TMEM59
protein-codingtransmembrane protein 59
Gene summary
This gene encodes a protein shown to regulate autophagy in response to bacterial infection. This protein may also regulate the retention of amyloid precursor protein (APP) in the Golgi apparatus through its control of APP glycosylation. Overexpression of this protein has been found to promote apoptosis in a glioma cell line. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2015]
- C1orf8
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~26.8 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 TMEM59 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_004872.5. 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 | 0 | |||||
| missense | 31 | 31 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 32 | 0 | 0 | 32 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_004863.2 | 8 | MANE Select | |
| Ensembl | ENSP00000234831.5 | 8 | MANE Select | |
| RefSeq | NP_001291972.1 | 8 | Standard | |
| RefSeq | NP_001291978.1 | 5 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- miR-targeted genes in epithelium - TarBase
- miR-targeted genes in lymphocytes - TarBase
- miR-targeted genes in squamous cell - TarBase
Biological Process
- proteolysis
- autophagy
- positive regulation of autophagy
- negative regulation of protein processing
- negative regulation of protein glycosylation in Golgi
Molecular Function
- endopeptidase activity
- protein binding
Cellular Component
- Golgi cis cisterna
- Golgi trans cisterna
- Golgi membrane
- lysosome
- lysosomal membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000234831
- Coding exons
- 8
- Length
- 21831
- Individuals with no LoFs
- 125592
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 155
- Defined
- 125747
- p
- 0.000617
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.438 | 151 | 167 | 0.905 | 0.00000782 | 2093 |
| Missense (PolyPhen) | 60 | 66.032 | 0.90865 | 819 | ||
| Synonymous | 0.225 | 65 | 67.4 | 0.965 | 0.00000353 | 620 |
| Loss of Function | 0.0446 | 18 | 18.2 | 0.989 | 8.36e-7 | 219 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.00016 | 0.00014 | rare |
| Ashkenazi Jewish | 0.010 | 0.010 | notable |
| East Asian | 0.00017 | 0.00016 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00030 | 0.00030 | rare |
| South Asian | 0.000066 | 0.000065 | rare |
| Other | 0.0013 | 0.0013 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Acts as a regulator of autophagy in response to S.aureus infection by promoting activation of LC3 (MAP1LC3A, MAP1LC3B or MAP1LC3C). Acts by interacting with ATG16L1, leading to promote a functional complex between LC3 and ATG16L1 and promoting LC3 lipidation and subsequent activation of autophagy (PubMed:27273576, PubMed:23376921). Modulates the O-glycosylation and complex N-glycosylation steps occurring during the Golgi maturation of several proteins such as APP, BACE1, SEAP or PRNP (PubMed:20427278). Inhibits APP transport to the cell surface and further shedding (PubMed:20427278). {ECO:0000269|PubMed:20427278, ECO:0000269|PubMed:23376921, ECO:0000269|PubMed:27273576}.;
Recessive Scores
- pRec
- 0.122
Intolerance Scores
- LoFtool
- 0.840
- RVIS EVS
- -0.25
- RVIS percentile EVS
- 35.75
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.808
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |