MBTPS2

membrane bound transcription factor peptidase, site 2

Basic information

Region (hg38): X:21839617-21885423

Previous symbols: [ "KFSD" ]

Links

ENSG00000012174NCBI:51360OMIM:300294HGNC:15455Uniprot:O43462AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

Phenotypes

GenCC

Source: genCC

  • 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: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Keratosis follicularis spinulosa decalvans, X-linked; IFAP syndrome 1 with or without BRESHECK syndrome; Olmsted syndrome, X-linked; Osteogenesis imperfecta, type XIXXLGeneralGenetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testingCraniofacial; Dermatologic; Gastrointestinal; Musculoskeletal; Neurologic; Ophthalmologic; Renal1552542; 10398262; 10694306; 8745901; 18984066; 19361614; 20672378; 22105905; 24313295; 27380894

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MBTPS2 gene.

  • 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.

EffectPLPVUSLBBSum
synonymous
3
clinvar
30
clinvar
6
clinvar
39
missense
10
clinvar
4
clinvar
77
clinvar
18
clinvar
4
clinvar
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: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
MBTPS2protein_codingprotein_codingENST00000379484 1145789
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
0.9980.0024800000.00
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense2.091121940.5770.00001433365
Missense in Polyphen956.7420.15861962
Synonymous0.1366970.40.9790.000005091063
Loss of Function3.89017.60.000.00000125295

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.000.00
Ashkenazi Jewish0.000.00
East Asian0.000.00
Finnish0.000.00
European (Non-Finnish)0.000.00
Middle Eastern0.000.00
South Asian0.000.00
Other0.000.00

dbNSFP

Source: dbNSFP

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

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

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