair (GO:0045739), positive regulation of DNA-templated transcription (GO:0045893), regulation of embryonic development (GO:0045995), regulation of cell cycle (GO:0051726), regulation of DNA strand elongation (GO:0060382), positive regulation of telomere maintenance in response to DNA damage (GO:1904507), DNA damage response (GO:0006974)

GO Molecular Function (3): zinc ion binding (GO:0008270), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (5): nucleoplasm (GO:0005654), nucleolus (GO:0005730), nuclear body (GO:0016604), Ino80 complex (GO:0031011), nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Deubiquitination	1
Global Genome Nucleotide Excision Repair (GG-NER)	1
Post-translational protein modification	1
DNA Repair	1
Nucleotide Excision Repair	1
Metabolism of proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA metabolic process	3
regulation of DNA metabolic process	3
DNA repair	2
positive regulation of response to stimulus	2
nuclear lumen	2
intracellular membraneless organelle	2
telomere organization	1
DNA replication	1
DNA damage response	1
regulation of cellular response to stress	1
chromatin organization	1
regulation of organelle organization	1
chromosome organization	1
regulation of DNA repair	1
positive regulation of DNA metabolic process	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
embryo development	1
regulation of multicellular organismal development	1
cell cycle	1
regulation of cellular process	1
DNA strand elongation	1
positive regulation of telomere maintenance	1
telomere maintenance in response to DNA damage	1
regulation of telomere maintenance in response to DNA damage	1
cellular response to stress	1
transition metal ion binding	1
binding	1
cation binding	1
cellular anatomical structure	1
nucleoplasm	1
nuclear chromosome	1
INO80-type complex	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1986 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
INO80B	RUVBL1	P82276	927
INO80B	K7ENP7	K7ENP7	915
INO80B	INO80C	Q6PI98	915
INO80B	RUVBL2	Q9Y230	864
INO80B	ZNHIT1	O43257	673
INO80B	ZNHIT3	Q15649	626
INO80B	ZNHIT6	Q9NWK9	598
INO80B	ZNHIT2	Q9UHR6	594
INO80B	ACTR8	Q9H981	575
INO80B	INO80	Q9ULG1	550
INO80B	INO80E	Q8NBZ0	522
INO80B	SRCAP	Q6ZRS2	511
INO80B	NFRKB	Q6P4R8	507
INO80B	WDR54	Q9H977	477
INO80B	ACTR5	Q9H9F9	471

IntAct

258 interactions, top by confidence:

A	B	Type	Score
RUVBL2	POLR3A	psi-mi:“MI:0914”(association)	0.640
RUVBL1	POLR3A	psi-mi:“MI:0914”(association)	0.640
INO80B	IGFBP2	psi-mi:“MI:0915”(physical association)	0.600
PNMA1	INO80B	psi-mi:“MI:0915”(physical association)	0.560
SSX2IP	INO80B	psi-mi:“MI:0915”(physical association)	0.560
INO80B	SSX2IP	psi-mi:“MI:0915”(physical association)	0.560
INO80B	BLZF1	psi-mi:“MI:0915”(physical association)	0.560
INO80B	CDR2	psi-mi:“MI:0915”(physical association)	0.560
INO80B	KANK2	psi-mi:“MI:0915”(physical association)	0.560
INO80B		psi-mi:“MI:0915”(physical association)	0.560
INO80B	RBM39	psi-mi:“MI:0915”(physical association)	0.560
INO80B	PLAGL2	psi-mi:“MI:0915”(physical association)	0.560
CYSRT1	INO80B	psi-mi:“MI:0915”(physical association)	0.560
CDR2	INO80B	psi-mi:“MI:0915”(physical association)	0.560
KANK2	INO80B	psi-mi:“MI:0915”(physical association)	0.560
BOLL	INO80B	psi-mi:“MI:0915”(physical association)	0.560
TNS2	INO80B	psi-mi:“MI:0915”(physical association)	0.560
	INO80B	psi-mi:“MI:0915”(physical association)	0.560
INO80B	TSPYL2	psi-mi:“MI:0915”(physical association)	0.560
TRIM27	INO80B	psi-mi:“MI:0915”(physical association)	0.560
KRTAP12-2	INO80B	psi-mi:“MI:0915”(physical association)	0.560
INO80B	PICK1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (230): INO80B (Two-hybrid), SSX2IP (Two-hybrid), INO80B (Affinity Capture-MS), INO80B (Proximity Label-MS), INO80B (Affinity Capture-MS), INO80B (Affinity Capture-MS), INO80B (Affinity Capture-MS), INO80B (Affinity Capture-MS), INO80B (Affinity Capture-MS), INO80B (Affinity Capture-MS), INO80B (Affinity Capture-MS), INO80B (Affinity Capture-MS), ALYREF (Affinity Capture-MS), CACTIN (Affinity Capture-MS), CDC42BPA (Affinity Capture-MS)

ESM2 similar proteins: A1A4P4, A1CH36, A2ALW5, A5AAL8, B0BN56, O42911, O70279, P0C2B7, P58468, P83565, Q0CLE8, Q1ECT8, Q290P4, Q2GVC2, Q3SZ86, Q4G0I0, Q4V7Q1, Q5B4U6, Q5BJW9, Q5RFR4, Q5XJW2, Q61733, Q6RUT7, Q753F1, Q7SDU5, Q7SHR9, Q80ZS3, Q86TS9, Q8BGX2, Q8BK72, Q8CHP5, Q8SPE7, Q8TAE8, Q8VD26, Q8WUQ7, Q96AN5, Q96DF8, Q9BRP8, Q9BSF4, Q9BYN8

Diamond homologs: Q99PT3, Q9C086

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
INO80B	“form complex”	“INO80 complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 88 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
protein stabilization	8	7.2×	2e-03
chromatin remodeling	7	6.9×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	45
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1033 predictions. Top by Δscore:

Variant	Effect	Δscore
2:74455507:G:GT	donor_gain	1.0000
2:74455596:GAG:G	donor_gain	1.0000
2:74455596:GAGG:G	donor_loss	1.0000
2:74455597:AGGT:A	donor_loss	1.0000
2:74455598:GGTGA:G	donor_loss	1.0000
2:74455600:T:G	donor_loss	1.0000
2:74455817:GT:G	acceptor_gain	1.0000
2:74456089:A:AG	acceptor_gain	1.0000
2:74456090:A:G	acceptor_gain	1.0000
2:74456091:C:G	acceptor_gain	1.0000
2:74456098:CCCA:C	acceptor_loss	1.0000
2:74456101:A:AC	acceptor_loss	1.0000
2:74456101:A:AG	acceptor_gain	1.0000
2:74456102:G:GT	acceptor_gain	1.0000
2:74456102:GA:G	acceptor_gain	1.0000
2:74456102:GAT:G	acceptor_gain	1.0000
2:74456268:GACAG:G	donor_gain	1.0000
2:74456269:ACAG:A	donor_gain	1.0000
2:74456270:CAG:C	donor_gain	1.0000
2:74456270:CAGG:C	donor_loss	1.0000
2:74456271:AGG:A	donor_loss	1.0000
2:74456273:G:C	donor_loss	1.0000
2:74456273:G:GG	donor_gain	1.0000
2:74457333:GCGA:G	acceptor_gain	1.0000
2:74455121:G:GG	donor_gain	0.9900
2:74455170:GCCGG:G	donor_gain	0.9900
2:74455174:GGTAA:G	donor_loss	0.9900
2:74455175:GTAAG:G	donor_loss	0.9900
2:74455176:T:A	donor_loss	0.9900
2:74455401:CACAG:C	acceptor_loss	0.9900

AlphaMissense

2257 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:74455559:T:A	L71H	1.000
2:74455565:T:C	I73T	1.000
2:74455565:T:G	I73S	1.000
2:74456188:G:C	W152C	1.000
2:74456188:G:T	W152C	1.000
2:74456272:G:C	Q180H	1.000
2:74456272:G:T	Q180H	1.000
2:74457509:T:A	I239N	1.000
2:74457518:T:C	L242P	1.000
2:74455559:T:C	L71P	0.999
2:74455565:T:A	I73N	0.999
2:74455930:T:A	W122R	0.999
2:74455930:T:C	W122R	0.999
2:74456186:T:A	W152R	0.999
2:74456186:T:C	W152R	0.999
2:74456190:T:C	L153P	0.999
2:74456195:G:C	A155P	0.999
2:74456199:T:C	L156P	0.999
2:74456214:T:C	L161P	0.999
2:74456226:G:A	G165E	0.999
2:74456226:G:T	G165V	0.999
2:74456262:C:T	T177I	0.999
2:74457498:G:C	K235N	0.999
2:74457498:G:T	K235N	0.999
2:74457518:T:A	L242H	0.999
2:74457793:T:A	C334S	0.999
2:74457793:T:C	C334R	0.999
2:74457794:G:C	C334S	0.999
2:74457796:T:G	Y335D	0.999
2:74455470:G:C	K41N	0.998

dbSNP variants (sampled 300 via entrez): RS1000432692 (2:74455148 C>T), RS1001347317 (2:74457113 C>T), RS1001842485 (2:74456842 T>C), RS1002445576 (2:74458181 C>T), RS1002997350 (2:74457021 C>T), RS1004309306 (2:74458131 G>A), RS1004525536 (2:74457652 C>G), RS1005783065 (2:74458443 T>G), RS1006253164 (2:74454142 A>C,G), RS1006701944 (2:74454022 C>A,T), RS1007413060 (2:74454987 C>A,G), RS1007876448 (2:74454701 T>C), RS1008715501 (2:74457241 C>T), RS1010142403 (2:74457165 G>A), RS1010170188 (2:74456857 A>G)

Disease associations

OMIM: gene MIM:616456 | 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
GCST90000025_756	Appendicular lean mass	7.000000e-10

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004980	appendicular lean mass

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

17 total (human), top 17 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases expression, increases methylation	2
GSK-J4	decreases expression	1
FR900359	affects phosphorylation	1
beta-lapachone	increases expression	1
cobaltous chloride	increases expression	1
CD 437	decreases expression	1
jinfukang	increases expression	1
Bortezomib	decreases expression	1
Amphotericin B	decreases expression	1
Caffeine	increases phosphorylation	1
Estradiol	increases expression	1
Quercetin	increases expression	1
Silicon Dioxide	decreases expression	1
Valproic Acid	affects expression	1
Cyclosporine	increases expression	1
Antirheumatic Agents	increases expression	1
Okadaic Acid	decreases expression	1

Clinical trials (associated diseases)

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