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    RTKN2 rhotekin 2 [ Homo sapiens (human) ]

    Gene ID: 219790, updated on 25-Nov-2025
    Official Symbol
    RTKN2provided by HGNC
    Official Full Name
    rhotekin 2provided by HGNC
    Primary source
    HGNC:HGNC:19364
    See related
    Ensembl:ENSG00000182010 MIM:618450; AllianceGenome:HGNC:19364
    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
    PLEKHK1; bA531F24.1
    Summary
    Involved in negative regulation of intrinsic apoptotic signaling pathway; positive regulation of NF-kappaB transcription factor activity; and positive regulation of non-canonical NF-kappaB signal transduction. Located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Jul 2025]
    Expression
    Biased expression in lung (RPKM 32.1) and testis (RPKM 2.2) See more
    Orthologs
    mouse all
    NEW
    Try the new Gene table
    Try the new Transcript table
    See RTKN2 in Genome Data Viewer
    Location:
    10q21.2
    Exon count:
    18
    Annotation release Status Assembly Chr Location
    RS_2025_08 current GRCh38.p14 (GCF_000001405.40) 10 NC_000010.11 (62183900..62268844, complement)
    RS_2025_08 current T2T-CHM13v2.0 (GCF_009914755.1) 10 NC_060934.1 (63049731..63125461, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 10 NC_000010.10 (63952845..64028603, complement)

    Chromosome 10 - NC_000010.11Genomic Context describing neighboring genes Neighboring gene CRISPRi-validated cis-regulatory element chr10.1925 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr10:63541146-63542345 Neighboring gene long intergenic non-protein coding RNA 2625 Neighboring gene Sharpr-MPRA regulatory region 13978 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3397 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3398 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2393 Neighboring gene H3K27ac hESC enhancer GRCh37_chr10:63661148-63661650 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2394 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3399 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3400 Neighboring gene AT-rich interaction domain 5B Neighboring gene NANOG hESC enhancer GRCh37_chr10:63746020-63746682 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3401 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3402 Neighboring gene uncharacterized LOC124902435 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3403 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3404 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3405 Neighboring gene Sharpr-MPRA regulatory region 11943 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3408 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3406 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3407 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr10:63810242-63811441 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3410 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3411 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3412 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2395 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3413 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3414 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2396 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_13587 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3415 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_13605 Neighboring gene NANOG hESC enhancer GRCh37_chr10:64024383-64024884 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2397 Neighboring gene long intergenic non-protein coding RNA 2621 Neighboring gene uncharacterized LOC283045 Neighboring gene RNA, 7SL, cytoplasmic 591, pseudogene Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr10:64143375-64144574 Neighboring gene zinc finger protein 365 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3416 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr10:64224563-64225064

    Go to nucleotide: Graphics FASTA GenBank

    • Project title: Tissue-specific circular RNA induction during human fetal development
    • Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
    • BioProject: PRJNA270632
    • Publication: PMID 26076956
    • Analysis date: Mon Apr 2 22:54:59 2018

    Related articles in PubMed

    1. Mechanisms of resistance to the cytotoxic effects of oxysterols in human leukemic cells. Gregorio-King CC, et al. J Steroid Biochem Mol Biol, 2004 Mar. PMID 15120425
    2. RTKN2 knockdown alleviates the malignancy of breast cancer cells by regulating the Wnt/β-catenin pathway. Zhang X, et al. Sci Rep, 2023 Dec 27. PMID 38155217, Free PMC Article
    3. Knockdown of Rhotekin 2 expression suppresses proliferation and invasion and induces apoptosis in hepatocellular carcinoma cells. Wei W, et al. Mol Med Rep, 2016 Jun. PMID 27081789
    4. Rhotekin 2 silencing inhibits proliferation and induces apoptosis in human osteosarcoma cells. Wang X, et al. Biosci Rep, 2018 Dec 21. PMID 30389712, Free PMC Article
    5. miR-1246 releases RTKN2-dependent resistance to UVB-induced apoptosis in HaCaT cells. Li W, et al. Mol Cell Biochem, 2014 Sep. PMID 24880483

    See all (34) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. CircZFR promotes colorectal cancer progression via stabilizing BCLAF1 and regulating the miR-3127-5p/RTKN2 axis.
      Title: CircZFR promotes colorectal cancer progression via stabilizing BCLAF1 and regulating the miR-3127-5p/RTKN2 axis.
    2. RTKN2 knockdown alleviates the malignancy of breast cancer cells by regulating the Wnt/beta-catenin pathway.
      Title: RTKN2 knockdown alleviates the malignancy of breast cancer cells by regulating the Wnt/β-catenin pathway.
    3. RTKN2 Inhibits the Growth, Migration, Invasion and Glycolysis of Lung Adenocarcinoma Cells by Inactivating the NF-kappaB Signalling Pathway.
      Title: RTKN2 Inhibits the Growth, Migration, Invasion and Glycolysis of Lung Adenocarcinoma Cells by Inactivating the NF-κB Signalling Pathway.
    4. CircRNA hsa_circRNA_104348 promotes hepatocellular carcinoma progression through modulating miR-187-3p/RTKN2 axis and activating Wnt/beta-catenin pathway.
      Title: CircRNA hsa_circRNA_104348 promotes hepatocellular carcinoma progression through modulating miR-187-3p/RTKN2 axis and activating Wnt/β-catenin pathway.
    5. These findings indicate that miR-181 functions as a tumor suppressor and plays a substantial role in inhibiting the tumorigenesis and reversing the metastasis of ovarian cancer through RTKN2-NF-kappaB signaling pathway in vitro
      Title: MicroRNA-181 Functions as an Antioncogene and Mediates NF-κB Pathway by Targeting RTKN2 in Ovarian Cancers.
    6. hese results suggested that RTKN2 is involved in the progression of human osteosarcoma, and may be a potential therapeutic target.
      Title: Rhotekin 2 silencing inhibits proliferation and induces apoptosis in human osteosarcoma cells.
    7. mutations in Pakistani patients with dilated cardiomyopathy rs375563861 (C2orf40), rs143187236 (MYOM3), and rs564181443 (RTKN2) have 3 fold or higher allele frequency in South Asians than in the global populations
      Title: Rare genetic mutations in Pakistani patients with dilated cardiomyopathy.
    8. RTKN2 was overexpressed in HCC tissues. RTKN2 served an important role in tumorigenesis and metastasis of HCC.
      Title: Knockdown of Rhotekin 2 expression suppresses proliferation and invasion and induces apoptosis in hepatocellular carcinoma cells.
    9. miR-1246 promotes UVB-induced apoptosis by downregulating RTKN2 expression and that UVB-upregulated miR-1246 released RTKN2-dependent resistance to UVB-induced apoptosis by targeting RTKN2 post-transcriptionally in keratinocyte cells.
      Title: miR-1246 releases RTKN2-dependent resistance to UVB-induced apoptosis in HaCaT cells.
    10. we identified two gene loci associated with rheumatoid arthritis susceptibility- NFKBIE and RTKN2
      Title: Functional variants in NFKBIE and RTKN2 involved in activation of the NF-κB pathway are associated with rheumatoid arthritis in Japanese.
    Submit: New GeneRIF Correction See all GeneRIFs (12)

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

    Review eQTL and phenotype association data in this region using PheGenI

    EBI GWAS Catalog

    Description
    Functional variants in NFKBIE and RTKN2 involved in activation of the NF-κB pathway are associated with rheumatoid arthritis in Japanese.
    EBI GWAS Catalog
    Genetics of rheumatoid arthritis contributes to biology and drug discovery.
    EBI GWAS Catalog
    Genome-wide association study identifies eight loci associated with blood pressure.
    EBI GWAS Catalog
    Genome-wide association study supports the role of the immunological system and of the neurodevelopmental processes in response to haloperidol treatment.
    EBI GWAS Catalog
    Meta-analysis followed by replication identifies loci in or near CDKN1B, TET3, CD80, DRAM1, and ARID5B as associated with systemic lupus erythematosus in Asians.
    EBI GWAS Catalog

    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Products Interactant Other Gene Complex Source Pubs Description

    Markers

    Homology

    Clone Names

    • DKFZp686J10120

    Gene Ontology Provided by GOA

    Process Evidence Code Pubs
    involved_in hemopoiesis IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    acts_upstream_of_or_within hemopoiesis IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in negative regulation of intrinsic apoptotic signaling pathway IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in positive regulation of NF-kappaB transcription factor activity IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in positive regulation of cell population proliferation IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    acts_upstream_of_or_within positive regulation of cell population proliferation IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in positive regulation of non-canonical NF-kappaB signal transduction IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in signal transduction IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    located_in cytoplasm IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in nucleus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in plasma membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
    Preferred Names
    rhotekin-2
    Names
    PH domain-containing family K member 1
    pleckstrin homology domain-containing family K member 1
    NP_660350.2

    Length

    • 609

    NEW Try the new Transcript table

    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.

    mRNA and Protein(s)

    1. NM_001282941.2 → NP_001269870.1  rhotekin-2 isoform 2

      See identical proteins and their annotated locations for NP_001269870.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (2) lacks several exons and its 3' terminal exon extends past a splice site that is used in variant 1. This results in a novel 3' coding region and 3' UTR, compared to variant 1. It encodes isoform 2 which is shorter and has a distinct C-terminus, compared to isoform 1.
      Source sequence(s)
      AC024597, BC141821, BX113509
      Consensus CDS
      CCDS73140.1
      UniProtKB/Swiss-Prot
      Q8IZC4
      Related
      ENSP00000378678.3, ENST00000395260.3
      Conserved Domains (2) summary
      smart00742
      Location:19 → 74
      Hr1; Rho effector or protein kinase C-related kinase homology region 1 homologues
      pfam08174
      Location:98 → 163
      Anillin; Cell division protein anillin

    2. NM_145307.4 → NP_660350.2  rhotekin-2 isoform 1

      See identical proteins and their annotated locations for NP_660350.2

      Status: VALIDATED

      Description
      Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).
      Source sequence(s)
      AL607150, AY150309, BC141821, BG029885, BX113509
      Consensus CDS
      CCDS7263.1
      UniProtKB/Swiss-Prot
      Q3ZCR1, Q68DZ6, Q8IZC4, Q8N8K1, Q8TAV2
      Related
      ENSP00000362894.3, ENST00000373789.8
      Conserved Domains (4) summary
      smart00742
      Location:19 → 74
      Hr1; Rho effector or protein kinase C-related kinase homology region 1 homologues
      cd13249
      Location:286 → 396
      PH_rhotekin2; Anillin Pleckstrin homology (PH) domain
      pfam00169
      Location:291 → 388
      PH; PH domain
      pfam08174
      Location:98 → 247
      Anillin; Cell division protein anillin

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2025_08

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000010.11 Reference GRCh38.p14 Primary Assembly

      Range
      62183900..62268844 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_017015844.3 → XP_016871333.1  rhotekin-2 isoform X4

    2. XM_011539457.4 → XP_011537759.1  rhotekin-2 isoform X2

      Conserved Domains (4) summary
      smart00742
      Location:19 → 74
      Hr1; Rho effector or protein kinase C-related kinase homology region 1 homologues
      cd13249
      Location:286 → 431
      PH_rhotekin2; Anillin Pleckstrin homology (PH) domain
      pfam00169
      Location:291 → 423
      PH; PH domain
      pfam08174
      Location:98 → 247
      Anillin; Cell division protein anillin

    3. XM_047424717.1 → XP_047280673.1  rhotekin-2 isoform X5

    4. XM_011539460.3 → XP_011537762.1  rhotekin-2 isoform X3

      Conserved Domains (4) summary
      smart00742
      Location:19 → 74
      Hr1; Rho effector or protein kinase C-related kinase homology region 1 homologues
      cd13249
      Location:286 → 431
      PH_rhotekin2; Anillin Pleckstrin homology (PH) domain
      pfam00169
      Location:291 → 423
      PH; PH domain
      pfam08174
      Location:98 → 247
      Anillin; Cell division protein anillin

    5. XM_011539456.3 → XP_011537758.1  rhotekin-2 isoform X1

      Related
      ENSP00000625750.1, ENST00000955691.1
      Conserved Domains (4) summary
      smart00742
      Location:19 → 74
      Hr1; Rho effector or protein kinase C-related kinase homology region 1 homologues
      cd13249
      Location:286 → 431
      PH_rhotekin2; Anillin Pleckstrin homology (PH) domain
      pfam00169
      Location:291 → 423
      PH; PH domain
      pfam08174
      Location:98 → 247
      Anillin; Cell division protein anillin

    6. XM_047424718.1 → XP_047280674.1  rhotekin-2 isoform X6

    RNA

    1. XR_945618.3 RNA Sequence

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060934.1 Alternate T2T-CHM13v2.0

      Range
      63049731..63125461 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q8IZC4.1 GenPept UniProtKB/Swiss-Prot:Q8IZC4

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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