PMEPA1
Basic information
Region (hg38): 20:57648392-57711536
Previous symbols: [ "TMEPAI" ]
Links
Phenotypes
GenCC
Source:
ClinVar
This is a list of variants' phenotypes submitted to
- not_specified (28 variants)
- Hereditary_disorder_of_connective_tissue (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the PMEPA1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000020182.5. 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 | 0 | |||||
| missense | 27 | 28 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 28 | 1 | 0 |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| PMEPA1 | protein_coding | protein_coding | ENST00000341744 | 4 | 63145 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.936 | 0.0640 | 111940 | 0 | 1 | 111941 | 0.00000447 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 1.21 | 128 | 173 | 0.742 | 0.0000114 | 1823 |
| Missense in Polyphen | 74 | 91.014 | 0.81306 | 804 | ||
| Synonymous | -0.996 | 91 | 79.7 | 1.14 | 0.00000592 | 570 |
| Loss of Function | 2.74 | 0 | 8.72 | 0.00 | 3.73e-7 | 105 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00 | 0.00 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.0000593 | 0.0000593 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.00 | 0.00 |
| Middle Eastern | 0.0000593 | 0.0000593 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Functions as a negative regulator of TGF-beta signaling and thereby probably plays a role in cell proliferation, differentiation, apoptosis, motility, extracellular matrix production and immunosuppression. In the canonical TGF-beta pathway, ZFYVE9/SARA recruits the intracellular signal transducer and transcriptional modulators SMAD2 and SMAD3 to the TGF-beta receptor. Phosphorylated by the receptor, SMAD2 and SMAD3 then form a heteromeric complex with SMAD4 that translocates to the nucleus to regulate transcription. Through interaction with SMAD2 and SMAD3, LDLRAD4 may compete with ZFYVE9 and SMAD4 and prevent propagation of the intracellular signal (PubMed:20129061, PubMed:24627487). Also involved in down-regulation of the androgen receptor (AR), enhancing ubiquitination and proteasome-mediated degradation of AR, probably by recruiting NEDD4 (PubMed:18703514). {ECO:0000269|PubMed:18703514, ECO:0000269|PubMed:20129061, ECO:0000269|PubMed:24627487}.;
- Pathway
- Signal Transduction;Signaling by TGF-beta Receptor Complex;Signaling by TGF-beta family members;Downregulation of TGF-beta receptor signaling;TGF-beta receptor signaling activates SMADs
(Consensus)
Recessive Scores
- pRec
- 0.167
Intolerance Scores
- loftool
- 0.401
- rvis_EVS
- 0.17
- rvis_percentile_EVS
- 65.76
Haploinsufficiency Scores
- pHI
- 0.223
- hipred
- Y
- hipred_score
- 0.629
- ghis
- 0.505
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.741
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Pmepa1
- Phenotype
Gene ontology
- Biological process
- negative regulation of SMAD protein complex assembly;negative regulation of transforming growth factor beta receptor signaling pathway;androgen receptor signaling pathway;negative regulation of pathway-restricted SMAD protein phosphorylation
- Cellular component
- Golgi membrane;plasma membrane;endosome membrane;integral component of membrane;early endosome membrane;intracellular membrane-bounded organelle
- Molecular function
- protein binding;WW domain binding;R-SMAD binding