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    TMEM175 transmembrane protein 175 [ Homo sapiens (human) ]

    Gene ID: 84286, updated on 10-Dec-2024

    Summary

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    Official Symbol
    TMEM175provided by HGNC
    Official Full Name
    transmembrane protein 175provided by HGNC
    Primary source
    HGNC:HGNC:28709
    See related
    Ensembl:ENSG00000127419 MIM:616660; AllianceGenome:HGNC:28709
    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
    hTMEM175
    Summary
    Enables arachidonate binding activity; potassium ion leak channel activity; and proton channel activity. Involved in lysosomal lumen pH elevation; potassium ion transmembrane transport; and proton transmembrane transport. Located in endosome membrane and lysosome. Is active in lysosomal membrane. [provided by Alliance of Genome Resources, Dec 2024]
    Expression
    Ubiquitous expression in spleen (RPKM 10.8), brain (RPKM 6.7) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See TMEM175 in Genome Data Viewer
    Location:
    4p16.3
    Exon count:
    13
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 4 NC_000004.12 (932460..958656)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 4 NC_060928.1 (930532..956764)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 4 NC_000004.11 (926248..952444)

    Chromosome 4 - NC_000004.12Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105374340 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr4:860125-861324 Neighboring gene cyclin G associated kinase Neighboring gene uncharacterized LOC105374341 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr4:872957-874156 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr4:880593-881094 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr4:881095-881594 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr4:905677-906582 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr4:906583-907488 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 15112 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 21139 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 15113 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 21140 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr4:938924-939517 Neighboring gene ReSE screen-validated silencer GRCh37_chr4:957241-957400 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr4:961731-962444 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr4:962445-963158 Neighboring gene uncharacterized LOC124900645 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr4:963506-964024 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr4:965861-966501 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 15114 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 15115 Neighboring gene diacylglycerol kinase theta Neighboring gene H3K4me1 hESC enhancer GRCh37_chr4:973450-974030 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 21141 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 21142 Neighboring gene ReSE screen-validated silencer GRCh37_chr4:981121-981298 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr4:983059-983560 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr4:983561-984060 Neighboring gene solute carrier family 26 member 1 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr4:986529-987340 Neighboring gene alpha-L-iduronidase

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • 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

    Bibliography

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    Related articles in PubMed

    1. pH regulates potassium conductance and drives a constitutive proton current in human TMEM175. Zheng W, et al. Sci Adv, 2022 Mar 25. PMID 35333573, Free PMC Article
    2. Functionalization of the TMEM175 p.M393T variant as a risk factor for Parkinson disease. Jinn S, et al. Hum Mol Genet, 2019 Oct 1. PMID 31261387, Free PMC Article
    3. Gating and selectivity mechanisms for the lysosomal K(+) channel TMEM175. Oh S, et al. Elife, 2020 Mar 31. PMID 32228865, Free PMC Article
    4. Genetic, Structural, and Functional Evidence Link TMEM175 to Synucleinopathies. Krohn L, et al. Ann Neurol, 2020 Jan. PMID 31658403
    5. Parkinson's disease-risk protein TMEM175 is a proton-activated proton channel in lysosomes. Hu M, et al. Cell, 2022 Jun 23. PMID 35750034, Free PMC Article

    See all (25) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Lysosomal LAMP proteins regulate lysosomal pH by direct inhibition of the TMEM175 channel.
      Title: Lysosomal LAMP proteins regulate lysosomal pH by direct inhibition of the TMEM175 channel.
    2. A growth-factor-activated lysosomal K(+) channel regulates Parkinson's pathology.
      Title: A growth-factor-activated lysosomal K(+) channel regulates Parkinson's pathology.
    3. Gating and selectivity mechanisms for the lysosomal K(+) channel TMEM175.
      Title: Gating and selectivity mechanisms for the lysosomal K(+) channel TMEM175.
    4. Data suggest that the TMEM175 p.M393T variant is responsible for the main signal in the chromosome 4p16.3 locus therefore conferring risk for Parkinson disease through its phosphorylation of alpha-synuclein.
      Title: Functionalization of the TMEM175 p.M393T variant as a risk factor for Parkinson disease.
    5. Coding variants in TMEM175 are likely to be responsible for the association in the TMEM175/GAK/DGKQ locus, which could be mediated by affecting glucosylceramidase activity.
      Title: Genetic, Structural, and Functional Evidence Link TMEM175 to Synucleinopathies.
    6. TMEM175 deficiency impairs lysosomal and mitochondrial function and increases alpha-synuclein aggregation.
      Title: TMEM175 deficiency impairs lysosomal and mitochondrial function and increases α-synuclein aggregation.
    7. structure of TMEM175 represents a novel architecture of a tetrameric cation channel whose ion selectivity mechanism appears to be distinct from that of the classical K(+) channel family
      Title: The lysosomal potassium channel TMEM175 adopts a novel tetrameric architecture.
    8. Data indicated that GBA and TMEM175/GAK significantly alter age at onset in PD.
      Title: Impact of Parkinson's disease risk loci on age at onset.
    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

    EBI GWAS Catalog

    Description
    Imputation of sequence variants for identification of genetic risks for Parkinson's disease: a meta-analysis of genome-wide association studies.
    EBI GWAS Catalog
    Large-scale meta-analysis of genome-wide association data identifies six new risk loci for Parkinson's disease.
    EBI GWAS Catalog
    Meta-analysis of genome-wide association studies in african americans provides insights into the genetic architecture of type 2 diabetes.
    EBI GWAS Catalog
    Web-based genome-wide association study identifies two novel loci and a substantial genetic component for Parkinson's disease.
    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)

    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • MGC4618

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables arachidonate binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables potassium channel activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables potassium ion leak channel activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables potassium ion leak channel activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables proton channel activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in lysosomal lumen pH elevation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in neuron cellular homeostasis ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in phagosome-lysosome fusion IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in potassium ion transmembrane transport IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in proton transmembrane transport IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in regulation of lysosomal lumen pH IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Component Evidence Code Pubs
    is_active_in endosome IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in endosome IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in endosome membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in lysosomal membrane HDA PubMed 
    is_active_in lysosomal membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in lysosomal membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    is_active_in lysosome IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in lysosome IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    endosomal/lysosomal proton channel TMEM175
    Names
    endosomal/lysomomal potassium channel TMEM175
    endosomal/lysosomal potassium channel TMEM175
    potassium channel TMEM175

    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.

    mRNA and Protein(s)

    1. NM_001297423.2 → NP_001284352.1  endosomal/lysosomal proton channel TMEM175 isoform 2

      See identical proteins and their annotated locations for NP_001284352.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (2) differs in its 5' UTR and uses a downstream start codon, compared to variant 1. The encoded isoform (2) has a shorter N-terminus, compared to isoform 1. Variants 2, 3, and 4 encode the same isoform.
      Source sequence(s)
      BC047738, DA168151
      Consensus CDS
      CCDS75087.1
      UniProtKB/TrEMBL
      A0A9K3Y7F1, D3DVN6, F6UWG6
      Related
      ENST00000438836.6
      Conserved Domains (1) summary
      pfam06736
      Location:178 → 274
      DUF1211; Protein of unknown function (DUF1211)

    2. NM_001297424.2 → NP_001284353.1  endosomal/lysosomal proton channel TMEM175 isoform 2

      See identical proteins and their annotated locations for NP_001284353.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (3) differs in its 5' UTR and uses a downstream start codon, compared to variant 1. The encoded isoform (2) has a shorter N-terminus, compared to isoform 1. Variants 2, 3, and 4 encode the same isoform.
      Source sequence(s)
      BC047738, BI819231
      Consensus CDS
      CCDS75087.1
      UniProtKB/TrEMBL
      A0A9K3Y7F1, D3DVN6, F6UWG6
      Related
      ENSP00000423669.1, ENST00000508204.5
      Conserved Domains (1) summary
      pfam06736
      Location:178 → 274
      DUF1211; Protein of unknown function (DUF1211)

    3. NM_001297425.2 → NP_001284354.1  endosomal/lysosomal proton channel TMEM175 isoform 2

      See identical proteins and their annotated locations for NP_001284354.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (4) differs in its 5' UTR and uses a downstream start codon, compared to variant 1. The encoded isoform (2) has a shorter N-terminus, compared to isoform 1. Variants 2, 3, and 4 encode the same isoform.
      Source sequence(s)
      BC047738, CB992640
      Consensus CDS
      CCDS75087.1
      UniProtKB/TrEMBL
      A0A9K3Y7F1, D3DVN6, F6UWG6
      Conserved Domains (1) summary
      pfam06736
      Location:178 → 274
      DUF1211; Protein of unknown function (DUF1211)

    4. NM_001297426.2 → NP_001284355.1  endosomal/lysosomal proton channel TMEM175 isoform 3

      See identical proteins and their annotated locations for NP_001284355.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (5) differs in its 5' UTR and uses a downstream start codon, compared to variant 1. The encoded isoform (3) has a shorter N-terminus, compared to isoform 1. Variants 5, 6, and 7 encode the same isoform.
      Source sequence(s)
      AL834199, BC047738, DA168151
      Consensus CDS
      CCDS75088.1
      UniProtKB/Swiss-Prot
      Q9BSA9
      Related
      ENSP00000485461.1, ENST00000622959.3
      Conserved Domains (1) summary
      pfam06736
      Location:144 → 240
      DUF1211; Protein of unknown function (DUF1211)

    5. NM_001297427.2 → NP_001284356.1  endosomal/lysosomal proton channel TMEM175 isoform 3

      See identical proteins and their annotated locations for NP_001284356.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (6) differs in its 5' UTR and uses a downstream start codon, compared to variant 1. The encoded isoform (3) has a shorter N-terminus, compared to isoform 1. Variants 5, 6, and 7 encode the same isoform.
      Source sequence(s)
      BC047738, BC063488, DA168151
      Consensus CDS
      CCDS75088.1
      UniProtKB/Swiss-Prot
      Q9BSA9
      Conserved Domains (1) summary
      pfam06736
      Location:144 → 240
      DUF1211; Protein of unknown function (DUF1211)

    6. NM_001297428.2 → NP_001284357.1  endosomal/lysosomal proton channel TMEM175 isoform 3

      See identical proteins and their annotated locations for NP_001284357.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (7) differs in its 5' UTR and uses a downstream start codon, compared to variant 1. The encoded isoform (3) has a shorter N-terminus, compared to isoform 1. Variants 5, 6, and 7 encode the same isoform.
      Source sequence(s)
      BC047738, CF242841, DA168151
      Consensus CDS
      CCDS75088.1
      UniProtKB/Swiss-Prot
      Q9BSA9
      Related
      ENSP00000427039.1, ENST00000515740.5
      Conserved Domains (1) summary
      pfam06736
      Location:144 → 240
      DUF1211; Protein of unknown function (DUF1211)

    7. NM_032326.4 → NP_115702.1  endosomal/lysosomal proton channel TMEM175 isoform 1

      See identical proteins and their annotated locations for NP_115702.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (1) encodes the longest isoform (1).
      Source sequence(s)
      BC005158, BC047738, DA168151
      Consensus CDS
      CCDS3341.1
      UniProtKB/Swiss-Prot
      D3DVN4, Q8ND13, Q9BSA9
      Related
      ENSP00000264771.4, ENST00000264771.9
      Conserved Domains (1) summary
      pfam06736
      Location:260 → 356
      DUF1211; Protein of unknown function (DUF1211)

    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_000004.12 Reference GRCh38.p14 Primary Assembly

      Range
      932460..958656
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_017008701.2 → XP_016864190.1  endosomal/lysosomal proton channel TMEM175 isoform X1

      UniProtKB/Swiss-Prot
      D3DVN4, Q8ND13, Q9BSA9
      Conserved Domains (1) summary
      pfam06736
      Location:260 → 356
      DUF1211; Protein of unknown function (DUF1211)

    2. XM_005272301.3 → XP_005272358.1  endosomal/lysosomal proton channel TMEM175 isoform X2

      Conserved Domains (1) summary
      pfam06736
      Location:232 → 328
      DUF1211; Protein of unknown function (DUF1211)

    3. XM_047416295.1 → XP_047272251.1  endosomal/lysosomal proton channel TMEM175 isoform X4

    4. XM_005272307.6 → XP_005272364.1  endosomal/lysosomal proton channel TMEM175 isoform X6

      Conserved Domains (2) summary
      pfam06736
      Location:35 → 124
      DUF1211; Protein of unknown function (DUF1211)
      cl01421
      Location:260 → 280
      DUF1211; Protein of unknown function (DUF1211)

    5. XM_047416293.1 → XP_047272249.1  endosomal/lysosomal proton channel TMEM175 isoform X3

      UniProtKB/TrEMBL
      A0A9K3Y7F1, D3DVN6, F6UWG6

    6. XM_047416294.1 → XP_047272250.1  endosomal/lysosomal proton channel TMEM175 isoform X3

      UniProtKB/TrEMBL
      A0A9K3Y7F1, D3DVN6, F6UWG6

    7. XM_047416296.1 → XP_047272252.1  endosomal/lysosomal proton channel TMEM175 isoform X5

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060928.1 Alternate T2T-CHM13v2.0

      Range
      930532..956764
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054351041.1 → XP_054207016.1  endosomal/lysosomal proton channel TMEM175 isoform X1

      UniProtKB/Swiss-Prot
      D3DVN4, Q8ND13, Q9BSA9

    2. XM_054351042.1 → XP_054207017.1  endosomal/lysosomal proton channel TMEM175 isoform X2

    3. XM_054351045.1 → XP_054207020.1  endosomal/lysosomal proton channel TMEM175 isoform X4

    4. XM_054351047.1 → XP_054207022.1  endosomal/lysosomal proton channel TMEM175 isoform X6

    5. XM_054351043.1 → XP_054207018.1  endosomal/lysosomal proton channel TMEM175 isoform X3

      UniProtKB/TrEMBL
      A0A9K3Y7F1, D3DVN6, F6UWG6

    6. XM_054351044.1 → XP_054207019.1  endosomal/lysosomal proton channel TMEM175 isoform X3

      UniProtKB/TrEMBL
      A0A9K3Y7F1, D3DVN6, F6UWG6

    7. XM_054351046.1 → XP_054207021.1  endosomal/lysosomal proton channel TMEM175 isoform X5

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q9BSA9.1 GenPept UniProtKB/Swiss-Prot:Q9BSA9

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