SYK
spleen associated tyrosine kinase, the group of Syk family tyrosine kinases|SH2 domain containing
Basic information
Region (hg38): 9:90801786-90898549
Links
Phenotypes
GenCC
Source:
- immunodeficiency 82 with systemic inflammation (Strong), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Immunodeficiency 82 with systemic inflammation | AD | Allergy/Immunology/Infectious; Oncologic | The condition may involve immunodeficiency, and awareness may allow early and agressive management of infections; Some inflammatory manifestations have been reported as responding to medications such as steroids; An increased risk of lymphoma has been reported, and awareness may allow early diagnosis and management | Allergy/Immunology/Infectious; Oncologic | 33782605 |
ClinVar
This is a list of variants' phenotypes submitted to
- not specified (17 variants)
- not provided (6 variants)
- Inborn genetic diseases (6 variants)
- Immunodeficiency 82 with systemic inflammation (5 variants)
- Arthritis;Colitis;Skin rash;Immunodeficiency;Decreased circulating antibody level (3 variants)
- Arthritis;Colitis;Skin rash;Immunodeficiency (1 variants)
- Joint swelling;Colitis;Skin rash;Immunodeficiency;Decreased circulating antibody level (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the SYK 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 | 5 | |||||
| missense | 12 | 17 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region ? | 2 | 2 | ||||
| non coding ? | 10 | 10 | ||||
| Total | 1 | 2 | 12 | 1 | 16 |
Highest pathogenic variant AF is 0.00000657
Variants in SYK
This is a list of pathogenic ClinVar variants found in the SYK region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 9-90843821-G-A | not specified | Benign (Jan 24, 2024) | ||
| 9-90844043-G-A | Uncertain significance (Jan 01, 2023) | |||
| 9-90844052-G-T | Long QT syndrome | Likely benign (-) | ||
| 9-90844090-C-T | SYK-related disorder | Likely benign (Nov 23, 2022) | ||
| 9-90844091-A-G | not specified | Uncertain significance (Dec 19, 2023) | ||
| 9-90844206-T-G | not specified | Uncertain significance (Apr 12, 2022) | ||
| 9-90844394-A-G | not specified | Benign (Jan 24, 2024) | ||
| 9-90845564-T-C | not specified | Uncertain significance (Mar 07, 2023) | ||
| 9-90862315-G-A | Immunodeficiency 82 with systemic inflammation | Uncertain significance (Oct 29, 2021) | ||
| 9-90862338-C-T | SYK-related disorder | Likely benign (Nov 23, 2022) | ||
| 9-90864595-G-C | Uncertain significance (Jul 04, 2023) | |||
| 9-90864655-A-C | Benign (Dec 31, 2019) | |||
| 9-90865202-C-T | not specified | Benign (Jan 24, 2024) | ||
| 9-90867065-G-A | not specified | Benign (Jan 24, 2024) | ||
| 9-90874226-G-A | not specified | Uncertain significance (Nov 02, 2023) | ||
| 9-90874382-G-A | not specified | Benign (Jan 24, 2024) | ||
| 9-90874692-C-A | Arthritis;Colitis;Skin rash;Immunodeficiency;Decreased circulating antibody level • Immunodeficiency 82 with systemic inflammation | Likely pathogenic (Dec 10, 2020) | ||
| 9-90874725-G-A | Arthritis;Colitis;Skin rash;Immunodeficiency | Uncertain significance (Dec 10, 2020) | ||
| 9-90874733-C-T | not specified | Benign (Jan 24, 2024) | ||
| 9-90874772-G-T | not specified | Uncertain significance (Jul 25, 2023) | ||
| 9-90877564-C-A | Benign (Dec 31, 2019) | |||
| 9-90877564-C-G | not specified | Benign (Jan 24, 2024) | ||
| 9-90877690-G-A | Immunodeficiency 82 with systemic inflammation | Uncertain significance (Mar 29, 2024) | ||
| 9-90877691-G-C | not specified | Benign (Jan 24, 2024) | ||
| 9-90877727-G-A | not specified | Benign (Jan 24, 2024) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| SYK | protein_coding | protein_coding | ENST00000375754 | 13 | 96763 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 1.00 | 0.000139 | 125741 | 0 | 7 | 125748 | 0.0000278 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 2.90 | 215 | 373 | 0.577 | 0.0000219 | 4159 |
| Missense in Polyphen | 81 | 201.72 | 0.40155 | 2219 | ||
| Synonymous | 0.704 | 139 | 150 | 0.927 | 0.00000988 | 1181 |
| Loss of Function | 5.10 | 2 | 34.1 | 0.0586 | 0.00000167 | 404 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000635 | 0.0000635 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.0000950 | 0.0000924 |
| European (Non-Finnish) | 0.0000177 | 0.0000176 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.000163 | 0.000163 |
dbNSFP
Source:
- Function
- FUNCTION: Non-receptor tyrosine kinase which mediates signal transduction downstream of a variety of transmembrane receptors including classical immunoreceptors like the B-cell receptor (BCR). Regulates several biological processes including innate and adaptive immunity, cell adhesion, osteoclast maturation, platelet activation and vascular development. Assembles into signaling complexes with activated receptors at the plasma membrane via interaction between its SH2 domains and the receptor tyrosine- phosphorylated ITAM domains. The association with the receptor can also be indirect and mediated by adapter proteins containing ITAM or partial hemITAM domains. The phosphorylation of the ITAM domains is generally mediated by SRC subfamily kinases upon engagement of the receptor. More rarely signal transduction via SYK could be ITAM-independent. Direct downstream effectors phosphorylated by SYK include VAV1, PLCG1, PI-3-kinase, LCP2 and BLNK. Initially identified as essential in B-cell receptor (BCR) signaling, it is necessary for the maturation of B-cells most probably at the pro-B to pre-B transition. Activated upon BCR engagement, it phosphorylates and activates BLNK an adapter linking the activated BCR to downstream signaling adapters and effectors. It also phosphorylates and activates PLCG1 and the PKC signaling pathway. It also phosphorylates BTK and regulates its activity in B-cell antigen receptor (BCR)-coupled signaling. In addition to its function downstream of BCR plays also a role in T- cell receptor signaling. Plays also a crucial role in the innate immune response to fungal, bacterial and viral pathogens. It is for instance activated by the membrane lectin CLEC7A. Upon stimulation by fungal proteins, CLEC7A together with SYK activates immune cells inducing the production of ROS. Also activates the inflammasome and NF-kappa-B-mediated transcription of chemokines and cytokines in presence of pathogens. Regulates neutrophil degranulation and phagocytosis through activation of the MAPK signaling cascade. Also mediates the activation of dendritic cells by cell necrosis stimuli. Also involved in mast cells activation. Involved in interleukin-3/IL3-mediated signaling pathway in basophils (By similarity). Also functions downstream of receptors mediating cell adhesion. Relays for instance, integrin-mediated neutrophils and macrophages activation and P-selectin receptor/SELPG-mediated recruitment of leukocytes to inflammatory loci. Plays also a role in non-immune processes. It is for instance involved in vascular development where it may regulate blood and lymphatic vascular separation. It is also required for osteoclast development and function. Functions in the activation of platelets by collagen, mediating PLCG2 phosphorylation and activation. May be coupled to the collagen receptor by the ITAM domain-containing FCER1G. Also activated by the membrane lectin CLEC1B that is required for activation of platelets by PDPN/podoplanin. Involved in platelet adhesion being activated by ITGB3 engaged by fibrinogen. Together with CEACAM20, enhances production of the cytokine CXCL8/IL-8 via the NFKB pathway and may thus have a role in the intestinal immune response (By similarity). {ECO:0000250|UniProtKB:P48025, ECO:0000269|PubMed:12387735, ECO:0000269|PubMed:12456653, ECO:0000269|PubMed:15388330, ECO:0000269|PubMed:19909739, ECO:0000269|PubMed:8657103, ECO:0000269|PubMed:9535867}.;
- Pathway
- PI3K-Akt signaling pathway - Homo sapiens (human);Platelet activation - Homo sapiens (human);B cell receptor signaling pathway - Homo sapiens (human);Fc epsilon RI signaling pathway - Homo sapiens (human);Fc gamma R-mediated phagocytosis - Homo sapiens (human);Kaposi,s sarcoma-associated herpesvirus infection - Homo sapiens (human);C-type lectin receptor signaling pathway - Homo sapiens (human);Tuberculosis - Homo sapiens (human);Natural killer cell mediated cytotoxicity - Homo sapiens (human);Phospholipase D signaling pathway - Homo sapiens (human);Viral carcinogenesis - Homo sapiens (human);Osteoclast differentiation - Homo sapiens (human);NF-kappa B signaling pathway - Homo sapiens (human);Epstein-Barr virus infection - Homo sapiens (human);Fc Epsilon Receptor I Signaling in Mast Cells;IL-5 Signaling Pathway;Regulation of toll-like receptor signaling pathway;RANKL-RANK (Receptor activator of NFKB (ligand)) Signaling Pathway;B Cell Receptor Signaling Pathway;IL-3 Signaling Pathway;Microglia Pathogen Phagocytosis Pathway;Fibrin Complement Receptor 3 Signaling Pathway;PI3K-Akt Signaling Pathway;IL-2 Signaling Pathway;Antigen activates B Cell Receptor (BCR) leading to generation of second messengers;Signal Transduction;Signaling by Interleukins;DAP12 signaling;DAP12 interactions;il 2 signaling pathway;ras-independent pathway in nk cell-mediated cytotoxicity;bcr signaling pathway;Cytokine Signaling in Immune system;B cell receptor signaling;Dectin-2 family;Signaling by the B Cell Receptor (BCR);FCGR activation;CLEC7A (Dectin-1) signaling;C-type lectin receptors (CLRs);Role of phospholipids in phagocytosis;Fcgamma receptor (FCGR) dependent phagocytosis;Integrin alphaIIb beta3 signaling;FCERI mediated MAPK activation;FCERI mediated Ca+2 mobilization;Fc epsilon receptor (FCERI) signaling;TCR;Innate Immune System;Immune System;Interleukin-2 family signaling;Adaptive Immune System;BCR;GPVI-mediated activation cascade;Platelet Aggregation (Plug Formation);Platelet activation, signaling and aggregation;IL-7 signaling;fc epsilon receptor i signaling in mast cells;Integrin signaling;Hemostasis;BCR signaling pathway;Thromboxane A2 receptor signaling;JAK STAT pathway and regulation;IL2;Regulation of actin dynamics for phagocytic cup formation;EPO signaling;IL3;IL2-mediated signaling events;Class I PI3K signaling events;Interleukin-2 signaling;IL4;IL5;TNFalpha;VEGF;Osteopontin-mediated events;GMCSF-mediated signaling events;Fc-epsilon receptor I signaling in mast cells;FAS (CD95) signaling pathway;Alpha-synuclein signaling;Atypical NF-kappaB pathway;Role of LAT2/NTAL/LAB on calcium mobilization;Regulation of signaling by CBL;Interleukin-3, 5 and GM-CSF signaling
(Consensus)
Recessive Scores
- pRec
- 0.665
Intolerance Scores
- loftool
- 0.00792
- rvis_EVS
- -0.76
- rvis_percentile_EVS
- 13.45
Haploinsufficiency Scores
- pHI
- 0.836
- hipred
- Y
- hipred_score
- 0.786
- ghis
- 0.612
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.990
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Syk
- Phenotype
- homeostasis/metabolism phenotype; cellular phenotype; endocrine/exocrine gland phenotype; 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); hematopoietic system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); 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); renal/urinary system phenotype; skeleton phenotype; immune system phenotype; liver/biliary system phenotype; respiratory system phenotype;
Zebrafish Information Network
- Gene name
- syk
- Affected structure
- thoracic duct
- Phenotype tag
- abnormal
- Phenotype quality
- aplastic
Gene ontology
- Biological process
- angiogenesis;lymph vessel development;positive regulation of receptor internalization;stimulatory C-type lectin receptor signaling pathway;adaptive immune response;macrophage activation involved in immune response;neutrophil activation involved in immune response;leukocyte activation involved in immune response;serotonin secretion by platelet;protein phosphorylation;protein import into nucleus;leukocyte cell-cell adhesion;integrin-mediated signaling pathway;activation of JUN kinase activity;cell population proliferation;animal organ morphogenesis;regulation of platelet activation;regulation of tumor necrosis factor-mediated signaling pathway;viral process;peptidyl-serine phosphorylation;peptidyl-tyrosine phosphorylation;leukotriene biosynthetic process;platelet activation;neutrophil chemotaxis;receptor internalization;positive regulation of type I interferon production;positive regulation of interleukin-4 production;regulation of superoxide anion generation;positive regulation of cell adhesion mediated by integrin;collagen-activated tyrosine kinase receptor signaling pathway;Fc-epsilon receptor signaling pathway;Fc-gamma receptor signaling pathway involved in phagocytosis;interleukin-2-mediated signaling pathway;interleukin-3-mediated signaling pathway;defense response to bacterium;positive regulation of mast cell degranulation;regulation of neutrophil degranulation;beta selection;innate immune response;positive regulation of interleukin-3 biosynthetic process;positive regulation of granulocyte macrophage colony-stimulating factor biosynthetic process;positive regulation of B cell differentiation;positive regulation of gamma-delta T cell differentiation;positive regulation of bone resorption;positive regulation of alpha-beta T cell differentiation;positive regulation of alpha-beta T cell proliferation;protein autophosphorylation;blood vessel morphogenesis;positive regulation of cytokine secretion;positive regulation of peptidyl-tyrosine phosphorylation;regulation of phagocytosis;positive regulation of calcium-mediated signaling;B cell receptor signaling pathway;regulation of DNA-binding transcription factor activity;regulation of ERK1 and ERK2 cascade;cellular response to molecule of fungal origin;cellular response to low-density lipoprotein particle stimulus;regulation of arachidonic acid secretion;regulation of platelet aggregation;positive regulation of cold-induced thermogenesis
- Cellular component
- nucleus;cytoplasm;cytosol;plasma membrane;B cell receptor complex;early phagosome;protein-containing complex;T cell receptor complex
- Molecular function
- phosphotyrosine residue binding;protein kinase activity;protein serine/threonine kinase activity;protein tyrosine kinase activity;non-membrane spanning protein tyrosine kinase activity;integrin binding;protein binding;ATP binding;protein kinase binding;phosphatase binding;Toll-like receptor binding;SH2 domain binding