TYROBP
transmembrane immune signaling adaptor TYROBP
Basic information
Region (hg38): 19:35904400-35908295
Previous symbols: [ "PLOSL" ]
Links
Phenotypes
GenCC
Source:
- polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 1 (Strong), mode of inheritance: AR
- polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 1 (Strong), mode of inheritance: AR
- polycystic lipomembranous osteodysplasia with sclerosing leukoencephaly (Supportive), mode of inheritance: AR
- polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 1 (Moderate), mode of inheritance: AR
- polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 1 (Strong), mode of inheritance: AR
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 1 (Nasu-Hakola disease) | AR | 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 | Musculoskeletal; Neurologic | 10888890; 12370476; 15049507; 15883308; 17125796; 22082900 |
ClinVar
This is a list of variants' phenotypes submitted to
- not provided (70 variants)
- Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 1 (21 variants)
- Inborn genetic diseases (14 variants)
- not specified (5 variants)
- 9 conditions (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the TYROBP gene is commonly pathogenic or not.
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.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 11 | 12 | ||||
| missense | 34 | 39 | ||||
| nonsense | 2 | |||||
| start loss | 0 | |||||
| frameshift | 1 | |||||
| inframe indel | 1 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region ? | 3 | 2 | 5 | |||
| non coding ? | 11 | 22 | ||||
| Total | 1 | 1 | 43 | 26 | 6 |
Variants in TYROBP
This is a list of pathogenic ClinVar variants found in the TYROBP region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| TYROBP | protein_coding | protein_coding | ENST00000262629 | 5 | 3895 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.202 | 0.758 | 125638 | 0 | 22 | 125660 | 0.0000875 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | -0.324 | 79 | 71.3 | 1.11 | 0.00000460 | 694 |
| Missense in Polyphen | 13 | 23.598 | 0.55089 | 278 | ||
| Synonymous | -0.843 | 41 | 34.7 | 1.18 | 0.00000239 | 256 |
| Loss of Function | 1.71 | 2 | 6.84 | 0.292 | 3.79e-7 | 67 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000625 | 0.0000625 |
| Ashkenazi Jewish | 0.0000996 | 0.0000993 |
| East Asian | 0.000163 | 0.000163 |
| Finnish | 0.000545 | 0.000508 |
| European (Non-Finnish) | 0.0000268 | 0.0000264 |
| Middle Eastern | 0.000163 | 0.000163 |
| South Asian | 0.00 | 0.00 |
| Other | 0.000331 | 0.000326 |
dbNSFP
Source:
- Function
- FUNCTION: Non-covalently associates with activating receptors of the CD300 family. Cross-linking of CD300-TYROBP complexes results in cellular activation. Involved for instance in neutrophil activation mediated by integrin.;
- Disease
- DISEASE: Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL) [MIM:221770]: Recessively inherited disease characterized by a combination of psychotic symptoms rapidly progressing to presenile dementia and bone cysts restricted to wrists and ankles. PLOSL has a global distribution, although most of the patients have been diagnosed in Finland and Japan, with an estimated population prevalence of 2x10(-6) in the Finns. {ECO:0000269|PubMed:10888890, ECO:0000269|PubMed:12370476}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Natural killer cell mediated cytotoxicity - Homo sapiens (human);Osteoclast differentiation - Homo sapiens (human);Microglia Pathogen Phagocytosis Pathway;TYROBP Causal Network;Fibrin Complement Receptor 3 Signaling Pathway;Developmental Biology;Neutrophil degranulation;DAP12 signaling;DAP12 interactions;Innate Immune System;Immune System;Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell;Adaptive Immune System;Other semaphorin interactions;Semaphorin interactions;Axon guidance;Signal regulatory protein family interactions;Cell-Cell communication;RANKL
(Consensus)
Recessive Scores
- pRec
- 0.311
Intolerance Scores
- loftool
- 0.185
- rvis_EVS
- 0.24
- rvis_percentile_EVS
- 68.98
Haploinsufficiency Scores
- pHI
- 0.141
- hipred
- Y
- hipred_score
- 0.624
- ghis
- 0.505
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.510
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Tyrobp
- Phenotype
- growth/size/body region phenotype; endocrine/exocrine gland phenotype; craniofacial phenotype; cellular phenotype; homeostasis/metabolism phenotype; skeleton phenotype; embryo phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); reproductive system phenotype; hematopoietic system phenotype; limbs/digits/tail 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); immune system phenotype;
Gene ontology
- Biological process
- macrophage activation involved in immune response;cellular defense response;signal transduction;integrin-mediated signaling pathway;osteoclast differentiation;intracellular signal transduction;neutrophil degranulation;innate immune response;regulation of immune response;regulation of osteoclast development
- Cellular component
- plasma membrane;integral component of plasma membrane;cell surface;secretory granule membrane
- Molecular function
- signaling receptor binding;protein binding;identical protein binding