TMEM175

transmembrane protein 175

Basic information

Region (hg38): 4:932386-958656

Links

ENSG00000127419 ∙ NCBI:84286 ∙ OMIM:616660 ∙ HGNC:28709 ∙ Uniprot:Q9BSA9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TMEM175 gene.

• Inborn genetic diseases (32 variants)
• not provided (4 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TMEM175 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				1	1	2
missense			29	1	2	32
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			2			2
Total	0	0	31	2	3

Variants in TMEM175

This is a list of pathogenic ClinVar variants found in the TMEM175 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
4-947744-C-G		not specified	Uncertain significance (Jul 25, 2023)
4-947753-G-A		not specified	Likely benign (Feb 05, 2024)
4-947788-T-G		not specified	Uncertain significance (Apr 18, 2023)
4-947802-G-C		not specified	Uncertain significance (Sep 27, 2021)
4-947815-G-A		not specified	Uncertain significance (Jul 06, 2021)
4-948135-C-T		not specified	Uncertain significance (Dec 06, 2022)
4-950422-A-C			Benign (Apr 19, 2019)
4-950466-G-A		not specified	Uncertain significance (Dec 19, 2022)
4-950487-A-C		not specified	Uncertain significance (Jun 22, 2021)
4-950496-G-A		not specified	Uncertain significance (Apr 07, 2022)
4-951229-A-G		not specified	Uncertain significance (Jul 14, 2022)
4-951235-G-A		not specified	Uncertain significance (Jan 31, 2024)
4-951698-T-A			Uncertain significance (Mar 01, 2024)
4-952371-C-T		not specified	Uncertain significance (Jun 23, 2023)
4-952438-T-C		TMEM175-related disorder	Benign (Jun 10, 2019)
4-952440-G-C		not specified	Uncertain significance (Dec 19, 2023)
4-953194-T-C		not specified	Uncertain significance (Jan 23, 2024)
4-953305-C-T		not specified	Uncertain significance (Jun 21, 2023)
4-955426-G-A		not specified	Uncertain significance (Nov 08, 2022)
4-955766-C-T		not specified	Uncertain significance (Feb 07, 2023)
4-955781-G-C		not specified	Uncertain significance (Oct 12, 2022)
4-955871-C-T		not specified	Uncertain significance (Jan 27, 2022)
4-957825-G-A		not specified	Uncertain significance (Sep 28, 2021)
4-957831-A-G			Likely benign (Mar 01, 2024)
4-957834-G-A		not specified	Uncertain significance (Dec 26, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TMEM175	protein_coding	protein_coding	ENST00000264771	10	26270

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.05e-9	0.509	125553	1	193	125747	0.000772

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.555	370	341	1.08	0.0000233	3217
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00137	0.00136
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.000763	0.000761
Finnish	0.00	0.00
European (Non-Finnish)	0.000608	0.000598
Middle Eastern	0.000763	0.000761
South Asian	0.00252	0.00249
Other	0.000829	0.000815

dbNSFP

Source: dbNSFP

• 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

Haploinsufficiency Scores

• pHI: 0.168
• hipred: N
• hipred_score: 0.318
• ghis: 0.482

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.248

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Tmem175

Gene ontology

• Biological process: regulation of lysosomal lumen pH;potassium ion transmembrane transport;phagosome-lysosome fusion
• Cellular component: lysosome;lysosomal membrane;endosome;endosome membrane;integral component of membrane
• Molecular function: potassium channel activity;potassium ion leak channel activity