ING1

Summary

ING1 (inhibitor of growth family member 1, HGNC:6062) is a protein-coding gene on chromosome 13q34, encoding Inhibitor of growth protein 1 (Q9UK53). Cooperates with p53/TP53 in the negative regulatory pathway of cell growth by modulating p53-dependent transcriptional activation.

This gene encodes a tumor suppressor protein that can induce cell growth arrest and apoptosis. The encoded protein is a nuclear protein that physically interacts with the tumor suppressor protein TP53 and is a component of the p53 signaling pathway. Reduced expression and rearrangement of this gene have been detected in various cancers. Multiple alternatively spliced transcript variants encoding distinct isoforms have been reported.

Source: NCBI Gene 3621 — RefSeq curated summary.

At a glance

• Gene–disease (curated): head and neck squamous cell carcinoma (No Known Disease Relationship, GenCC)
• GWAS associations: 4
• Clinical variants (ClinVar): 99 total — 3 pathogenic
• Phenotypes (HPO): 2
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 2 cancer types
• MANE Select transcript: NM_198219

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6062
Approved symbol	ING1
Name	inhibitor of growth family member 1
Location	13q34
Locus type	gene with protein product
Status	Approved
Aliases	p33ING1, p33ING1b, p24ING1c, p33, p47, p47ING1a
Ensembl gene	ENSG00000153487
Ensembl biotype	protein_coding
OMIM	601566
Entrez	3621

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 6 protein_coding

ENST00000333219, ENST00000338450, ENST00000375774, ENST00000375775, ENST00000464141, ENST00000715208

RefSeq mRNA: 5 — MANE Select: NM_198219 NM_001267728, NM_005537, NM_198217, NM_198218, NM_198219

CCDS: CCDS9515, CCDS9516, CCDS9517, CCDS9518

Canonical transcript exons

ENST00000333219 — 2 exons

Exon	Start	End
ENSE00001801377	110719229	110723339
ENSE00004026200	110713700	110714285

Expression profiles

Bgee: expression breadth ubiquitous, 261 present calls, max score 90.22.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 15.6454 / max 433.9727, expressed in 1790 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
136073	7.3541	1684
136072	4.0050	1233
136074	3.6620	1524
136075	0.6244	250

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
stromal cell of endometrium	CL:0002255	90.22	gold quality
ganglionic eminence	UBERON:0004023	89.68	gold quality
ventricular zone	UBERON:0003053	89.22	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	88.14	gold quality
left testis	UBERON:0004533	87.95	gold quality
right testis	UBERON:0004534	87.59	gold quality
monocyte	CL:0000576	87.39	gold quality
endothelial cell	CL:0000115	87.35	gold quality
endometrium epithelium	UBERON:0004811	87.28	gold quality
embryo	UBERON:0000922	87.25	gold quality
cortical plate	UBERON:0005343	87.25	gold quality
mononuclear cell	CL:0000842	87.19	gold quality
leukocyte	CL:0000738	86.98	gold quality
blood	UBERON:0000178	86.45	gold quality
decidua	UBERON:0002450	86.44	gold quality
testis	UBERON:0000473	86.09	gold quality
left ovary	UBERON:0002119	85.96	gold quality
epithelium of bronchus	UBERON:0002031	85.88	gold quality
bronchial epithelial cell	CL:0002328	85.87	gold quality
parotid gland	UBERON:0001831	85.74	gold quality
bronchus	UBERON:0002185	85.59	gold quality
metanephric glomerulus	UBERON:0004736	85.53	gold quality
renal glomerulus	UBERON:0000074	85.48	gold quality
secondary oocyte	CL:0000655	85.22	gold quality
cauda epididymis	UBERON:0004360	84.84	gold quality
sural nerve	UBERON:0015488	84.73	gold quality
epithelium of nasopharynx	UBERON:0001951	84.50	gold quality
olfactory bulb	UBERON:0002264	84.49	gold quality
type B pancreatic cell	CL:0000169	84.42	gold quality
ovary	UBERON:0000992	84.38	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.22

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

7 targets.

Target	Regulation
AFP	Repression
BAX	Activation
CASP3	Activation
CDKN1A	Activation
FAT1	Unknown
PCNA	Unknown
TP53	Activation

Upstream regulators (CollecTRI, top): RUNX3, TP53

miRNA regulators (miRDB)

72 targeting ING1, 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-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-570-3P	99.96	72.41	4910
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
HSA-MIR-548H-5P	99.94	71.24	3488
HSA-MIR-548I	99.94	71.25	3481
HSA-MIR-548J-5P	99.94	71.14	3489
HSA-MIR-548O-5P	99.94	71.24	3488

Literature-anchored findings (GeneRIF, showing 40)

• ING1 in normal and neoplastic tissues. (PMID:11991811)
• PBLs from pts with haematological malignancies and controls expressed mainly the p33/ING1 transcript, with low levels of p24/ING1 and p33/ING1 mRNA were found. Genetic changes in p33/ING1 play no role in these malignancies. (PMID:12008079)
• role in differential regulation of histone acetylation (PMID:12015309)
• Data suggest that p33(ING1) cooperates with p53 in UVB-induced apoptosis via the mitochondrial cell death pathway in melanoma cells. (PMID:12243754)
• overexpression and mutation of the ING1 gene are infrequent in human basal cell carcinoma (PMID:12632089)
• ING1 expression is frequently associated with adenocarcinoma of the esophagogastric junction tumorigenesis, further supporting its role as a tumor suppressor gene, and ING1 expression is independent of p53 status (PMID:12637159)
• ING1b gene expression plays an important role in carcinogenesis of non-small cell lung cancer (PMID:14581367)
• Deregulated expression and mislocalization of ING1 proteins are common events in gliomas and glioblastomas (PMID:14676120)
• ING1 mutations abrogate its enhancement in nucleotide excision repair in melanoma. (PMID:15201991)
• Decreased expression of the candidate tumor suppressor gene ING1 is associated with advanced neuroblastomas (PMID:15375504)
• ING tumor suppressors are involved in signalling pathways [review] (PMID:15526165)
• Mutation and loss of expression are not the main reasons for the disfunction of p33(ING1b) in pancreatic carcinoma (PMID:15534913)
• p33ING1 expression induces features of cellular senescence through two silencing domains and interaction with Ras (PMID:15601862)
• p33ING1b enhances taxol-induced apoptosis through p53-dependent pathway in human osteosarcoma cells; p33ING1b may be an important marker and/or therapeutic target in the prevention and treatment of osteosarcoma (PMID:15662138)
• Down regulation of p33ING1b is associated with the pathogenesis of ovarian cancers (PMID:15677627)
• Loss or inactivation of p33(ING1b) normal function may be an important mechanism for the development of hepatocellular carcinoma retaining wild-type p53. (PMID:15800978)
• p33(ING1b) and p47(ING1a) mRNA expressions are closely related with the carcinogenesis and progression of human sporadic colorectal cancer (PMID:16273637)
• p33ING1b prominently enhances etoposide-induced apoptosis through p53-dependent pathways in human osteosarcoma cells. (PMID:16325212)
• ING1 expression was up-regulated in all 7 lung cancer cell lines that had a p53 mutation. (PMID:16465410)
• Subcellular targeting of ING1 by phosphorylation-dependent 14-3-3 binding regulates P21 expression. (PMID:16581770)
• Interaction with p33ING1 represents a novel mechanism for the tumour suppression function of adp ribosylation factors. (PMID:16607280)
• ING1b acts as a chromatin accessibility factor for DNA damage recognition proteins upon genotoxic injury. (PMID:17379210)
• p33(ING1b) is a downstream target of the ATM/ATR response cascade to genotoxic stress. More importantly, our data indicate that the Ser-126 residue plays a key role in regulating the expression of cyclin B1 and proliferation of melanoma cells (PMID:17585055)
• The transfer of p33(ING1b) protein from the nucleus to the cytoplasm may result in loss of normal cellular function of the protein, which might play a role in the tumourigenesis and metastasis of oral squamous cell carcinoma (PMID:17805569)
• the interaction between Alien and the tumor suppressors p33ING1 and p33ING2 reveals a novel cellular protein network (PMID:17929852)
• Data show that p33(ING1b) is degraded in the 20S proteasome and that NAD(P)H quinone oxidoreductase 1 (NQO1), previously shown to modulate the degradation of p53 in the 20S proteasome, inhibits the degradation of p33(ING1b). (PMID:18388957)
• ING1b is up-regulated in hepatocellular carcinoma during the progression process and may contribute the alternation of general expression level of ING1 (PMID:18450387)
• Results show that both DNA repair and apoptotic activities of ING1 require the interaction of the C-terminal plant homeodomain (PHD) finger with histone H3 trimethylated at Lys4 (H3K4me3). (PMID:18533182)
• ING1 binds karyopherin proteins and disruption of this interaction affects cell localization and ING activity as a transcriptional regulator. (PMID:18655775)
• Altered ratios of ING1 splicing isoforms may contribute to establishing the senescent phenotype. (PMID:18691180)
• Using across-species (yeast, fly, and human) bioinformatics-based approach, study shows that ING1 interacts specifically with the three proteins tested; p38MAPK, MEKK4 and RAD50. (PMID:18801192)
• Tethering by laminin A stabilizes and targets the ING1 tumor suppressor. (PMID:18836436)
• ING1 variants may modulate p53 activity and subsequently inhibit hepatoma cell growth by at least two possible mechanisms. (PMID:19085961)
• Nuclear localization of ING1b is highly correlated with well-differentiated HCC cell lines whereas poorly differentiated HCC cells reveal nuclear exclusion, which is independent of p53 mutation status. (PMID:19132896)
• ING1 proteins regulate the expression of proteins that are critical for angiogenesis in glioblastoma multiforme (GBM) such as the angiopoietins. (PMID:20066899)
• p33ING1 triggers a senescent phenotype in cultured primary fibroblasts in a p53-dependent fashion. (PMID:21078114)
• AZT upregulates the expression of p33ING1b, a possible mechanism in regulating senescence and apoptosis of TJ905 cells. (PMID:21176536)
• Loss of ING1 is associated with non-small cell lung cancer. (PMID:21286670)
• relocation of p33ING1b from the nucleus to the cytoplasm, where the protein is tethered by 14-3-3eta, participates in tumorigenesis and progression in HNSCC (PMID:21432775)
• Data show that ectopic expression of miR-622 promoted invasion, tumorigenesis and metastasis of gastric cancer cells, and that ING1 is a direct target of miR-622. (PMID:21528065)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ing1	ENSDARG00000019116
mus_musculus	Ing1	ENSMUSG00000045969
rattus_norvegicus	Ing1	ENSRNOG00000014520
drosophila_melanogaster	CG7379	FBGN0038546
caenorhabditis_elegans		WBGENE00020287

Paralogs (4): ING3 (ENSG00000071243), ING4 (ENSG00000111653), ING5 (ENSG00000168395), ING2 (ENSG00000168556)

Protein

Protein identifiers

Inhibitor of growth protein 1 — Q9UK53 (reviewed: Q9UK53)

All UniProt accessions (3): Q9UK53, A0A087WXF7, A0A0C4DFW2

UniProt curated annotations — full annotation on UniProt →

Function. Cooperates with p53/TP53 in the negative regulatory pathway of cell growth by modulating p53-dependent transcriptional activation. Implicated as a tumor suppressor gene.

Subunit / interactions. Interacts with H3K4me3 and to a lesser extent with H3K4me2. Interacts with TP53. Isoform 2 interacts with RSL1D1.

Subcellular location. Nucleus.

Tissue specificity. Isoform 2 was expressed in all normal tissues and cells examined, as well as in all breast cancer and melanoma cell lines examined. Isoform 3 was expressed in testis, liver, and kidney, weakly expressed in colon and brain and not expressed in breast and cultured melanocytes. Isoform 4 was highly expressed in testis and weakly expressed in brain, but not expressed in breast, colon, kidney, melanocytes, breast cancer or melanoma cell lines.

Disease relevance. Squamous cell carcinoma of the head and neck (HNSCC) [MIM:275355] A non-melanoma skin cancer affecting the head and neck. The hallmark of cutaneous SCC is malignant transformation of normal epidermal keratinocytes. The disease is caused by variants affecting the gene represented in this entry.

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).

Similarity. Belongs to the ING family.

Isoforms (5)

UniProt ID	Names	Canonical?
Q9UK53-1	1, p47ING1a, ING1-ALT2	yes
Q9UK53-2	2, p33ING1b, Variant A
Q9UK53-3	3, p24ING1c, ING1-ALT1, Variant B
Q9UK53-4	4, Variant C
Q9UK53-5	5

RefSeq proteins (5): NP_001254657, NP_005528, NP_937860, NP_937861, NP_937862* (*=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
IPR028643	ING1_PHD_Znf	Domain
IPR028651	ING_fam	Family

Pfam: PF12998

UniProt features (39 total): binding site 8, sequence conflict 6, site 4, splice variant 4, sequence variant 4, region of interest 2, strand 2, helix 2, compositionally biased region 2, chain 1, zinc finger region 1, cross-link 1, mutagenesis site 1, turn 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2QIC	X-RAY DIFFRACTION	2.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UK53-F1	58.65	0.21

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): 355 (histone h3k4me3 binding); 366 (histone h3k4me3 binding); 370 (histone h3k4me3 binding); 378 (histone h3k4me3 binding)

Ligand- & substrate-binding residues (8): 380; 383; 396; 399; 356; 358; 369; 374

Post-translational modifications (1): 278

Mutagenesis-validated functional residues (1):

Position	Phenotype
378	unable to stimulate dna repair after uv irradiation or promote dna-damage-induced apoptosis.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 279 (showing top): GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_NEGATIVE_REGULATION_OF_CELL_GROWTH, GOBP_GROWTH, SATO_SILENCED_BY_DEACETYLATION_IN_PANCREATIC_CANCER, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_ORGANELLE, GOBP_NUCLEAR_TRANSPORT, GOBP_NEGATIVE_REGULATION_OF_MULTICELLULAR_ORGANISMAL_PROCESS, MODULE_379, GOBP_REGULATION_OF_TRANSMEMBRANE_RECEPTOR_PROTEIN_SERINE_THREONINE_KINASE_SIGNALING_PATHWAY, GOBP_RESPONSE_TO_TRANSFORMING_GROWTH_FACTOR_BETA, chr13q34, GOBP_MAINTENANCE_OF_CELL_NUMBER, GOBP_REGULATION_OF_STEM_CELL_POPULATION_MAINTENANCE, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_TRANSFORMING_GROWTH_FACTOR_BETA_STIMULUS

GO Biological Process (11): negative regulation of transcription by RNA polymerase II (GO:0000122), protein import into nucleus (GO:0006606), negative regulation of cell population proliferation (GO:0008285), negative regulation of cell growth (GO:0030308), negative regulation of cell migration (GO:0030336), negative regulation of transforming growth factor beta receptor signaling pathway (GO:0030512), regulation of programmed cell death (GO:0043067), positive regulation of DNA-templated transcription (GO:0045893), negative regulation of stem cell population maintenance (GO:1902455), positive regulation of stem cell population maintenance (GO:1902459), chromatin organization (GO:0006325)

GO Molecular Function (4): zinc ion binding (GO:0008270), histone H3K4me3 reader activity (GO:0140002), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (2): nucleus (GO:0005634), Sin3-type complex (GO:0070822)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
negative regulation of cellular process	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
intracellular protein transport	1
protein localization to nucleus	1
import into nucleus	1
establishment of protein localization to organelle	1
cell population proliferation	1
regulation of cell population proliferation	1
regulation of cell growth	1
cell growth	1
negative regulation of growth	1
cell migration	1
regulation of cell migration	1
negative regulation of cell motility	1
transforming growth factor beta receptor signaling pathway	1
regulation of transforming growth factor beta receptor signaling pathway	1
negative regulation of transmembrane receptor protein serine/threonine kinase signaling pathway	1
programmed cell death	1
regulation of cellular process	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
positive regulation of RNA biosynthetic process	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 component organization	1
transition metal ion binding	1
histone H3 reader activity	1
binding	1
cation binding	1
intracellular membrane-bounded organelle	1
histone deacetylase complex	1
nuclear chromosome	1
chromatin	1

Protein interactions and networks

STRING

2538 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ING1	HDAC1	Q13547	951
ING1	SPINK5	Q9NQ38	920
ING1	SIN3A	Q96ST3	913
ING1	SPINK9	Q5DT21	890
ING1	ING5	Q8WYH8	888
ING1	PCLAF	Q15004	885
ING1	ARID4A	P29374	879
ING1	ARID4B	Q4LE39	876
ING1	RBBP4	P31149	875
ING1	BRMS1L	Q5PSV4	840
ING1	SAP30	O75446	836
ING1	BRMS1	Q9HCU9	824
ING1	H3C14	Q71DI3	807
ING1	H3-5	Q6NXT2	806
ING1	H3-7	Q5TEC6	806

IntAct

53 interactions, top by confidence:

A	B	Type	Score
UBC	TP53	psi-mi:“MI:0914”(association)	0.960
HDAC2	KDM1A	psi-mi:“MI:0914”(association)	0.890
HDAC1	CDK2AP1	psi-mi:“MI:0914”(association)	0.840
SGF29	NDC80	psi-mi:“MI:0914”(association)	0.840
RBBP7	CDK2AP1	psi-mi:“MI:0914”(association)	0.840
RBBP7	HAT1	psi-mi:“MI:0914”(association)	0.730
SINHCAF	TNRC18	psi-mi:“MI:0914”(association)	0.640
NQO1	ING1	psi-mi:“MI:0407”(direct interaction)	0.540
NQO1	ING1	psi-mi:“MI:0915”(physical association)	0.540
FHL2	CNOT1	psi-mi:“MI:0914”(association)	0.530
RBBP7	SMARCA5	psi-mi:“MI:0914”(association)	0.530
RBBP7	EPOP	psi-mi:“MI:0914”(association)	0.530
ING1		psi-mi:“MI:0407”(direct interaction)	0.440
GPC1	GANAB	psi-mi:“MI:0915”(physical association)	0.400
ING1	CTRL	psi-mi:“MI:0915”(physical association)	0.400
FOXK2	PHF20L1	psi-mi:“MI:0914”(association)	0.350
	TAF4	psi-mi:“MI:0914”(association)	0.350
P		psi-mi:“MI:0914”(association)	0.350
MRGBP	RSL1D1	psi-mi:“MI:0914”(association)	0.350
TGIF2LX	TNRC18	psi-mi:“MI:0914”(association)	0.350
ING1	TNRC18	psi-mi:“MI:0914”(association)	0.350
DKK2	LRP5	psi-mi:“MI:0914”(association)	0.350
ING1	SIN3B	psi-mi:“MI:0914”(association)	0.350
RBBP4	PHF20L1	psi-mi:“MI:0914”(association)	0.350
ZNF704	ADAM10	psi-mi:“MI:0914”(association)	0.350

BioGRID (197): USP7 (Affinity Capture-Western), ING1 (Affinity Capture-Western), ING1 (Affinity Capture-MS), ING1 (Affinity Capture-MS), ING1 (Affinity Capture-MS), ING1 (Affinity Capture-MS), ING1 (Affinity Capture-MS), ING1 (Affinity Capture-MS), ING1 (Affinity Capture-MS), HIF1A (Affinity Capture-Western), ING1 (Affinity Capture-Western), ING1 (Affinity Capture-MS), ING1 (Affinity Capture-MS), ING1 (Affinity Capture-MS), ING1 (Affinity Capture-MS)

ESM2 similar proteins: A0A2R6W1B1, A0FKI7, A2XC52, A2XTW9, A2Y0Q2, B8AMA8, B8B8I3, F4I9G2, O94972, P07106, P20067, P41135, P85828, Q5EAE9, Q5EAH9, Q5R7V3, Q5T8D3, Q5XEM9, Q5XG73, Q5XI67, Q6EPZ2, Q6GPE9, Q6IE24, Q6PCX9, Q70EL1, Q75IR6, Q76N89, Q7XUW3, Q84TV4, Q86UB2, Q8BJL1, Q8BL06, Q8CBX9, Q8H383, Q8H8C6, Q8K3A6, Q8K4P8, Q8LA16, Q8TB52, Q96S38

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

SIGNOR signaling

8 interactions.

A	Effect	B	Mechanism
ING1	“down-regulates quantity by repression”	AFP	“transcriptional regulation”
ING1	“up-regulates quantity by expression”	CDKN1A	“transcriptional regulation”
ING1	“down-regulates activity”	SIRT2	binding
ING1	“up-regulates quantity by expression”	BAX	“transcriptional regulation”
ING1	“up-regulates quantity by expression”	CASP3	“transcriptional regulation”
ING1	“up-regulates quantity by expression”	TP53	“transcriptional regulation”
RUNX3	“up-regulates quantity by expression”	ING1	“transcriptional regulation”
SRC	“down-regulates activity”	ING1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 62 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
Activation of BAD and translocation to mitochondria	7	98.7×	4e-11
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	7	87.1×	8e-11
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	7	87.1×	8e-11
Activation of BH3-only proteins	7	64.4×	8e-10
RHO GTPases activate PKNs	9	52.9×	2e-11
Regulation of TP53 Activity through Acetylation	5	42.3×	3e-06
Intrinsic Pathway for Apoptosis	7	38.0×	4e-08
FOXO-mediated transcription	5	31.1×	1e-05

GO biological processes:

GO term	Partners	Fold	FDR
negative regulation of stem cell population maintenance	5	62.8×	2e-06
protein targeting	5	30.0×	5e-05
positive regulation of stem cell population maintenance	5	28.2×	7e-05
negative regulation of transforming growth factor beta receptor signaling pathway	6	17.1×	8e-05
intracellular protein localization	8	13.7×	1e-05
negative regulation of cell migration	6	11.0×	9e-04
brain development	6	7.8×	4e-03
chromatin remodeling	6	7.2×	6e-03

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 2 cancer types — COADREAD, UCEC.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	0
Uncertain significance	79
Likely benign	7
Benign	2

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
8067	NM_198219.3(ING1):c.644G>C (p.Cys215Ser)	Pathogenic
8068	NM_198219.3(ING1):c.647A>G (p.Asn216Ser)	Pathogenic
8069	NM_198219.3(ING1):c.575C>A (p.Ala192Asp)	Pathogenic

SpliceAI

614 predictions. Top by Δscore:

Variant	Effect	Δscore
13:110714284:AGG:A	donor_loss	1.0000
13:110714285:GGTA:G	donor_loss	1.0000
13:110714286:GTACG:G	donor_loss	1.0000
13:110714287:T:A	donor_loss	1.0000
13:110719228:GA:G	acceptor_gain	1.0000
13:110716475:G:GT	donor_gain	0.9900
13:110719227:A:AG	acceptor_gain	0.9900
13:110719227:A:C	acceptor_loss	0.9900
13:110719228:G:GG	acceptor_gain	0.9900
13:110719228:G:GT	acceptor_loss	0.9900
13:110719228:GAGA:G	acceptor_gain	0.9900
13:110719228:GAGAT:G	acceptor_gain	0.9900
13:110714284:AG:A	donor_gain	0.9700
13:110714285:GG:G	donor_gain	0.9700
13:110714286:G:GG	donor_gain	0.9700
13:110719226:CAGAG:C	acceptor_gain	0.9700
13:110719227:AGAGA:A	acceptor_gain	0.9700
13:110719220:T:TA	acceptor_gain	0.9600
13:110719839:C:T	donor_gain	0.9500
13:110716475:G:T	donor_gain	0.9400
13:110716497:G:GG	donor_gain	0.9400
13:110719225:CCAGA:C	acceptor_gain	0.9400
13:110723095:AAACT:A	acceptor_gain	0.9300
13:110716471:G:GG	donor_gain	0.9200
13:110716425:C:G	donor_gain	0.9100
13:110716492:GCTTA:G	donor_gain	0.9100
13:110716507:GTT:G	donor_gain	0.9100
13:110714812:T:TA	donor_gain	0.9000
13:110714813:A:AA	donor_gain	0.9000
13:110714543:TAGTG:T	donor_gain	0.8900

AlphaMissense

1861 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
13:110719709:A:G	D349G	1.000
13:110719717:G:A	E352K	1.000
13:110719718:A:C	E352A	1.000
13:110719718:A:G	E352G	1.000
13:110719718:A:T	E352V	1.000
13:110719719:A:C	E352D	1.000
13:110719719:A:T	E352D	1.000
13:110719720:C:T	P353S	1.000
13:110719726:T:A	Y355N	1.000
13:110719726:T:C	Y355H	1.000
13:110719726:T:G	Y355D	1.000
13:110719727:A:G	Y355C	1.000
13:110719729:T:A	C356S	1.000
13:110719729:T:C	C356R	1.000
13:110719729:T:G	C356G	1.000
13:110719730:G:A	C356Y	1.000
13:110719730:G:C	C356S	1.000
13:110719730:G:T	C356F	1.000
13:110719731:T:G	C356W	1.000
13:110719735:T:A	C358S	1.000
13:110719735:T:C	C358R	1.000
13:110719736:G:A	C358Y	1.000
13:110719736:G:C	C358S	1.000
13:110719736:G:T	C358F	1.000
13:110719737:C:G	C358W	1.000
13:110719742:A:C	Q360P	1.000
13:110719744:G:C	V361L	1.000
13:110719745:T:A	V361D	1.000
13:110719745:T:C	V361A	1.000
13:110719748:C:A	S362Y	1.000

dbSNP variants (sampled 300 via entrez): RS1000032526 (13:110721481 C>T), RS1000045668 (13:110720322 A>C,G,T), RS1000153806 (13:110723709 C>A,G), RS1000266983 (13:110718075 C>T), RS1000294668 (13:110718437 T>A), RS1000478664 (13:110713607 G>A), RS1000849177 (13:110713490 G>A,T), RS1001085561 (13:110719483 G>A), RS1001128742 (13:110713629 G>A), RS1001205055 (13:110714587 T>G), RS1001433526 (13:110719177 G>T), RS1001531158 (13:110712428 G>A,C,T), RS1001655851 (13:110716081 G>C,T), RS1001709760 (13:110716286 C>G,T), RS1001730989 (13:110717614 G>A,T)

Disease associations

OMIM: gene MIM:601566 | disease phenotypes: MIM:275355

GenCC curated gene-disease

Disease	Classification	Inheritance
head and neck squamous cell carcinoma	No Known Disease Relationship	Unknown

Mondo (1): head and neck squamous cell carcinoma (MONDO:0010150)

Orphanet (1): Squamous cell carcinoma of head and neck (Orphanet:67037)

HPO phenotypes

2 total (2 of 2 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0002860	Squamous cell carcinoma

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST006218_58	Erosive tooth wear (severe vs non-severe)	3.000000e-09
GCST006218_59	Erosive tooth wear (severe vs non-severe)	8.000000e-08
GCST006218_60	Erosive tooth wear (severe vs non-severe)	2.000000e-09
GCST006585_857	Blood protein levels	4.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Decitabine	affects expression, affects methylation	2
Cisplatin	decreases expression, affects expression	2
Tobacco Smoke Pollution	increases expression	2
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
methylselenic acid	affects expression	1
trichostatin A	affects expression	1
arsenite	affects binding, increases reaction	1
avobenzone	increases expression	1
polyhexamethyleneguanidine	increases expression	1
abrine	increases expression	1
(4-amino-1,4-dihydro-3-(2-pyridyl)-5-thioxo-1,2,4-triazole)copper(II)	increases expression	1
(+)-JQ1 compound	increases expression	1
PCI 5002	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Acetaminophen	increases expression	1
Diethylstilbestrol	decreases expression	1
Ketoconazole	decreases expression	1
Menthol	increases expression	1
Naled	affects expression	1
Phthalic Acids	increases methylation	1
Plant Oils	increases expression	1
Smoke	decreases expression	1
Thiram	increases expression	1
Tretinoin	increases expression	1
Urethane	increases expression	1
Zinc	affects cotreatment, increases expression	1
Asbestos, Crocidolite	increases expression	1
Cadmium Chloride	increases expression	1
Okadaic Acid	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01344356	PHASE4	COMPLETED	Stereotactic Body Radiotherapy for Head and Neck Tumors
NCT03196843	PHASE4	UNKNOWN	Radiotherapy Combine With Raltitrexed Versus Radiotherapy Alone in Older Patients With HNSCC.
NCT03998696	PHASE4	COMPLETED	An Experimental Study to Compare Treatment Response and Toxicities of Concurrent Chemoradiation With Weekly Cisplatin and Three Weekly Cisplatin in Locally Advanced Head and Neck Cancer.
NCT04489888	PHASE4	COMPLETED	A Study of Pembrolizumab (MK-3475) Plus Carboplatin and Paclitaxel as First-line Treatment of Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma (MK-3475-B10/KEYNOTE B10)
NCT04766827	PHASE4	UNKNOWN	Albumin-bound Paclitaxel Combined With Cisplatin Versus Docetaxel Combined With Cisplatin Induced Chemotherapy in Advanced Head and Neck Squamous Tummor
NCT06162377	PHASE4	RECRUITING	Methylnatrexone In Resectable Head and Neck Squamous Cell Carcinoma (MINK). A Window of Opportunity Pilot Study.
NCT07405086	PHASE4	RECRUITING	Morning Versus Afternoon Administration of Immunotherapy for the Treatment of Advanced or Metastatic Solid Tumors, The Knight SHIFT Study
NCT00050388	PHASE3	COMPLETED	Phase II Trial of Allovectin-7® for Head and Neck Cancer
NCT00174837	PHASE3	COMPLETED	TRACE: Tirapazamine-Radiation And Cisplatin Evaluation
NCT00206219	PHASE3	COMPLETED	Head and Neck Phase III Iressa Versus Methotrexate Refractory: Iressa Versus Methotrexate (IMEX)
NCT00442455	PHASE3	COMPLETED	Erlotinib,Radiation and Cisplatin in Patients With Complete Resected Squamous Cell Carcinoma of the Head and Neck
NCT00609284	PHASE3	COMPLETED	Randomized Trial of Concomitant Chemotherapy in Patients With Locally Advanced HNSCC Treated by Radiotherapy-erbitux
NCT00911326	PHASE3	TERMINATED	Evaluation of Sentinel Lymph Nodes in Head and Neck Squamous Cell Carcinoma
NCT00999700	PHASE3	UNKNOWN	Induction Chemotherapy Followed by Cetuximab Plus Definitive Radiotherapy Versus Radiation Plus Cisplatin
NCT01012258	PHASE3	COMPLETED	Cetuximab With Radiotherapy for Locally Advanced Squamous Cell Carcinoma of the Head and Neck in Chinese Subjects
NCT01086826	PHASE3	COMPLETED	Treatment of Patients With Locally Advanced Squamous Cell Carcinoma of the Head and Neck
NCT01177956	PHASE3	COMPLETED	A Trial to Determine the Safety and Anti-tumor Activity Profile of the Combination of Cetuximab and Concomitant Cisplatin Plus 5-Fluorouracil (5-FU) in Subjects With Recurrent and/or Metastatic Squamous Cell Carcinoma in Head and Neck
NCT01427478	PHASE3	COMPLETED	Evaluation of Afatinib in Maintenance Therapy in Squamous Cell Carcinoma of the Head and Neck
NCT01864850	PHASE3	COMPLETED	Non Inferiority Trial of Standard RT Versus Hypofractionated Split Course in Elderly Vulnerable Patients With HNSCC
NCT01931150	PHASE3	COMPLETED	Study of Prophylactic Topical Dapsone 5% Gel Versus Moisturizer for Cetuximab-induced Papulopustular (Acneiform) Rash in Patients With mCRC or HNSCC Without Previous or Concurrent RT
NCT01950689	PHASE3	COMPLETED	NIMRAD (A Randomised Placebo-controlled Trial of Synchronous NIMorazole Versus RADiotherapy Alone in Patients With Locally Advanced Head and Neck Squamous Cell Carcinoma Not Suitable for Synchronous Chemotherapy or Cetuximab)
NCT02105636	PHASE3	COMPLETED	Trial of Nivolumab vs Therapy of Investigator’s Choice in Recurrent or Metastatic Head and Neck Carcinoma (CheckMate 141)
NCT02551159	PHASE3	COMPLETED	Phase III Open Label Study of MEDI 4736 With/Without Tremelimumab Versus Standard of Care (SOC) in Recurrent/Metastatic Head and Neck Cancer
NCT02661152	PHASE3	UNKNOWN	DAHANCA 30: A Randomized Non-inferiority Trial of Hypoxia-profile Guided Hypoxic Modification of Radiotherapy of HNSCC.
NCT02715596	PHASE3	COMPLETED	Changes in Body Composition After EPA Supplementation in Head and Neck Patients
NCT02952586	PHASE3	TERMINATED	Study To Compare Avelumab In Combination With Standard of Care Chemoradiotherapy (SoC CRT) Versus SoC CRT for Definitive Treatment In Patients With Locally Advanced Squamous Cell Carcinoma Of The Head And Neck (JAVELIN HEAD AND NECK 100)
NCT02998385	PHASE3	ACTIVE_NOT_RECRUITING	Chemo-radiotherapy Versus Radiotherapy in the Treatment of Salivary Glands and Nasal Tumors (IMRT or Protontherapy)
NCT02999087	PHASE3	ACTIVE_NOT_RECRUITING	Randomized Trial of Avelumab-cetuximab-radiotherapy Versus SOCs in LA SCCHN (REACH)
NCT03340896	PHASE3	ACTIVE_NOT_RECRUITING	Trial of Laryngeal Preservation Comparing Induced CT Followed by RT vs CT Concomitant to RT
NCT03349710	PHASE3	COMPLETED	Nivolumab or Nivolumab Plus Cisplatin, in Combination With Radiotherapy in Patients With Cisplatin-ineligible or Eligible Locally Advanced Squamous Cell Head and Neck Cancer
NCT03519048	PHASE3	ACTIVE_NOT_RECRUITING	Multicentric Comparative Study Between a Conventional and an Intensive Follow up Strategy After Treatment of a Head and Neck Squamous Cell Carcinoma
NCT03576417	PHASE3	ACTIVE_NOT_RECRUITING	A Trial Evaluating the Addition of Nivolumab to Cisplatin-RT for Treatment of Cancers of the Head and Neck
NCT03855384	PHASE3	UNKNOWN	Study of TQB2450 in Patients With Recurrent or Metastatic Squamous Cell Cancer of the Head and Neck（R/M SCCHN）
NCT04146402	PHASE3	UNKNOWN	SCT-I10A Plus Standard Chemotherapy in First-line Recurrent/ Metastatic Head and Neck Squamous Cell Carcinoma
NCT04157985	PHASE3	COMPLETED	Evaluating Length of Treatment With PD-1/PD-L1 Inhibitor in Advanced Solid Tumors
NCT04199104	PHASE3	COMPLETED	A Study of Pembrolizumab (MK-3475) With or Without Lenvatinib (E7080/MK-7902) as First Line (1L) Intervention in a Programmed Cell Death-ligand 1 (PD-L1) Selected Population With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma (R/M HNSCC) (MK-7902-010) (KEYNOTE-010)
NCT04459715	PHASE3	TERMINATED	A Study of Xevinapant (Debio 1143) in Combination With Platinum-Based Chemotherapy and Standard Fractionation Intensity-Modulated Radiotherapy in Participants With Locally Advanced Squamous Cell Carcinoma of the Head and Neck, Suitable for Definitive Chemoradiotherapy (TrilynX)
NCT04590963	PHASE3	ACTIVE_NOT_RECRUITING	Assessment of Efficacy and Safety of Monalizumab Plus Cetuximab Compared to Placebo Plus Cetuximab in Recurrent or Metastatic Head and Neck Cancer
NCT04747054	PHASE3	RECRUITING	Study on the Efficacy of Treatment by Radiotherapy and Pembrolizumab in Newly Diagnosed Metastatic Head & Neck Cancers
NCT04780750	PHASE3	UNKNOWN	Concurent Chemoradiotherapy in Head and Neck Cancers