U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

TMEM175 transmembrane protein 175 [ Homo sapiens (human) ]

Gene ID: 84286, updated on 5-Mar-2024

Summary

Go to the top of the page Help
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 potassium ion leak channel activity. Involved in potassium ion transmembrane transport. Located in endosome and lysosome. Is integral component of endosome membrane and integral component of lysosomal membrane. [provided by Alliance of Genome Resources, Apr 2022]
Expression
Ubiquitous expression in spleen (RPKM 10.8), brain (RPKM 6.7) 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:
4p16.3
Exon count:
13
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 4 NC_000004.12 (932460..958656)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 4 NC_060928.1 (930532..956764)
105.20220307 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

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. 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. Gating and selectivity mechanisms for the lysosomal K(+) channel TMEM175. Oh S, et al. Elife, 2020 Mar 31. PMID 32228865, Free PMC Article
  3. Genetic, Structural, and Functional Evidence Link TMEM175 to Synucleinopathies. Krohn L, et al. Ann Neurol, 2020 Jan. PMID 31658403
  4. 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
  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 (24) 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

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

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

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

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

  • MGC4618

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables arachidonic acid 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

Go to the top of the page Help
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)

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.

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_2023_10

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

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