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RHBDF2 rhomboid 5 homolog 2 [ Homo sapiens (human) ]

Gene ID: 79651, updated on 16-Apr-2024

Summary

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Official Symbol
RHBDF2provided by HGNC
Official Full Name
rhomboid 5 homolog 2provided by HGNC
Primary source
HGNC:HGNC:20788
See related
Ensembl:ENSG00000129667 MIM:614404; AllianceGenome:HGNC:20788
Gene type
protein coding
RefSeq status
VALIDATED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
TOC; TOCG; RHBDL5; RHBDL6; iRhom2
Summary
Predicted to enable protein transporter activity. Predicted to be involved in negative regulation of protein secretion and regulation of epidermal growth factor receptor signaling pathway. Located in plasma membrane. Implicated in palmoplantar keratoderma-esophageal carcinoma syndrome. [provided by Alliance of Genome Resources, Apr 2022]
Expression
Broad expression in spleen (RPKM 8.7), appendix (RPKM 7.3) and 25 other tissues See more
Orthologs
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Genomic context

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Location:
17q25.1
Exon count:
21
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 17 NC_000017.11 (76470893..76501427, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 17 NC_060941.1 (77367469..77398038, complement)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 17 NC_000017.10 (74466975..74497509, complement)

Chromosome 17 - NC_000017.11Genomic Context describing neighboring genes Neighboring gene ubiquitin conjugating enzyme E2 O Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:74429943-74430443 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:74432809-74433310 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:74437133-74437650 Neighboring gene ribosomal protein L7 pseudogene 49 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 12806 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 12807 Neighboring gene ReSE screen-validated silencer GRCh37_chr17:74449240-74449408 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9016 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 12808 Neighboring gene aralkylamine N-acetyltransferase Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:74469380-74469890 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9018 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9019 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9020 Neighboring gene Sharpr-MPRA regulatory region 10531 Neighboring gene MPRA-validated peak3008 silencer Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:74487839-74488704 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr17:74496763-74497432 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 12809 Neighboring gene ReSE screen-validated silencer GRCh37_chr17:74506318-74506528 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr17:74508911-74509513 Neighboring gene ReSE screen-validated silencer GRCh37_chr17:74518115-74518272 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 12810 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:74525989-74526722 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr17:74526723-74527456 Neighboring gene cytoglobin Neighboring gene photoreceptor disc component Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:74543392-74543895 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 12811 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr17:74553466-74554266 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr17:74554267-74555068 Neighboring gene small nucleolar RNA, C/D box 1C Neighboring gene small nucleolar RNA host gene 16

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. RHBDF2 is correlated with immune infiltrates in hepatocellular carcinoma and may have potential as a biomarker. Gong H, et al. FEBS Open Bio, 2023 May. PMID 36943228, Free PMC Article
  2. iRhom2 regulates ERBB signalling to promote KRAS-driven tumour growth of lung cancer cells. Sieber B, et al. J Cell Sci, 2022 Sep 1. PMID 35971826, Free PMC Article
  3. The Threshold Effect: Lipopolysaccharide-Induced Inflammatory Responses in Primary Macrophages Are Differentially Regulated in an iRhom2-Dependent Manner. Skurski J, et al. Front Cell Infect Microbiol, 2020. PMID 33585287, Free PMC Article
  4. iRhom2 in the pathogenesis of oral squamous cell carcinoma. Agwae ME, et al. Mol Biol Rep, 2020 May. PMID 32236893, Free PMC Article
  5. The molecular, cellular and pathophysiological roles of iRhom pseudoproteases. Dulloo I, et al. Open Biol, 2019 Mar 29. PMID 30890028, Free PMC Article

See all (48) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. iRhom2 regulates ectodomain shedding and surface expression of the major histocompatibility complex (MHC) class I.
    Title: iRhom2 regulates ectodomain shedding and surface expression of the major histocompatibility complex (MHC) class I.
  2. Cleavage of the pseudoprotease iRhom2 by the signal peptidase complex reveals an ER-to-nucleus signaling pathway.
    Title: Cleavage of the pseudoprotease iRhom2 by the signal peptidase complex reveals an ER-to-nucleus signaling pathway.
  3. Palmitoyltransferase ZDHHC3 Aggravates Nonalcoholic Steatohepatitis by Targeting S-Palmitoylated IRHOM2.
    Title: Palmitoyltransferase ZDHHC3 Aggravates Nonalcoholic Steatohepatitis by Targeting S-Palmitoylated IRHOM2.
  4. EGFR stimulation enables IL-6 trans-signalling via iRhom2-dependent ADAM17 activation in mammary epithelial cells.
    Title: EGFR stimulation enables IL-6 trans-signalling via iRhom2-dependent ADAM17 activation in mammary epithelial cells.
  5. RHBDF2 is correlated with immune infiltrates in hepatocellular carcinoma and may have potential as a biomarker.
    Title: RHBDF2 is correlated with immune infiltrates in hepatocellular carcinoma and may have potential as a biomarker.
  6. iRhom2 regulates ERBB signalling to promote KRAS-driven tumour growth of lung cancer cells.
    Title: iRhom2 regulates ERBB signalling to promote KRAS-driven tumour growth of lung cancer cells.
  7. Deficiency in Inactive Rhomboid Protein2 (iRhom2) Alleviates Alcoholic Liver Fibrosis by Suppressing Inflammation and Oxidative Stress.
    Title: Deficiency in Inactive Rhomboid Protein2 (iRhom2) Alleviates Alcoholic Liver Fibrosis by Suppressing Inflammation and Oxidative Stress.
  8. Attenuation of Excess TNF-alpha Release in Crohn's Disease by Silencing of iRHOMs 1/2 and the Restoration of TGF-beta Mediated Immunosuppression Through Modulation of TACE Trafficking.
    Title: Attenuation of Excess TNF-α Release in Crohn's Disease by Silencing of iRHOMs 1/2 and the Restoration of TGF-β Mediated Immunosuppression Through Modulation of TACE Trafficking.
  9. Inflammatory activation of surface molecule shedding by upregulation of the pseudoprotease iRhom2 in colon epithelial cells.
    Title: Inflammatory activation of surface molecule shedding by upregulation of the pseudoprotease iRhom2 in colon epithelial cells.
  10. iRhom2 Promotes Hepatic Steatosis by Activating MAP3K7-Dependent Pathway.
    Title: iRhom2 Promotes Hepatic Steatosis by Activating MAP3K7-Dependent Pathway.
Submit: New GeneRIF Correction See all GeneRIFs (30)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description Tests
Palmoplantar keratoderma-esophageal carcinoma syndrome
MedGen: C1835664 OMIM: 148500 GeneReviews: Not available
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Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • FLJ22341

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables growth factor binding IEA
Inferred from Electronic Annotation
more info
  
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein transporter activity TAS
Traceable Author Statement
more info
  
NOT enables serine-type endopeptidase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
Process Evidence Code Pubs
involved_in negative regulation of inflammatory response to antigenic stimulus TAS
Traceable Author Statement
more info
  
involved_in negative regulation of protein secretion ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in protein localization to plasma membrane IEA
Inferred from Electronic Annotation
more info
  
involved_in protein transport IEA
Inferred from Electronic Annotation
more info
  
involved_in regulation of epidermal growth factor receptor signaling pathway IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in regulation of protein secretion IBA
Inferred from Biological aspect of Ancestor
more info
  
Component Evidence Code Pubs
located_in Golgi lumen TAS
Traceable Author Statement
more info
  
is_active_in endoplasmic reticulum membrane IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in endoplasmic reticulum membrane ISS
Inferred from Sequence or Structural Similarity
more info
  
located_in endoplasmic reticulum membrane TAS
Traceable Author Statement
more info
  
located_in plasma membrane IDA
Inferred from Direct Assay
more info
 PubMed 

General protein information

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Preferred Names
inactive rhomboid protein 2
Names
rhomboid family member 2
rhomboid veinlet-like protein 5
rhomboid veinlet-like protein 6

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_032852.1 RefSeqGene

    Range
    5001..35535
    Download
    GenBank, FASTA, Sequence Viewer (Graphics), LRG_532

mRNA and Protein(s)

  1. NM_001005498.4 → NP_001005498.2  inactive rhomboid protein 2 isoform 2

    See identical proteins and their annotated locations for NP_001005498.2

    Status: VALIDATED

    Description
    Transcript Variant: This variant (2) differs in the 5' UTR and uses an alternate, in frame splice site in the 5' coding region compared to isoform 1. This results in a shorter protein (isoform 2), compared to isoform 1.
    Source sequence(s)
    AC015802
    Consensus CDS
    CCDS32744.1
    UniProtKB/Swiss-Prot
    Q6PJF5
    Related
    ENSP00000501790.1, ENST00000675367.1
    Conserved Domains (3) summary
    pfam01694
    Location:622 → 762
    Rhomboid; Rhomboid family
    pfam12595
    Location:99 → 305
    Rhomboid_SP; Rhomboid serine protease
    cl21488
    Location:716 → 812
    ECF_trnsprt; ECF transporter, substrate-specific component

  2. NM_001376228.1 → NP_001363157.1  inactive rhomboid protein 2 isoform 2

    Status: VALIDATED

    Source sequence(s)
    AC015802
    Consensus CDS
    CCDS32744.1
    Conserved Domains (3) summary
    pfam01694
    Location:622 → 762
    Rhomboid; Rhomboid family
    pfam12595
    Location:99 → 305
    Rhomboid_SP; Rhomboid serine protease
    cl21488
    Location:716 → 812
    ECF_trnsprt; ECF transporter, substrate-specific component

  3. NM_001376229.1 → NP_001363158.1  inactive rhomboid protein 2 isoform 2

    Status: VALIDATED

    Source sequence(s)
    AC015802
    Consensus CDS
    CCDS32744.1
    Conserved Domains (3) summary
    pfam01694
    Location:622 → 762
    Rhomboid; Rhomboid family
    pfam12595
    Location:99 → 305
    Rhomboid_SP; Rhomboid serine protease
    cl21488
    Location:716 → 812
    ECF_trnsprt; ECF transporter, substrate-specific component

  4. NM_001376230.1 → NP_001363159.1  inactive rhomboid protein 2 isoform 2

    Status: VALIDATED

    Source sequence(s)
    AC015802
    Consensus CDS
    CCDS32744.1
    Conserved Domains (3) summary
    pfam01694
    Location:622 → 762
    Rhomboid; Rhomboid family
    pfam12595
    Location:99 → 305
    Rhomboid_SP; Rhomboid serine protease
    cl21488
    Location:716 → 812
    ECF_trnsprt; ECF transporter, substrate-specific component

  5. NM_024599.5 → NP_078875.4  inactive rhomboid protein 2 isoform 1

    See identical proteins and their annotated locations for NP_078875.4

    Status: VALIDATED

    Description
    Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).
    Source sequence(s)
    AC015802, AK292135, AL833680, BC035829, DC337840, DC348660
    Consensus CDS
    CCDS32743.1
    UniProtKB/Swiss-Prot
    A6NEM3, A8K801, Q5U607, Q5YGQ8, Q6PJF5, Q9H6E9
    Related
    ENSP00000322775.3, ENST00000313080.8
    Conserved Domains (3) summary
    pfam01694
    Location:648 → 789
    Rhomboid; Rhomboid family
    pfam12595
    Location:128 → 334
    Rhomboid_SP; Rhomboid serine protease
    cl19823
    Location:748 → 832
    GtrA; GtrA-like protein

RNA

  1. NR_164785.1 RNA Sequence

    Status: VALIDATED

    Source sequence(s)
    AC015802

  2. NR_164786.1 RNA Sequence

    Status: VALIDATED

    Source sequence(s)
    AC015802

  3. NR_164787.1 RNA Sequence

    Status: VALIDATED

    Source sequence(s)
    AC015802

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000017.11 Reference GRCh38.p14 Primary Assembly

    Range
    76470893..76501427 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_011525251.3 → XP_011523553.1  inactive rhomboid protein 2 isoform X2

    See identical proteins and their annotated locations for XP_011523553.1

    UniProtKB/Swiss-Prot
    Q6PJF5
    Conserved Domains (3) summary
    pfam01694
    Location:622 → 762
    Rhomboid; Rhomboid family
    pfam12595
    Location:99 → 305
    Rhomboid_SP; Rhomboid serine protease
    cl21488
    Location:716 → 812
    ECF_trnsprt; ECF transporter, substrate-specific component

  2. XM_047436744.1 → XP_047292700.1  inactive rhomboid protein 2 isoform X1

    UniProtKB/Swiss-Prot
    A6NEM3, A8K801, Q5U607, Q5YGQ8, Q6PJF5, Q9H6E9

  3. XM_011525250.3 → XP_011523552.1  inactive rhomboid protein 2 isoform X2

    See identical proteins and their annotated locations for XP_011523552.1

    UniProtKB/Swiss-Prot
    Q6PJF5
    Conserved Domains (3) summary
    pfam01694
    Location:622 → 762
    Rhomboid; Rhomboid family
    pfam12595
    Location:99 → 305
    Rhomboid_SP; Rhomboid serine protease
    cl21488
    Location:716 → 812
    ECF_trnsprt; ECF transporter, substrate-specific component

  4. XM_047436745.1 → XP_047292701.1  inactive rhomboid protein 2 isoform X1

    UniProtKB/Swiss-Prot
    A6NEM3, A8K801, Q5U607, Q5YGQ8, Q6PJF5, Q9H6E9

  5. XM_047436752.1 → XP_047292708.1  inactive rhomboid protein 2 isoform X2

  6. XM_047436747.1 → XP_047292703.1  inactive rhomboid protein 2 isoform X1

    UniProtKB/Swiss-Prot
    A6NEM3, A8K801, Q5U607, Q5YGQ8, Q6PJF5, Q9H6E9

  7. XM_005257669.4 → XP_005257726.1  inactive rhomboid protein 2 isoform X1

    See identical proteins and their annotated locations for XP_005257726.1

    UniProtKB/Swiss-Prot
    A6NEM3, A8K801, Q5U607, Q5YGQ8, Q6PJF5, Q9H6E9
    Conserved Domains (3) summary
    pfam01694
    Location:648 → 789
    Rhomboid; Rhomboid family
    pfam12595
    Location:128 → 334
    Rhomboid_SP; Rhomboid serine protease
    cl19823
    Location:748 → 832
    GtrA; GtrA-like protein

  8. XM_047436751.1 → XP_047292707.1  inactive rhomboid protein 2 isoform X2

  9. XM_047436746.1 → XP_047292702.1  inactive rhomboid protein 2 isoform X1

    UniProtKB/Swiss-Prot
    A6NEM3, A8K801, Q5U607, Q5YGQ8, Q6PJF5, Q9H6E9

  10. XM_047436755.1 → XP_047292711.1  inactive rhomboid protein 2 isoform X2

  11. XM_047436743.1 → XP_047292699.1  inactive rhomboid protein 2 isoform X1

    UniProtKB/Swiss-Prot
    A6NEM3, A8K801, Q5U607, Q5YGQ8, Q6PJF5, Q9H6E9

  12. XM_047436756.1 → XP_047292712.1  inactive rhomboid protein 2 isoform X2

  13. XM_047436750.1 → XP_047292706.1  inactive rhomboid protein 2 isoform X1

    UniProtKB/Swiss-Prot
    A6NEM3, A8K801, Q5U607, Q5YGQ8, Q6PJF5, Q9H6E9

  14. XM_011525249.3 → XP_011523551.1  inactive rhomboid protein 2 isoform X2

    See identical proteins and their annotated locations for XP_011523551.1

    UniProtKB/Swiss-Prot
    Q6PJF5
    Conserved Domains (3) summary
    pfam01694
    Location:622 → 762
    Rhomboid; Rhomboid family
    pfam12595
    Location:99 → 305
    Rhomboid_SP; Rhomboid serine protease
    cl21488
    Location:716 → 812
    ECF_trnsprt; ECF transporter, substrate-specific component

  15. XM_047436749.1 → XP_047292705.1  inactive rhomboid protein 2 isoform X1

    UniProtKB/Swiss-Prot
    A6NEM3, A8K801, Q5U607, Q5YGQ8, Q6PJF5, Q9H6E9

  16. XM_047436753.1 → XP_047292709.1  inactive rhomboid protein 2 isoform X2

  17. XM_047436748.1 → XP_047292704.1  inactive rhomboid protein 2 isoform X1

    UniProtKB/Swiss-Prot
    A6NEM3, A8K801, Q5U607, Q5YGQ8, Q6PJF5, Q9H6E9

  18. XM_047436757.1 → XP_047292713.1  inactive rhomboid protein 2 isoform X3

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060941.1 Alternate T2T-CHM13v2.0

    Range
    77367469..77398038 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054317223.1 → XP_054173198.1  inactive rhomboid protein 2 isoform X2

  2. XM_054317224.1 → XP_054173199.1  inactive rhomboid protein 2 isoform X2

  3. XM_054317222.1 → XP_054173197.1  inactive rhomboid protein 2 isoform X2

  4. XM_054317210.1 → XP_054173185.1  inactive rhomboid protein 2 isoform X1

  5. XM_054317217.1 → XP_054173192.1  inactive rhomboid protein 2 isoform X2

  6. XM_054317211.1 → XP_054173186.1  inactive rhomboid protein 2 isoform X1

  7. XM_054317220.1 → XP_054173195.1  inactive rhomboid protein 2 isoform X2

  8. XM_054317214.1 → XP_054173189.1  inactive rhomboid protein 2 isoform X1

  9. XM_054317213.1 → XP_054173188.1  inactive rhomboid protein 2 isoform X1

  10. XM_054317219.1 → XP_054173194.1  inactive rhomboid protein 2 isoform X2

  11. XM_054317212.1 → XP_054173187.1  inactive rhomboid protein 2 isoform X1

  12. XM_054317209.1 → XP_054173184.1  inactive rhomboid protein 2 isoform X1

  13. XM_054317218.1 → XP_054173193.1  inactive rhomboid protein 2 isoform X2

  14. XM_054317216.1 → XP_054173191.1  inactive rhomboid protein 2 isoform X1

  15. XM_054317221.1 → XP_054173196.1  inactive rhomboid protein 2 isoform X2

  16. XM_054317215.1 → XP_054173190.1  inactive rhomboid protein 2 isoform X1

  17. XM_054317225.1 → XP_054173200.1  inactive rhomboid protein 2 isoform X3

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q6PJF5.2 GenPept UniProtKB/Swiss-Prot:Q6PJF5

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