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
• Regional missense constraint (gnomAD): 2 of 5 regions constrained (≈28% of expected missense variation)
• GTEx eGene: eQTL in 19 tissues, sQTL in 11 (q < 0.05)
• Constraint (gnomAD): pLI 0.99 (loss-of-function intolerant), LOEUF 0.44 (moderately constrained)
• 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: 3 — 3 protein_coding

MANE Select: ENST00000302327

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2

ENST00000302327, ENST00000412117, ENST00001141703

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.

Highest expression (Bgee): amniotic fluid, jejunal mucosa, adrenal gland, adrenal gland cortex, adrenal tissue.

Genetic regulation across tissues (GTEx eQTL / sQTL)

ING2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 19 tissues and its splicing (sQTL) in 11 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 30 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Testis	sqtl	3.2e-13	-0.90	4:183504746:G:A
Heart Left Ventricle	eqtl	1.9e-11	+0.36	4:183506427:A:G
Thyroid	eqtl	3.4e-09	+0.29	4:183506427:A:G
Colon Transverse	eqtl	1.1e-08	+0.27	4:183507591:A:G
Heart Atrial Appendage	eqtl	3.7e-08	+0.36	4:183506427:A:G
Colon Sigmoid	eqtl	9.4e-07	+0.29	4:183481018:G:A
Esophagus Mucosa	eqtl	4.3e-06	+0.21	4:183507591:A:G
Thyroid	sqtl	6.3e-06	-0.41	4:183506427:A:G
Cells Cultured fibroblasts	eqtl	2.6e-05	+0.16	4:183520896:C:T
Pancreas	eqtl	4.6e-05	+0.26	4:183507591:A:G
Skin Not Sun Exposed Suprapubic	sqtl	7.2e-05	-0.42	4:183506427:A:G
Skin Sun Exposed Lower leg	eqtl	7.2e-05	+0.19	4:183507591:A:G
Artery Tibial	eqtl	2.8e-04	+0.22	4:183544531:A:G
Breast Mammary Tissue	eqtl	4.7e-04	+0.24	4:183506427:A:G
Skin Sun Exposed Lower leg	sqtl	5.7e-04	-0.37	4:183481018:G:A
Cells Cultured fibroblasts	sqtl	7.8e-04	-0.27	4:183481018:G:A
Artery Aorta	eqtl	8.7e-04	+0.35	4:183544618:C:T
Adipose Subcutaneous	eqtl	2.1e-03	+0.18	4:183507591:A:G
Nerve Tibial	eqtl	2.5e-03	-0.21	4:183602955:C:CTT
Artery Tibial	sqtl	4.5e-03	-1.12	4:183444517:A:C

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

showing 100 of 297 tissues 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
hindlimb stylopod muscle	UBERON:0004252	84.56	gold quality
secondary oocyte	CL:0000655	84.34	gold quality
bronchus	UBERON:0002185	84.28	gold quality
oocyte	CL:0000023	84.02	gold quality
monocyte	CL:0000576	83.89	gold quality
duodenum	UBERON:0002114	83.87	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	83.72	gold quality
jejunum	UBERON:0002115	83.66	gold quality
vastus lateralis	UBERON:0001379	83.65	gold quality
gastrocnemius	UBERON:0001388	83.62	gold quality
mucosa of stomach	UBERON:0001199	83.57	gold quality
mononuclear cell	CL:0000842	83.46	gold quality
pituitary gland	UBERON:0000007	83.31	gold quality
muscle of leg	UBERON:0001383	83.20	gold quality
islet of Langerhans	UBERON:0000006	83.18	gold quality
esophagus squamous epithelium	UBERON:0006920	83.16	gold quality
lower esophagus muscularis layer	UBERON:0035833	83.12	gold quality
mucosa of sigmoid colon	UBERON:0004993	83.11	gold quality
leukocyte	CL:0000738	83.08	gold quality
nasal cavity mucosa	UBERON:0001826	83.06	gold quality
lower esophagus	UBERON:0013473	83.06	gold quality
quadriceps femoris	UBERON:0001377	83.05	gold quality
skeletal muscle organ	UBERON:0014892	82.96	gold quality
muscle organ	UBERON:0001630	82.95	gold quality
epithelium of esophagus	UBERON:0001976	82.87	gold quality
adenohypophysis	UBERON:0002196	82.84	gold quality
colonic mucosa	UBERON:0000317	82.79	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	82.45	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	82.38	gold quality
gingiva	UBERON:0001828	82.31	gold quality
tendon of biceps brachii	UBERON:0008188	82.24	gold quality
corpus epididymis	UBERON:0004359	82.13	gold quality
sperm	CL:0000019	81.78	gold quality
nephron tubule	UBERON:0001231	81.72	gold quality
bone marrow	UBERON:0002371	81.42	gold quality
metanephros	UBERON:0000081	81.37	gold quality
embryo	UBERON:0000922	81.28	gold quality
ventricular zone	UBERON:0003053	81.23	gold quality
gingival epithelium	UBERON:0001949	81.21	gold quality
esophagus	UBERON:0001043	81.07	gold quality
male germ cell	CL:0000015	81.06	gold quality
skeletal muscle tissue	UBERON:0001134	80.73	gold quality
gall bladder	UBERON:0002110	80.70	gold quality
stromal cell of endometrium	CL:0002255	80.44	gold quality
germinal epithelium of ovary	UBERON:0001304	80.38	gold quality
tendon	UBERON:0000043	80.35	gold quality
placenta	UBERON:0001987	80.34	gold quality
pancreas	UBERON:0001264	80.28	gold quality
trabecular bone tissue	UBERON:0002483	80.21	gold quality
ganglionic eminence	UBERON:0004023	80.17	gold quality
kidney epithelium	UBERON:0004819	79.94	gold quality
body of pancreas	UBERON:0001150	79.66	gold quality
renal glomerulus	UBERON:0000074	79.60	gold quality
seminal vesicle	UBERON:0000998	79.57	gold quality
squamous epithelium	UBERON:0006914	79.37	gold quality
esophagus mucosa	UBERON:0002469	79.25	gold quality
metanephric glomerulus	UBERON:0004736	79.17	gold quality
calcaneal tendon	UBERON:0003701	79.08	gold quality
muscle tissue	UBERON:0002385	79.01	gold quality
epithelium of nasopharynx	UBERON:0001951	78.83	gold quality
cortex of kidney	UBERON:0001225	78.78	gold quality
ileal mucosa	UBERON:0000331	78.42	gold quality
nasal cavity epithelium	UBERON:0005384	78.42	gold quality
rectum	UBERON:0001052	78.40	gold quality
descending thoracic aorta	UBERON:0002345	78.34	gold quality
granulocyte	CL:0000094	78.19	gold quality
medial globus pallidus	UBERON:0002477	78.13	gold quality
deltoid	UBERON:0001476	78.08	gold quality
prefrontal cortex	UBERON:0000451	78.06	gold quality
lower lobe of lung	UBERON:0008949	77.99	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

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Ovary	tissue	32.5	high
Adrenal gland	tissue	20.9	high
Bone marrow	tissue	20.4	low
Testis	tissue	17.8	high
Cerebellum	tissue	16.5	low
Prefrontal cortex	tissue	15.5
Cerebral cortex	tissue	15.5	medium
Occipital cortex	tissue	15.0
Pancreas	tissue	14.9	medium
Somatosensory cortex	tissue	14.9
Motor cortex	tissue	14.6
Retrosplenial and cingulate cortex	tissue	14.6
Pituitary gland	tissue	14.2
Hippocampal formation	tissue	13.9
Entorhinal cortex	tissue	13.9
Tongue	tissue	13.8
Skeletal muscle	tissue	13.6	low
Small intestine	tissue	13.5	high
Retrosplenial cortex	tissue	13.5
Temporal cortex	tissue	13.0
Frontal cortex	tissue	11.9
Insular cortex	tissue	11.8
Thymus	tissue	11.7
Locus coeruleus	tissue	11.5
Septum	tissue	11.3
Thalamus	tissue	11.2
Periaqueductal gray	tissue	11.2
Olfactory bulb	tissue	11.1
Choroid plexus	tissue	11.0
Basal ganglia	tissue	10.7	medium
Postcentral gyrus	tissue	10.6
Pons	tissue	10.4
Nucleus accumbens	tissue	10.3
Amygdala	tissue	10.2
Superior colliculi	tissue	10.1
Putamen	tissue	9.9
Duodenum	tissue	9.9	medium
Midbrain	tissue	9.8
Hypothalamus	tissue	9.8
Epididymis	tissue	9.6	medium
Liver	tissue	9.6	medium
Ventral forebrain	tissue	9.6
Kidney	tissue	9.4	medium
Esophagus	tissue	9.0	medium
Substantia nigra	tissue	8.8
Hippocampus	tissue	8.8	medium
Medulla oblongata	tissue	8.5
Corpus callosum	tissue	8.5
Gallbladder	tissue	8.3	high
Retina	tissue	7.9
Breast	tissue	7.8	medium
Fallopian tube	tissue	7.7	medium
Salivary gland	tissue	7.6	medium
Spinal cord	tissue	7.5
Thyroid gland	tissue	7.4	medium
Stomach 1	tissue	7.2	medium
Adipose tissue	tissue	6.8	medium
Urinary bladder	tissue	6.7	medium
Colon	tissue	6.5	medium
Rectum	tissue	6.2	medium

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Paraventricular nucleus (19.5), Arcuate nucleus (17.3), Ventromedial nucleus (16.0), Orbitofrontal gyrus, anterior (15.0), Subiculum (13.6).

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

4 targets:

Target	Regulation
AFP	Repression
BCL2	Repression
MMP13	Activation
TMEM71	Unknown

Upstream regulators (CollecTRI, top): NFKB, TP53

miRNA regulators (miRDB)

Targeting ING2 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 115 miRNAs:

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

Functional genomics

gnomAD constraint: pLI 0.995, LOEUF 0.436, missense Z 2.06 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000302327 splits into 5 regions with different missense tolerance; 2 are missense-constrained (≈28% of the expected missense variation). Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
4:183,505,196–183,510,365	80 / 102.4	0.78	no
4:183,510,366–183,510,416	2 / 18.0	0.11	yes (p 1.6e-04)
4:183,510,417–183,510,708	115 / 120.1	0.96	no
4:183,510,709–183,510,905	22 / 77.0	0.29	yes (p 3.6e-10)
4:183,510,906–183,510,949	20 / 17.3	1.16	no

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)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1916510) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 30 distinct phenotype terms.

Mouse phenotype (MP)	Records
spleen hyperplasia	1
small testis	1
increased Leydig cell number	1
seminiferous tubule degeneration	1
abnormal prostate gland morphology	1
hyperactivity	1
male infertility	1
increased sarcoma incidence	1
increased vertical activity	1
increased mean corpuscular volume	1
asthenozoospermia	1
globozoospermia	1
oligozoospermia	1
increased circulating alanine transaminase level	1
decreased testis weight	1
decreased male germ cell number	1
increased circulating bilirubin level	1
teratozoospermia	1
abnormal cell physiology	1
increased apoptosis	1
arrest of male meiosis	1
enlarged sperm head	1
coiled sperm flagellum	1
short sperm flagellum	1
increased histiocytic sarcoma incidence	1

+5 more (showing top 25).

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Pongo abelii	Q5RBA1	99.5%	Diamond
Bos taurus	Q3T095	98.4%	Diamond
Xenopus tropicalis	Q66KD5	97.4%	Diamond
Xenopus laevis	Q7ZX31	97.4%	Diamond
Gallus gallus	Q5ZKY4	96.8%	Diamond
Arabidopsis thaliana	Q9LIQ6	76.4%	Diamond
Nakaseomyces glabratus CBS 138	Q6FSB1	75.6%	Diamond
Dictyostelium discoideum	Q54PN9	74.5%	Diamond
Saccharomyces cerevisiae S288C	P38806	73.3%	Diamond
Eremothecium gossypii ATCC 10895	Q757W2	71.1%	Diamond
Debaryomyces hansenii CBS767	Q6BNL6	70.2%	Diamond
Kluyveromyces lactis NRRL Y-1140	Q6CXN0	68.9%	Diamond
Candida albicans SC5314	Q5AHB8	66.7%	Diamond
Schizosaccharomyces pombe 972h-	O74736	66.0%	Diamond
Yarrowia lipolytica CLIB122	Q6C5V7	58.9%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
ING2-DT	ncRNA	389247
RWDD4	protein-coding	201965
CDKN2AIP	protein-coding	55602

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

Predicted structure (AlphaFold)

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

Human Protein Atlas

Protein class: Predicted intracellular proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoplasm

Antibody reliability (HPA): IH supported · IF supported

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)

Position	Role
214	histone h3k4me3 binding
225	histone h3k4me3 binding
229	histone h3k4me3 binding
237	histone h3k4me3 binding

Ligand- & substrate-binding residues (8)

Position	Role
217	Zn(2+)
228	Zn(2+)
233	Zn(2+)
239	Zn(2+)
242	Zn(2+)
255	Zn(2+)
258	Zn(2+)
215	Zn(2+)

Post-translational modifications (1)

Type	Positions
Glycyl lysine isopeptide (lys-gly) (interchain with g-cter in sumo1)	195

Function

Pathways and Gene Ontology

Reactome pathways

2 curated (TAS) of 12; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

12 pathways:

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

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), DNA-templated transcription (GO:0006351), 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)

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

10 top-level categories:

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

showing 60 of 74 GO namespaces:

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
gene expression	1
RNA biosynthetic process	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
tube development	1
reproductive structure development	1
animal gross anatomical part developmental process	1
intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator	1
regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator	1
negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage	1
negative regulation of intrinsic apoptotic signaling pathway by p53 class mediator	1
negative regulation of developmental process	1
negative regulation of multicellular organismal process	1
positive regulation of developmental process	1
positive regulation of multicellular organismal process	1
cellular senescence	1
nucleic acid binding	1
transition metal ion binding	1
histone deacetylase activity	1
enzyme regulator activity	1
histone deacetylase binding	1
anion binding	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 12 of 36 annotations. The rest are phylogenetic / computational / electronic (IEA).

12 experimentally-supported GO terms:

GO term	NS	Evidence
positive regulation of DNA-templated transcription	BP	direct assay
positive regulation of transforming growth factor beta receptor signaling pathway	BP	direct assay
regulation of DNA-templated transcription	BP	direct assay
CCAAT-binding factor complex	CC	direct assay
Sin3-type complex	CC	direct assay
nucleoplasm	CC	direct assay
nucleus	CC	direct assay
plasma membrane	CC	mutant phenotype
DNA binding	MF	direct assay
histone H3K4me3 reader activity	MF	direct assay
phosphatidylinositol binding	MF	direct assay
protein-containing complex binding	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 1,078 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ING2	TAF3	Q5VWG9	773
ING2	BPTF	Q12830	755
ING2	PHF21A	Q96BD5	703
ING2	BRMS1L	Q5PSV4	655
ING2	ARID4A	P29374	611
ING2	HDAC1	Q13547	604
ING2	SIN3A	Q96ST3	603
ING2	KDM4A	O75164	602
ING2	KAT7	O95251	599
ING2	BRMS1	Q9HCU9	597
ING2	SAP30	O75446	588
ING2	MORF4L1	Q9UBU8	571
ING2	KAT2A	Q92830	535
ING2	WDR5	P61964	512
ING2	H4C7	Q99525	509

IntAct

Human interaction partners of ING2 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

11 partners by confidence:

Partner	Interaction type	MIscore	Records
SIN3A	physical association	0.670	1
SMURF1	direct interaction	0.540	4
PCNA	direct interaction	0.540	3
EP300	physical association	0.400	1
H3-3A	physical association	0.400	1
SUMO1	physical association	0.400	1
TP53	physical association	0.400	1
UBC	physical association	0.400	1
TARS3	association	0.350	1
TARSL2	association	0.350	1
TNRC18	association	0.350	1

BioGRID (128 interactions; top human partners by supporting records): HDAC1 (Affinity Capture-MS; 9 records), SIN3A (Affinity Capture-MS; 7 records), RBBP7 (Affinity Capture-MS; 6 records), SAP30 (Affinity Capture-MS; 5 records), FAM60A (Affinity Capture-MS; 4 records), RBBP4 (Affinity Capture-MS; 4 records), SMURF1 (Biochemical Activity; 4 records), ARID4A (Affinity Capture-MS; 3 records), ARID4B (Affinity Capture-MS; 3 records), BRMS1L (Affinity Capture-MS; 3 records), HDAC2 (Affinity Capture-MS; 3 records), SAP130 (Affinity Capture-MS; 3 records), SUDS3 (Affinity Capture-MS; 3 records), APP (Reconstituted Complex; 2 records), BAHCC1 (Affinity Capture-MS; 2 records)

SIGNOR signaling

2 signaling interactions:

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

Protein complexes (CORUM) (1)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

1 complexes by size:

Complex	Subunits	Members
★ ING2 complex	13	BRMS1L, SAP30, SIN3A, SUDS3, ARID4A, BRMS1, HDAC1, HDAC2, ING2, RBBP4, RBBP7, SAP130, ARID4B

Disease & clinical

Genetic variants

Variant evidence for ING2: 18 ClinVar records (0 pathogenic / likely pathogenic).

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

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 16 predictions of 346):

Position(s)	Effect	Δscore	Sites
4:183505368	donor_loss	1.0000	2
4:183510280–183510281	acceptor_loss	1.0000	6
4:183505369	donor_loss	0.9900
4:183505328	donor_gain	0.9800
4:183505368	donor_loss	0.9600
4:183506957	donor_gain	0.9600
4:183505369	donor_loss	0.9500
4:183506618	donor_gain	0.9100
4:183507032	donor_gain	0.8500
4:183506927	donor_gain	0.8200

AlphaMissense

830 missense substitutions predicted likely pathogenic (of 1,850 scored), across 186 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M225	9	1.000	1.000
H239	8	0.999	1.000
D229	8	0.998	1.000
F240	8	0.992	1.000
D98	8	0.989	0.997
D208	8	0.989	0.998
F238	8	0.989	1.000
D53	8	0.975	0.995
C215	7	1.000	1.000
C217	7	1.000	1.000
C228	7	1.000	1.000
C233	7	1.000	1.000
W237	7	1.000	1.000
C242	7	1.000	1.000
W253	7	1.000	1.000
C255	7	1.000	1.000
E211	7	0.999	0.999
C258	7	0.999	1.000
E236	7	0.994	0.999
R259	7	0.989	0.999

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

2 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	2.14e-05
Lung Adenocarcinoma (TCGA)	unfavorable	4.14e-05

Disease associations

OMIM: gene MIM:604215 | disease phenotypes:

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3784904 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

6 measured of 6 human assays (6 total across all organisms); most potent 6 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
P-Sulfonatocalix[4]Arene	KD	15 nM
CHEMBL4176148	KD	16 nM
CHEMBL4168964	KD	50 nM
3-{[4-(2-aminoethoxy)-3,5-diiodophenyl]carbonyl}-2-butyl-1-benzofuran	IC50	97000 nM
CHEMBL5284035	IC50	105000 nM
WAG-005	IC50	390000 nM

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	affects cotreatment, increases expression	1
Ketoconazole	decreases expression	1
Polycyclic Aromatic Hydrocarbons	affects cotreatment, increases abundance, increases expression	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)

Via MONDO — disease-level, not drug-specific.

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for ING2 across ~30M SureChEMBL compounds — explore on Sugi Predict.