MBTPS2
membrane bound transcription factor peptidase, site 2
Basic information
Region (hg38): X:21839617-21885423
Previous symbols: [ "KFSD" ]
Links
Phenotypes
GenCC
Source:
- osteogenesis imperfecta (Supportive), mode of inheritance: AD
- IFAP syndrome 1, with or without BRESHECK syndrome (Supportive), mode of inheritance: AD
- keratosis follicularis spinulosa decalvans (Supportive), mode of inheritance: AD
- mutilating palmoplantar keratoderma with periorificial keratotic plaques (Supportive), mode of inheritance: AD
- BRESEK syndrome (Supportive), mode of inheritance: XL
- keratosis follicularis spinulosa decalvans, X-linked (Limited), mode of inheritance: XL
- IFAP syndrome 1, with or without BRESHECK syndrome (Strong), mode of inheritance: XL
- Olmsted syndrome, X-linked (Limited), mode of inheritance: XL
- osteogenesis imperfecta, type 19 (Limited), mode of inheritance: XL
- IFAP syndrome 1, with or without BRESHECK syndrome (Strong), mode of inheritance: XL
- osteogenesis imperfecta, type 19 (Strong), mode of inheritance: XL
- IFAP syndrome 1, with or without BRESHECK syndrome (Definitive), mode of inheritance: XL
- keratosis follicularis spinulosa decalvans (Definitive), mode of inheritance: XL
- Olmsted syndrome, X-linked (Strong), mode of inheritance: XL
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Keratosis follicularis spinulosa decalvans, X-linked; IFAP syndrome 1 with or without BRESHECK syndrome; Olmsted syndrome, X-linked; Osteogenesis imperfecta, type XIX | XL | General | Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing | Craniofacial; Dermatologic; Gastrointestinal; Musculoskeletal; Neurologic; Ophthalmologic; Renal | 1552542; 10398262; 10694306; 8745901; 18984066; 19361614; 20672378; 22105905; 24313295; 27380894 |
ClinVar
This is a list of variants' phenotypes submitted to
- not_provided (163 variants)
- not_specified (38 variants)
- Inborn_genetic_diseases (28 variants)
- IFAP_syndrome_1,_with_or_without_BRESHECK_syndrome (14 variants)
- MBTPS2-related_disorder (12 variants)
- Osteogenesis_imperfecta,_type_19 (6 variants)
- Olmsted_syndrome,_X-linked (5 variants)
- Keratosis_follicularis_spinulosa_decalvans,_X-linked (4 variants)
- Osteogenesis_imperfecta (4 variants)
- Intellectual_disability (3 variants)
- Dystonia,_early-onset,_and/or_spastic_paraplegia (1 variants)
- Congenital_heart_disease (1 variants)
- Abnormality_of_neuronal_migration (1 variants)
- Skeletal_dysplasia (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the MBTPS2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000015884.4. 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 | 30 | 39 | ||||
| missense | 10 | 77 | 18 | 113 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 10 | 4 | 80 | 48 | 10 |
Highest pathogenic variant AF is 9.10803e-7
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| MBTPS2 | protein_coding | protein_coding | ENST00000379484 | 11 | 45789 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.998 | 0.00248 | 0 | 0 | 0 | 0 | 0.00 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 2.09 | 112 | 194 | 0.577 | 0.0000143 | 3365 |
| Missense in Polyphen | 9 | 56.742 | 0.15861 | 962 | ||
| Synonymous | 0.136 | 69 | 70.4 | 0.979 | 0.00000509 | 1063 |
| Loss of Function | 3.89 | 0 | 17.6 | 0.00 | 0.00000125 | 295 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00 | 0.00 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.00 | 0.00 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Intramembrane proteolysis of sterol-regulatory element- binding proteins (SREBPs) within the first transmembrane segment thereby releasing the N-terminal segment with a portion of the transmembrane segment attached. Site-2 cleavage comes after site-1 cleavage which takes place in the lumenal loop.;
- Disease
- DISEASE: Olmsted syndrome, X-linked (OLMSX) [MIM:300918]: A rare congenital disorder characterized by bilateral mutilating palmoplantar keratoderma and periorificial keratotic plaques with severe itching at all lesions. Diffuse alopecia, constriction of digits, and onychodystrophy have also been reported. Infections and squamous cell carcinomas can arise on the keratotic areas. The digital constriction may progress to autoamputation of fingers and toes. {ECO:0000269|PubMed:22931912}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Keratosis follicularis spinulosa decalvans X-linked (KFSDX) [MIM:308800]: A rare disorder affecting the skin and the eye. Affected men show thickening of the skin of the neck, ears, and extremities, especially the palms and soles, loss of eyebrows, eyelashes and beard, thickening of the eyelids with blepharitis and ectropion, and corneal degeneration. {ECO:0000269|PubMed:20672378}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Protein processing in endoplasmic reticulum - Homo sapiens (human);Sterol Regulatory Element-Binding Proteins (SREBP) signalling;ATF6 (ATF6-alpha) activates chaperones;Metabolism of lipids;Unfolded Protein Response (UPR);Metabolism of proteins;Regulation of cholesterol biosynthesis by SREBP (SREBF);Metabolism;CREB3 factors activate genes;Transport of small molecules;Metabolism of steroids;srebp control of lipid synthesis;Assembly of active LPL and LIPC lipase complexes;Plasma lipoprotein assembly, remodeling, and clearance;Plasma lipoprotein remodeling
(Consensus)
Intolerance Scores
- loftool
- 0.0889
- rvis_EVS
- -0.56
- rvis_percentile_EVS
- 19.31
Haploinsufficiency Scores
- pHI
- 0.240
- hipred
- Y
- hipred_score
- 0.728
- ghis
- 0.678
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- S
- essential_gene_gene_trap
- K
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.843
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Mbtps2
- Phenotype
Zebrafish Information Network
- Gene name
- mbtps2
- Affected structure
- lipid localization
- Phenotype tag
- abnormal
- Phenotype quality
- disrupted
Gene ontology
- Biological process
- cholesterol metabolic process;endoplasmic reticulum unfolded protein response;membrane protein intracellular domain proteolysis;response to endoplasmic reticulum stress;ATF6-mediated unfolded protein response;regulation of cholesterol biosynthetic process;positive regulation of DNA-binding transcription factor activity;bone maturation;positive regulation of transcription from RNA polymerase II promoter in response to endoplasmic reticulum stress
- Cellular component
- Golgi membrane;cytoplasm;endoplasmic reticulum membrane;integral component of membrane
- Molecular function
- metalloendopeptidase activity;metal ion binding