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    PLEKHM1 pleckstrin homology and RUN domain containing M1 [ Homo sapiens (human) ]

    Gene ID: 9842, updated on 3-Apr-2024

    Summary

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    Official Symbol
    PLEKHM1provided by HGNC
    Official Full Name
    pleckstrin homology and RUN domain containing M1provided by HGNC
    Primary source
    HGNC:HGNC:29017
    See related
    Ensembl:ENSG00000225190 MIM:611466; AllianceGenome:HGNC:29017
    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
    B2; AP162; OPTA3; OPTB6
    Summary
    The protein encoded by this gene is essential for bone resorption, and may play a critical role in vesicular transport in the osteoclast. Mutations in this gene are associated with autosomal recessive osteopetrosis type 6 (OPTB6). Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Sep 2009]
    Expression
    Ubiquitous expression in esophagus (RPKM 12.9), bone marrow (RPKM 10.7) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    Location:
    17q21.31
    Exon count:
    17
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 17 NC_000017.11 (45434209..45490721, complement)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 17 NC_060941.1 (46286496..46344437, complement)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 17 NC_000017.10 (43513266..43568087, complement)

    Chromosome 17 - NC_000017.11Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105371796 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr17:43448585-43449784 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr17:43450691-43451263 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr17:43451264-43451835 Neighboring gene H3K27ac hESC enhancer GRCh37_chr17:43453675-43454480 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr17:43462245-43463212 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:43471827-43472486 Neighboring gene ReSE screen-validated silencer GRCh37_chr17:43473118-43473275 Neighboring gene Rho GTPase activating protein 27 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:43488992-43489492 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr17:43501589-43502093 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr17:43501082-43501588 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr17:43502838-43503408 Neighboring gene uncharacterized LOC124904016 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:43507020-43507520 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:43507521-43508021 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:43513205-43513858 Neighboring gene uncharacterized LOC124904113 Neighboring gene microRNA 4315-1 Neighboring gene uncharacterized LOC105369225 Neighboring gene leucine rich repeat containing 37 member A4, pseudogene Neighboring gene ADP ribosylation factor like GTPase 17A pseudogene

    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. Novel adapter protein AP162 connects a sialyl-Le(x)-positive mucin with an apoptotic signal transduction pathway. Hartel-Schenk S, et al. Glycoconj J, 2001 Nov-Dec. PMID 12820725
    2. Osteopetrosis associated with PLEKHM1 and SNX10 genes, both involved in osteoclast vesicular trafficking. Huybrechts Y, et al. Bone, 2022 Nov. PMID 35981699
    3. Characterization of a Relatively Malignant Form of Osteopetrosis Caused by a Novel Mutation in the PLEKHM1 Gene. Bo T, et al. J Bone Miner Res, 2016 Nov. PMID 27291868
    4. PLEKHM1: Adapting to life at the lysosome. McEwan DG, et al. Autophagy, 2015 Apr 3. PMID 25905573, Free PMC Article
    5. Rubicon and PLEKHM1 negatively regulate the endocytic/autophagic pathway via a novel Rab7-binding domain. Tabata K, et al. Mol Biol Cell, 2010 Dec. PMID 20943950, Free PMC Article

    See all (28) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Osteopetrosis associated with PLEKHM1 and SNX10 genes, both involved in osteoclast vesicular trafficking.
      Title: Osteopetrosis associated with PLEKHM1 and SNX10 genes, both involved in osteoclast vesicular trafficking.
    2. The endolysosomal adaptor PLEKHM1 is a direct target for both mTOR and MAPK pathways.
      Title: The endolysosomal adaptor PLEKHM1 is a direct target for both mTOR and MAPK pathways.
    3. identified PLEKHM1 as an endolysosomal adaptor platform that acts as a central hub to integrate endocytic and autophagic pathways at the lysosome
      Title: PLEKHM1: Adapting to life at the lysosome.
    4. Authors show that Pleckstrin homology domain-containing protein family member 1 (PLEKHM1), a lysosomal adaptor, is targeted by Salmonella through direct interaction with SifA.
      Title: PLEKHM1 regulates Salmonella-containing vacuole biogenesis and infection.
    5. PLEKHM1 regulates autophagosome-lysosome fusion through homotypic fusion and protein sorting complex and LC3/GABARAP proteins.
      Title: PLEKHM1 regulates autophagosome-lysosome fusion through HOPS complex and LC3/GABARAP proteins.
    6. Rubicon and PLEKHM1 specifically and directly interact with Rab7 via their RH domain; this interaction is critical for their function; show Rubicon but not PLEKHM1 uniquely regulates membrane trafficking via simultaneously binding both Rab7 and PI3-kinase
      Title: Rubicon and PLEKHM1 negatively regulate the endocytic/autophagic pathway via a novel Rab7-binding domain.
    7. heterozygous mutation (R714C) of the osteopetrosis gene, pleckstrin homolog domain containing family M (with run domain) member 1 (PLEKHM1), impairs vesicular acidification and increases TRACP secretion in osteoclasts
      Title: A new heterozygous mutation (R714C) of the osteopetrosis gene, pleckstrin homolog domain containing family M (with run domain) member 1 (PLEKHM1), impairs vesicular acidification and increases TRACP secretion in osteoclasts.
    8. PLEKHM1 is a novel gene implicated in the development of osteopetrosis, with a putative critical function in vesicular transport in the osteoclast.
      Title: Involvement of PLEKHM1 in osteoclastic vesicular transport and osteopetrosis in incisors absent rats and humans.
    9. These data indicate that B2 is a novel, ubiquitously expressed protein with a putative adapter function. The protein has been named AP162.
      Title: Novel adapter protein AP162 connects a sialyl-Le(x)-positive mucin with an apoptotic signal transduction pathway.
    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
    Autosomal recessive osteopetrosis 6
    MedGen: C1969093 OMIM: 611497 GeneReviews: Not available
    		Compare labs
    Osteopetrosis, autosomal dominant 3
    MedGen: C4748197 OMIM: 618107 GeneReviews: Not available
    		Compare labs

    EBI GWAS Catalog

    Description
    Genome-wide association study confirms SNPs in SNCA and the MAPT region as common risk factors for Parkinson disease.
    EBI GWAS Catalog
    Genome-wide association study in BRCA1 mutation carriers identifies novel loci associated with breast and ovarian cancer risk.
    EBI GWAS Catalog

    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

    • KIAA0356

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables metal ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in autophagosome-lysosome fusion IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in late endosome to lysosome transport IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in lysosome localization IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in lysosome localization ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in positive regulation of bone resorption ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in positive regulation of ruffle assembly ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in protein transport IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    located_in autolysosome IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in autolysosome membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in intracellular membrane-bounded organelle IDA
    Inferred from Direct Assay
    more info
    		  
    located_in late endosome membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in lysosome IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in nucleolus IDA
    Inferred from Direct Assay
    more info
    		  

    General protein information

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    Preferred Names
    pleckstrin homology domain-containing family M member 1
    Names
    162 kDa adapter protein
    PH domain-containing family M member 1
    pleckstrin homology domain containing, family M (with RUN domain) member 1

    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_012932.1 RefSeqGene

      Range
      5060..59881
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001352825.2 → NP_001339754.1  pleckstrin homology domain-containing family M member 1 isoform 2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) lacks multiple 3' exons, compared to variant 1, and encodes a protein (isoform 2) with a shorter and novel C-terminus, compared to isoform 1.
      Source sequence(s)
      AC091132, AK025379
      Consensus CDS
      CCDS92344.1
      UniProtKB/TrEMBL
      A0A8V8TPW0
      Related
      ENSP00000514814.1, ENST00000700125.1
      Conserved Domains (4) summary
      smart00233
      Location:685 → 777
      PH; Pleckstrin homology domain
      cd13321
      Location:499 → 629
      PH_PLEKHM1; Pleckstrin homology domain-containing family M member 1 Pleckstrin homology (PH) domain
      pfam02759
      Location:49 → 180
      RUN; RUN domain
      pfam12287
      Location:306 → 463
      Caprin-1_C; Cytoplasmic activation/proliferation-associated protein-1 C term

    2. NM_014798.3 → NP_055613.1  pleckstrin homology domain-containing family M member 1 isoform 1

      See identical proteins and their annotated locations for NP_055613.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longest transcript and encodes isoform 1.
      Source sequence(s)
      BC064361, DB064851
      Consensus CDS
      CCDS32671.1
      UniProtKB/Swiss-Prot
      Q6P2R5, Q8TEL9, Q9NPP5, Q9NYA0, Q9Y4G2
      UniProtKB/TrEMBL
      B4DR59
      Related
      ENSP00000389913.3, ENST00000430334.8
      Conserved Domains (5) summary
      smart00233
      Location:685 → 777
      PH; Pleckstrin homology domain
      cd13321
      Location:499 → 629
      PH_PLEKHM1; Pleckstrin homology domain-containing family M member 1 Pleckstrin homology (PH) domain
      pfam02759
      Location:49 → 182
      RUN; RUN domain
      pfam12287
      Location:306 → 463
      Caprin-1_C; Cytoplasmic activation/proliferation-associated protein-1 C term
      pfam13901
      Location:846 → 1048
      zf-RING_9; Putative zinc-RING and/or ribbon

    RNA

    1. NR_027774.2 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) is missing an exon in the 5' coding region compared to variant 1. This variant is represented as non-coding because the use of the translational start codon as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
      Source sequence(s)
      AK299116, BC064361, DB064851
      Related
      ENST00000579197.5

    2. NR_027782.2 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) is missing an exon in the 5' coding region compared to variant 1. This variant is represented as non-coding because the use of the translational start codon as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
      Source sequence(s)
      BC053848, BC064361, DB064851

    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
      45434209..45490721 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047437188.1 → XP_047293144.1  pleckstrin homology domain-containing family M member 1 isoform X1

      UniProtKB/Swiss-Prot
      Q6P2R5, Q8TEL9, Q9NPP5, Q9NYA0, Q9Y4G2

    2. XM_017025452.2 → XP_016880941.1  pleckstrin homology domain-containing family M member 1 isoform X5

      UniProtKB/TrEMBL
      B4DR59

    3. XM_047437190.1 → XP_047293146.1  pleckstrin homology domain-containing family M member 1 isoform X4

    4. XM_017025451.2 → XP_016880940.1  pleckstrin homology domain-containing family M member 1 isoform X1

      UniProtKB/Swiss-Prot
      Q6P2R5, Q8TEL9, Q9NPP5, Q9NYA0, Q9Y4G2
      UniProtKB/TrEMBL
      B4DR59
      Conserved Domains (5) summary
      smart00233
      Location:685 → 777
      PH; Pleckstrin homology domain
      cd13321
      Location:499 → 629
      PH_PLEKHM1; Pleckstrin homology domain-containing family M member 1 Pleckstrin homology (PH) domain
      pfam02759
      Location:49 → 182
      RUN; RUN domain
      pfam12287
      Location:306 → 463
      Caprin-1_C; Cytoplasmic activation/proliferation-associated protein-1 C term
      pfam13901
      Location:846 → 1048
      zf-RING_9; Putative zinc-RING and/or ribbon

    5. XM_011525525.1 → XP_011523827.1  pleckstrin homology domain-containing family M member 1 isoform X2

      See identical proteins and their annotated locations for XP_011523827.1

      UniProtKB/TrEMBL
      B4DR59
      Conserved Domains (5) summary
      smart00233
      Location:634 → 726
      PH; Pleckstrin homology domain
      cd13321
      Location:448 → 578
      PH_PLEKHM1; Pleckstrin homology domain-containing family M member 1 Pleckstrin homology (PH) domain
      pfam02759
      Location:46 → 131
      RUN; RUN domain
      pfam12287
      Location:255 → 412
      Caprin-1_C; Cytoplasmic activation/proliferation-associated protein-1 C term
      pfam13901
      Location:795 → 997
      zf-RING_9; Putative zinc-RING and/or ribbon

    6. XM_006722201.5 → XP_006722264.1  pleckstrin homology domain-containing family M member 1 isoform X7

      See identical proteins and their annotated locations for XP_006722264.1

      UniProtKB/TrEMBL
      B4DR59
      Conserved Domains (5) summary
      smart00233
      Location:555 → 647
      PH; Pleckstrin homology domain
      cd13321
      Location:369 → 499
      PH_PLEKHM1; Pleckstrin homology domain-containing family M member 1 Pleckstrin homology (PH) domain
      pfam12287
      Location:176 → 333
      Caprin-1_C; Cytoplasmic activation/proliferation-associated protein-1 C term
      pfam13901
      Location:716 → 918
      zf-RING_9; Putative zinc-RING and/or ribbon
      cl02689
      Location:1 → 52
      RUN; RUN domain

    7. XM_047437192.1 → XP_047293148.1  pleckstrin homology domain-containing family M member 1 isoform X7

    8. XM_011525528.3 → XP_011523830.1  pleckstrin homology domain-containing family M member 1 isoform X8

      See identical proteins and their annotated locations for XP_011523830.1

      Conserved Domains (3) summary
      smart00233
      Location:164 → 256
      PH; Pleckstrin homology domain
      pfam13901
      Location:325 → 527
      zf-RING_9; Putative zinc-RING and/or ribbon
      cl17171
      Location:4 → 108
      PH-like; Pleckstrin homology-like domain

    9. XM_047437189.1 → XP_047293145.1  pleckstrin homology domain-containing family M member 1 isoform X3

    10. XM_047437191.1 → XP_047293147.1  pleckstrin homology domain-containing family M member 1 isoform X6

    Reference GRCh38.p14 ALT_REF_LOCI_1

    Genomic

    1. NT_167251.2 Reference GRCh38.p14 ALT_REF_LOCI_1

      Range
      124584..181162 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054328579.1 → XP_054184554.1  pleckstrin homology domain-containing family M member 1 isoform X1

      UniProtKB/Swiss-Prot
      Q6P2R5, Q8TEL9, Q9NPP5, Q9NYA0, Q9Y4G2

    2. XM_054328582.1 → XP_054184557.1  pleckstrin homology domain-containing family M member 1 isoform X5

    3. XM_054328580.1 → XP_054184555.1  pleckstrin homology domain-containing family M member 1 isoform X2

    4. XM_054328584.1 → XP_054184559.1  pleckstrin homology domain-containing family M member 1 isoform X7

    5. XM_054328585.1 → XP_054184560.1  pleckstrin homology domain-containing family M member 1 isoform X7

    6. XM_054328586.1 → XP_054184561.1  pleckstrin homology domain-containing family M member 1 isoform X8

    7. XM_054328583.1 → XP_054184558.1  pleckstrin homology domain-containing family M member 1 isoform X6

    8. XM_054328581.1 → XP_054184556.1  pleckstrin homology domain-containing family M member 1 isoform X3

    Reference GRCh38.p14 ALT_REF_LOCI_2

    Genomic

    1. NT_187663.1 Reference GRCh38.p14 ALT_REF_LOCI_2

      Range
      124714..180876 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054330128.1 → XP_054186103.1  pleckstrin homology domain-containing family M member 1 isoform X1

      UniProtKB/Swiss-Prot
      Q6P2R5, Q8TEL9, Q9NPP5, Q9NYA0, Q9Y4G2

    2. XM_054330132.1 → XP_054186107.1  pleckstrin homology domain-containing family M member 1 isoform X5

    3. XM_054330129.1 → XP_054186104.1  pleckstrin homology domain-containing family M member 1 isoform X2

    4. XM_054330131.1 → XP_054186106.1  pleckstrin homology domain-containing family M member 1 isoform X4

    5. XM_054330134.1 → XP_054186109.1  pleckstrin homology domain-containing family M member 1 isoform X7

    6. XM_054330135.1 → XP_054186110.1  pleckstrin homology domain-containing family M member 1 isoform X7

    7. XM_054330136.1 → XP_054186111.1  pleckstrin homology domain-containing family M member 1 isoform X8

    8. XM_054330133.1 → XP_054186108.1  pleckstrin homology domain-containing family M member 1 isoform X6

    9. XM_054330130.1 → XP_054186105.1  pleckstrin homology domain-containing family M member 1 isoform X3

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060941.1 Alternate T2T-CHM13v2.0

      Range
      46286496..46344437 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054318026.1 → XP_054174001.1  pleckstrin homology domain-containing family M member 1 isoform X1

      UniProtKB/Swiss-Prot
      Q6P2R5, Q8TEL9, Q9NPP5, Q9NYA0, Q9Y4G2

    2. XM_054318030.1 → XP_054174005.1  pleckstrin homology domain-containing family M member 1 isoform X5

    3. XM_054318027.1 → XP_054174002.1  pleckstrin homology domain-containing family M member 1 isoform X2

    4. XM_054318029.1 → XP_054174004.1  pleckstrin homology domain-containing family M member 1 isoform X4

    5. XM_054318032.1 → XP_054174007.1  pleckstrin homology domain-containing family M member 1 isoform X7

    6. XM_054318033.1 → XP_054174008.1  pleckstrin homology domain-containing family M member 1 isoform X7

    7. XM_054318034.1 → XP_054174009.1  pleckstrin homology domain-containing family M member 1 isoform X8

    8. XM_054318031.1 → XP_054174006.1  pleckstrin homology domain-containing family M member 1 isoform X6

    9. XM_054318028.1 → XP_054174003.1  pleckstrin homology domain-containing family M member 1 isoform X3

    RNA

    1. XR_008484971.1 RNA Sequence

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q9Y4G2.3 GenPept UniProtKB/Swiss-Prot:Q9Y4G2

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