Aliases for RHBDF2 Gene

Aliases for RHBDF2 Gene

  • Rhomboid 5 Homolog 2 2 3 4 5
  • Rhomboid Veinlet-Like Protein 5 3 4
  • Rhomboid Veinlet-Like Protein 6 3 4
  • Inactive Rhomboid Protein 2 3 4
  • Rhomboid Family Member 2 3 4
  • RHBDL6 3 4
  • RHBDL5 3 4
  • IRhom2 3 4
  • Rhomboid, Veinlet-Like 6 (Drosophila) 2
  • Rhomboid 5 Homolog 2 (Drosophila) 2
  • Tylosis With Oesophageal Cancer 2
  • IRHOM2 4
  • TOCG 3
  • TEC 3
  • TOC 3

External Ids for RHBDF2 Gene

Previous HGNC Symbols for RHBDF2 Gene

  • RHBDL6
  • TOC

Previous GeneCards Identifiers for RHBDF2 Gene

  • GC17M071979
  • GC17M074466
  • GC17M069894

Summaries for RHBDF2 Gene

GeneCards Summary for RHBDF2 Gene

RHBDF2 (Rhomboid 5 Homolog 2) is a Protein Coding gene. Diseases associated with RHBDF2 include Tylosis With Esophageal Cancer and Palmoplantar Keratoderma, Nonepidermolytic. Gene Ontology (GO) annotations related to this gene include serine-type endopeptidase activity and growth factor binding. An important paralog of this gene is RHBDF1.

UniProtKB/Swiss-Prot Summary for RHBDF2 Gene

  • Regulates ADAM17 protease, a sheddase of the epidermal growth factor (EGF) receptor ligands and TNF, thereby plays a role in sleep, cell survival, proliferation, migration and inflammation. Does not exhibit any protease activity on its own.

Gene Wiki entry for RHBDF2 Gene

Additional gene information for RHBDF2 Gene

No data available for Entrez Gene Summary , CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for RHBDF2 Gene

Genomics for RHBDF2 Gene

GeneHancer (GH) Regulatory Elements for RHBDF2 Gene

Promoters and enhancers for RHBDF2 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around RHBDF2 on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the RHBDF2 gene promoter:
  • Bach1
  • HEN1
  • Ik-1
  • p300
  • PPAR-gamma1
  • PPAR-gamma2
  • Sp1
  • STAT1
  • STAT1alpha
  • STAT1beta

Genomic Locations for RHBDF2 Gene

Genomic Locations for RHBDF2 Gene
chr17:76,470,891-76,501,790
(GRCh38/hg38)
Size:
30,900 bases
Orientation:
Minus strand
chr17:74,466,973-74,497,872
(GRCh37/hg19)
Size:
30,900 bases
Orientation:
Minus strand

Genomic View for RHBDF2 Gene

Genes around RHBDF2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
RHBDF2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for RHBDF2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for RHBDF2 Gene

Proteins for RHBDF2 Gene

  • Protein details for RHBDF2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q6PJF5-RHDF2_HUMAN
    Recommended name:
    Inactive rhomboid protein 2
    Protein Accession:
    Q6PJF5
    Secondary Accessions:
    • A6NEM3
    • A8K801
    • Q5U607
    • Q5YGQ8
    • Q9H6E9

    Protein attributes for RHBDF2 Gene

    Size:
    856 amino acids
    Molecular mass:
    96686 Da
    Quaternary structure:
    • Interacts with EGF (By similarity). Interacts (via cytoplasmic N-terminus) with FRMD8/iTAP; this interaction leads to mutual protein stabilization (PubMed:29897333, PubMed:29897336). Interacts with ADAM17/TACE (PubMed:29897333, PubMed:29897336).
    SequenceCaution:
    • Sequence=AAH35829.1; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence={ECO:0000305}; Sequence=BAB15310.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305};

    Alternative splice isoforms for RHBDF2 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for RHBDF2 Gene

Post-translational modifications for RHBDF2 Gene

  • Ubiquitination at Lys337
  • Modification sites at PhosphoSitePlus

No data available for DME Specific Peptides for RHBDF2 Gene

Domains & Families for RHBDF2 Gene

Gene Families for RHBDF2 Gene

HGNC:
Human Protein Atlas (HPA):
  • Disease related genes
  • Enzymes
  • Potential drug targets
  • Predicted intracellular proteins
  • Predicted membrane proteins

Protein Domains for RHBDF2 Gene

Suggested Antigen Peptide Sequences for RHBDF2 Gene

GenScript: Design optimal peptide antigens:
  • Rhomboid veinlet-like protein 6 (RHDF2_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q6PJF5

UniProtKB/Swiss-Prot:

RHDF2_HUMAN :
  • Belongs to the peptidase S54 family.
Family:
  • Belongs to the peptidase S54 family.
genes like me logo Genes that share domains with RHBDF2: view

Function for RHBDF2 Gene

Molecular function for RHBDF2 Gene

UniProtKB/Swiss-Prot Function:
Regulates ADAM17 protease, a sheddase of the epidermal growth factor (EGF) receptor ligands and TNF, thereby plays a role in sleep, cell survival, proliferation, migration and inflammation. Does not exhibit any protease activity on its own.

Phenotypes From GWAS Catalog for RHBDF2 Gene

Gene Ontology (GO) - Molecular Function for RHBDF2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004252 NOT serine-type endopeptidase activity IBA 21873635
GO:0005515 protein binding IPI 29897333
GO:0019838 growth factor binding IEA --
genes like me logo Genes that share ontologies with RHBDF2: view
genes like me logo Genes that share phenotypes with RHBDF2: view

Human Phenotype Ontology for RHBDF2 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for RHBDF2 Gene

MGI Knock Outs for RHBDF2:

Animal Model Products

  • Taconic Biosciences Mouse Models for RHBDF2

CRISPR Products

Clone Products

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for RHBDF2 Gene

Localization for RHBDF2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for RHBDF2 Gene

Endoplasmic reticulum membrane; Multi-pass membrane protein. Cell membrane.

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 RHBDF2 gene
Compartment Confidence
plasma membrane 5
endoplasmic reticulum 4
peroxisome 0

Gene Ontology (GO) - Cellular Components for RHBDF2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005783 endoplasmic reticulum IEA --
GO:0005789 endoplasmic reticulum membrane IBA,ISS --
GO:0005886 plasma membrane IEA,IDA 22265016
GO:0016020 membrane IEA --
GO:0016021 integral component of membrane IEA --
genes like me logo Genes that share ontologies with RHBDF2: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for RHBDF2 Gene

Pathways & Interactions for RHBDF2 Gene

PathCards logo

SuperPathways for RHBDF2 Gene

No Data Available

Gene Ontology (GO) - Biological Process for RHBDF2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006508 proteolysis IEA --
GO:0015031 protein transport IEA --
GO:0042058 regulation of epidermal growth factor receptor signaling pathway IBA 21873635
GO:0050708 regulation of protein secretion IBA 21873635
GO:0050709 negative regulation of protein secretion ISS --
genes like me logo Genes that share ontologies with RHBDF2: view

No data available for Pathways by source and SIGNOR curated interactions for RHBDF2 Gene

Drugs & Compounds for RHBDF2 Gene

(4) Drugs for RHBDF2 Gene - From: PharmGKB

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Fentanyl Approved, Illicit, Investigational, Vet_approved Pharma Full agonist, Agonist, Partial agonist 1122
Morphine Approved, Investigational Pharma Full agonist, Agonist, Partial agonist 1307
Oxycodone Approved, Illicit, Investigational Pharma 496
opioids Pharma 0
genes like me logo Genes that share compounds with RHBDF2: view

Transcripts for RHBDF2 Gene

mRNA/cDNA for RHBDF2 Gene

CRISPR Products

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for RHBDF2 Gene

ExUns: 1a · 1b · 1c ^ 2 ^ 3 ^ 4a · 4b · 4c · 4d ^ 5a · 5b ^ 6a · 6b ^ 7a · 7b ^ 8a · 8b · 8c ^ 9 ^ 10 ^ 11 ^ 12a · 12b ^ 13 ^ 14 ^ 15a ·
SP1: - - -
SP2: - -
SP3:
SP4: - - - -
SP5: - - -
SP6: - -
SP7: - - -
SP8: - - - - -
SP9: -
SP10:
SP11:
SP12: - -

ExUns: 15b ^ 16 ^ 17 ^ 18 ^ 19a · 19b ^ 20 ^ 21a · 21b · 21c · 21d
SP1: -
SP2: -
SP3: -
SP4:
SP5:
SP6:
SP7:
SP8:
SP9:
SP10:
SP11:
SP12:

Relevant External Links for RHBDF2 Gene

GeneLoc Exon Structure for
RHBDF2
ECgene alternative splicing isoforms for
RHBDF2

Expression for RHBDF2 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for RHBDF2 Gene

mRNA differential expression in normal tissues according to GTEx for RHBDF2 Gene

This gene is overexpressed in Whole Blood (x7.7).

Protein differential expression in normal tissues from HIPED for RHBDF2 Gene

This gene is overexpressed in Peripheral blood mononuclear cells (24.5), Lung (21.6), and Liver, secretome (12.7).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for RHBDF2 Gene



NURSA nuclear receptor signaling pathways regulating expression of RHBDF2 Gene:

RHBDF2

SOURCE GeneReport for Unigene cluster for RHBDF2 Gene:

Hs.464157

mRNA Expression by UniProt/SwissProt for RHBDF2 Gene:

Q6PJF5-RHDF2_HUMAN
Tissue specificity: Found in the epidermis and esophageal epithelium.

Evidence on tissue expression from TISSUES for RHBDF2 Gene

  • Spleen(4.3)
  • Kidney(4.2)
  • Liver(4.1)
  • Eye(4)
  • Skin(2.3)

Phenotype-based relationships between genes and organs from Gene ORGANizer for RHBDF2 Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
Systems:
  • cardiovascular
  • digestive
  • integumentary
  • nervous
  • skeletal muscle
Regions:
Head and neck:
  • brain
  • ear
  • head
  • mouth
Thorax:
  • esophagus
  • heart
  • heart valve
Abdomen:
  • abdominal wall
  • intestine
  • large intestine
  • liver
  • small intestine
  • stomach
Limb:
  • foot
  • hand
  • lower limb
  • upper limb
General:
  • skin
genes like me logo Genes that share expression patterns with RHBDF2: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery and Protein tissue co-expression partners for RHBDF2 Gene

Orthologs for RHBDF2 Gene

This gene was present in the common ancestor of animals.

Orthologs for RHBDF2 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia RHBDF2 33 32
  • 99.3 (n)
OneToOne
dog
(Canis familiaris)
Mammalia RHBDF2 33 32
  • 91.53 (n)
OneToOne
cow
(Bos Taurus)
Mammalia RHBDF2 33 32
  • 89.18 (n)
OneToOne
mouse
(Mus musculus)
Mammalia Rhbdf2 17 33 32
  • 88.24 (n)
rat
(Rattus norvegicus)
Mammalia Rhbdf2 32
  • 87.5 (n)
oppossum
(Monodelphis domestica)
Mammalia RHBDF2 33
  • 85 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia RHBDF2 33
  • 79 (a)
OneToOne
chicken
(Gallus gallus)
Aves RHBDF2 33 32
  • 77.71 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia RHBDF2 33
  • 75 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia rhbdf2 32
  • 71.91 (n)
zebrafish
(Danio rerio)
Actinopterygii si:ch211-218l14.9 33
  • 54 (a)
ManyToMany
fruit fly
(Drosophila melanogaster)
Insecta rho-5 33
  • 13 (a)
OneToMany
worm
(Caenorhabditis elegans)
Secernentea rom-4 33 32
  • 50.23 (n)
ManyToMany
rom-3 33
  • 21 (a)
ManyToMany
sea squirt
(Ciona savignyi)
Ascidiacea -- 33
  • 58 (a)
ManyToMany
-- 33
  • 51 (a)
ManyToMany
Species where no ortholog for RHBDF2 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya 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)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • 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 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)

Evolution for RHBDF2 Gene

ENSEMBL:
Gene Tree for RHBDF2 (if available)
TreeFam:
Gene Tree for RHBDF2 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for RHBDF2: view image

Paralogs for RHBDF2 Gene

Paralogs for RHBDF2 Gene

(2) SIMAP similar genes for RHBDF2 Gene using alignment to 11 proteins:

  • RHDF2_HUMAN
  • K7EIY3_HUMAN
  • K7EJ10_HUMAN
  • K7EJD6_HUMAN
  • K7EKA3_HUMAN
  • K7EKI1_HUMAN
  • K7ELA9_HUMAN
  • K7EPN8_HUMAN
  • K7EPV3_HUMAN
  • K7EQ53_HUMAN
  • K7EQT5_HUMAN
genes like me logo Genes that share paralogs with RHBDF2: view

Variants for RHBDF2 Gene

Sequence variations from dbSNP and Humsavar for RHBDF2 Gene

SNP ID Clin Chr 17 pos Variation AA Info Type
rs111924263 benign, Howel-Evans syndrome 76,471,053(-) G/A/C 3_prime_UTR_variant, non_coding_transcript_variant
rs114238341 likely-benign, Howel-Evans syndrome 76,479,273(-) C/A/T coding_sequence_variant, missense_variant, non_coding_transcript_variant
rs114994065 likely-benign, Howel-Evans syndrome 76,473,827(-) A/G intron_variant
rs115094923 likely-benign, Howel-Evans syndrome 76,471,852(-) G/A coding_sequence_variant, non_coding_transcript_variant, synonymous_variant
rs11553544 likely-benign, Howel-Evans syndrome 76,471,122(-) C/T 3_prime_UTR_variant, non_coding_transcript_variant

Structural Variations from Database of Genomic Variants (DGV) for RHBDF2 Gene

Variant ID Type Subtype PubMed ID
nsv1058263 CNV gain 25217958
nsv525148 CNV loss 19592680
nsv833549 CNV gain 17160897

Variation tolerance for RHBDF2 Gene

Residual Variation Intolerance Score: 45.4% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 4.99; 68.31% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for RHBDF2 Gene

Human Gene Mutation Database (HGMD)
RHBDF2
SNPedia medical, phenotypic, and genealogical associations of SNPs for
RHBDF2

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for RHBDF2 Gene

Disorders for RHBDF2 Gene

MalaCards: The human disease database

(7) MalaCards diseases for RHBDF2 Gene - From: HGMD, OMIM, ClinVar, GTR, Orphanet, DISEASES, and GeneCards

- elite association - COSMIC cancer census association via MalaCards

UniProtKB/Swiss-Prot

RHDF2_HUMAN
  • Tylosis with esophageal cancer (TOC) [MIM:148500]: An autosomal dominant syndrome characterized by diffuse palmoplantar keratoderma, oral leukokeratosis, and a high lifetime risk of esophageal cancer. {ECO:0000269 PubMed:22265016}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Additional Disease Information for RHBDF2

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with RHBDF2: view

No data available for Genatlas for RHBDF2 Gene

Publications for RHBDF2 Gene

  1. RHBDF2 mutations are associated with tylosis, a familial esophageal cancer syndrome. (PMID: 22265016) Blaydon DC … Kelsell DP (American journal of human genetics 2012) 2 3 4 56
  2. FRMD8 promotes inflammatory and growth factor signalling by stabilising the iRhom/ADAM17 sheddase complex. (PMID: 29897336) Künzel U … Freeman M (eLife 2018) 3 4 56
  3. iTAP, a novel iRhom interactor, controls TNF secretion by policing the stability of iRhom/TACE. (PMID: 29897333) Oikonomidi I … Adrain C (eLife 2018) 3 4 56
  4. Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study. (PMID: 20628086) Bailey SD … DREAM investigators (Diabetes care 2010) 3 43 56
  5. Complete sequencing and characterization of 21,243 full-length human cDNAs. (PMID: 14702039) Ota T … Sugano S (Nature genetics 2004) 3 4 56

Products for RHBDF2 Gene

Sources for RHBDF2 Gene