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

Summary

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

Location:: 17q21.31

Exon count:: 17

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	17	NC_000017.11 (45434209..45490721, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	17	NC_060941.1 (46286496..46344437, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	17	NC_000017.10 (43513266..43568087, complement)

Chromosome 17 - NC_000017.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Downregulation of MYBL1 in endothelial cells contributes to atherosclerosis by repressing PLEKHM1-inducing autophagy.
Title: Downregulation of MYBL1 in endothelial cells contributes to atherosclerosis by repressing PLEKHM1-inducing autophagy.
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.
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.
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.
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.
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.
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.
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.
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.
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.

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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 EBI GWAS CatalogPubMed
Genome-wide association study in BRCA1 mutation carriers identifies novel loci associated with breast and ovarian cancer risk. EBI GWAS Catalog EBI GWAS CatalogPubMed

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

WI-15095 (e-PCR)
- UniSTS:61805

D17S1557 (e-PCR)
- UniSTS:33162

SHGC-52535 (e-PCR)
- UniSTS:24203

D17S633 (e-PCR)
- UniSTS:147119

RH48419 (e-PCR)
- UniSTS:42694

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

NG_012932.1 RefSeqGene

Range

5060..59881

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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
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

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
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_2024_08

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000017.11 Reference GRCh38.p14 Primary Assembly

Range

45434209..45490721 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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

UniProtKB/Swiss-Prot

Q6P2R5, Q8TEL9, Q9NPP5, Q9NYA0, Q9Y4G2
XM_017025452.2 → XP_016880941.1 pleckstrin homology domain-containing family M member 1 isoform X5

UniProtKB/TrEMBL

B4DR59
XM_047437190.1 → XP_047293146.1 pleckstrin homology domain-containing family M member 1 isoform X4
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
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
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
XM_047437192.1 → XP_047293148.1 pleckstrin homology domain-containing family M member 1 isoform X7
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
XM_047437189.1 → XP_047293145.1 pleckstrin homology domain-containing family M member 1 isoform X3
XM_047437191.1 → XP_047293147.1 pleckstrin homology domain-containing family M member 1 isoform X6

Reference GRCh38.p14 ALT_REF_LOCI_1

Genomic

NT_167251.2 Reference GRCh38.p14 ALT_REF_LOCI_1

Range

124584..181162 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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

UniProtKB/Swiss-Prot

Q6P2R5, Q8TEL9, Q9NPP5, Q9NYA0, Q9Y4G2
XM_054328582.1 → XP_054184557.1 pleckstrin homology domain-containing family M member 1 isoform X5
XM_054328580.1 → XP_054184555.1 pleckstrin homology domain-containing family M member 1 isoform X2
XM_054328584.1 → XP_054184559.1 pleckstrin homology domain-containing family M member 1 isoform X7
XM_054328585.1 → XP_054184560.1 pleckstrin homology domain-containing family M member 1 isoform X7
XM_054328586.1 → XP_054184561.1 pleckstrin homology domain-containing family M member 1 isoform X8
XM_054328583.1 → XP_054184558.1 pleckstrin homology domain-containing family M member 1 isoform X6
XM_054328581.1 → XP_054184556.1 pleckstrin homology domain-containing family M member 1 isoform X3

Reference GRCh38.p14 ALT_REF_LOCI_2

Genomic

NT_187663.1 Reference GRCh38.p14 ALT_REF_LOCI_2

Range

124714..180876 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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

UniProtKB/Swiss-Prot

Q6P2R5, Q8TEL9, Q9NPP5, Q9NYA0, Q9Y4G2
XM_054330132.1 → XP_054186107.1 pleckstrin homology domain-containing family M member 1 isoform X5
XM_054330129.1 → XP_054186104.1 pleckstrin homology domain-containing family M member 1 isoform X2
XM_054330131.1 → XP_054186106.1 pleckstrin homology domain-containing family M member 1 isoform X4
XM_054330134.1 → XP_054186109.1 pleckstrin homology domain-containing family M member 1 isoform X7
XM_054330135.1 → XP_054186110.1 pleckstrin homology domain-containing family M member 1 isoform X7
XM_054330136.1 → XP_054186111.1 pleckstrin homology domain-containing family M member 1 isoform X8
XM_054330133.1 → XP_054186108.1 pleckstrin homology domain-containing family M member 1 isoform X6
XM_054330130.1 → XP_054186105.1 pleckstrin homology domain-containing family M member 1 isoform X3

Alternate T2T-CHM13v2.0

Genomic

NC_060941.1 Alternate T2T-CHM13v2.0

Range

46286496..46344437 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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

UniProtKB/Swiss-Prot

Q6P2R5, Q8TEL9, Q9NPP5, Q9NYA0, Q9Y4G2
XM_054318030.1 → XP_054174005.1 pleckstrin homology domain-containing family M member 1 isoform X5
XM_054318027.1 → XP_054174002.1 pleckstrin homology domain-containing family M member 1 isoform X2
XM_054318029.1 → XP_054174004.1 pleckstrin homology domain-containing family M member 1 isoform X4
XM_054318032.1 → XP_054174007.1 pleckstrin homology domain-containing family M member 1 isoform X7
XM_054318033.1 → XP_054174008.1 pleckstrin homology domain-containing family M member 1 isoform X7
XM_054318034.1 → XP_054174009.1 pleckstrin homology domain-containing family M member 1 isoform X8
XM_054318031.1 → XP_054174006.1 pleckstrin homology domain-containing family M member 1 isoform X6
XM_054318028.1 → XP_054174003.1 pleckstrin homology domain-containing family M member 1 isoform X3