Gene Details | GeDiPNet - Complete Gene Info, Disease Associations & Pathways

Gene Gene information from NCBI Gene database. Gene miRNA Transcription factors Gene ontology Other IDs Protein Pathways Associated diseases
Entrez ID	4855
Gene name	Notch receptor 4
Gene symbol	NOTCH4
Synonyms (NCBI Gene)	INT3
Chromosome	6
Chromosome location	6p21.32
Summary	This gene encodes a member of the NOTCH family of proteins. Members of this Type I transmembrane protein family share structural characteristics including an extracellular domain consisting of multiple epidermal growth factor-like (EGF) repeats, and an in

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miRTarBase ID	miRNA	Experiments	Reference
MIRT003211	hsa-miR-181c-5p	Luciferase reporter assayqRT-PCRWestern blot	20080834
MIRT006192	hsa-miR-34c-5p	EMSALuciferase reporter assayWestern blot	22074923
MIRT006192	hsa-miR-34c-5p	EMSALuciferase reporter assayWestern blot	22074923
MIRT006192	hsa-miR-34c-5p	EMSALuciferase reporter assayWestern blot	22074923
MIRT006192	hsa-miR-34c-5p	EMSALuciferase reporter assayWestern blot	22074923
MIRT006192	hsa-miR-34c-5p	EMSALuciferase reporter assayWestern blot	22074923
MIRT006192	hsa-miR-34c-5p	EMSALuciferase reporter assayWestern blot	22074923
MIRT006192	hsa-miR-34c-5p	EMSALuciferase reporter assayWestern blot	22074923
MIRT006192	hsa-miR-34c-5p	EMSALuciferase reporter assayWestern blot	22074923
MIRT006192	hsa-miR-34c-5p	EMSALuciferase reporter assayWestern blot	22074923
MIRT040767	hsa-miR-18a-3p	CLASH	23622248
MIRT732953	hsa-miR-7-5p	Immunoprecipitaion (IP)Luciferase reporter assayqRT-PCRWestern blotting	33118329
MIRT2055043	hsa-miR-1254	CLIP-seq
MIRT2055044	hsa-miR-128	CLIP-seq
MIRT2055045	hsa-miR-3116	CLIP-seq
MIRT2055046	hsa-miR-3144-5p	CLIP-seq
MIRT2055047	hsa-miR-3191	CLIP-seq
MIRT2055048	hsa-miR-34a	CLIP-seq
MIRT2055049	hsa-miR-4265	CLIP-seq
MIRT2055050	hsa-miR-4296	CLIP-seq
MIRT2055051	hsa-miR-4322	CLIP-seq
MIRT2055052	hsa-miR-4417	CLIP-seq
MIRT2055053	hsa-miR-449a	CLIP-seq
MIRT2055054	hsa-miR-449b	CLIP-seq
MIRT2055055	hsa-miR-4652-5p	CLIP-seq
MIRT2055056	hsa-miR-4672	CLIP-seq
MIRT2055057	hsa-miR-491-5p	CLIP-seq
MIRT2055058	hsa-miR-515-3p	CLIP-seq
MIRT2055059	hsa-miR-519e	CLIP-seq
MIRT2055060	hsa-miR-550a	CLIP-seq
MIRT2055061	hsa-miR-661	CLIP-seq
MIRT2055046	hsa-miR-3144-5p	CLIP-seq
MIRT2055047	hsa-miR-3191	CLIP-seq
MIRT2055048	hsa-miR-34a	CLIP-seq
MIRT2055049	hsa-miR-4265	CLIP-seq
MIRT2055050	hsa-miR-4296	CLIP-seq
MIRT2055051	hsa-miR-4322	CLIP-seq
MIRT2055052	hsa-miR-4417	CLIP-seq
MIRT2055053	hsa-miR-449a	CLIP-seq
MIRT2055054	hsa-miR-449b	CLIP-seq
MIRT2055055	hsa-miR-4652-5p	CLIP-seq
MIRT2284018	hsa-miR-4708-3p	CLIP-seq
MIRT2284019	hsa-miR-4781-5p	CLIP-seq
MIRT2055057	hsa-miR-491-5p	CLIP-seq
MIRT2055046	hsa-miR-3144-5p	CLIP-seq
MIRT2055047	hsa-miR-3191	CLIP-seq
MIRT2055048	hsa-miR-34a	CLIP-seq
MIRT2055049	hsa-miR-4265	CLIP-seq
MIRT2055050	hsa-miR-4296	CLIP-seq
MIRT2055051	hsa-miR-4322	CLIP-seq
MIRT2055052	hsa-miR-4417	CLIP-seq
MIRT2055053	hsa-miR-449a	CLIP-seq
MIRT2055054	hsa-miR-449b	CLIP-seq
MIRT2055055	hsa-miR-4652-5p	CLIP-seq
MIRT2055057	hsa-miR-491-5p	CLIP-seq
MIRT2055046	hsa-miR-3144-5p	CLIP-seq
MIRT2055047	hsa-miR-3191	CLIP-seq
MIRT2055048	hsa-miR-34a	CLIP-seq
MIRT2055049	hsa-miR-4265	CLIP-seq
MIRT2055050	hsa-miR-4296	CLIP-seq
MIRT2055051	hsa-miR-4322	CLIP-seq
MIRT2055052	hsa-miR-4417	CLIP-seq
MIRT2055053	hsa-miR-449a	CLIP-seq
MIRT2055054	hsa-miR-449b	CLIP-seq
MIRT2055055	hsa-miR-4652-5p	CLIP-seq
MIRT2055057	hsa-miR-491-5p	CLIP-seq

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Transcription factor	Regulation	Reference
PPARG	Unknown	20436223

Show/Hide all (51)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000122	Process	Negative regulation of transcription by RNA polymerase II	IMP	17984306
GO:0000139	Component	Golgi membrane	IEA
GO:0000139	Component	Golgi membrane	TAS
GO:0001554	Process	Luteolysis	IEA
GO:0001569	Process	Branching involved in blood vessel morphogenesis	ISS
GO:0001709	Process	Cell fate determination	TAS	11823422
GO:0001763	Process	Morphogenesis of a branching structure	ISS
GO:0001837	Process	Epithelial to mesenchymal transition	IMP	17984306
GO:0001886	Process	Endothelial cell morphogenesis	IEA
GO:0001944	Process	Vasculature development	ISS
GO:0003713	Function	Transcription coactivator activity	IDA	18239137
GO:0005112	Function	Notch binding	IBA
GO:0005509	Function	Calcium ion binding	IEA
GO:0005509	Function	Calcium ion binding	TAS	11823422
GO:0005515	Function	Protein binding	IPI	7671825, 11101851, 32814053
GO:0005576	Component	Extracellular region	TAS
GO:0005634	Component	Nucleus	IEA
GO:0005634	Component	Nucleus	TAS	8681805
GO:0005654	Component	Nucleoplasm	IEA
GO:0005654	Component	Nucleoplasm	TAS
GO:0005789	Component	Endoplasmic reticulum membrane	IEA
GO:0005789	Component	Endoplasmic reticulum membrane	TAS
GO:0005829	Component	Cytosol	IEA
GO:0005829	Component	Cytosol	TAS
GO:0005886	Component	Plasma membrane	IEA
GO:0005886	Component	Plasma membrane	TAS	9168133, 11823422
GO:0006355	Process	Regulation of DNA-templated transcription	IEA
GO:0007219	Process	Notch signaling pathway	IEA
GO:0007221	Process	Positive regulation of transcription of Notch receptor target	TAS	18663143
GO:0009888	Process	Tissue development	IEA
GO:0009986	Component	Cell surface	IDA	11823422
GO:0016020	Component	Membrane	IEA
GO:0030097	Process	Hemopoiesis	TAS	11532344
GO:0030154	Process	Cell differentiation	IEA
GO:0030154	Process	Cell differentiation	NAS	11823422
GO:0030879	Process	Mammary gland development	IDA	9576833
GO:0038023	Function	Signaling receptor activity	IEA
GO:0038023	Function	Signaling receptor activity	TAS	11823422
GO:0045446	Process	Endothelial cell differentiation	IEA
GO:0045595	Process	Regulation of cell differentiation	IEA
GO:0045596	Process	Negative regulation of cell differentiation	NAS	11823422
GO:0045602	Process	Negative regulation of endothelial cell differentiation	ISS
GO:0045893	Process	Positive regulation of DNA-templated transcription	IEA
GO:0045893	Process	Positive regulation of DNA-templated transcription	TAS	11823422
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IDA	18239137
GO:0048468	Process	Cell development	IEA
GO:0050793	Process	Regulation of developmental process	IEA
GO:0051094	Process	Positive regulation of developmental process	IEA
GO:0051152	Process	Positive regulation of smooth muscle cell differentiation	IDA	18239137
GO:0060354	Process	Negative regulation of cell adhesion molecule production	IMP	17984306
GO:2000048	Process	Negative regulation of cell-cell adhesion mediated by cadherin	IMP	17984306

MIM	HGNC	e!Ensembl
164951	7884	ENSG00000204301

Q99466

Protein name

Neurogenic locus notch homolog protein 4 (Notch 4) (hNotch4) [Cleaved into: Notch 4 extracellular truncation; Notch 4 intracellular domain]

Protein function

Functions as a receptor for membrane-bound ligands Jagged1, Jagged2 and Delta1 to regulate cell-fate determination. Upon ligand activation through the released notch intracellular domain (NICD) it forms a transcriptional activator complex with R

PDB

7OR3 , 7OR5 , 7OR7

Family and domains

Pfam

Accession	ID	Position in sequence	Description	Type
PF12661	hEGF	35 → 57	Human growth factor-like EGF	Domain
PF12661	hEGF	127 → 149	Human growth factor-like EGF	Domain
PF00008	EGF	160 → 189	EGF-like domain	Domain
PF07645	EGF_CA	194 → 238	Calcium-binding EGF domain	Domain
PF00008	EGF	238 → 272	EGF-like domain	Domain
PF00008	EGF	280 → 308	EGF-like domain	Domain
PF07645	EGF_CA	314 → 356	Calcium-binding EGF domain	Domain
PF12661	hEGF	364 → 385	Human growth factor-like EGF	Domain
PF07645	EGF_CA	432 → 474	Calcium-binding EGF domain	Domain
PF00008	EGF	479 → 509	EGF-like domain	Domain
PF00008	EGF	517 → 547	EGF-like domain	Domain
PF07645	EGF_CA	551 → 590	Calcium-binding EGF domain	Domain
PF00008	EGF	593 → 623	EGF-like domain	Domain
PF00008	EGF	695 → 725	EGF-like domain	Domain
PF00008	EGF	771 → 801	EGF-like domain	Domain
PF00008	EGF	810 → 838	EGF-like domain	Domain
PF07645	EGF_CA	845 → 886	Calcium-binding EGF domain	Domain
PF00008	EGF	896 → 926	EGF-like domain	Domain
PF00008	EGF	934 → 964	EGF-like domain	Domain
PF00008	EGF	972 → 1002	EGF-like domain	Domain
PF00008	EGF	1050 → 1083	EGF-like domain	Domain
PF00066	Notch	1167 → 1204	LNR domain	Domain
PF00066	Notch	1211 → 1246	LNR domain	Domain
PF00066	Notch	1248 → 1285	LNR domain	Domain
PF06816	NOD	1295 → 1344	NOTCH protein	Family
PF07684	NODP	1378 → 1440	NOTCH protein	Family
PF12796	Ank_2	1638 → 1731	Ankyrin repeats (3 copies)	Repeat
PF12796	Ank_2	1712 → 1797	Ankyrin repeats (3 copies)	Repeat

Tissue specificity

TISSUE SPECIFICITY: Highly expressed in the heart, moderately in the lung and placenta and at low levels in the liver, skeletal muscle, kidney, pancreas, spleen, lymph node, thymus, bone marrow and fetal liver. No expression was seen in adult brain or per

Sequence

MQPPSLLLLLLLLLLLCVSVVRPRGLLCGSFPEPCANGGTCLSLSLGQGTCQCAPGFLGE
TCQFPDPCQNAQLCQNGGSCQALLPAPLGLPSSPSPLTPSFLCTCLPGFTGERCQAKLED
PCPPSFCSKRGRCHIQASGRPQCSCMPGWTGEQCQLRDFCSANPCVNGGVCLATYPQIQC
HCPPGFEGHACERDVNECFQDPGPCPKGTSCHNTLGSFQCLCPVGQEGPRCELRAGPCPP
RGCSNGGTCQLMPEKDSTFHLCLCPPGFIGPDCEVNPDNCVSHQCQNGGTCQDGLDTYTC
LCPETWTGWDCSEDVDECETQGPPHCRNGGTCQNSAGSFHCVCVSGWGGTSCEENLDDCI
AATCAPGSTCIDRVGSFSCLCPPGRTGLLCHLEDMCLSQPCHGDAQCSTNPLTGSTLCLC
QPGYSGPTCHQDLDECLMAQQGPSPCEHGGSCLNTPGSFNCLCPPGYTGSRCEADHNECL
SQPCHPGSTCLDLLATFHCLCPPGLEGQLCEVETNECASAPCLNHADCHDLLNGFQCICL
PGFSGTRCEEDIDECRSSPCANGGQCQDQPGAFHCKCLPGFEGPRCQTEVDECLSDPCPV
GASCLDLPGAFFCLCPSGFTGQLCEVPLCAPNLCQPKQICKDQKDKANCLCPDGSPGCAP
PEDNCTCHHGHCQRSSCVCDVGWTGPECEAELGGCISAPCAHGGTCYPQPSGYNCTCPTG
YTGPTCSEEMTACHSGPCLNGGSCNPSPGGYYCTCPPSHTGPQCQTSTDYCVSAPCFNGG
TCVNRPGTFSCLCAMGFQGPRCEGKLRPSCADSPCRNRATCQDSPQGPRCLCPTGYTGGS
CQTLMDLCAQKPCPRNSHCLQTGPSFHCLCLQGWTGPLCNLPLSSCQKAALSQGIDVSSL
CHNGGLCVDSGPSYFCHCPPGFQGSLCQDHVNPCESRPCQNGATCMAQPSGYLCQCAPGY
DGQNCSKELDACQSQPCHNHGTCTPKPGGFHCACPPGFVGLRCEGDVDECLDQPCHPTGT
AACHSLANAFYCQCLPGHTGQWCEVEIDPCHSQPCFHGGTCEATAGSPLGFICHCPKGFE
GPTCSHRAPSCGFHHCHHGGLCLPSPKPGFPPRCACLSGYGGPDCLTPPAPKGCGPPSPC
LYNGSCSETTGLGGPGFRCSCPHSSPGPRCQKPGAKGCEGRSGDGACDAGCSGPGGNWDG
GDCSLGVPDPWKGCPSHSRCWLLFRDGQCHPQCDSEECLFDGYDCETPPACTPAYDQYCH
DHFHNGHCEKGCNTAECGWDGGDCRPEDGDPEWGPSLALLVVLSPPALDQQLFALARVLS
LTLRVGLWVRKDRDGRDMVYPYPGARAEEKLGGTRDPTYQERAAPQTQPLGKETDSLSAG
FVVVMGVDLSRCGPDHPASRCPWDPGLLLRFLAAMAAVGALEPLLPGPLLAVHPHAGTAP
PANQLPWPVLCSPVAGVILLALGALLVLQLIRRRRREHGALWLPPGFTRRPRTQSAPHRR
RPPLGEDSIGLKALKPKAEVDEDGVVMCSGPEEGEEVGQAEETGPPSTCQLWSLSGGCGA
LPQAAMLTPPQESEMEAPDLDTRGPDGVTPLMSAVCCGEVQSGTFQGAWLGCPEPWEPLL
DGGACPQAHTVGTGETPLHLAARFSRPTAARRLLEAGANPNQPDRAGRTPLHAAVAADAR
EVCQLLLRSRQTAVDARTEDGTTPLMLAARLAVEDLVEELIAAQADVGARDKWGKTALHW
AAAVNNARAARSLLQAGADKDAQDNREQTPLFLAAREGAVEVAQLLLGLGAARELRDQAG
LAPADVAHQRNHWDLLTLLEGAGPPEARHKATPGREAGPFPRARTVSVSVPPHGGGALPR
CRTLSAGAGPRGGGACLQARTWSVDLAARGGGAYSHCRSLSGVGAGGGPTPRGRRFSAGM
RGPRPNPAIMRGRYGVAAGRGGRVSTDDWPCDWVALGACGSASNIPIPPPCLTPSPERGS
PQLDCGPPALQEMPINQGGEGKK

Sequence length

2003

Interactions

View interactions

	KEGG		Reactome
	Endocrine resistance Notch signaling pathway Thyroid hormone signaling pathway Human papillomavirus infection Pathways in cancer MicroRNAs in cancer Breast cancer		Pre-NOTCH Transcription and Translation Pre-NOTCH Processing in Golgi Notch-HLH transcription pathway Defective LFNG causes SCDO3 NOTCH4 Intracellular Domain Regulates Transcription NOTCH4 Activation and Transmission of Signal to the Nucleus Negative regulation of NOTCH4 signaling

Show/Hide Unknown Diseases (15)

Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
Unknown Diseases with uncertain, conflicting, or no pathogenic evidence in ClinVar
Adrenocortical carcinoma, hereditary	Benign	rs3134942	RCV005919943
Aganglionic megacolon	Uncertain significance	rs745883985	RCV000984699
Anophthalmia-microphthalmia syndrome	Benign; Likely benign	rs150079294	RCV000207397
Cerebral arteriovenous malformation	Uncertain significance	rs755664291	RCV002640755
Cervical cancer	Benign	rs9469093	RCV005915749
Cholangiocarcinoma	Benign	rs3134942	RCV005919946
Clear cell carcinoma of kidney	Benign; Likely benign	rs150079294	RCV005893793
Familial pancreatic carcinoma	Benign	rs118154954	RCV005907257
Gastric cancer	Benign	rs9469093, rs118154954	RCV005915751 RCV005907259
Hepatocellular carcinoma	Benign; Likely benign	rs150079294, rs118154954	RCV005893791 RCV005907255
Malignant tumor of esophagus	Benign; Likely benign	rs9469093, rs150079294, rs118154954	RCV005915748 RCV005893792 RCV005907256
Ovarian serous cystadenocarcinoma	Benign	rs9469093	RCV005915752
Sarcoma	Benign; Likely benign	rs9469093, rs150079294, rs118154954	RCV005915750 RCV005893794 RCV005907258
Thymoma	Benign	rs3134942, rs118154954	RCV005919945 RCV005907260
Uterine carcinosarcoma	Benign	rs3134942	RCV005919944

Show/Hide Text Mining Associations (87)

Disease Name	Relationship Type	References
Associations from Text MiningDisease associations identified through Pubtator
Acquired Immunodeficiency Syndrome	Associate	21107268
Adenocarcinoma	Inhibit	29769567
Adenocarcinoma of Lung	Associate	29769567, 37268635
Alzheimer Disease	Associate	14966150
Anxiety	Associate	36814110
Arthritis Psoriatic	Associate	23161900
Arthritis Rheumatoid	Associate	14730600, 19143814, 23161900, 26686423
Asthma	Associate	21804548, 27177148, 31605414, 32929274, 39643224
Astrocytoma	Associate	19424825
Atrioventricular Septal Defect	Associate	33093519
Autoimmune Diseases	Associate	32960812
Brain Neoplasms	Associate	19424825, 31483290
Breast Neoplasms	Associate	20030805, 21679465, 22965833, 24716804, 24919951, 25663545, 26323259, 28617548, 29807833, 34284787, 38087296
CADASIL	Associate	23028706
Capillary Malformation Arteriovenous Malformation	Associate	30573741
Carcinoma Adenoid Cystic	Associate	24238845
Carcinoma Ductal	Associate	25120811
Carcinoma Hepatocellular	Associate	20165882, 28423575, 28568708, 33118329
Carcinoma Non Small Cell Lung	Associate	30593175, 34284787
Carcinoma Renal Cell	Associate	34284787, 34870494
Carcinoma Small Cell	Associate	28951314
Carcinoma Verrucous	Inhibit	29162408
Celiac Disease	Associate	36814110
Central Serous Chorioretinopathy	Associate	37079300
CHARGE Syndrome	Associate	15710038
Cholangiocarcinoma	Associate	25031748
Cholangitis Sclerosing	Associate	25521205
Colonic Neoplasms	Associate	37108670
Colorectal Neoplasms	Associate	34284787
COVID 19	Associate	37567834
Death	Associate	28568708
Dementia	Associate	21297263
Diabetes Mellitus Type 1	Associate	19143814
Down Syndrome	Associate	33093519
Dyspnea	Associate	37567834
Familial Mediterranean Fever	Associate	31957891
Fibrosis	Associate	23576639
Glioblastoma	Associate	23787764, 26472724
Glycogen Storage Disease Type II	Associate	37079300
Graves Disease	Associate	24684463
Headache	Associate	23566281
Hemangioblastoma	Associate	21663414
Hemangioma	Stimulate	19349369
Hemangioma	Associate	20069356
Hemophilia A	Associate	16460442
Inflammation	Stimulate	23395714
Inflammation	Associate	32929274, 32960812
Inflammatory Breast Neoplasms	Associate	28270211, 30086764
Leiomyosarcoma	Associate	35682660
Leukemia Myelogenous Chronic BCR ABL Positive	Associate	35815090
Leukemia Myeloid Acute	Associate	31551439
Lung Neoplasms	Associate	39595659
Lupus Erythematosus Systemic	Associate	26686423
Lymphatic Metastasis	Associate	30593175
Macular Degeneration	Associate	22694956
Malocclusion Angle Class III	Associate	34039391
Mammary Neoplasms Animal	Associate	15535842
Medulloblastoma	Associate	19424825
Melanoma	Associate	21159651, 26801977, 27234159, 34284787, 35967450
Migraine Disorders	Associate	23566281, 36814110
Multiple Sclerosis	Associate	21654846
Neoplasm Metastasis	Stimulate	27234159, 30593175
Neoplasm Metastasis	Associate	33722295
Neoplasms	Associate	18691378, 22074923, 23226563, 24143218, 25663545, 26472724, 27234159, 30593175, 32079522, 33219256, 34284787, 35967450, 36911742, 37108670
Neoplasms	Inhibit	26801977
Non Muscle Invasive Bladder Neoplasms	Associate	27626805
Odontogenic Tumor Squamous	Associate	20554499
Ovarian Neoplasms	Associate	28415574, 37796700
Pancreatic Neoplasms	Associate	16327489, 33498866
Post Acute COVID 19 Syndrome	Associate	36282598
Prostatic Intraepithelial Neoplasia	Associate	26341090
Prostatic Neoplasms Castration Resistant	Associate	36246971
Pulmonary Disease Chronic Obstructive	Associate	27117828, 29874112, 32753590
Sarcoidosis	Associate	22952805, 33276795
Sarcoma Alveolar Soft Part	Associate	35628499
Schizophrenia	Associate	23395714, 36814110
Scleroderma Systemic	Associate	25569146
Sjogren's Syndrome	Associate	26686423
Squamous Cell Carcinoma of Head and Neck	Associate	23287992, 29146722, 29162408, 31093971
Stomach Neoplasms	Associate	27363496, 31399040, 32028262, 34925644
Tetralogy of Fallot	Associate	33000281
Tuberculosis	Associate	36817473
Tuberculosis	Stimulate	36817473
Tuberculosis Pulmonary	Associate	36817473
Urinary Bladder Neoplasms	Associate	34284787
Uterine Diseases	Associate	18691378
Vasculitis	Associate	25030430, 32960812, 33721342

NOTCH4 (notch receptor 4)