TMEM175
protein-codingtransmembrane protein 175
Gene summary
Enables arachidonate binding activity; potassium ion leak channel activity; and proton channel activity. Involved in monoatomic cation transmembrane transport and regulation of intracellular pH. Located in endosome membrane and lysosome. Is active in lysosomal membrane. [provided by Alliance of Genome Resources, Jun 2026]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~26.3 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to TMEM175 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_032326.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 2 | 2 | 1 | 5 | ||
| missense | 98 | 5 | 103 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 4 | 4 | ||||
| Total | 0 | 0 | 105 | 7 | 1 | 113 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_115702.1 | 10 | MANE Select | |
| Ensembl | ENSP00000264771.4 | 10 | MANE Select | |
| RefSeq | NP_001284352.1 | 8 | Standard | |
| RefSeq | NP_001284353.1 | 8 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- regulation of lysosomal lumen pH
- potassium ion transmembrane transport
- phagosome-lysosome fusion
Molecular Function
- potassium channel activity
- potassium ion leak channel activity
Cellular Component
- lysosome
- lysosomal membrane
- endosome
- endosome membrane
- integral component of membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000264771
- Coding exons
- 10
- Length
- 26270
- Individuals with no LoFs
- 125553
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 193
- Defined
- 125747
- p
- 0.000772
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.555 | 370 | 341 | 1.08 | 0.0000233 | 3217 |
| Missense (PolyPhen) | 113 | 115.27 | 0.98032 | 1161 | ||
| Synonymous | -1.22 | 184 | 164 | 1.12 | 0.0000125 | 1100 |
| Loss of Function | 1.10 | 16 | 21.5 | 0.745 | 0.00000111 | 207 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00093 | 0.00092 | rare |
| Latino/Admixed American | 0.00043 | 0.00043 | rare |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0.00076 | 0.00076 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00061 | 0.00060 | rare |
| South Asian | 0.0025 | 0.0025 | notable |
| Other | 0.00083 | 0.00081 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Organelle-specific potassium channel specifically responsible for potassium conductance in endosomes and lysosomes. Forms a potassium-permeable leak-like channel, which regulates lumenal pH stability and is required for autophagosome-lysosome fusion. Constitutes the major lysosomal potassium channel. {ECO:0000269|PubMed:26317472, ECO:0000269|PubMed:28723891}.;
- Disease
- DISEASE: Parkinson disease (PARK) [MIM:168600]: A complex neurodegenerative disorder characterized by bradykinesia, resting tremor, muscular rigidity and postural instability. Additional features are characteristic postural abnormalities, dysautonomia, dystonic cramps, and dementia. The pathology of Parkinson disease involves the loss of dopaminergic neurons in the substantia nigra and the presence of Lewy bodies (intraneuronal accumulations of aggregated proteins), in surviving neurons in various areas of the brain. The disease is progressive and usually manifests after the age of 50 years, although early-onset cases (before 50 years) are known. The majority of the cases are sporadic suggesting a multifactorial etiology based on environmental and genetic factors. However, some patients present with a positive family history for the disease. Familial forms of the disease usually begin at earlier ages and are associated with atypical clinical features. {ECO:0000269|PubMed:28193887}. Note=Disease susceptibility may be associated with variations affecting the gene represented in this entry. TMEM175 defects result in unstable lysosomal pH, leading to decreased lysosomal catalytic activity, decreased glucocerebrosidase activity, impaired autophagosome clearance by the lysosome and decreased mitochondrial respiration (PubMed:28193887). {ECO:0000269|PubMed:28193887}.;
Intolerance Scores
- LoFtool
- 0.800
- RVIS EVS
- 0.81
- RVIS percentile EVS
- 87.74
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.248
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |