This gene encodes a member of the epidermal growth factor (EGF) family of proteins. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed to generate the secreted growth factor. A secreted form and a membrane-anchored form of this protein bind to multiple different EGF receptors. This protei... See more...

Aliases for BTC Gene

Aliases for BTC Gene

  • Betacellulin 2 3 5
  • Probetacellulin 3 4
  • BTC 5

External Ids for BTC Gene

Previous GeneCards Identifiers for BTC Gene

  • GC04M075557
  • GC04M075843
  • GC04M076062
  • GC04M076128
  • GC04M076129
  • GC04M076027
  • GC04M075889
  • GC04M075669
  • GC04M071418

Summaries for BTC Gene

Entrez Gene Summary for BTC Gene

  • This gene encodes a member of the epidermal growth factor (EGF) family of proteins. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed to generate the secreted growth factor. A secreted form and a membrane-anchored form of this protein bind to multiple different EGF receptors. This protein promotes pancreatic cell proliferation and insulin secretion, as well as retinal vascular permeability. Mutations in this gene may be associated with type 2 diabetes in human patients. [provided by RefSeq, Nov 2015]

GeneCards Summary for BTC Gene

BTC (Betacellulin) is a Protein Coding gene. Diseases associated with BTC include Squamous Blepharitis and Insulinoma. Among its related pathways are RET signaling and Nanog in Mammalian ESC Pluripotency. Gene Ontology (GO) annotations related to this gene include growth factor activity and epidermal growth factor receptor binding. An important paralog of this gene is TGFA.

UniProtKB/Swiss-Prot Summary for BTC Gene

  • Growth factor that binds to EGFR, ERBB4 and other EGF receptor family members. Potent mitogen for retinal pigment epithelial cells and vascular smooth muscle cells.

Gene Wiki entry for BTC Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for BTC Gene

Genomics for BTC Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for BTC Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH04J074793 Promoter/Enhancer 1.4 Ensembl ENCODE CraniofacialAtlas 288.4 +0.4 432 1.8 YY1 FEZF1 ZNF341 CTCF SIN3A RXRA SMC3 GABPB1 HNF4A MAZ BTC HSALNG0035227 AREG
GH04J074796 Enhancer 0.2 FANTOM5 267 -1.6 -1589 0.4 BTC HSALNG0035228 PARM1
GH04J074932 Promoter/Enhancer 2.1 EPDnew FANTOM5 Ensembl ENCODE CraniofacialAtlas 6.3 -139.3 -139278 2.8 ZNF654 ZNF600 POLR2A ZBTB10 ZNF592 ZNF341 CTCF SIN3A SMC3 GABPB1 PARM1 lnc-BTC-1 BTC KR153194-145 THAP6
GH04J074768 Enhancer 0.9 Ensembl ENCODE 4.6 +25.4 25369 1.3 NFIC ZEB1 FOXA2 FOSL2 JUND TCF7L2 ZFP37 HNF4A HMG20A CTCF BTC HSALNG0035227 AREG
GH04J074682 Enhancer 1.2 Ensembl ENCODE dbSUPER 0.1 +111.6 111648 1.5 NCOR1 IKZF1 ZNF592 NFIC REST BHLHE40 MBD2 ARNT EP300 TAF9B HSALNG0035223 HSALNG0035221 BTC AREG
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around BTC on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for BTC

Top Transcription factor binding sites by QIAGEN in the BTC gene promoter:
  • CREB
  • deltaCREB
  • FOXI1
  • FOXO1
  • FOXO1a
  • FOXO4
  • HFH-3

Genomic Locations for BTC Gene

Latest Assembly
chr4:74,744,759-74,794,718
(GRCh38/hg38)
Size:
49,960 bases
Orientation:
Minus strand

Previous Assembly
chr4:75,669,969-75,719,733
(GRCh37/hg19 by Entrez Gene)
Size:
49,765 bases
Orientation:
Minus strand

chr4:75,669,969-75,719,896
(GRCh37/hg19 by Ensembl)
Size:
49,928 bases
Orientation:
Minus strand

Genomic View for BTC Gene

Genes around BTC on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
BTC Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for BTC Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for BTC Gene

Proteins for BTC Gene

  • Protein details for BTC Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P35070-BTC_HUMAN
    Recommended name:
    Probetacellulin
    Protein Accession:
    P35070
    Secondary Accessions:
    • Q96F48

    Protein attributes for BTC Gene

    Size:
    178 amino acids
    Molecular mass:
    19746 Da
    Quaternary structure:
    • Monomer. Interacts with EGFR and ERBB4.

    Three dimensional structures from OCA and Proteopedia for BTC Gene

neXtProt entry for BTC Gene

Post-translational modifications for BTC Gene

  • Glycosylation at Asn34
  • Modification sites at PhosphoSitePlus

Other Protein References for BTC Gene

No data available for DME Specific Peptides for BTC Gene

Domains & Families for BTC Gene

Gene Families for BTC Gene

Human Protein Atlas (HPA):
  • Predicted intracellular proteins
  • Predicted membrane proteins
  • Predicted secreted proteins

Protein Domains for BTC Gene

InterPro:
Blocks:
  • Type I EGF
  • Type I EGF signature

Suggested Antigen Peptide Sequences for BTC Gene

GenScript: Design optimal peptide antigens:
  • Probetacellulin (BTC_HUMAN)
genes like me logo Genes that share domains with BTC: view

No data available for Graphical View of Domain Structure and UniProtKB/Swiss-Prot for BTC Gene

Function for BTC Gene

Molecular function for BTC Gene

UniProtKB/Swiss-Prot Function:
Growth factor that binds to EGFR, ERBB4 and other EGF receptor family members. Potent mitogen for retinal pigment epithelial cells and vascular smooth muscle cells.
GENATLAS Biochemistry:
betacellulin,ECF family

Phenotypes From GWAS Catalog for BTC Gene

Gene Ontology (GO) - Molecular Function for BTC Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005154 epidermal growth factor receptor binding IEA,IBA 21873635
GO:0005515 protein binding IPI 19740107
GO:0008083 growth factor activity TAS,IBA 21873635
genes like me logo Genes that share ontologies with BTC: view
genes like me logo Genes that share phenotypes with BTC: view

Animal Models for BTC Gene

MGI Knock Outs for BTC:
  • Btc Btc<tm1Dcl>

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for BTC

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for BTC Gene

Localization for BTC Gene

Subcellular locations from UniProtKB/Swiss-Prot for BTC Gene

[Betacellulin]: Secreted, extracellular space.
[Probetacellulin]: Cell membrane. Single-pass type I membrane protein.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for BTC gene
Compartment Confidence
plasma membrane 5
extracellular 5
cytoskeleton 2
nucleus 2
mitochondrion 1
peroxisome 1
endoplasmic reticulum 1
endosome 1
cytosol 1
lysosome 1
golgi apparatus 1

Gene Ontology (GO) - Cellular Components for BTC Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region TAS --
GO:0005615 extracellular space IBA 21873635
GO:0005886 plasma membrane IEA --
GO:0016020 membrane IEA --
GO:0016021 integral component of membrane IEA --
genes like me logo Genes that share ontologies with BTC: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for BTC Gene

Pathways & Interactions for BTC Gene

PathCards logo

SuperPathways for BTC Gene

SuperPathway Contained pathways
1 RET signaling
2 Apoptotic Pathways in Synovial Fibroblasts
.85
.85
.84
.84
.74
.72
.66
.65
.64
.62
.61
.60
.57
.57
3 Signaling by ERBB2
4 PI3K/AKT activation
5 GPCR Pathway
.73
.73
.62
.59
.58
.58
.55
genes like me logo Genes that share pathways with BTC: view

Pathways by source for BTC Gene

1 KEGG pathway for BTC Gene
2 GeneGo (Thomson Reuters) pathways for BTC Gene
  • Development EGFR signaling pathway
  • Development ERBB-family signaling
55 Qiagen pathways for BTC Gene
  • 14-3-3 Induced Intracellular Signaling
  • Actin-Based Motility by Rho Family GTPases
  • Activation of cAMP-Dependent PKA
  • Activation of PKA through GPCR
  • Activation of PKC through GPCR

SIGNOR curated interactions for BTC Gene

Activates:
Is activated by:

Gene Ontology (GO) - Biological Process for BTC Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000165 MAPK cascade TAS --
GO:0007165 signal transduction TAS --
GO:0007173 epidermal growth factor receptor signaling pathway TAS --
GO:0008284 positive regulation of cell proliferation TAS,IBA 21873635
GO:0035810 positive regulation of urine volume IEA --
genes like me logo Genes that share ontologies with BTC: view

Drugs & Compounds for BTC Gene

(26) Drugs for BTC Gene - From: ClinicalTrials and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Cetuximab Approved Pharma EGFR Inhibitors, Therapeutic Antibodies, Epidermal growth factor receptor (EGFR) inhibitors 902
Cisplatin Approved Pharma Inhibits DNA synthesis,chemotherapy drug, Potent pro-apoptotic anticancer agent; activates caspase-3, Platinum 3624
Durvalumab Approved, Investigational Pharma 543
Gemcitabine Approved Pharma Ribonucleotide reductase and DNA synthesis inhibitor, Nucleoside Analogs 2590
Lenvatinib Approved, Investigational Pharma Kinase Inhibitors, Vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR) inhibitors 216

(7) Additional Compounds for BTC Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with BTC: view

Transcripts for BTC Gene

mRNA/cDNA for BTC Gene

2 REFSEQ mRNAs :
8 NCBI additional mRNA sequence :
2 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for BTC

Alternative Splicing Database (ASD) splice patterns (SP) for BTC Gene

No ASD Table

Relevant External Links for BTC Gene

GeneLoc Exon Structure for
BTC

Expression for BTC Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for BTC Gene

mRNA differential expression in normal tissues according to GTEx for BTC Gene

This gene is overexpressed in Colon - Sigmoid (x7.9), Esophagus - Muscularis (x6.5), and Esophagus - Gastroesophageal Junction (x6.4).

Protein differential expression in normal tissues from HIPED for BTC Gene

This gene is overexpressed in Colon (26.4), Gallbladder (24.5), and Retina (18.1).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for BTC Gene



Transcriptomic regulation report from SPP (The Signaling Pathways Project) for BTC

SOURCE GeneReport for Unigene cluster for BTC Gene:

Hs.710156

mRNA Expression by UniProt/SwissProt for BTC Gene:

P35070-BTC_HUMAN
Tissue specificity: Synthesized in several tissues and tumor cells. Predominantly expressed in pancreas and small intestine.

Evidence on tissue expression from TISSUES for BTC Gene

  • Skin(2.2)
  • Pancreas(2.2)
  • Intestine(2)
genes like me logo Genes that share expression patterns with BTC: view

Primer products for research

No data available for Protein tissue co-expression partners and Phenotype-based relationships between genes and organs from Gene ORGANizer for BTC Gene

Orthologs for BTC Gene

This gene was present in the common ancestor of chordates.

Orthologs for BTC Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia BTC 29 30
  • 99.25 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia BTC 29 30
  • 89.14 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia LOC482682 29
  • 85.56 (n)
BTC 30
  • 74 (a)
OneToOne
Mouse
(Mus musculus)
Mammalia Btc 29 16 30
  • 78.53 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Btc 29
  • 78.53 (n)
Platypus
(Ornithorhynchus anatinus)
Mammalia BTC 30
  • 55 (a)
OneToOne
Chicken
(Gallus gallus)
Aves BTC 29 30
  • 60.28 (n)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia LOC100497610 29
  • 60.87 (n)
Zebrafish
(Danio rerio)
Actinopterygii btc 29 30
  • 56.05 (n)
OneToOne
Species where no ortholog for BTC was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Fruit Fly (Drosophila melanogaster)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Lizard (Anolis carolinensis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Oppossum (Monodelphis domestica)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)

Evolution for BTC Gene

ENSEMBL:
Gene Tree for BTC (if available)
TreeFam:
Gene Tree for BTC (if available)
Aminode:
Evolutionary constrained regions (ECRs) for BTC: view image
Alliance of Genome Resources:
Additional Orthologs for BTC

Paralogs for BTC Gene

Paralogs for BTC Gene

(1) SIMAP similar genes for BTC Gene using alignment to 2 proteins:

  • BTC_HUMAN
  • H0Y8Q5_HUMAN
genes like me logo Genes that share paralogs with BTC: view

Variants for BTC Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for BTC Gene

SNP ID Clinical significance and condition Chr 04 pos Variation AA Info Type
rs56320257 Benign: not provided 74,770,091(-) G/Ap.Leu44Phe
NM_001729.4(BTC):c.130C>T (p.Leu44Phe)
MISSENSE
rs11938093 -- p.Leu124Met
rs28549760 -- p.Cys7Gly

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for BTC Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Structural Variations from Database of Genomic Variants (DGV) for BTC Gene

Variant ID Type Subtype PubMed ID
esv3601020 CNV loss 21293372
nsv1009099 CNV gain 25217958
nsv4390 CNV deletion 18451855
nsv7363 OTHER inversion 18451855

Variation tolerance for BTC Gene

Residual Variation Intolerance Score: 91.6% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 11.13; 92.29% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for BTC Gene

Human Gene Mutation Database (HGMD)
BTC
SNPedia medical, phenotypic, and genealogical associations of SNPs for
BTC
Leiden Open Variation Database (LOVD)
BTC

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for BTC Gene

Disorders for BTC Gene

MalaCards: The human disease database

(5) MalaCards diseases for BTC Gene - From: COP and GCD

Disorder Aliases PubMed IDs
squamous blepharitis
insulinoma
  • insulin-producing tumor of islet cells
vallecula cancer
  • malignant tumor of vallecula
mixed cell adenoma
squamous cell carcinoma, head and neck
  • hnscc
- elite association - COSMIC cancer census association via MalaCards
Search BTC in MalaCards View complete list of genes associated with diseases

Additional Disease Information for BTC

Human Genome Epidemiology Navigator
(HuGE)
Atlas
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
Open Targets Platform
genes like me logo Genes that share disorders with BTC: view

No data available for UniProtKB/Swiss-Prot and Genatlas for BTC Gene

Publications for BTC Gene

  1. Cloning and expression of cDNA encoding human betacellulin, a new member of the EGF family. (PMID: 8439318) Sasada R … Igarashi K (Biochemical and biophysical research communications 1993) 2 3 4 22
  2. Association of a polymorphism in the betacellulin gene with type 1 diabetes mellitus in two populations. (PMID: 16683131) Silver KD … Mitchell BD (Journal of molecular medicine (Berlin, Germany) 2006) 3 22 40
  3. Analysis of coding variants in the betacellulin gene in type 2 diabetes and insulin secretion in African American subjects. (PMID: 16869959) Elbein SC … Silver KD (BMC medical genetics 2006) 3 22 40
  4. Molecular scanning of the betacellulin gene for mutations in type 2 diabetic patients. (PMID: 15936459) Nakagawa T … Nanjo K (Diabetes research and clinical practice 2005) 3 22 40
  5. A functional variant in the human betacellulin gene promoter is associated with type 2 diabetes. (PMID: 16306376) Nakano Y … Nanjo K (Diabetes 2005) 3 22 40

Products for BTC Gene

  • Addgene plasmids for BTC

Sources for BTC Gene