ING2

Summary

ING2 (inhibitor of growth family member 2, HGNC:6063) is a protein-coding gene on chromosome 4q35.1, encoding Inhibitor of growth protein 2 (Q9H160). Seems to be involved in p53/TP53 activation and p53/TP53-dependent apoptotic pathways, probably by enhancing acetylation of p53/TP53.

This gene is a member of the inhibitor of growth (ING) family. Members of the ING family associate with and modulate the activity of histone acetyltransferase (HAT) and histone deacetylase (HDAC) complexes and function in DNA repair and apoptosis. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 3622 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 18 total
• Druggable target: yes
• MANE Select transcript: NM_001564

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6063
Approved symbol	ING2
Name	inhibitor of growth family member 2
Location	4q35.1
Locus type	gene with protein product
Status	Approved
Aliases	p33ING2
Ensembl gene	ENSG00000168556
Ensembl biotype	protein_coding
OMIM	604215
Entrez	3622

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000302327, ENST00000412117

RefSeq mRNA: 2 — MANE Select: NM_001564 NM_001291959, NM_001564

CCDS: CCDS3833

Canonical transcript exons

ENST00000302327 — 2 exons

Exon	Start	End
ENSE00001150351	183510282	183512429
ENSE00001200068	183505058	183505367

Expression profiles

Bgee: expression breadth ubiquitous, 291 present calls, max score 91.68.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 3.7155 / max 45.7408, expressed in 1564 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
50794	3.4895	1439
50793	2.2695	1214
50795	1.4460	998

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
amniotic fluid	UBERON:0000173	91.68	gold quality
jejunal mucosa	UBERON:0000399	91.46	gold quality
right adrenal gland	UBERON:0001233	90.00	gold quality
right adrenal gland cortex	UBERON:0035827	89.92	gold quality
adrenal tissue	UBERON:0018303	89.24	gold quality
buccal mucosa cell	CL:0002336	89.21	silver quality
adrenal cortex	UBERON:0001235	89.01	gold quality
left adrenal gland	UBERON:0001234	88.99	gold quality
left adrenal gland cortex	UBERON:0035825	88.90	gold quality
adrenal gland	UBERON:0002369	88.51	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.97	gold quality
palpebral conjunctiva	UBERON:0001812	87.92	gold quality
bronchial epithelial cell	CL:0002328	87.46	gold quality
eye	UBERON:0000970	87.27	gold quality
left testis	UBERON:0004533	86.88	gold quality
right testis	UBERON:0004534	86.43	gold quality
testis	UBERON:0000473	86.41	gold quality
left ovary	UBERON:0002119	86.14	gold quality
cortical plate	UBERON:0005343	85.64	gold quality
ovary	UBERON:0000992	85.58	gold quality
oral cavity	UBERON:0000167	85.51	gold quality
cartilage tissue	UBERON:0002418	85.34	gold quality
right ovary	UBERON:0002118	85.21	gold quality
biceps brachii	UBERON:0001507	85.19	gold quality
epithelium of bronchus	UBERON:0002031	84.99	gold quality
caput epididymis	UBERON:0004358	84.98	gold quality
pigmented layer of retina	UBERON:0001782	84.95	gold quality
retina	UBERON:0000966	84.93	gold quality
parotid gland	UBERON:0001831	84.92	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.91	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.91

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

115 targeting ING2, 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-3646	100.00	73.56	5283
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-3666	99.90	73.24	1833
HSA-MIR-130A-3P	99.90	73.31	1861

Literature-anchored findings (GeneRIF, showing 33)

• p33ING2/ING1L is a DNA damage-inducible gene that negatively regulates cell proliferation through activation of p53 by enhancing its acetylation. (PMID:11481424)
• The ING1L gene may be involved in basal cell carcinogenesis. (PMID:15005689)
• P33ING2 cooperates with p53 to regulate apoptosis via activation of both the mitochondrial/intrinsic and death-receptor/extrinsic apoptotic pathways. (PMID:15748897)
• ING2 can act as a cofactor of p300 for p53 acetylation and thereby plays a positive regulatory role during p53-mediated replicative senescence. (PMID:16024799)
• The expression of ING2 was down-regulated in 6 of 7 lung cancer cell lines that had a p53 mutation. (PMID:16465410)
• Observations suggest that p33ING2 is required for the initial DNA damage sensing and chromatin remodeling in the nucleotide excision repair process. (PMID:16488987)
• The data showed that nuclear ING2 expression was significantly reduced in radial growth phase (RGP), vertical growth phase (VGP), and metastatic melanomas compared with dysplastic nevi (P < 0.05). (PMID:16755297)
• Deletion of leucine zipper-like (LZL)abrogated the association between ING2 and p53, suggesting that ING2 modulates p53-dependent chromatin remodeling, apoptosis and DNA repair. (PMID:16782091)
• molecular modeling and docking of the 5-methylenephosphonate or 5-phosphothionate analogues to the C-terminus PtdInsP-binding region of ING2 revealed a number of complementary surface and electrostatic contacts between the lipids and ING2 (PMID:17469822)
• the interaction between Alien and the tumor suppressors p33ING1 and p33ING2 reveals a novel cellular protein network (PMID:17929852)
• Decreased expression of ING2 gene is associated with hepatocellular carcinoma (PMID:18160212)
• ING2 collaborates with SnoN to mediate TGF-beta-induced Smad-dependent transcription and cellular responses (PMID:18334480)
• p53-mediated mir34a, mir34b, and mir34c up-regulation and ING2 down-regulation may be involved in the senescence pathway. (PMID:18451145)
• ING2 C-terminus recruits histone methyltransferase activity, which correlates with silencing function (PMID:18513492)
• ING2a knockdown suppressed cell growth only in the presence of p53, ING2b knockdown had no effect on cell growth, and knockdown of both induced cell cycle arrest and apoptosis independently of p53. (PMID:18951897)
• ING2 loss of heterozygosity is associated with advanced staging in head and neck squamous cell carcinoma and determines survival rate. (PMID:18998165)
• ING2 is upregulated in colon cancer and increases invasion by enhanced MMP13 expression. (PMID:19437536)
• found that ING2 interacts with proliferating cell nuclear antigen and regulates its amount to the chromatin fraction, allowing normal replication progression and normal cell proliferation. (PMID:19730436)
• expression is downregulated in non-small cell lung carcinoma (PMID:19962781)
• sumoylation of ING2 enhances its binding to the Sin3A/HDAC complex and is required to regulate gene transcriptions (PMID:20676127)
• Data show that inhibition of ING2 expression accelerates progression of cells from G(1) to S-phase, and is accompanied by a decrease of p21 expression, and that regulation of p21 by ING2 is independent of p53. (PMID:20890119)
• Study establishes ING2 as a novel regulator of spermatogenesis functioning, and provides an animal model to study idiopathic and iatrogenic infertility in men. (PMID:21124965)
• findings support a model in which PtdIns(5)P functions as a sub-nuclear trafficking factor that stabilizes ING2 at discrete genomic sites (PMID:23823870)
• It was concluded that ING2 not only plays an essential role in the growth and invasion of MGC-803 cells but also represents a potential approach to chemosensitization therapy in human gastric cancer. (PMID:23864195)
• Decreased expression of ING2 gene is associated with non-small cell lung cancer. (PMID:24712846)
• Results suggest that ING2 acts as a tumor suppressor in osteosarcoma. (PMID:25190103)
• It is thought that ING2 gene expression level could contribute to the development of BCC but not be associated with the stage and the prognosis of the tumor. (PMID:25613071)
• ING2 may be involved in the repair and regeneration of organs or tissues and is associated with breast and gynecological carcinogenesis. (PMID:26717876)
• Our findings provide evidence for a novel crosstalk and a crossregulation between ING1 and ING2 in regulating androgen receptor-mediated transactivation and suggest that ING2 acts as a novel corepressor that inhibits AR signaling, prostate cancer cell growth, and migration. (PMID:27305909)
• Findings provide evidence that ING2 is a direct target of miR92a. (PMID:31180538)
• Integrated analysis of DNA methylation and mRNA expression profiles to identify key genes involved in the regrowth of clinically non-functioning pituitary adenoma. (PMID:32015217)
• Inhibitor of growth 2 regulates the high glucose-induced cell cycle arrest and epithelial-to-mesenchymal transition in renal proximal tubular cells. (PMID:32424454)
• ING2 tumor suppressive protein translocates into mitochondria and is involved in cellular metabolism homeostasis. (PMID:34017078)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ing2	ENSDARG00000104907
mus_musculus	Ing2	ENSMUSG00000063049
rattus_norvegicus	Ing2	ENSRNOG00000013480
drosophila_melanogaster	CG7379	FBGN0038546
caenorhabditis_elegans		WBGENE00020287

Paralogs (4): ING3 (ENSG00000071243), ING4 (ENSG00000111653), ING1 (ENSG00000153487), ING5 (ENSG00000168395)

Protein

Protein identifiers

Inhibitor of growth protein 2 — Q9H160 (reviewed: Q9H160)

Alternative names: Inhibitor of growth 1-like protein, p32, p33ING2

All UniProt accessions (2): Q9H160, C9J4X5

UniProt curated annotations — full annotation on UniProt →

Function. Seems to be involved in p53/TP53 activation and p53/TP53-dependent apoptotic pathways, probably by enhancing acetylation of p53/TP53. Component of a mSin3A-like corepressor complex, which is probably involved in deacetylation of nucleosomal histones. ING2 activity seems to be modulated by binding to phosphoinositides (PtdInsPs).

Subunit / interactions. Interacts with H3K4me3 and to a lesser extent with H3K4me2. Component of a mSin3A-like complex at least consisting of SIN3A, HDAC1, HDAC2, RBBP4/RbAp48, RBBP7/RbAp46, SAP30 and ING2.

Subcellular location. Nucleus.

Tissue specificity. Widely expressed. Higher expressed in colon-cancer tumor than in normal colon tissues.

Post-translational modifications. Sumoylation enhances its association with SIN3A and is required for binding to some target gene promoters, this is the case for TMEM71.

Domain organisation. The PHD-type zinc finger mediates the binding to H3K4me3. The polybasic region (PBR) is responsive to the binding to phosphoinositides (PtdInsPs), including phosphatidylinositol 5-phosphate (PtdIns(5)P).

Induction. Induced by the DNA-damaging agents etoposide and neocarzinostatin.

Miscellaneous. Low expression except in testis, where it reaches half of ING2a levels.

Similarity. Belongs to the ING family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9H160-1	ING2a	yes
Q9H160-2	ING2b

RefSeq proteins (2): NP_001278888, NP_001555* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001965	Znf_PHD	Domain
IPR011011	Znf_FYVE_PHD	Homologous_superfamily
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR019786	Zinc_finger_PHD-type_CS	Conserved_site
IPR019787	Znf_PHD-finger	Domain
IPR024610	ING_N_histone-binding	Domain
IPR028651	ING_fam	Family
IPR042019	ING2_PHD	Domain

Pfam: PF12998

UniProt features (24 total): binding site 8, site 4, region of interest 3, compositionally biased region 3, chain 1, zinc finger region 1, cross-link 1, splice variant 1, sequence conflict 1, coiled-coil region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H160-F1	75.87	0.41

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 (4): 214 (histone h3k4me3 binding); 225 (histone h3k4me3 binding); 229 (histone h3k4me3 binding); 237 (histone h3k4me3 binding)

Ligand- & substrate-binding residues (8): 217; 228; 233; 239; 242; 255; 258; 215

Post-translational modifications (1): 195

Function

Pathways and Gene Ontology

Reactome pathways

12 pathways

ID	Pathway
R-HSA-3899300	SUMOylation of transcription cofactors
R-HSA-6811555	PI5P Regulates TP53 Acetylation
R-HSA-212436	Generic Transcription Pathway
R-HSA-2990846	SUMOylation
R-HSA-3108232	SUMO E3 ligases SUMOylate target proteins
R-HSA-3700989	Transcriptional Regulation by TP53
R-HSA-392499	Metabolism of proteins
R-HSA-5633007	Regulation of TP53 Activity
R-HSA-597592	Post-translational protein modification
R-HSA-6804758	Regulation of TP53 Activity through Acetylation
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-74160	Gene expression (Transcription)

MSigDB gene sets: 286 (showing top): GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, GOBP_INTRINSIC_APOPTOTIC_SIGNALING_PATHWAY_IN_RESPONSE_TO_DNA_DAMAGE_BY_P53_CLASS_MEDIATOR, WWTAAGGC_UNKNOWN, YAGI_AML_WITH_INV_16_TRANSLOCATION, TGCGCANK_UNKNOWN, GOBP_NEGATIVE_REGULATION_OF_INTRINSIC_APOPTOTIC_SIGNALING_PATHWAY_BY_P53_CLASS_MEDIATOR, GOBP_MALE_GAMETE_GENERATION, GOBP_CELLULAR_SENESCENCE, CTATGCA_MIR153, GOBP_NEGATIVE_REGULATION_OF_INTRINSIC_APOPTOTIC_SIGNALING_PATHWAY_IN_RESPONSE_TO_DNA_DAMAGE, GOBP_POSITIVE_REGULATION_OF_CELLULAR_RESPONSE_TO_TRANSFORMING_GROWTH_FACTOR_BETA_STIMULUS, SP1_Q2_01, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, GOBP_ASYMMETRIC_CELL_DIVISION, GOBP_STEM_CELL_DIVISION

GO Biological Process (21): negative regulation of transcription by RNA polymerase II (GO:0000122), regulation of DNA-templated transcription (GO:0006355), DNA damage response (GO:0006974), male meiosis I (GO:0007141), signal transduction (GO:0007165), spermatogenesis (GO:0007283), spermatid development (GO:0007286), flagellated sperm motility (GO:0030317), negative regulation of cell migration (GO:0030336), positive regulation of transforming growth factor beta receptor signaling pathway (GO:0030511), negative regulation of transforming growth factor beta receptor signaling pathway (GO:0030512), negative regulation of gene expression, epigenetic (GO:0045814), positive regulation of DNA-templated transcription (GO:0045893), male germ-line stem cell asymmetric division (GO:0048133), seminiferous tubule development (GO:0072520), negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator (GO:1902166), negative regulation of stem cell population maintenance (GO:1902455), positive regulation of stem cell population maintenance (GO:1902459), regulation of cellular senescence (GO:2000772), chromatin organization (GO:0006325), negative regulation of apoptotic signaling pathway (GO:2001234)

GO Molecular Function (10): DNA binding (GO:0003677), chromatin binding (GO:0003682), zinc ion binding (GO:0008270), histone deacetylase regulator activity (GO:0035033), phosphatidylinositol binding (GO:0035091), protein-containing complex binding (GO:0044877), histone H3K4me3 reader activity (GO:0140002), histone reader activity (GO:0140566), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (5): nucleus (GO:0005634), nucleoplasm (GO:0005654), plasma membrane (GO:0005886), CCAAT-binding factor complex (GO:0016602), Sin3-type complex (GO:0070822)

Reactome top-level categories

Rollup of top-10 pathways:

Category	Pathways
SUMO E3 ligases SUMOylate target proteins	1
Regulation of TP53 Activity through Acetylation	1
RNA Polymerase II Transcription	1
Post-translational protein modification	1
SUMOylation	1
Generic Transcription Pathway	1
Transcriptional Regulation by TP53	1
Metabolism of proteins	1
Regulation of TP53 Activity	1
Gene expression (Transcription)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	3
DNA-templated transcription	2
male gamete generation	2
regulation of cellular process	2
transforming growth factor beta receptor signaling pathway	2
regulation of transforming growth factor beta receptor signaling pathway	2
stem cell population maintenance	2
regulation of stem cell population maintenance	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
cellular response to stress	1
meiosis I	1
male meiotic nuclear division	1
meiotic cell cycle	1
cell communication	1
cellular process	1
signaling	1
cellular response to stimulus	1
developmental process involved in reproduction	1
germ cell development	1
spermatid differentiation	1
cilium-dependent cell motility	1
cilium movement involved in cell motility	1
sperm motility	1
cell migration	1
regulation of cell migration	1
negative regulation of cell motility	1
positive regulation of transmembrane receptor protein serine/threonine kinase signaling pathway	1
positive regulation of cellular response to transforming growth factor beta stimulus	1
negative regulation of transmembrane receptor protein serine/threonine kinase signaling pathway	1
negative regulation of gene expression	1
epigenetic regulation of gene expression	1
regulation of DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
spermatogenesis	1
germline stem cell asymmetric division	1
male gonad development	1

Protein interactions and networks

STRING

1534 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ING2	SIN3A	Q96ST3	926
ING2	H3-3A	P06351	909
ING2	H3-5	Q6NXT2	909
ING2	H3C1	P02295	908
ING2	H3-4	Q16695	908
ING2	H3-7	Q5TEC6	908
ING2	H3C14	Q71DI3	908
ING2	SAP30	O75446	902
ING2	TAF3	Q5VWG9	816
ING2	ARID4A	P29374	798
ING2	HDAC1	Q13547	792
ING2	BRMS1L	Q5PSV4	780
ING2	BPTF	Q12830	774
ING2	BRMS1	Q9HCU9	752
ING2	SAP30L	Q9HAJ7	698
ING2	PHF21A	Q96BD5	698

IntAct

67 interactions, top by confidence:

A	B	Type	Score
HDAC1	CDK2AP1	psi-mi:“MI:0914”(association)	0.840
RBBP7	CDK2AP1	psi-mi:“MI:0914”(association)	0.840
RBBP4	CDK2AP1	psi-mi:“MI:0914”(association)	0.790
HDAC1	ZNF609	psi-mi:“MI:0914”(association)	0.730
RBBP7	HAT1	psi-mi:“MI:0914”(association)	0.730
ING2	SIN3A	psi-mi:“MI:0915”(physical association)	0.670
FOXK2	DVL2	psi-mi:“MI:0914”(association)	0.640
SINHCAF	TNRC18	psi-mi:“MI:0914”(association)	0.640
ZNF704	SAP30	psi-mi:“MI:0914”(association)	0.640
ING2	PCNA	psi-mi:“MI:0407”(direct interaction)	0.540
ING2	PCNA	psi-mi:“MI:0915”(physical association)	0.540
PCNA	ING2	psi-mi:“MI:0915”(physical association)	0.540
ING2	SMURF1	psi-mi:“MI:0407”(direct interaction)	0.540
ING2	SMURF1	psi-mi:“MI:0915”(physical association)	0.540
SMURF1	ING2	psi-mi:“MI:0915”(physical association)	0.540
FHL2	CNOT1	psi-mi:“MI:0914”(association)	0.530
RBBP7	EPOP	psi-mi:“MI:0914”(association)	0.530
SAP30	TNRC18	psi-mi:“MI:0914”(association)	0.530
	ING2	psi-mi:“MI:0407”(direct interaction)	0.440
ING2		psi-mi:“MI:0407”(direct interaction)	0.440
SUMO1	ING2	psi-mi:“MI:0915”(physical association)	0.400
UBC	ING2	psi-mi:“MI:0915”(physical association)	0.400
ING2	SMURF1	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (128): ING2 (Affinity Capture-MS), ING2 (Reconstituted Complex), ING2 (Affinity Capture-MS), ING2 (Affinity Capture-MS), ING2 (Affinity Capture-MS), ING2 (Affinity Capture-MS), ING2 (Affinity Capture-MS), ING2 (Affinity Capture-MS), SIN3B (Affinity Capture-MS), ARID4B (Affinity Capture-MS), SAP130 (Affinity Capture-MS), HDAC1 (Affinity Capture-MS), RBBP7 (Affinity Capture-MS), CENPH (Affinity Capture-MS), BRMS1L (Affinity Capture-MS)

ESM2 similar proteins: A0A286Y9D1, A0JMK9, A2BIL7, A8DZJ1, B2KF05, B2RRD7, B4KLY7, F4IDY7, O15042, O94880, O97159, P55201, P97496, Q05913, Q20448, Q2T9V9, Q3T095, Q4V7A6, Q5EA28, Q5R7X2, Q61103, Q63ZP1, Q6DD45, Q6FSB1, Q6GQJ2, Q6IE81, Q6IE82, Q6NV83, Q6NWE1, Q6P2L6, Q6ZPI0, Q7KRW8, Q7ZVP1, Q803A0, Q8BRB7, Q8WML3, Q8WUB8, Q92613, Q92785, Q92922

Diamond homologs: B3H615, O42871, O74736, P50947, Q08465, Q3T095, Q498T3, Q54PN9, Q5AHB8, Q5RBA1, Q5ZK36, Q5ZKY4, Q66KD5, Q6BNL6, Q6C5V7, Q6CXN0, Q757W2, Q7ZX31, Q8C0D7, Q8VEK6, Q9ESK4, Q9H160, Q9LIQ6, Q9NXR8, Q9QXV3, Q9UK53, Q9UNL4, Q9VJY8, A3QMD7, P38806, Q6FSB1, Q8WYH8, Q9D8Y8, P34447, Q5F489, Q5EAW9, Q5VWG9, Q8C9B9, Q9BTC0, Q5HZG4

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
ING2	“down-regulates quantity by repression”	AFP	“transcriptional regulation”
ING2	“up-regulates quantity by expression”	MMP13	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 57 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.

Reactome pathways:

Pathway	Partners	Fold	FDR
Regulation of TP53 Activity through Acetylation	5	53.1×	2e-05
NuRD complex assembly	6	19.7×	1e-04
Negative Regulation of CDH1 Gene Transcription	6	16.8×	2e-04
Interaction of NuRD complexes with transcription factors	5	14.8×	2e-03
HDACs deacetylate histones	5	14.0×	2e-03
RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function	5	14.0×	2e-03
Potential therapeutics for SARS	5	13.3×	2e-03
Activation of anterior HOX genes in hindbrain development during early embryogenesis	5	10.6×	3e-03

GO biological processes:

GO term	Partners	Fold	FDR
negative regulation of stem cell population maintenance	7	97.5×	2e-10
positive regulation of stem cell population maintenance	7	43.8×	3e-08
negative regulation of transforming growth factor beta receptor signaling pathway	9	28.4×	4e-09
negative regulation of cell migration	7	14.2×	4e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	18
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

684 predictions. Top by Δscore:

Variant	Effect	Δscore
4:183505366:AGG:A	donor_loss	1.0000
4:183505367:GGT:G	donor_loss	1.0000
4:183505368:GTAG:G	donor_loss	1.0000
4:183510280:A:AG	acceptor_gain	1.0000
4:183510281:G:GA	acceptor_gain	1.0000
4:183510281:GA:G	acceptor_gain	1.0000
4:183510281:GAA:G	acceptor_gain	1.0000
4:183510281:GAAA:G	acceptor_gain	1.0000
4:183510281:GAAAC:G	acceptor_gain	1.0000
4:183505366:AG:A	donor_gain	0.9900
4:183505367:GG:G	donor_gain	0.9900
4:183505368:G:GG	donor_gain	0.9900
4:183505369:T:A	donor_loss	0.9900
4:183506317:GC:G	donor_gain	0.9900
4:183506358:G:GT	donor_gain	0.9900
4:183510276:TTTTA:T	acceptor_gain	0.9900
4:183510277:TTTAG:T	acceptor_gain	0.9900
4:183510278:TTAG:T	acceptor_gain	0.9900
4:183510279:TAGA:T	acceptor_gain	0.9900
4:183510280:A:AC	acceptor_gain	0.9900
4:183510281:G:T	acceptor_gain	0.9900
4:183505328:A:T	donor_gain	0.9800
4:183506319:G:GG	donor_gain	0.9700
4:183506509:G:GA	donor_gain	0.9700
4:183506957:T:G	donor_gain	0.9600
4:183505368:G:T	donor_gain	0.9500
4:183506929:T:TA	donor_gain	0.9500
4:183506930:A:AA	donor_gain	0.9500
4:183508503:GGT:G	donor_gain	0.9500
4:183508504:GTG:G	donor_gain	0.9500

AlphaMissense

1850 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:183510378:T:C	L90P	1.000
4:183510749:T:A	Y214N	1.000
4:183510749:T:C	Y214H	1.000
4:183510749:T:G	Y214D	1.000
4:183510750:A:G	Y214C	1.000
4:183510752:T:A	C215S	1.000
4:183510752:T:C	C215R	1.000
4:183510752:T:G	C215G	1.000
4:183510753:G:A	C215Y	1.000
4:183510753:G:C	C215S	1.000
4:183510753:G:T	C215F	1.000
4:183510754:C:G	C215W	1.000
4:183510758:T:A	C217S	1.000
4:183510758:T:C	C217R	1.000
4:183510759:G:A	C217Y	1.000
4:183510759:G:C	C217S	1.000
4:183510759:G:T	C217F	1.000
4:183510760:C:G	C217W	1.000
4:183510765:A:C	Q219P	1.000
4:183510771:C:T	S221F	1.000
4:183510776:G:A	G223R	1.000
4:183510776:G:C	G223R	1.000
4:183510776:G:T	G223W	1.000
4:183510777:G:A	G223E	1.000
4:183510777:G:C	G223A	1.000
4:183510777:G:T	G223V	1.000
4:183510782:A:G	M225V	1.000
4:183510783:T:A	M225K	1.000
4:183510783:T:C	M225T	1.000
4:183510783:T:G	M225R	1.000

dbSNP variants (sampled 300 via entrez): RS1000190736 (4:183512641 T>A,G), RS1000251885 (4:183505941 C>A,G,T), RS1001017642 (4:183506923 C>G), RS10013043 (4:183510140 A>C), RS1001470999 (4:183507598 A>C), RS1001524727 (4:183507859 T>C), RS1001918647 (4:183511149 T>C), RS1001921813 (4:183505118 G>A,C), RS1002069202 (4:183503933 G>C), RS1002544721 (4:183503583 G>A), RS1002641620 (4:183503105 T>C), RS1002748219 (4:183505777 C>CACCT), RS1003216928 (4:183505629 A>T), RS1003409001 (4:183504599 A>C), RS10034997 (4:183509758 G>C,T)

Disease associations

OMIM: gene MIM:604215 | 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: yes

ChEMBL targets (1): CHEMBL3784904 (SINGLE PROTEIN)

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

ChEMBL bioactivities

3 potent at pChembl≥5 of 5 total, top 3 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.82	Kd	15	nM	CHEMBL1092710
7.79	Kd	16.2	nM	CHEMBL4176148
7.30	Kd	50	nM	CHEMBL4168964

PubChem BioAssay actives

3 with measured affinity, of 8 total; 3 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
25,26,27,28-tetrahydroxypentacyclo[19.3.1.13,7.19,13.115,19]octacosa-1(24),3,5,7(28),9,11,13(27),15(26),16,18,21(25),22-dodecaene-5,11,17,23-tetrasulfonic acid	1506824: Binding affinity to 15N-labeled GST-tagged ING2 PHD finger domain (212 to 264 residues) (unknown origin) expressed in Escherichia coli Rosetta2 BL21(DE3) pLysS cells by NMR Spectroscopy method	kd	0.0150	uM
4-[(25,26,27,28-tetrahydroxy-11,17,23-trisulfo-5-pentacyclo[19.3.1.13,7.19,13.115,19]octacosa-1(25),3,5,7(28),9(27),10,12,15(26),16,18,21,23-dodecaenyl)sulfamoyl]benzoic acid	1506824: Binding affinity to 15N-labeled GST-tagged ING2 PHD finger domain (212 to 264 residues) (unknown origin) expressed in Escherichia coli Rosetta2 BL21(DE3) pLysS cells by NMR Spectroscopy method	kd	0.0162	uM
23-benzamido-25,26,27,28-tetrahydroxypentacyclo[19.3.1.13,7.19,13.115,19]octacosa-1(24),3(28),4,6,9,11,13(27),15,17,19(26),21(25),22-dodecaene-5,11,17-trisulfonic acid	1506824: Binding affinity to 15N-labeled GST-tagged ING2 PHD finger domain (212 to 264 residues) (unknown origin) expressed in Escherichia coli Rosetta2 BL21(DE3) pLysS cells by NMR Spectroscopy method	kd	0.0500	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
GSK-J4	increases expression	1
TAK-243	decreases sumoylation	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, increases expression	1
sodium arsenite	increases expression	1
cobaltous chloride	increases expression	1
ICG 001	decreases expression	1
MT19c compound	increases expression	1
Temozolomide	decreases expression	1
Acetaminophen	increases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Diethylstilbestrol	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Formaldehyde	decreases expression	1
Gasoline	affects cotreatment, increases abundance, increases expression	1
Indomethacin	increases expression, affects cotreatment	1
Ketoconazole	decreases expression	1
Polycyclic Aromatic Hydrocarbons	increases expression, affects cotreatment, increases abundance	1
Thiram	increases expression	1
Tretinoin	decreases expression	1
Urethane	decreases expression	1
Valproic Acid	increases expression	1
Vincristine	decreases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
Cyclosporine	decreases expression	1
Copper Sulfate	decreases expression	1
Lactic Acid	affects expression	1
Particulate Matter	affects cotreatment, increases abundance, increases expression	1

ChEMBL screening assays

4 unique, capped per target: 4 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3791708	Binding	Inhibition of recombinant GST-tagged ING2 PHD (201 to 281 residues) (unknown origin) using biotin-H3K4me3 ( 1 to 14 residues) peptide substrate by fluorescence polarization assay	Recent Progress in Histone Demethylase Inhibitors. — J Med Chem

Clinical trials (associated diseases)

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