TMEM108
Basic information
Region (hg38): 3:133038391-133397775
Links
Phenotypes
GenCC
Source:
ClinVar
This is a list of variants' phenotypes submitted to
- not_specified (87 variants)
- not_provided (2 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the TMEM108 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000023943.4. Only rare variants are included in the table.
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.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 2 | |||||
| missense | 78 | 87 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 78 | 9 | 2 |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| TMEM108 | protein_coding | protein_coding | ENST00000321871 | 4 | 359402 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.996 | 0.00445 | 125706 | 0 | 23 | 125729 | 0.0000915 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.667 | 313 | 348 | 0.899 | 0.0000201 | 3646 |
| Missense in Polyphen | 93 | 114.4 | 0.81292 | 1222 | ||
| Synonymous | -0.0810 | 145 | 144 | 1.01 | 0.00000862 | 1346 |
| Loss of Function | 3.71 | 0 | 16.0 | 0.00 | 9.33e-7 | 165 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000342 | 0.000305 |
| Ashkenazi Jewish | 0.000103 | 0.0000992 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.0000483 | 0.0000462 |
| European (Non-Finnish) | 0.000142 | 0.000132 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Transmembrane protein required for proper cognitive functions. Involved in the development of dentate gyrus (DG) neuron circuitry, is neccessary for AMPA receptors surface expression and proper excitatory postsynaptic currents of DG granule neurons. Regulates the organization and stability of the microtubule network of sensory neurons to allow axonal transport. Through the interaction with DST, mediates the docking of the dynein/dynactin motor complex to vesicle cargos for retrograde axonal transport. In hippocampal neurons, required for BDNF- dependent dendrite outgrowth. Cooperates with SH3GL2 and recruits the WAVE1 complex to facilitate actin-dependent BDNF:NTRK2 early endocytic trafficking and mediate signaling from early endosomes. {ECO:0000250|UniProtKB:Q8BHE4}.;
Intolerance Scores
- loftool
- 0.289
- rvis_EVS
- -1.4
- rvis_percentile_EVS
- 4.22
Haploinsufficiency Scores
- pHI
- 0.388
- hipred
- N
- hipred_score
- 0.376
- ghis
- 0.625
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- N
- gene_indispensability_score
- 0.412
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Tmem108
- Phenotype
- muscle phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan);
Gene ontology
- Biological process
- receptor-mediated endocytosis;retrograde axonal transport;biological_process;dentate gyrus development;neuron projection development;positive regulation of neurotrophin TRK receptor signaling pathway;postsynaptic density organization;dendrite extension;modulation of excitatory postsynaptic potential;cellular response to brain-derived neurotrophic factor stimulus
- Cellular component
- cellular_component;early endosome;endosome membrane;postsynaptic density;integral component of membrane;cell junction;axon;dendrite;somatodendritic compartment;postsynaptic membrane;axon cytoplasm
- Molecular function
- molecular_function