U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

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

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

Summary

Go to the top of the page Help
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
NEW
Try the new Gene table
Try the new Transcript table

Genomic context

Go to the top of the page Help
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

Go to the top of the page Help

Go to nucleotide: Graphics FASTA GenBank

Expression

Go to the top of the page Help
  • 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

Go to the top of the pageHelp

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

Go to the top of the page Help

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

Go to the top of the page Help

See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Pathways from PubChem

Go to the top of the page

Interactions

Go to the top of the page Help
Products Interactant Other Gene Complex Source Pubs Description

General gene information

Go to the top of the page Help

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

Go to the top of the page Help
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)

Go to the top of the page Help

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.

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

Gene LinkOut

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

Chemical Information
Molecular Biology Databases
Research Materials
Tools
Miscellaneous