ING5

Summary

ING5 (inhibitor of growth family member 5, HGNC:19421) is a protein-coding gene on chromosome 2q37.3, encoding Inhibitor of growth protein 5 (Q8WYH8). Component of the HBO1 complex, which specifically mediates acetylation of histone H3 at ‘Lys-14’ (H3K14ac) and, to a lower extent, acetylation of histone H4.

This gene encodes a tumor suppressor protein that inhibits cell growth and induces apoptosis. This protein contains a PHD-type zinc finger. It interacts with tumor suppressor p53 and p300, a component of the histone acetyl transferase complex, suggesting a role in transcriptional regulation. Alternative splicing and the use of multiple promoters and 3’ terminal exons results in multiple transcript variants.

Source: NCBI Gene 84289 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 32 total
• MANE Select transcript: NM_032329

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19421
Approved symbol	ING5
Name	inhibitor of growth family member 5
Location	2q37.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ23842, p28ING5
Ensembl gene	ENSG00000168395
Ensembl biotype	protein_coding
OMIM	608525
Entrez	84289

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 10 protein_coding, 5 protein_coding_CDS_not_defined, 4 retained_intron, 1 nonsense_mediated_decay

ENST00000313552, ENST00000406941, ENST00000433036, ENST00000445620, ENST00000474238, ENST00000482774, ENST00000484145, ENST00000486061, ENST00000489509, ENST00000492488, ENST00000493261, ENST00000493578, ENST00000636051, ENST00000895897, ENST00000895898, ENST00000895899, ENST00000919535, ENST00000919536, ENST00000919537, ENST00000948226

RefSeq mRNA: 3 — MANE Select: NM_032329 NM_001330161, NM_001330162, NM_032329

CCDS: CCDS33425, CCDS82585, CCDS82586

Canonical transcript exons

ENST00000313552 — 8 exons

Exon	Start	End
ENSE00001681400	241724989	241729478
ENSE00001850216	241702039	241702102
ENSE00003478894	241722939	241723074
ENSE00003495219	241709216	241709382
ENSE00003508278	241723210	241723271
ENSE00003542668	241711978	241712071
ENSE00003595821	241711377	241711488
ENSE00003641292	241704653	241704724

Expression profiles

Bgee: expression breadth ubiquitous, 254 present calls, max score 97.41.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 17.2881 / max 252.8718, expressed in 1810 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
26551	8.6003	1714
26550	6.9956	1747
26552	1.1817	642
202649	0.3185	141
26549	0.1921	73

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	97.41	gold quality
right uterine tube	UBERON:0001302	95.65	gold quality
left ovary	UBERON:0002119	94.09	gold quality
right hemisphere of cerebellum	UBERON:0014890	93.93	gold quality
body of pancreas	UBERON:0001150	93.91	gold quality
cerebellar hemisphere	UBERON:0002245	93.71	gold quality
right lobe of thyroid gland	UBERON:0001119	93.67	gold quality
left lobe of thyroid gland	UBERON:0001120	93.55	gold quality
cerebellar cortex	UBERON:0002129	93.52	gold quality
right ovary	UBERON:0002118	93.49	gold quality
pituitary gland	UBERON:0000007	93.38	gold quality
adenohypophysis	UBERON:0002196	93.09	gold quality
thyroid gland	UBERON:0002046	92.98	gold quality
cerebellum	UBERON:0002037	92.89	gold quality
endocervix	UBERON:0000458	92.34	gold quality
minor salivary gland	UBERON:0001830	92.07	gold quality
left uterine tube	UBERON:0001303	91.88	gold quality
endothelial cell	CL:0000115	91.78	gold quality
lower esophagus mucosa	UBERON:0035834	91.76	gold quality
body of stomach	UBERON:0001161	91.63	gold quality
tibial nerve	UBERON:0001323	91.56	gold quality
ovary	UBERON:0000992	91.51	gold quality
hypothalamus	UBERON:0001898	91.32	gold quality
body of uterus	UBERON:0009853	91.21	gold quality
apex of heart	UBERON:0002098	91.06	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	91.00	gold quality
Brodmann (1909) area 9	UBERON:0013540	90.99	gold quality
small intestine Peyer’s patch	UBERON:0003454	90.97	gold quality
right lung	UBERON:0002167	90.95	gold quality
fundus of stomach	UBERON:0001160	90.85	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.71

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): BRPF1

miRNA regulators (miRDB)

136 targeting ING5, 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-8485	100.00	77.57	4731
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-196A-5P	100.00	68.16	684
HSA-MIR-196B-5P	100.00	68.16	681
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-6845-3P	99.94	66.88	1439
HSA-MIR-548A-5P	99.94	71.27	3482

Literature-anchored findings (GeneRIF, showing 33)

• p29ING4 and p28ING5 may be significant modulators of p53 function. (PMID:12750254)
• the PHD domain of ING5 has the characteristic tertiary fold of a zinc finger. (PMID:18623064)
• Our study indicates for the first time, that oncogenic ras and loss of Smad signaling cooperate to upregulate EGFR and erbB2, which plays a role in promoting invasion. (PMID:20131318)
• Tumor-specific mutation and down-regulation of ING5 mRNA suggested it as a tumor suppressor gene in oral squamous cell carcinoma (PMID:20131318)
• ING5 may function as a tumor suppressor gene or oncogene tightly linked with p53 status, and may play an important role in the prognosis of head and neck squamous cell carcinoma (HNSCC) patients. (PMID:20182888)
• ). Survival analysis indicated that nuclear ING5 was closely linked to favorable prognosis of carcinoma patients (P < .05), albeit not independent. (PMID:21062663)
• EBNA3C negatively regulate p53-mediated functions by interacting with ING4 and ING5. (PMID:21177815)
• Aberrant inhibitor of growth 5 expression may contribute to pathogenesis, growth, and invasion of colorectal carcinomas. (PMID:21193223)
• Results indicate that ING5 is a growth suppressor with suppressed expression in AML whose functions depend on its interaction with INCA1. (PMID:21750715)
• ING5 down-regulation promotes bone mesenchymal stem cell proliferation. (PMID:22384930)
• Data indicate that ING5 associates with Tip60 (KAT5) to form a complex with p53. (PMID:23576563)
• Identified ING5 as a novel CDK2 substrate. ING5 is phosphorylated at a single site, threonine 152, by cyclin E/CDK2 and cyclin A/CDK2. This site is also phosphorylated in cells in a cell cycle dependent manner, consistent with it being a CDK2 substrate. (PMID:25860957)
• Loss of ING5 expression is associated with lung cancer. (PMID:25938545)
• Suggest that ING5 expression might be a good marker for gastric carcinogenesis and its subsequent progression by inhibiting proliferation, growth, migration, invasion and metastasis. (PMID:25980581)
• Results showed that ING5 gene expression is inhibited by miR-193a-3p and is instrumental in miR-193a-3p’s role in activating BCa chemoresistance. (PMID:25991669)
• miR-331-3p is upregulated by HBV and promotes proliferation of hepatocellular carcinoma cells though repression of ING5 expression. (PMID:26497554)
• Data suggest that inhibitor of growth protein 5 (ING5) downregulation might involved in carcinogenesis, growth, and invasion of lung cancer and could be considered as a promising marker to gauge the aggressiveness of lung cancer. (PMID:27409347)
• miR-1307 could promote ovarian cancer chemoresistance by targeting the ING5 expression and miR-1307 might serve as a therapeutic target for ovarian cancer. (PMID:28086946)
• We revealed that miR-24 had the opposite effects to those of ING5 on breast cancer cells and could accelerate xenografted tumor growth in vivo. Our findings uncover the tumor-suppressive role of ING5 and the regulatory pathway of ING5 in breast cancer and may provide insights into the molecular mechanisms of breast carcinogenesis (PMID:28490335)
• ING5 promotes brain tumor initiating cells stemness by maintaining intracellular calcium levels and activating the follicle stimulating hormone pathway. (PMID:28925404)
• Overexpression of ING5 inhibited cell proliferation, neoplasm invasion and epithelial-mesenchymal transition of thyroid cancer cells. (PMID:29272787)
• ING5 inhibits cell proliferation and invasion in esophageal squamous cell carcinoma through regulation of the Akt/NF-kappaB/MMP-9 signaling pathway. (PMID:29326045)
• our results demonstrate, for the first time that overexpression of ING5 in osteosarcoma cells induces apoptosis (PMID:29528777)
• Nucleocytoplasmic translocation of ING5 protein occurs in breast cancer, and the high expression of nuclear ING5 is inversely related to some poor clinicopathological behaviors of breast cancer. (PMID:29595458)
• The Hepatitis B virus X protein (HBx) downregulates the expression of the miR-181b target gene ING5, resulting in the promotion of HCC cell proliferation. (PMID:29604207)
• Results show that ING5 overexpression promotes phosphorylation-dependent degradation of beta-catenin, leading to downregulated Wnt/beta- catenin signaling and inhibition of lung cancer invasion and epithelial-mesenchymal transition. (PMID:30810286)
• ING5 forms homodimers through its N-terminal domain, which folds independently into an elongated coiled-coil structure. (PMID:31026448)
• The data suggest that miR-376c-3p downregulated ING5 to exert protective effects against oxygen-glucose deprivation-induced cell injury in cultured human and rat cells. (PMID:31844418)
• LncRNA CASC2 inhibits hypoxia-induced pulmonary artery smooth muscle cell proliferation and migration by regulating the miR-222/ING5 axis. (PMID:32206065)
• MiR-193 promotes cell proliferation and invasion by ING5/PI3K/AKT pathway of triple-negative breast cancer. (PMID:32271430)
• ING5 Inhibits Migration and Invasion of Esophageal Cancer Cells by Downregulating the IL-6/CXCL12 Signaling Pathway. (PMID:34520285)
• Hsa_circ_0010729 is Involved in Oxygen-Glucose Deprivation/Reoxygenation-Induced Human Microvascular Endothelial Cell Deprivation by Targeting miR-665/ING5. (PMID:35482130)
• ING5 overexpression upregulates miR-34c-5p/Snail1 to inhibit EMT and invasion of lung cancer cells. (PMID:37249332)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ing5a	ENSDARG00000022413
danio_rerio	ing5b	ENSDARG00000068175
mus_musculus	Ing5	ENSMUSG00000026283
rattus_norvegicus	Ing5	ENSRNOG00000018988
drosophila_melanogaster	Ing5	FBGN0032516

Paralogs (4): ING3 (ENSG00000071243), ING4 (ENSG00000111653), ING1 (ENSG00000153487), ING2 (ENSG00000168556)

Protein

Protein identifiers

Inhibitor of growth protein 5 — Q8WYH8 (reviewed: Q8WYH8)

Alternative names: p28ING5

All UniProt accessions (3): Q8WYH8, A0A1B0GW41, E9PEN0

UniProt curated annotations — full annotation on UniProt →

Function. Component of the HBO1 complex, which specifically mediates acetylation of histone H3 at ‘Lys-14’ (H3K14ac) and, to a lower extent, acetylation of histone H4. Component of the MOZ/MORF complex which has a histone H3 acetyltransferase activity. Through chromatin acetylation it may regulate DNA replication and may function as a transcriptional coactivator. Inhibits cell growth, induces a delay in S-phase progression and enhances Fas-induced apoptosis in an INCA1-dependent manner.

Subunit / interactions. Component of the HBO1 complex composed of KAT7/HBO1, MEAF6, ING5, and one scaffold subunit: complexes containing BRPF scaffold (BRPF1, BRD1/BRPF2 or BRPF3) direct KAT7/HBO1 specificity towards H3K14ac, while complexes containing JADE scaffold (JADE1, JADE2 and JADE3) mediate acetylation of histone H4. Component of the MOZ/MORF complex composed at least of ING5, KAT6A, KAT6B, MEAF6 and one of BRPF1, BRD1/BRPF2 and BRPF3. Interacts with H3K4me3 and to a lesser extent with H3K4me2. Interacts with EP300 and p53/TP53. Interacts with INCA1.

Subcellular location. Nucleus. Chromosome.

Tissue specificity. Down-regulated in bone marrow cells in acute myeloid leukemia patients as compared with normal bone marrow cells.

Domain organisation. The PHD-type zinc finger mediates the binding to H3K4me3.

Similarity. Belongs to the ING family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8WYH8-1	1	yes
Q8WYH8-2	2

RefSeq proteins (3): NP_001317090, NP_001317091, NP_115705* (*=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

Pfam: PF12998

UniProt features (30 total): binding site 8, helix 8, site 4, modified residue 3, strand 2, chain 1, zinc finger region 1, splice variant 1, region of interest 1, turn 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
3C6W	X-RAY DIFFRACTION	1.75
5MTO	X-RAY DIFFRACTION	3.1
5ME8	X-RAY DIFFRACTION	3.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8WYH8-F1	79.38	0.53

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): 188 (histone h3k4me3 binding); 199 (histone h3k4me3 binding); 203 (histone h3k4me3 binding); 211 (histone h3k4me3 binding)

Ligand- & substrate-binding residues (8): 232; 189; 191; 202; 207; 213; 216; 229

Post-translational modifications (3): 114, 118, 126

Function

Pathways and Gene Ontology

Reactome pathways

9 pathways

ID	Pathway
R-HSA-3214847	HATs acetylate histones
R-HSA-6804758	Regulation of TP53 Activity through Acetylation
R-HSA-212436	Generic Transcription Pathway
R-HSA-3247509	Chromatin modifying enzymes
R-HSA-3700989	Transcriptional Regulation by TP53
R-HSA-4839726	Chromatin organization
R-HSA-5633007	Regulation of TP53 Activity
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-74160	Gene expression (Transcription)

MSigDB gene sets: 136 (showing top): ACTACCT_MIR196A_MIR196B, SHEPARD_CRASH_AND_BURN_MUTANT_UP, GAUSSMANN_MLL_AF4_FUSION_TARGETS_G_DN, GOBP_GROWTH, GOBP_REGULATION_OF_HEMOPOIESIS, GOBP_APOPTOTIC_SIGNALING_PATHWAY, GOBP_PROTEIN_ACETYLATION, GOBP_REGULATION_OF_CELL_CYCLE, GOBP_DNA_BIOSYNTHETIC_PROCESS, GOBP_REGULATION_OF_DNA_BIOSYNTHETIC_PROCESS, GOBP_PROTEIN_ACYLATION, CTTTGTA_MIR524, IVANOVA_HEMATOPOIESIS_EARLY_PROGENITOR, GOBP_DNA_REPLICATION, GOBP_REGULATION_OF_CELL_DEVELOPMENT

GO Biological Process (17): regulation of cell growth (GO:0001558), regulation of DNA replication (GO:0006275), regulation of DNA-templated transcription (GO:0006355), protein acetylation (GO:0006473), negative regulation of cell population proliferation (GO:0008285), positive regulation of apoptotic process (GO:0043065), negative regulation of growth (GO:0045926), fibroblast proliferation (GO:0048144), negative regulation of fibroblast proliferation (GO:0048147), regulation of developmental process (GO:0050793), regulation of cell cycle (GO:0051726), apoptotic signaling pathway (GO:0097190), DNA replication-dependent chromatin disassembly (GO:0140889), regulation of hemopoiesis (GO:1903706), regulation of DNA biosynthetic process (GO:2000278), positive regulation of apoptotic signaling pathway (GO:2001235), chromatin organization (GO:0006325)

GO Molecular Function (5): chromatin binding (GO:0003682), zinc ion binding (GO:0008270), histone H3K4me3 reader activity (GO:0140002), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (5): histone acetyltransferase complex (GO:0000123), nucleus (GO:0005634), nucleoplasm (GO:0005654), MOZ/MORF histone acetyltransferase complex (GO:0070776), chromosome (GO:0005694)

Reactome top-level categories

Rollup of top-7 pathways:

Category	Pathways
Chromatin modifying enzymes	1
Regulation of TP53 Activity	1
RNA Polymerase II Transcription	1
Chromatin organization	1
Generic Transcription Pathway	1
Transcriptional Regulation by TP53	1
Gene expression (Transcription)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of growth	2
regulation of DNA metabolic process	2
cell population proliferation	2
apoptotic process	2
binding	2
cell growth	1
regulation of cellular component organization	1
DNA replication	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
protein acylation	1
regulation of cell population proliferation	1
negative regulation of cellular process	1
regulation of apoptotic process	1
positive regulation of programmed cell death	1
growth	1
negative regulation of biological process	1
negative regulation of cell population proliferation	1
fibroblast proliferation	1
regulation of fibroblast proliferation	1
developmental process	1
regulation of biological process	1
cell cycle	1
regulation of cellular process	1
signal transduction	1
chromatin organization	1
regulation of immune system process	1
hemopoiesis	1
regulation of cell development	1
regulation of multicellular organismal development	1
regulation of macromolecule biosynthetic process	1
DNA biosynthetic process	1
positive regulation of signal transduction	1
positive regulation of apoptotic process	1
apoptotic signaling pathway	1
regulation of apoptotic signaling pathway	1
cellular component organization	1
transition metal ion binding	1
histone H3 reader activity	1

Protein interactions and networks

STRING

1628 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ING5	MEAF6	Q9HAF1	995
ING5	BRPF1	P55201	993
ING5	KAT7	O95251	987
ING5	ASXL2	Q76L83	982
ING5	KAT6B	Q8WYB5	974
ING5	JADE1	Q6IE81	913
ING5	ING1	Q9UK53	888
ING5	TP53	P04637	851
ING5	EP300	Q09472	829
ING5	KAT5	Q92993	696
ING5	ING4	Q9UNL4	635
ING5	H4C7	Q99525	632
ING5	H4C16	P02304	602
ING5	EGLN1	Q9GZT9	526
ING5	INCA1	Q0VD86	517

IntAct

143 interactions, top by confidence:

A	B	Type	Score
ING5	NAV2	psi-mi:“MI:0915”(physical association)	0.740
JADE2	ING5	psi-mi:“MI:0915”(physical association)	0.740
NAV2	ING5	psi-mi:“MI:0915”(physical association)	0.740
ING5	JADE2	psi-mi:“MI:0915”(physical association)	0.740
HGS	ING5	psi-mi:“MI:0915”(physical association)	0.720
ING5	KXD1	psi-mi:“MI:0915”(physical association)	0.670
KXD1	ING5	psi-mi:“MI:0915”(physical association)	0.670
INCA1	ING5	psi-mi:“MI:0915”(physical association)	0.630
ING5	ARFIP2	psi-mi:“MI:0915”(physical association)	0.560
DEUP1	ING5	psi-mi:“MI:0915”(physical association)	0.560
	ING5	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-7	ING5	psi-mi:“MI:0915”(physical association)	0.560
ING5	ICA1	psi-mi:“MI:0915”(physical association)	0.560
ING5	KRT40	psi-mi:“MI:0915”(physical association)	0.560
C3orf62	ING5	psi-mi:“MI:0915”(physical association)	0.560
ING5	SMARCE1	psi-mi:“MI:0915”(physical association)	0.560
ING5	CDCA7L	psi-mi:“MI:0915”(physical association)	0.560
CEP44	ING5	psi-mi:“MI:0915”(physical association)	0.560
MBIP	ING5	psi-mi:“MI:0915”(physical association)	0.560
IKZF3	ING5	psi-mi:“MI:0915”(physical association)	0.560
ARFIP2	ING5	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (187): ING5 (Two-hybrid), ING5 (Two-hybrid), ING5 (Two-hybrid), ING5 (Two-hybrid), ING5 (Two-hybrid), ING5 (Two-hybrid), ING5 (Two-hybrid), ING5 (Two-hybrid), ING5 (Two-hybrid), ING5 (Two-hybrid), NAV2 (Two-hybrid), KRT40 (Two-hybrid), CCDC67 (Two-hybrid), C3orf62 (Two-hybrid), KRTAP10-7 (Two-hybrid)

ESM2 similar proteins: A1Z7A6, B3H615, O13870, O42871, O43150, O74508, O74736, O94740, O97902, P30630, P38806, P50947, P62484, Q09459, Q10580, Q177A7, Q1AAU6, Q2UTN6, Q3T095, Q561X3, Q5AHB8, Q5AL52, Q5M8Y7, Q5XG48, Q5ZK36, Q5ZKY4, Q6BNL6, Q6C5V7, Q6CL17, Q6CXN0, Q6FQJ1, Q6FSB1, Q755J9, Q757W2, Q7QH62, Q7SIG6, Q7YZA2, Q8C0D7, Q8IQQ4, Q8WYH8

Diamond homologs: A3QMD7, O74736, P38806, Q08465, Q3T095, Q54PN9, Q5AHB8, Q5ZKY4, Q6BNL6, Q6C5V7, Q6CXN0, Q6FSB1, Q757W2, Q8C0D7, Q8WYH8, Q9D8Y8, Q9LIQ6, Q9UNL4, Q9VJY8, B3H615, O42871, P50947, Q498T3, Q5RBA1, Q5ZK36, Q66KD5, Q7ZX31, Q8VEK6, Q9NXR8, Q9QXV3, Q9UK53, Q9ESK4, Q9H160, P34447, Q5F489, Q5EAW9, Q5VWG9, Q8C9B9, Q9BTC0, Q6P2L6

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
CDK2	“up-regulates quantity”	ING5	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 71 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
HATs acetylate histones	9	15.9×	1e-06
Regulation of TP53 Activity	5	14.8×	1e-03
Chromatin organization	8	14.5×	1e-05
Chromatin modifying enzymes	8	12.8×	2e-05
Transcriptional Regulation by TP53	7	9.7×	5e-04

GO biological processes:

GO term	Partners	Fold	FDR
regulation of DNA replication	5	28.6×	2e-04
regulation of cell cycle	7	8.2×	2e-03
chromatin remodeling	7	8.0×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	21
Likely benign	0
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

2031 predictions. Top by Δscore:

Variant	Effect	Δscore
2:241702098:GGACA:G	donor_gain	1.0000
2:241702099:GACA:G	donor_gain	1.0000
2:241702099:GACAG:G	donor_gain	1.0000
2:241702103:G:GG	donor_gain	1.0000
2:241704645:C:CA	acceptor_gain	1.0000
2:241704647:TTTCA:T	acceptor_loss	1.0000
2:241704648:TTCA:T	acceptor_loss	1.0000
2:241704649:TCA:T	acceptor_loss	1.0000
2:241704650:CAG:C	acceptor_loss	1.0000
2:241704651:A:AG	acceptor_gain	1.0000
2:241704651:A:T	acceptor_loss	1.0000
2:241704651:AG:A	acceptor_gain	1.0000
2:241704652:G:GA	acceptor_gain	1.0000
2:241704652:GG:G	acceptor_gain	1.0000
2:241704652:GGT:G	acceptor_gain	1.0000
2:241704722:AAG:A	donor_loss	1.0000
2:241704724:GGTG:G	donor_loss	1.0000
2:241704726:T:A	donor_loss	1.0000
2:241709212:TCA:T	acceptor_loss	1.0000
2:241709213:CAG:C	acceptor_loss	1.0000
2:241709214:A:AG	acceptor_gain	1.0000
2:241709215:G:GG	acceptor_gain	1.0000
2:241709215:GATA:G	acceptor_gain	1.0000
2:241709215:GATAA:G	acceptor_gain	1.0000
2:241709335:G:GT	donor_gain	1.0000
2:241709379:GATG:G	donor_gain	1.0000
2:241709380:ATGGT:A	donor_loss	1.0000
2:241709381:TGGT:T	donor_loss	1.0000
2:241709382:GGT:G	donor_loss	1.0000
2:241709383:G:GG	donor_gain	1.0000

AlphaMissense

1598 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:241702097:T:C	L11P	1.000
2:241704665:T:C	L17P	1.000
2:241704677:T:C	L21P	1.000
2:241704695:T:C	L27P	1.000
2:241704707:T:C	L31P	1.000
2:241709352:A:C	K82N	1.000
2:241709352:A:T	K82N	1.000
2:241709360:T:C	L85P	1.000
2:241709362:G:C	A86P	1.000
2:241709363:C:A	A86D	1.000
2:241709369:A:C	Q88P	1.000
2:241709374:T:G	Y90D	1.000
2:241711380:G:C	D94H	1.000
2:241711381:A:C	D94A	1.000
2:241711381:A:T	D94V	1.000
2:241711390:T:A	I97N	1.000
2:241711393:G:C	R98P	1.000
2:241711399:T:A	L100H	1.000
2:241711399:T:C	L100P	1.000
2:241711401:G:C	D101H	1.000
2:241711401:G:T	D101Y	1.000
2:241711402:A:C	D101A	1.000
2:241711402:A:T	D101V	1.000
2:241711411:T:C	L104P	1.000
2:241722992:T:C	M179T	1.000
2:241722992:T:G	M179R	1.000
2:241722998:T:A	V181E	1.000
2:241723000:G:C	D182H	1.000
2:241723001:A:C	D182A	1.000
2:241723001:A:G	D182G	1.000

dbSNP variants (sampled 300 via entrez): RS1000005372 (2:241697563 T>C), RS1000182821 (2:241723679 C>T), RS1000242398 (2:241688233 T>C), RS1000242627 (2:241720308 C>G,T), RS1000279918 (2:241723687 T>C), RS1000323486 (2:241698468 CATT>C), RS1000354385 (2:241714052 G>A), RS1000361693 (2:241692824 G>A,T), RS1000361796 (2:241693086 C>A,G), RS1000397321 (2:241708592 C>A), RS1000472141 (2:241686872 G>A,C), RS1000560332 (2:241699119 G>A), RS1000692742 (2:241687951 C>G,T), RS1000719980 (2:241729249 A>G), RS1000844585 (2:241709943 A>T)

Disease associations

OMIM: gene MIM:608525 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST007993_16	Asthma (adult onset)	2.000000e-11
GCST007995_12	Asthma (childhood onset)	2.000000e-20
GCST009798_13	Asthma	5.000000e-36
GCST010083_133	Hemoglobin levels	2.000000e-09
GCST90002383_353	Hematocrit	2.000000e-12
GCST90002384_196	Hemoglobin	8.000000e-11
GCST90002401_433	Platelet distribution width	5.000000e-63

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:1002011	adult onset asthma
EFO:0004509	hemoglobin measurement
EFO:0004348	hematocrit
EFO:0007984	platelet component distribution width

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression	7
trichostatin A	affects expression, decreases expression	2
sodium arsenite	increases abundance, decreases expression	2
Tobacco Smoke Pollution	decreases expression, increases expression	2
Aflatoxin B1	decreases expression, increases methylation	2
aristolochic acid I	increases expression	1
FR900359	decreases phosphorylation	1
bisphenol F	decreases methylation	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
bisphenol A	affects cotreatment, decreases expression	1
afimoxifene	affects response to substance	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
butyraldehyde	decreases expression	1
aflatoxin B2	decreases methylation	1
coumarin	decreases phosphorylation	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
bisphenol S	decreases expression, affects cotreatment	1
Sunitinib	decreases expression	1
Arsenic Trioxide	increases expression	1
Vorinostat	decreases expression	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Air Pollutants	affects cotreatment, increases abundance, increases oxidation	1
Arsenic	decreases expression, increases abundance	1
Benzene	increases expression	1
Benzo(a)pyrene	decreases expression	1
Caffeine	decreases phosphorylation	1

Clinical trials (associated diseases)

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