Gene: NOTCH4

Alternate names for this Gene: INT3

Gene 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 intracellular domain consisting of multiple different domain types. Notch signaling is an evolutionarily conserved intercellular signaling pathway that regulates interactions between physically adjacent cells through binding of Notch family receptors to their cognate ligands. The encoded preproprotein is proteolytically processed in the trans-Golgi network to generate two polypeptide chains that heterodimerize to form the mature cell-surface receptor. This receptor may play a role in vascular, renal and hepatic development. Mutations in this gene may be associated with schizophrenia. Alternative splicing results in multiple transcript variants, at least one of which encodes an isoform that is proteolytically processed.

Gene is located in Chromosome: 6

Location in Chromosome : 6p21.32

Description of this Gene: notch receptor 4

Type of Gene: protein-coding

rs8192591 in NOTCH4 gene and ACQUIRED IMMUNODEFICIENCY SYNDROME, PROGRESSION TO PMID 20041166 2009 Common genetic variation and the control of HIV-1 in humans.

rs8192591 in NOTCH4 gene and AIDS, PROGRESSION TO PMID 20041166 2009 Common genetic variation and the control of HIV-1 in humans.

rs3830041 in NOTCH4 gene and Adenocarcinoma of large intestine PMID 30529582 2019 Large-Scale Genome-Wide Association Study of East Asians Identifies Loci Associated With Risk for Colorectal Cancer.

rs3134942 in NOTCH4 gene and Adenocarcinoma of lung (disorder) PMID 19836008 2009 A genome-wide association study of lung cancer identifies a region of chromosome 5p15 associated with risk for adenocarcinoma.

rs2071277 in NOTCH4 gene and Age related macular degeneration PMID 22694956 2012 Using a replication sample of 1411 advanced AMD cases and 1431 examined controls, we confirmed a novel association between AMD and single-nucleotide polymorphisms on chromosome 6p21.3 at TNXB (tenascin XB)-FKBPL (FK506 binding protein like) [rs12153855/rs9391734; discovery P =4.3 × 10(-7), replication P =3.0 × 10(-4), combined P =1.3 × 10(-9), odds ratio (OR) = 1.4, 95% confidence interval (CI) = 1.3-1.6] and the neighbouring gene NOTCH4 (Notch 4) (rs2071277; discovery P =3.2 × 10(-8), replication P =3.8 × 10(-5), combined P =2.0 × 10(-11), OR = 1.3, 95% CI = 1.2-1.4).

PMID 22694956 2012 Genome-wide association study of age-related macular degeneration identifies associated variants in the TNXB-FKBPL-NOTCH4 region of chromosome 6p21.3.

rs391755 in NOTCH4 gene and Allergic Reaction PMID 23817569 2013 A genome-wide association meta-analysis of self-reported allergy identifies shared and allergy-specific susceptibility loci.

rs115695709 in NOTCH4 gene and Aspartate aminotransferase measurement PMID 29403010 2018 Genetic analysis of quantitative traits in the Japanese population links cell types to complex human diseases.

rs404860 in NOTCH4 gene and Asthma PMID 21804548 2011 We observed the most significant association with adult asthma at rs404860 in the major histocompatiblity complex region (P = 4.07 × 10(-23)), which is close to rs2070600, a SNP previously reported for association with FEV(1)/FVC in genome-wide association studies for lung function.

rs16869834 in NOTCH4 gene and Blood Protein Measurement PMID 29875488 2018 Genomic atlas of the human plasma proteome.

rs3132947 in NOTCH4 gene and Body mass index PMID 31453325 2019 Genotype-by-environment interactions inferred from genetic effects on phenotypic variability in the UK Biobank.

rs2071278 in NOTCH4 gene and C4 complement assay (procedure) PMID 23028341 2012 Genome-wide association study for serum complement C3 and C4 levels in healthy Chinese subjects.

rs3830041 in NOTCH4 gene and COLORECTAL CANCER, SUSCEPTIBILITY TO, 1 PMID 30529582 2019 Large-Scale Genome-Wide Association Study of East Asians Identifies Loci Associated With Risk for Colorectal Cancer.

rs3830041 in NOTCH4 gene and COLORECTAL CANCER, SUSCEPTIBILITY TO, 10 PMID 30529582 2019 Large-Scale Genome-Wide Association Study of East Asians Identifies Loci Associated With Risk for Colorectal Cancer.

rs3830041 in NOTCH4 gene and COLORECTAL CANCER, SUSCEPTIBILITY TO, 12 PMID 30529582 2019 Large-Scale Genome-Wide Association Study of East Asians Identifies Loci Associated With Risk for Colorectal Cancer.

rs3830041 in NOTCH4 gene and COLORECTAL CANCER, SUSCEPTIBILITY TO, 3 PMID 30529582 2019 Large-Scale Genome-Wide Association Study of East Asians Identifies Loci Associated With Risk for Colorectal Cancer.

rs115344853 in NOTCH4 gene and Child Development Disorders, Pervasive PMID 28540026 2017 Meta-analysis of GWAS of over 16,000 individuals with autism spectrum disorder highlights a novel locus at 10q24.32 and a significant overlap with schizophrenia.

rs3830041 in NOTCH4 gene and Colorectal Carcinoma PMID 30529582 2019 Large-Scale Genome-Wide Association Study of East Asians Identifies Loci Associated With Risk for Colorectal Cancer.

rs3830041 in NOTCH4 gene and Colorectal Neoplasms PMID 30529582 2019 Large-Scale Genome-Wide Association Study of East Asians Identifies Loci Associated With Risk for Colorectal Cancer.

rs2071286 in NOTCH4 gene and Cryoglobulinemia PMID 25030430 2014 Genome-wide association study of hepatitis C virus- and cryoglobulin-related vasculitis.

rs206015 in NOTCH4 gene and Diabetes Mellitus, Insulin-Dependent PMID 17632545 2007 A genome-wide association study identifies KIAA0350 as a type 1 diabetes gene.

rs8192591 in NOTCH4 gene and HIV-1, RESISTANCE TO PMID 20041166 2009 Common genetic variation and the control of HIV-1 in humans.

rs8192591 in NOTCH4 gene and HUMAN IMMUNODEFICIENCY VIRUS TYPE 1, SUSCEPTIBILITY TO PMID 20041166 2009 Common genetic variation and the control of HIV-1 in humans.

rs422951 in NOTCH4 gene and Hepatitis B, Chronic PMID 25802187 2015 Genetic variants in five novel loci including CFB and CD40 predispose to chronic hepatitis B.

rs2071286 in NOTCH4 gene and Hepatitis C, Chronic PMID 25030430 2014 Genome-wide association study of hepatitis C virus- and cryoglobulin-related vasculitis.

rs3132947 in NOTCH4 gene and Hip circumference PMID 31453325 2019 Genotype-by-environment interactions inferred from genetic effects on phenotypic variability in the UK Biobank.

rs3131296 in NOTCH4 gene and Lupus Erythematosus, Systemic PMID 24871463 2014 GWAS identifies novel SLE susceptibility genes and explains the association of the HLA region.

rs3830041 in NOTCH4 gene and Malignant neoplasm of large intestine PMID 30529582 2019 Large-Scale Genome-Wide Association Study of East Asians Identifies Loci Associated With Risk for Colorectal Cancer.

rs3134942 in NOTCH4 gene and Malignant neoplasm of lung PMID 22899653 2012 Influence of common genetic variation on lung cancer risk: meta-analysis of 14 900 cases and 29 485 controls.

rs3096702 in NOTCH4 gene and Malignant neoplasm of prostate PMID 23535732 2013 Identification of 23 new prostate cancer susceptibility loci using the iCOGS custom genotyping array.

rs3830041 in NOTCH4 gene and Malignant tumor of colon PMID 30529582 2019 Large-Scale Genome-Wide Association Study of East Asians Identifies Loci Associated With Risk for Colorectal Cancer.

rs3131294 in NOTCH4 gene and Multiple Sclerosis PMID 17660530 2007 Risk alleles for multiple sclerosis identified by a genomewide study.

PMID 20598377 2010 Evidence for VAV2 and ZNF433 as susceptibility genes for multiple sclerosis.

rs3131296 in NOTCH4 gene and Myasthenia Gravis PMID 23055271 2012 Risk for myasthenia gravis maps to a (151) Pro→Ala change in TNIP1 and to human leukocyte antigen-B*08.

rs3134931 in NOTCH4 gene and Myeloperoxidase Measurement PMID 23620142 2013 Genome-wide and gene-centric analyses of circulating myeloperoxidase levels in the charge and care consortia.

rs415929 in NOTCH4 gene and Narcolepsy PMID 19629137 2009 Genome-wide association database developed in the Japanese Integrated Database Project.

rs138753323 in NOTCH4 gene and Oral Ulcer PMID 30837455 2019 Genome wide analysis for mouth ulcers identifies associations at immune regulatory loci.

rs2071286 in NOTCH4 gene and Pemphigus Vulgaris PMID 22437316 2012 Population-specific association between a polymorphic variant in ST18, encoding a pro-apoptotic molecule, and pemphigus vulgaris.

rs3096702 in NOTCH4 gene and Prostate carcinoma PMID 29892016 2018 Association analyses of more than 140,000 men identify 63 new prostate cancer susceptibility loci.

PMID 23535732 2013 Identification of 23 new prostate cancer susceptibility loci using the iCOGS custom genotyping array.

rs8192575 in NOTCH4 gene and Pulmonary function PMID 20010835 2010 Meta-analyses of genome-wide association studies identify multiple loci associated with pulmonary function.

rs8192575 in NOTCH4 gene and Pulmonary function (finding) PMID 20010835 2010 Meta-analyses of genome-wide association studies identify multiple loci associated with pulmonary function.

rs35565902 in NOTCH4 gene and Reticulocyte count (procedure) PMID 27863252 2016 The Allelic Landscape of Human Blood Cell Trait Variation and Links to Common Complex Disease.

rs206015 in NOTCH4 gene and Rheumatoid Arthritis PMID 17804836 2007 TRAF1-C5 as a risk locus for rheumatoid arthritis--a genomewide study.

PMID 21156761 2011 A genome-wide association study suggests contrasting associations in ACPA-positive versus ACPA-negative rheumatoid arthritis.

PMID 19503088 2009 REL, encoding a member of the NF-kappaB family of transcription factors, is a newly defined risk locus for rheumatoid arthritis.

rs715299 in NOTCH4 gene and Sarcoidosis PMID 22952805 2012 Genome-wide association study of African and European Americans implicates multiple shared and ethnic specific loci in sarcoidosis susceptibility.

rs115344853 in NOTCH4 gene and Schizophrenia PMID 30285260 2019 Genome-Wide Association Study Detected Novel Susceptibility Genes for Schizophrenia and Shared Trans-Populations/Diseases Genetic Effect.

PMID 28540026 2017 Meta-analysis of GWAS of over 16,000 individuals with autism spectrum disorder highlights a novel locus at 10q24.32 and a significant overlap with schizophrenia.

PMID 19571808 2009 Common variants conferring risk of schizophrenia.

PMID 21791550 2011 Common variants at VRK2 and TCF4 conferring risk of schizophrenia.

PMID 23894747 2013 A comprehensive family-based replication study of schizophrenia genes.

rs41270472 in NOTCH4 gene and Serum iron measurement PMID 28334935 2017 Genome-wide association study of iron traits and relation to diabetes in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL): potential genomic intersection of iron and glucose regulation?

rs2071286 in NOTCH4 gene and Systemic Scleroderma PMID 20383147 2010 Genome-wide association study of systemic sclerosis identifies CD247 as a new susceptibility locus.

PMID 21779181 2011 Identification of novel genetic markers associated with clinical phenotypes of systemic sclerosis through a genome-wide association strategy.

rs3131296 in NOTCH4 gene and Vitiligo PMID 20526339 2010 Genome-wide association study for vitiligo identifies susceptibility loci at 6q27 and the MHC.

rs147499485 in NOTCH4 gene and White Blood Cell Count procedure PMID 29403010 2018 Genetic analysis of quantitative traits in the Japanese population links cell types to complex human diseases.