The protein encoded by this gene is a member of the rhomboid family of integral membrane proteins. This family contains proteins that are related to Drosophila rhomboid protein. Members of this family are found in both prokaryotes and eukaryotes and are thought to function as intramembrane serine proteases. The encoded protein is thought to release soluble growth factors by pro... See more...

Aliases for RHBDL2 Gene

Aliases for RHBDL2 Gene

  • Rhomboid Like 2 2 3 5
  • Rhomboid (Veinlet, Drosophila)-Like 2 2 3
  • Rhomboid-Related Protein 2 3 4
  • Rhomboid-Like Protein 2 3 4
  • RRP2 3 4
  • Rhomboid, Veinlet-Like 2 (Drosophila) 2
  • Rhomboid, Veinlet-Like 2 3
  • Rhomboid Protease 2 3
  • EC 3.4.21.105 4

External Ids for RHBDL2 Gene

Previous GeneCards Identifiers for RHBDL2 Gene

  • GC01M039276
  • GC01M038359
  • GC01M038815
  • GC01M038765
  • GC01M039021
  • GC01M039124
  • GC01M039351
  • GC01M037469

Summaries for RHBDL2 Gene

Entrez Gene Summary for RHBDL2 Gene

  • The protein encoded by this gene is a member of the rhomboid family of integral membrane proteins. This family contains proteins that are related to Drosophila rhomboid protein. Members of this family are found in both prokaryotes and eukaryotes and are thought to function as intramembrane serine proteases. The encoded protein is thought to release soluble growth factors by proteolytic cleavage of certain membrane-bound substrates, including ephrin B2 and ephrin B3. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2015]

GeneCards Summary for RHBDL2 Gene

RHBDL2 (Rhomboid Like 2) is a Protein Coding gene. Gene Ontology (GO) annotations related to this gene include serine-type endopeptidase activity. An important paralog of this gene is RHBDL1.

UniProtKB/Swiss-Prot Summary for RHBDL2 Gene

  • Involved in regulated intramembrane proteolysis and the subsequent release of functional polypeptides from their membrane anchors. Known substrate: EFNB3.

Additional gene information for RHBDL2 Gene

No data available for CIViC Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for RHBDL2 Gene

Genomics for RHBDL2 Gene

GeneHancer (GH) Regulatory Elements for RHBDL2 Gene

Promoters and enhancers for RHBDL2 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
GH01J038940 Promoter/Enhancer 1.2 EPDnew Ensembl ENCODE 750.6 +0.4 361 2 ZNF121 SAP130 FOXA2 DRAP1 POLR2A TFAP4 KDM1A FOXA3 ELF1 RHBDL2 NDUFS5 RF00017-169 ENSG00000228436 RF00017-168
GH01J038930 Promoter 0.3 EPDnew 750.4 +11.6 11604 0.1 lnc-AKIRIN1-5 RHBDL2 RNU6-605P RF00026-028 ENSG00000228436 RF00017-168
GH01J038989 Promoter/Enhancer 2.4 EPDnew Ensembl ENCODE CraniofacialAtlas dbSUPER 11 -51.6 -51611 8.3 SP1 SREBF1 SIX5 ZBTB6 FOXA1 SMARCE1 RBPJ POLR2A NR2F6 ATF1 AKIRIN1 NDUFS5 PPIEL PPIE TRIT1 RHBDL2 GJA9 MYCBP UTP11 ENSG00000228436
GH01J038871 Promoter/Enhancer 2 EPDnew Ensembl ENCODE CraniofacialAtlas 5.3 +68.6 68629 2.8 SP1 ZBTB40 POLR2A CREB1 HCFC1 MIXL1 ELF1 L3MBTL2 ZFP41 RAD21 MYCBP ENSG00000273637 lnc-AKIRIN1-15 SF3A3 PPIE PABPC4-AS1 INPP5B AKIRIN1 SNORA55 PPIEL
GH01J039046 Enhancer 1 Ensembl ENCODE 10.7 -106.2 -106161 2.8 SMARCE1 L3MBTL2 RBM39 DACH1 SP1 CBFA2T2 SMARCA4 ZNF384 TRIM24 IKZF1 lnc-NDUFS5-2 NDUFS5 PPIE KIAA0754 MACF1 RHBDL2 PPIEL TRIT1 AKIRIN1 ENSG00000228436
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around RHBDL2 on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the RHBDL2 gene promoter:
  • Bach1
  • MRF-2
  • NF-AT
  • NF-AT1
  • NF-AT2
  • NF-AT3
  • NF-AT4
  • POU2F1
  • POU2F1a
  • Roaz

Genomic Locations for RHBDL2 Gene

Genomic Locations for RHBDL2 Gene
chr1:38,885,806-38,941,830
(GRCh38/hg38)
Size:
56,025 bases
Orientation:
Minus strand
chr1:39,351,479-39,407,471
(GRCh37/hg19)
Size:
55,993 bases
Orientation:
Minus strand

Genomic View for RHBDL2 Gene

Genes around RHBDL2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
RHBDL2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for RHBDL2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for RHBDL2 Gene

Proteins for RHBDL2 Gene

  • Protein details for RHBDL2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9NX52-RHBL2_HUMAN
    Recommended name:
    Rhomboid-related protein 2
    Protein Accession:
    Q9NX52
    Secondary Accessions:
    • B2RNT3
    • B9EH75
    • Q6P175
    • Q8NER8
    • Q96E02

    Protein attributes for RHBDL2 Gene

    Size:
    303 amino acids
    Molecular mass:
    34021 Da
    Quaternary structure:
    No Data Available
    SequenceCaution:
    • Sequence=AAH13103.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305}; Sequence=BAA91168.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305};

    Alternative splice isoforms for RHBDL2 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for RHBDL2 Gene

Post-translational modifications for RHBDL2 Gene

  • Proteolytic processing of the proenzyme produces a N-terminal fragment (NTF) and a C-terminal fragment (CTF). The processing is required for activation of the protease.
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for RHBDL2 Gene

No data available for DME Specific Peptides for RHBDL2 Gene

Domains & Families for RHBDL2 Gene

Gene Families for RHBDL2 Gene

HGNC:
Human Protein Atlas (HPA):
  • Enzymes
  • Predicted membrane proteins

Protein Domains for RHBDL2 Gene

Suggested Antigen Peptide Sequences for RHBDL2 Gene

GenScript: Design optimal peptide antigens:
  • cDNA FLJ40302 fis, clone TESTI2029196, highly similar to Rhomboid-related protein 2 (EC 3.4.21.105) (B3KUN4_HUMAN)
  • Rhomboid-like protein 2 (RHBL2_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q9NX52

UniProtKB/Swiss-Prot:

RHBL2_HUMAN :
  • Belongs to the peptidase S54 family.
Family:
  • Belongs to the peptidase S54 family.
genes like me logo Genes that share domains with RHBDL2: view

Function for RHBDL2 Gene

Molecular function for RHBDL2 Gene

UniProtKB/Swiss-Prot Function:
Involved in regulated intramembrane proteolysis and the subsequent release of functional polypeptides from their membrane anchors. Known substrate: EFNB3.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=Cleaves type-1 transmembrane domains using a catalytic dyad composed of serine and histidine that are contributed by different transmembrane domains.; EC=3.4.21.105; Evidence=. ;.

Enzyme Numbers (IUBMB) for RHBDL2 Gene

Phenotypes From GWAS Catalog for RHBDL2 Gene

Gene Ontology (GO) - Molecular Function for RHBDL2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004252 serine-type endopeptidase activity IDA 19850051
GO:0008233 peptidase activity IEA --
GO:0008236 serine-type peptidase activity IEA --
GO:0016787 hydrolase activity IEA --
genes like me logo Genes that share ontologies with RHBDL2: view
genes like me logo Genes that share phenotypes with RHBDL2: view

Animal Model Products

  • Taconic Biosciences Mouse Models for RHBDL2

CRISPR Products

Clone Products

No data available for Human Phenotype Ontology , Animal Models , Transcription Factor Targets and HOMER Transcription for RHBDL2 Gene

Localization for RHBDL2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for RHBDL2 Gene

Rhomboid-related protein 2, C-terminal fragment: Cell membrane; Multi-pass 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 RHBDL2 gene
Compartment Confidence
plasma membrane 5
peroxisome 1
nucleus 0
endoplasmic reticulum 0
lysosome 0
golgi apparatus 0

Gene Ontology (GO) - Cellular Components for RHBDL2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005886 plasma membrane IEA,IDA 19850051
GO:0016020 membrane IEA --
GO:0016021 integral component of membrane IEA --
genes like me logo Genes that share ontologies with RHBDL2: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for RHBDL2 Gene

Pathways & Interactions for RHBDL2 Gene

PathCards logo

SuperPathways for RHBDL2 Gene

No Data Available

Gene Ontology (GO) - Biological Process for RHBDL2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006508 proteolysis IEA --
genes like me logo Genes that share ontologies with RHBDL2: view

No data available for Pathways by source and SIGNOR curated interactions for RHBDL2 Gene

Drugs & Compounds for RHBDL2 Gene

No Compound Related Data Available

Transcripts for RHBDL2 Gene

mRNA/cDNA for RHBDL2 Gene

CRISPR Products

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for RHBDL2 Gene

No ASD Table

Relevant External Links for RHBDL2 Gene

GeneLoc Exon Structure for
RHBDL2
ECgene alternative splicing isoforms for
RHBDL2

Expression for RHBDL2 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for RHBDL2 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for RHBDL2 Gene

This gene is overexpressed in Esophagus - Mucosa (x5.7) and Brain - Spinal cord (cervical c-1) (x4.8).

Protein differential expression in normal tissues from HIPED for RHBDL2 Gene

This gene is overexpressed in Testis (44.4), Frontal cortex (14.6), and Peripheral blood mononuclear cells (10.0).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for RHBDL2 Gene



Protein tissue co-expression partners for RHBDL2 Gene

NURSA nuclear receptor signaling pathways regulating expression of RHBDL2 Gene:

RHBDL2

SOURCE GeneReport for Unigene cluster for RHBDL2 Gene:

Hs.524626

Evidence on tissue expression from TISSUES for RHBDL2 Gene

  • Adrenal gland(4.1)
genes like me logo Genes that share expression patterns with RHBDL2: view

No data available for mRNA Expression by UniProt/SwissProt and Phenotype-based relationships between genes and organs from Gene ORGANizer for RHBDL2 Gene

Orthologs for RHBDL2 Gene

This gene was present in the common ancestor of animals.

Orthologs for RHBDL2 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia RHBDL2 33 32
  • 99.45 (n)
OneToOne
dog
(Canis familiaris)
Mammalia RHBDL2 33 32
  • 90.32 (n)
OneToOne
cow
(Bos Taurus)
Mammalia RHBDL2 33 32
  • 88.33 (n)
OneToOne
rat
(Rattus norvegicus)
Mammalia Rhbdl2 32
  • 85.12 (n)
mouse
(Mus musculus)
Mammalia Rhbdl2 17 33 32
  • 84.44 (n)
platypus
(Ornithorhynchus anatinus)
Mammalia RHBDL2 33
  • 67 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia RHBDL2 33
  • 58 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia RHBDL2 33
  • 68 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia rhbdl2 32
  • 70.83 (n)
zebrafish
(Danio rerio)
Actinopterygii rhbdl2 33 32
  • 68.77 (n)
OneToOne
zgc55533 32
fruit fly
(Drosophila melanogaster)
Insecta rho-6 33
  • 27 (a)
OneToOne
worm
(Caenorhabditis elegans)
Secernentea rom-1 33 32
  • 51.85 (n)
OneToMany
rom-2 33
  • 19 (a)
OneToMany
sea squirt
(Ciona savignyi)
Ascidiacea -- 33
  • 51 (a)
OneToOne
Species where no ortholog for RHBDL2 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)
  • chicken (Gallus gallus)
  • 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 RHBDL2 Gene

ENSEMBL:
Gene Tree for RHBDL2 (if available)
TreeFam:
Gene Tree for RHBDL2 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for RHBDL2: view image

Paralogs for RHBDL2 Gene

Paralogs for RHBDL2 Gene

(2) SIMAP similar genes for RHBDL2 Gene using alignment to 3 proteins:

  • RHBL2_HUMAN
  • B3KUN4_HUMAN
  • B7Z1Y9_HUMAN
genes like me logo Genes that share paralogs with RHBDL2: view

Variants for RHBDL2 Gene

Sequence variations from dbSNP and Humsavar for RHBDL2 Gene

SNP ID Clin Chr 01 pos Variation AA Info Type
rs1000057518 -- 38,937,332(-) T/C genic_upstream_transcript_variant, intron_variant
rs1000062621 -- 38,917,345(-) A/G intron_variant
rs1000093054 -- 38,902,641(-) C/T intron_variant
rs1000204716 -- 38,905,145(-) A/C intron_variant
rs1000291755 -- 38,940,231(-) G/A genic_upstream_transcript_variant, intron_variant

Structural Variations from Database of Genomic Variants (DGV) for RHBDL2 Gene

Variant ID Type Subtype PubMed ID
esv3585774 CNV loss 21293372
esv3585775 CNV loss 21293372
nsv1145336 CNV deletion 24896259
nsv1160833 CNV duplication 26073780
nsv435884 CNV deletion 17901297
nsv518731 CNV loss 19592680

Variation tolerance for RHBDL2 Gene

Residual Variation Intolerance Score: 65.3% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 10.10; 90.23% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for RHBDL2 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
RHBDL2

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for RHBDL2 Gene

Disorders for RHBDL2 Gene

Additional Disease Information for RHBDL2

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology

No disorders were found for RHBDL2 Gene.

No data available for MalaCards , UniProtKB/Swiss-Prot and Genatlas for RHBDL2 Gene

Publications for RHBDL2 Gene

  1. Intramembrane cleavage of ephrinB3 by the human rhomboid family protease, RHBDL2. (PMID: 15047175) Pascall JC … Brown KD (Biochemical and biophysical research communications 2004) 3 4 23 56
  2. Meta-analyses identify 13 loci associated with age at menopause and highlight DNA repair and immune pathways. (PMID: 22267201) Stolk L … Lunetta KL (Nature genetics 2012) 3 43 56
  3. Inherited genetic variant predisposes to aggressive but not indolent prostate cancer. (PMID: 20080650) Xu J … Isaacs WB (Proceedings of the National Academy of Sciences of the United States of America 2010) 3 43 56
  4. The processing of human rhomboid intramembrane serine protease RHBDL2 is required for its proteolytic activity. (PMID: 19850051) Lei X … Li YM (Journal of molecular biology 2009) 3 4 56
  5. The DNA sequence and biological annotation of human chromosome 1. (PMID: 16710414) Gregory SG … Prigmore E (Nature 2006) 3 4 56

Products for RHBDL2 Gene

Sources for RHBDL2 Gene