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    DMXL2 Dmx like 2 [ Homo sapiens (human) ]

    Gene ID: 23312, updated on 10-Dec-2024

    Summary

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    Official Symbol
    DMXL2provided by HGNC
    Official Full Name
    Dmx like 2provided by HGNC
    Primary source
    HGNC:HGNC:2938
    See related
    Ensembl:ENSG00000104093 MIM:612186; AllianceGenome:HGNC:2938
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    RC3; DEE81; PEPNS; DFNA71; EIEE81
    Summary
    This gene encodes a protein with 12 WD domains. Proteins with WD domains are involved in many functions including participation in signal transduction pathways. Participation of the encoded protein in regulation of the Notch signaling pathway has been demonstrated in vitro using several human cell lines (PMID:20810660). A gene encoding a similar protein is located on chromosome 5. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2011]
    Expression
    Ubiquitous expression in brain (RPKM 8.0), bone marrow (RPKM 7.9) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See DMXL2 in Genome Data Viewer
    Location:
    15q21.2
    Exon count:
    47
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 15 NC_000015.10 (51447791..51622771, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 15 NC_060939.1 (49255566..49430224, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 15 NC_000015.9 (51739988..51914968, complement)

    Chromosome 15 - NC_000015.10Genomic Context describing neighboring genes Neighboring gene cytochrome P450 family 19 subfamily A member 1 Neighboring gene uncharacterized LOC112268146 Neighboring gene ReSE screen-validated silencer GRCh37_chr15:51621311-51621511 Neighboring gene CYP19A1 promoter I.1 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr15:51678296-51678796 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr15:51682661-51683516 Neighboring gene gliomedin Neighboring gene MED14-independent group 3 enhancer GRCh37_chr15:51741640-51742839 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr15:51861014-51861520 Neighboring gene Sharpr-MPRA regulatory region 1269 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9404 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 6432 Neighboring gene uncharacterized LOC105370816 Neighboring gene CRISPRi-validated cis-regulatory element chr15.1149 Neighboring gene CRISPRi-validated cis-regulatory element chr15.1151 Neighboring gene Sharpr-MPRA regulatory region 12802 Neighboring gene secretogranin III

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Bibliography

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    Related articles in PubMed

    1. DMXL2 drives epithelial to mesenchymal transition in hormonal therapy resistant breast cancer through Notch hyper-activation. Faronato M, et al. Oncotarget, 2015 Sep 8. PMID 26093085, Free PMC Article
    2. Rare copy number variations affecting the synaptic gene DMXL2 in neurodevelopmental disorders. Costain G, et al. J Neurodev Disord, 2019 Feb 7. PMID 30732576, Free PMC Article
    3. Biallelic DMXL2 mutations impair autophagy and cause Ohtahara syndrome with progressive course. Esposito A, et al. Brain, 2019 Dec 1. PMID 31688942
    4. A novel variant in DMXL2 gene is associated with autosomal dominant non-syndromic hearing impairment (DFNA71) in a Cameroonian family. Wonkam-Tingang E, et al. Exp Biol Med (Maywood), 2021 Jul. PMID 33715530, Free PMC Article
    5. Rabconnectin-3 is a functional regulator of mammalian Notch signaling. Sethi N, et al. J Biol Chem, 2010 Nov 5. PMID 20810660, Free PMC Article

    See all (41) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. A novel variant in DMXL2 gene is associated with autosomal dominant non-syndromic hearing impairment (DFNA71) in a Cameroonian family.
      Title: A novel variant in DMXL2 gene is associated with autosomal dominant non-syndromic hearing impairment (DFNA71) in a Cameroonian family.
    2. Disruption of DMXL2 may predispose to NDDs including autism spectrum disorder.
      Title: Rare copy number variations affecting the synaptic gene DMXL2 in neurodevelopmental disorders.
    3. Impaired lysosomal function and autophagy caused by biallelic DMXL2 mutations affect neuronal development and synapse formation and result in Ohtahara syndrome with profound developmental impairment and reduced life expectancy.
      Title: Biallelic DMXL2 mutations impair autophagy and cause Ohtahara syndrome with progressive course.
    4. Data indicated that the p.Arg2417His variant in DMXL2 is associated with dominant, nonsyndromic hearing loss and suggested an important role of DMXL2 in inner ear function.
      Title: A dominant variant in DMXL2 is linked to nonsyndromic hearing loss.
    5. authors demonstrate that DMXL2 is a transmembrane protein with a potential extra-cellular domain. These findings identify DMXL2 as a novel, functional biomarker for ERalpha positive breast cancer.
      Title: DMXL2 drives epithelial to mesenchymal transition in hormonal therapy resistant breast cancer through Notch hyper-activation.
    6. Haploinsufficiency of Dmxl2, encoding a synaptic protein, causes infertility associated with a loss of GnRH neurons in humans and mice.
      Title: Haploinsufficiency of Dmxl2, encoding a synaptic protein, causes infertility associated with a loss of GnRH neurons in mouse.
    7. an important role for Rabconnectin-3 and V-ATPase activity in the Notch signaling pathway in mammalian cells.
      Title: Rabconnectin-3 is a functional regulator of mammalian Notch signaling.
    8. Observational study of gene-disease association. (HuGE Navigator)
      Title: Gene variants associated with ischemic stroke: the cardiovascular health study.
    Submit: New GeneRIF Correction

    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
    Developmental and epileptic encephalopathy, 81
    MedGen: C5231450 OMIM: 618663 GeneReviews: Not available
    		Compare labs
    Hearing loss, autosomal dominant 71
    MedGen: C4539881 OMIM: 617605 GeneReviews: Not available
    		Compare labs
    Polyendocrine-polyneuropathy syndrome
    MedGen: C4015261 OMIM: 616113 GeneReviews: Not available
    		Compare labs

    Copy number response

    Description
    Copy number response
    Haploinsufficency

    No evidence available (Last evaluated 2012-04-04)

    ClinGen Genome Curation Page
    Triplosensitivity

    No evidence available (Last evaluated 2012-04-04)

    ClinGen Genome Curation Page

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • FLJ26672, KIAA0856

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables small GTPase binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in vacuolar acidification IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Component Evidence Code Pubs
    part_of RAVE complex IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in extracellular space HDA PubMed 
    located_in neuronal dense core vesicle IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in synaptic vesicle IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in synaptic vesicle membrane IEA
    Inferred from Electronic Annotation
    more info
    		  

    General protein information

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    Preferred Names
    dmX-like protein 2
    Names
    rabconnectin-3

    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_017155.1 RefSeqGene

      Range
      5000..179980
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001174116.3 → NP_001167587.1  dmX-like protein 2 isoform 1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes isoform 1.
      Source sequence(s)
      AC020892, AC066613
      Consensus CDS
      CCDS53946.1
      UniProtKB/Swiss-Prot
      Q8TDJ6
      Related
      ENSP00000441858.2, ENST00000543779.6
      Conserved Domains (4) summary
      COG2319
      Location:2778 → 2984
      WD40; WD40 repeat [General function prediction only]
      pfam12234
      Location:1171 → 1902
      Rav1p_C; RAVE protein 1 C terminal
      sd00039
      Location:2811 → 2851
      7WD40; WD40 repeat [structural motif]
      cl02567
      Location:2767 → 3019
      WD40; WD40 domain, found in a number of eukaryotic proteins that cover a wide variety of functions including adaptor/regulatory modules in signal transduction, pre-mRNA processing and cytoskeleton assembly; typically contains a GH dipeptide 11-24 residues from ...

    2. NM_001174117.3 → NP_001167588.1  dmX-like protein 2 isoform 3

      See identical proteins and their annotated locations for NP_001167588.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) lacks two coding exons compared to variant 1. The resulting protein (isoform 3) is shorter but has the same N- and C- termini compared to isoform 1.
      Source sequence(s)
      AC020892, AC066613
      Consensus CDS
      CCDS53945.1
      UniProtKB/Swiss-Prot
      Q8TDJ6
      Related
      ENSP00000400855.3, ENST00000449909.7
      Conserved Domains (4) summary
      COG2319
      Location:2135 → 2347
      WD40; WD40 repeat [General function prediction only]
      pfam12234
      Location:923 → 1266
      Rav1p_C; RAVE protein 1 C terminal
      sd00039
      Location:2174 → 2214
      7WD40; WD40 repeat [structural motif]
      cl02567
      Location:2130 → 2382
      WD40; WD40 domain, found in a number of eukaryotic proteins that cover a wide variety of functions including adaptor/regulatory modules in signal transduction, pre-mRNA processing and cytoskeleton assembly; typically contains a GH dipeptide 11-24 residues from ...

    3. NM_001378457.1 → NP_001365386.1  dmX-like protein 2 isoform 4

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) represents the longest transcript and encodes the longest isoform (4).
      Source sequence(s)
      AC020892, AC066613
      Consensus CDS
      CCDS91998.1
      UniProtKB/TrEMBL
      H0YLM8
      Related
      ENSP00000453267.2, ENST00000560891.6
      Conserved Domains (3) summary
      sd00039
      Location:2832 → 2872
      7WD40; WD40 repeat [structural motif]
      pfam12234
      Location:1171 → 1902
      Rav1p_C; RAVE protein 1 C terminal
      cl29593
      Location:2788 → 3040
      WD40; WD40 domain, found in a number of eukaryotic proteins that cover a wide variety of functions including adaptor/regulatory modules in signal transduction, pre-mRNA processing and cytoskeleton assembly; typically contains a GH dipeptide 11-24 residues from ...

    4. NM_001378458.1 → NP_001365387.1  dmX-like protein 2 isoform 5

      Status: REVIEWED

      Source sequence(s)
      AC020892, AC066613
      Conserved Domains (3) summary
      sd00039
      Location:2831 → 2871
      7WD40; WD40 repeat [structural motif]
      pfam12234
      Location:1171 → 1902
      Rav1p_C; RAVE protein 1 C terminal
      cl29593
      Location:2787 → 3039
      WD40; WD40 domain, found in a number of eukaryotic proteins that cover a wide variety of functions including adaptor/regulatory modules in signal transduction, pre-mRNA processing and cytoskeleton assembly; typically contains a GH dipeptide 11-24 residues from ...

    5. NM_001378459.1 → NP_001365388.1  dmX-like protein 2 isoform 6

      Status: REVIEWED

      Source sequence(s)
      AC020892, AC066613
      Conserved Domains (3) summary
      sd00039
      Location:2736 → 2776
      7WD40; WD40 repeat [structural motif]
      pfam12234
      Location:1171 → 1902
      Rav1p_C; RAVE protein 1 C terminal
      cl29593
      Location:2692 → 2944
      WD40; WD40 domain, found in a number of eukaryotic proteins that cover a wide variety of functions including adaptor/regulatory modules in signal transduction, pre-mRNA processing and cytoskeleton assembly; typically contains a GH dipeptide 11-24 residues from ...

    6. NM_001378460.1 → NP_001365389.1  dmX-like protein 2 isoform 7

      Status: REVIEWED

      Source sequence(s)
      AC020892, AC066613
      Conserved Domains (3) summary
      sd00039
      Location:2137 → 2177
      7WD40; WD40 repeat [structural motif]
      pfam12234
      Location:909 → 1229
      Rav1p_C; RAVE protein 1 C terminal
      cl29593
      Location:2093 → 2345
      WD40; WD40 domain, found in a number of eukaryotic proteins that cover a wide variety of functions including adaptor/regulatory modules in signal transduction, pre-mRNA processing and cytoskeleton assembly; typically contains a GH dipeptide 11-24 residues from ...

    7. NM_001378461.1 → NP_001365390.1  dmX-like protein 2 isoform 8

      Status: REVIEWED

      Source sequence(s)
      AC020892, AC066613
      Conserved Domains (2) summary
      sd00039
      Location:61 → 102
      7WD40; WD40 repeat [structural motif]
      pfam12234
      Location:1171 → 1902
      Rav1p_C; RAVE protein 1 C terminal

    8. NM_001378462.1 → NP_001365391.1  dmX-like protein 2 isoform 9

      Status: REVIEWED

      Source sequence(s)
      AC020892, AC066613
      Conserved Domains (2) summary
      sd00039
      Location:61 → 102
      7WD40; WD40 repeat [structural motif]
      pfam12234
      Location:1171 → 1902
      Rav1p_C; RAVE protein 1 C terminal

    9. NM_001378463.1 → NP_001365392.1  dmX-like protein 2 isoform 10

      Status: REVIEWED

      Source sequence(s)
      AC020892, AC066613
      Conserved Domains (2) summary
      sd00039
      Location:61 → 102
      7WD40; WD40 repeat [structural motif]
      pfam12234
      Location:1171 → 1902
      Rav1p_C; RAVE protein 1 C terminal

    10. NM_001378464.1 → NP_001365393.1  dmX-like protein 2 isoform 11

      Status: REVIEWED

      Source sequence(s)
      AC020892, AC066613
      Conserved Domains (2) summary
      sd00039
      Location:61 → 102
      7WD40; WD40 repeat [structural motif]
      pfam12234
      Location:1091 → 1822
      Rav1p_C; RAVE protein 1 C terminal

    11. NM_015263.5 → NP_056078.2  dmX-like protein 2 isoform 2

      See identical proteins and their annotated locations for NP_056078.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) uses an alternate in-frame splice site in the 3' coding region compared to variant 1. The resulting protein (isoform 2) is shorter compared to isoform 1.
      Source sequence(s)
      AC020892, AC066613
      Consensus CDS
      CCDS10141.1
      UniProtKB/Swiss-Prot
      B2RTR3, B7ZMH3, F5GWF1, O94938, Q8TDJ6
      Related
      ENSP00000251076.5, ENST00000251076.9
      Conserved Domains (4) summary
      COG2319
      Location:2777 → 2983
      WD40; WD40 repeat [General function prediction only]
      pfam12234
      Location:1171 → 1902
      Rav1p_C; RAVE protein 1 C terminal
      sd00039
      Location:2810 → 2850
      7WD40; WD40 repeat [structural motif]
      cl02567
      Location:2766 → 3018
      WD40; WD40 domain, found in a number of eukaryotic proteins that cover a wide variety of functions including adaptor/regulatory modules in signal transduction, pre-mRNA processing and cytoskeleton assembly; typically contains a GH dipeptide 11-24 residues from ...

    RNA

    1. NR_165648.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AC020892, AC066613

    2. NR_165649.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AC020892, AC066613

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000015.10 Reference GRCh38.p14 Primary Assembly

      Range
      51447791..51622771 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047432317.1 → XP_047288273.1  dmX-like protein 2 isoform X3

    2. XM_047432316.1 → XP_047288272.1  dmX-like protein 2 isoform X3

    3. XM_047432318.1 → XP_047288274.1  dmX-like protein 2 isoform X4

    4. XM_047432315.1 → XP_047288271.1  dmX-like protein 2 isoform X2

    5. XM_047432314.1 → XP_047288270.1  dmX-like protein 2 isoform X1

    6. XM_047432320.1 → XP_047288276.1  dmX-like protein 2 isoform X6

    7. XM_047432319.1 → XP_047288275.1  dmX-like protein 2 isoform X5

    8. XM_047432321.1 → XP_047288277.1  dmX-like protein 2 isoform X7

    RNA

    1. XR_007064435.1 RNA Sequence

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060939.1 Alternate T2T-CHM13v2.0

      Range
      49255566..49430224 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054377618.1 → XP_054233593.1  dmX-like protein 2 isoform X4

    2. XM_054377617.1 → XP_054233592.1  dmX-like protein 2 isoform X2

    3. XM_054377616.1 → XP_054233591.1  dmX-like protein 2 isoform X1

    4. XM_054377620.1 → XP_054233595.1  dmX-like protein 2 isoform X6

    5. XM_054377619.1 → XP_054233594.1  dmX-like protein 2 isoform X5

    6. XM_054377621.1 → XP_054233596.1  dmX-like protein 2 isoform X7

    RNA

    1. XR_008488931.1 RNA Sequence

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q8TDJ6.2 GenPept UniProtKB/Swiss-Prot:Q8TDJ6

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