SYK (Tyrosine-protein kinase SYK) variants and mutations
SYK (also known as Tyrosine-protein kinase SYK) is a human protein-coding gene encoding a tyrosine-protein kinase protein. It transmits signals from immunoreceptors containing ITAM motifs, including the B-cell receptor and Fc receptors, to downstream calcium, NF-kappaB, and MAPK pathways. Aberrant activity contributes to B-cell malignancy and autoimmune inflammation and is therapeutically targetable. This analysis covers 1,221 SYK variants and mutations. Of these, 55% have computational variant effect predictions. Disease context includes immunodeficiency 82 with systemic inflammation, cutaneous leishmaniasis, and Immunodeficiency. Example SYK variants include A2G, A2T, and A2V.
Variant analysis overview
- Gene: SYK
- Protein: Tyrosine-protein kinase SYK
- UniProt accession: P43405
- Organism: Homo sapiens
- Variants analyzed: 1221
- Variant scope: all variants
- Completed: 2026-08-19
Variant and mutation evidence
- Variant composition: 971 unspecified-consequence records; 100 missense variants; 134 synonymous variants; 7 frameshift variants; 3 stop-gained variants; 4 in-frame deletions; 1 splice-region variants; 1 substitution
- Prediction scores: 673 variants have prediction scores (55% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: immunodeficiency 82 with systemic inflammation, cutaneous leishmaniasis, Immunodeficiency, Decreased circulating immunoglobulin concentration, autoimmune thrombocytopenic purpura, Thrombocytopenia, colitis, Skin rash, Arthritis, rheumatoid arthritis, lung carcinoma, agammaglobulinemia.
Protein structure and variant hotspots
- Protein features: 3 domains; 2 binding sites; 31 post-translational modification sites.
- Structural context: 840 variants have structural context.
- PTM context: 43 variants overlap post-translational modification sites.
Data sources
Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, 3D Hotspot Analysis, Interaction Network Analysis, Protein Data Bank, AlphaFold DB, gnomAD constraint, Open Targets, MaveDB, LitVar.
Notable SYK variants
Examples include A2G, A2T, A2V, A2S, A2D, A2A, S3N, S3R. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- A2G (p.Ala2Gly), Ensembl rs2118627787
- A2T (p.Ala2Thr), Ensembl rs201301123, REVEL 0.11, CADD 19.20, Uncertain significance, not specified
- A2V (p.Ala2Val), cosmic curated COSV10748, Ensembl rs2118627787, REVEL 0.09, CADD 16.00
- A2S (p.Ala2Ser), gnomAD 9-90843902-G-T, REVEL 0.09, CADD 13.90
- A2D (p.Ala2Asp), gnomAD 9-90843903-C-A, REVEL 0.36, CADD 15.80
- A2A (p.Ala2Ala), gnomAD 9-90843904-C-A, CADD 3.07
- S3N (p.Ser3Asn), cosmic curated COSV65328, Ensembl rs2118627825, REVEL 0.13, CADD 7.10
- S3R (p.Ser3Arg), TOPMed rs1233984148, REVEL 0.29, CADD 8.70
- S3T (p.Ser3Thr), Ensembl rs2118627825
- S3I (p.Ser3Ile), gnomAD 9-90843906-G-T, REVEL 0.10, CADD 14.20
- S3S (p.Ser3Ser), rs1233984148, gnomAD 9-90843907-C-T, CADD 6.01
- S4N (p.Ser4Asn), Ensembl rs1587850524
- S4G (p.Ser4Gly), gnomAD 9-90843908-A-G, REVEL 0.15, CADD 10.60
- S4I (p.Ser4Ile), gnomAD 9-90843909-G-T, REVEL 0.12, CADD 12.50
- S4S (p.Ser4Ser), rs199823436, gnomAD 9-90843910-C-T, CADD 5.59
- S4R (p.Ser4Arg), gnomAD 9-90843910-C-G, REVEL 0.20, CADD 14.30
- G5A (p.Gly5Ala), 1000Genomes rs2118628028
- G5D (p.Gly5Asp), 1000Genomes rs2118628028, REVEL 0.18, CADD 6.16
- G5R (p.Gly5Arg), ESP rs146743944, ExAC rs146743944, TOPMed rs146743944, gnomAD rs146743944, REVEL 0.19, CADD 1.01
- G5S (p.Gly5Ser), cosmic curated COSV10943, ESP rs146743944, ExAC rs146743944, TOPMed rs146743944, REVEL 0.12, CADD 0.42, Likely benign, not specified
- G5C (p.Gly5Cys), gnomAD 9-90843911-G-T, REVEL 0.19, CADD 4.75
- G5V (p.Gly5Val), gnomAD 9-90843912-G-T, REVEL 0.21, CADD 8.13
- G5G (p.Gly5Gly), gnomAD 9-90843913-C-A, CADD 4.90
- M6I (p.Met6Ile), Ensembl rs2118628166, REVEL 0.14, CADD 11.40
- M6T (p.Met6Thr), ExAC rs201350143, TOPMed rs201350143, gnomAD rs201350143, REVEL 0.17, CADD 12.10
- M6V (p.Met6Val), ExAC rs758533611, gnomAD rs758533611, REVEL 0.12, CADD 13.40
- A7G (p.Ala7Gly), ExAC rs756007618, TOPMed rs756007618, gnomAD rs756007618, REVEL 0.13, CADD 14.10
- A7P (p.Ala7Pro), ExAC rs752678021
- A7T (p.Ala7Thr), ExAC rs752678021, REVEL 0.10, CADD 10.90
- A7V (p.Ala7Val), ExAC rs756007618, TOPMed rs756007618, gnomAD rs756007618, REVEL 0.06, CADD 14.10
- A7S (p.Ala7Ser), gnomAD 9-90843917-G-T, REVEL 0.09, CADD 10.20
- A7D (p.Ala7Asp), gnomAD 9-90843918-C-A, REVEL 0.12, CADD 14.10
- A7A (p.Ala7Ala), gnomAD 9-90843919-T-C, CADD 2.60
- D8E (p.Asp8Glu), TOPMed rs1303089710, gnomAD rs1303089710, NCI-TCGA TCGA novel, REVEL 0.36, CADD 17.80, Variant assessed as somatic; high impact.
- D8G (p.Asp8Gly), Ensembl rs2118628317
- D8N (p.Asp8Asn), cosmic curated COSV65328, Ensembl rs2118628288, REVEL 0.23, CADD 22.80
- D8Y (p.Asp8Tyr), gnomAD 9-90843920-G-T, REVEL 0.61, CADD 26.00
- D8D (p.Asp8Asp), rs1303089710, gnomAD 9-90843922-C-T, CADD 8.78
- S9G (p.Ser9Gly), Ensembl rs2118628381, REVEL 0.09, CADD 11.50
- S9N (p.Ser9Asn), Ensembl rs2118628410, REVEL 0.06, CADD 4.17
- S9R (p.Ser9Arg), cosmic curated COSV10748, REVEL 0.20, CADD 4.60
- S9C (p.Ser9Cys), gnomAD 9-90843923-A-T, REVEL 0.20, CADD 16.90
- S9I (p.Ser9Ile), gnomAD 9-90843924-G-T, REVEL 0.10, CADD 6.73
- S9S (p.Ser9Ser), rs201458538, gnomAD 9-90843925-C-T, CADD 5.12
- A10P (p.Ala10Pro), ExAC rs199606629, TOPMed rs199606629, gnomAD rs199606629, REVEL 0.43, CADD 28.20
- A10S (p.Ala10Ser), ExAC rs199606629, TOPMed rs199606629, gnomAD rs199606629, REVEL 0.32, CADD 24.20
- A10T (p.Ala10Thr), ExAC rs199606629, TOPMed rs199606629, gnomAD rs199606629, REVEL 0.35, CADD 26.40
- A10A (p.Ala10Ala), gnomAD 9-90843928-C-T, CADD 9.82
- N11T (p.Asn11Thr), Ensembl rs2118628512
- N11S (p.Asn11Ser), gnomAD 9-90843930-A-G, REVEL 0.01, CADD 12.70
- N11N (p.Asn11Asn), rs1010285262, gnomAD 9-90843931-C-T, CADD 9.91
- N11K (p.Asn11Lys), gnomAD 9-90843931-C-A, REVEL 0.06, CADD 14.70
- H12Q (p.His12Gln), TOPMed rs1373206128, gnomAD rs1373206128, REVEL 0.03, CADD 18.00
- H12N (p.His12Asn), gnomAD 9-90843932-C-A, REVEL 0.03, CADD 14.20
- H12H (p.His12His), rs1373206128, gnomAD 9-90843934-C-T, CADD 9.94
- L13M (p.Leu13Met), gnomAD 9-90843935-C-A, REVEL 0.26, CADD 22.50
- L13Q (p.Leu13Gln), gnomAD 9-90843936-T-A, REVEL 0.47, CADD 28.50
- L13L (p.Leu13Leu), gnomAD 9-90843937-G-T, CADD 10.20
- P14H (p.Pro14His), NCI-TCGA Cosmic COSV1010, cosmic curated COSV10100, Variant assessed as somatic; moderate impact.
- P14S (p.Pro14Ser), gnomAD 9-90843938-C-T, REVEL 0.19, CADD 22.90
- P14T (p.Pro14Thr), gnomAD 9-90843938-C-A, REVEL 0.13, CADD 22.60
- P14L (p.Pro14Leu), gnomAD 9-90843939-C-T, REVEL 0.18, CADD 23.10
- P14P (p.Pro14Pro), gnomAD 9-90843940-C-A, CADD 8.82
- F15L (p.Phe15Leu), Ensembl rs2118628639, REVEL 0.69, CADD 24.90
- F16I (p.Phe16Ile), cosmic curated COSV65329
- F16L (p.Phe16Leu), Ensembl rs1021305539, REVEL 0.43, CADD 24.60
- F17L (p.Phe17Leu), NCI-TCGA Cosmic COSV1010, cosmic curated COSV10100, REVEL 0.23, CADD 24.80, Variant assessed as somatic; moderate impact.
- F17Y (p.Phe17Tyr), NCI-TCGA Cosmic COSV1010, cosmic curated COSV10100, Variant assessed as somatic; moderate impact.
- F17S (p.Phe17Ser), rs2118628727, gnomAD 9-90843943-CT-C, CADD 27.80
- F17F (p.Phe17Phe), rs200626943, gnomAD 9-90843949-C-T, CADD 2.86
- G18D (p.Gly18Asp), cosmic curated COSV65328, Ensembl rs2118628863, REVEL 0.69, CADD 27.70
- G18R (p.Gly18Arg), ExAC rs752280694, gnomAD rs752280694
- G18S (p.Gly18Ser), ExAC rs752280694, gnomAD rs752280694, REVEL 0.51, CADD 32.00
- G18C (p.Gly18Cys), gnomAD 9-90843950-G-T, REVEL 0.65, CADD 29.70
- G18G (p.Gly18Gly), rs2118628902, gnomAD 9-90843952-C-T, CADD 11.50
- N19S (p.Asn19Ser), ExAC rs745568763, TOPMed rs745568763, gnomAD rs745568763, REVEL 0.33, CADD 19.30
- N19Y (p.Asn19Tyr), gnomAD 9-90843953-A-T, REVEL 0.86, CADD 26.80
- N19D (p.Asn19Asp), gnomAD 9-90843953-A-G, REVEL 0.60, CADD 24.10
- N19K (p.Asn19Lys), gnomAD 9-90843955-C-A, REVEL 0.51, CADD 21.10
- N19N (p.Asn19Asn), rs771597099, gnomAD 9-90843955-C-T, CADD 9.16
- I20V (p.Ile20Val), ExAC rs774928285, TOPMed rs774928285, gnomAD rs774928285, REVEL 0.53, CADD 23.20, Uncertain significance, not specified
- I20I (p.Ile20Ile), rs1826472008, gnomAD 9-90843958-C-T, CADD 12.80
- T21I (p.Thr21Ile), ExAC rs758018137, gnomAD rs758018137
- T21N (p.Thr21Asn), ExAC rs758018137, gnomAD rs758018137, REVEL 0.15, CADD 24.70
- T21S (p.Thr21Ser), ExAC rs758018137, gnomAD rs758018137, REVEL 0.20, CADD 22.30
- T21T (p.Thr21Thr), gnomAD 9-90843961-C-A, CADD 7.71
- R22G (p.Arg22Gly), NCI-TCGA TCGA novel, Ensembl rs1564088424, Uncertain significance
- R22L (p.Arg22Leu), ESP rs140421546, ExAC rs140421546, TOPMed rs140421546, gnomAD rs140421546, REVEL 0.95, CADD 29.80
- R22P (p.Arg22Pro), ESP rs140421546, ExAC rs140421546, TOPMed rs140421546, gnomAD rs140421546
- R22Q (p.Arg22Gln), cosmic curated COSV65328, ESP rs140421546, ExAC rs140421546, TOPMed rs140421546, REVEL 0.91, CADD 31.00
- R22W (p.Arg22Trp), rs1564088424, Ensembl rs1564088424, REVEL 0.89, CADD 26.90, Uncertain significance, not provided
- R22R (p.Arg22Arg), gnomAD 9-90843962-C-A, CADD 12.40
- E23K (p.Glu23Lys), Ensembl rs2118629309, REVEL 0.66, CADD 25.00
- E23Q (p.Glu23Gln), Ensembl rs2118629309
- E23* (p.Glu23Ter), gnomAD 9-90843965-G-T, CADD 38.00
- E23E (p.Glu23Glu), rs1484384291, gnomAD 9-90843967-G-A, CADD 10.30
- E24V (p.Glu24Val), Ensembl rs2118629371
- E24G (p.Glu24Gly), gnomAD 9-90843969-A-G, REVEL 0.85, CADD 31.00
- A25E (p.Ala25Glu), Ensembl rs2118629439, REVEL 0.47, CADD 26.00
- A25G (p.Ala25Gly), Ensembl rs2118629439
- A25T (p.Ala25Thr), Ensembl rs752718360, REVEL 0.28, CADD 27.00
- A25A (p.Ala25Ala), gnomAD 9-90843973-A-G, CADD 3.83
- E26K (p.Glu26Lys), cosmic curated COSV65328
- E26del (p.Glu26del), gnomAD 9-90843972-CAGA-C, CADD 21.20
- D27E (p.Asp27Glu), Ensembl rs200577589
- D27G (p.Asp27Gly), TOPMed rs1826473169
- D27H (p.Asp27His), TOPMed rs1826473029
- D27N (p.Asp27Asn), cosmic curated COSV65325
- D27Y (p.Asp27Tyr), gnomAD 9-90843977-G-T, REVEL 0.63, CADD 25.30
- Y28D (p.Tyr28Asp), NCI-TCGA Cosmic COSV6532, cosmic curated COSV65326, Variant assessed as somatic; moderate impact.
- L29M (p.Leu29Met), TOPMed rs1276343036, gnomAD rs1276343036, REVEL 0.43, CADD 24.20
- L29V (p.Leu29Val), cosmic curated COSV65327, TOPMed rs1276343036, gnomAD rs1276343036
- L29L (p.Leu29Leu), rs1276343036, gnomAD 9-90843983-C-T, CADD 11.10
- V30D (p.Val30Asp), ExAC rs765749869, gnomAD rs765749869
- V30G (p.Val30Gly), ExAC rs765749869, gnomAD rs765749869, REVEL 0.25, CADD 22.30
- V30I (p.Val30Ile), gnomAD 9-90843986-G-A, REVEL 0.19, CADD 20.40
- V30V (p.Val30Val), rs2118629729, gnomAD 9-90843988-C-G, CADD 7.77
- Q31* (p.Gln31Ter), cosmic curated COSV65325
- Q31H (p.Gln31His), Ensembl rs2118629836
- Q31K (p.Gln31Lys), Ensembl rs2118629762
- Q31R (p.Gln31Arg), TOPMed rs1826473835, REVEL 0.62, CADD 23.30
- Q31L (p.Gln31Leu), gnomAD 9-90843990-A-T, REVEL 0.39, CADD 21.50
- Q31Q (p.Gln31Gln), gnomAD 9-90843991-G-A, CADD 9.73
- G32V (p.Gly32Val), cosmic curated COSV10531
- G32E (p.Gly32Glu), gnomAD 9-90843993-G-A, REVEL 0.05, CADD 21.90
- G32G (p.Gly32Gly), rs773557717, gnomAD 9-90843994-G-C, CADD 1.54
- G33A (p.Gly33Ala), ExAC rs766412303, TOPMed rs766412303, gnomAD rs766412303, REVEL 0.24, CADD 26.30
- G33D (p.Gly33Asp), cosmic curated COSV65326, ExAC rs766412303, TOPMed rs766412303, gnomAD rs766412303, REVEL 0.50, CADD 27.50
- G33S (p.Gly33Ser), cosmic curated COSV65330, ExAC rs201364101, TOPMed rs201364101, gnomAD rs201364101, REVEL 0.22, CADD 24.40
- G33V (p.Gly33Val), gnomAD 9-90843996-G-T, REVEL 0.60, CADD 27.30
- G33G (p.Gly33Gly), rs1377864077, gnomAD 9-90843997-C-T, CADD 11.70
- M34I (p.Met34Ile), gnomAD rs1174684222, REVEL 0.41, CADD 23.40
- M34R (p.Met34Arg), ExAC rs756261006, TOPMed rs756261006, gnomAD rs756261006, REVEL 0.58, CADD 23.90
- M34H (p.Met34His), rs1182878074, gnomAD 9-90843990-A-AG, CADD 28.00
- S35N (p.Ser35Asn), TOPMed rs1277403436, REVEL 0.08, CADD 14.80
- S35R (p.Ser35Arg), Ensembl rs2118630296, REVEL 0.37, CADD 0.13
- D36E (p.Asp36Glu), TOPMed rs1225805514
- D36N (p.Asp36Asn), Ensembl rs2118630345, REVEL 0.34, CADD 22.50
- D36D (p.Asp36Asp), rs1225805514, gnomAD 9-90844006-T-C, CADD 3.17
- G37E (p.Gly37Glu), Ensembl rs2118630447
- G37R (p.Gly37Arg), cosmic curated COSV65325
- G37V (p.Gly37Val), Ensembl rs2118630447
- G37G (p.Gly37Gly), rs1400590058, gnomAD 9-90844009-G-C, CADD 8.37
- L38F (p.Leu38Phe), Ensembl rs2118630553, REVEL 0.69, CADD 24.50
- L38V (p.Leu38Val), Ensembl rs2118630553
- Y39F (p.Tyr39Phe), Ensembl rs2118630650
- Y39H (p.Tyr39His), rs1434639334, NCI-TCGA Cosmic COSV1010, cosmic curated COSV10100, gnomAD rs1434639334, AlphaMissense 0.93, MetaLR 0.85, Variant assessed as somatic; moderate impact.
- L40F (p.Leu40Phe), TOPMed rs1352390840, gnomAD rs1352390840, REVEL 0.49, CADD 25.70
- L40M (p.Leu40Met), ExAC rs764046624, gnomAD rs764046624, REVEL 0.58, CADD 23.70
- L40L (p.Leu40Leu), rs1352390840, gnomAD 9-90844018-G-A, CADD 10.90
- L41Q (p.Leu41Gln), Ensembl rs2118630852
- L41L (p.Leu41Leu), rs2118630815, gnomAD 9-90844019-C-T, CADD 12.00
- L41P (p.Leu41Pro), gnomAD 9-90844020-T-C, REVEL 0.96, CADD 29.10
- R42C (p.Arg42Cys), cosmic curated COSV65325, Ensembl rs2118630902, REVEL 0.95, CADD 28.70
- R42H (p.Arg42His), rs1408106520, NCI-TCGA Cosmic COSV6532, cosmic curated COSV65326, REVEL 0.96, CADD 31.00, Variant assessed as somatic; moderate impact.
- R42L (p.Arg42Leu), TOPMed rs1408106520, gnomAD rs1408106520, REVEL 0.98, CADD 31.00
- R42P (p.Arg42Pro), cosmic curated COSV65326
- R42R (p.Arg42Arg), rs753813101, gnomAD 9-90844024-C-T, CADD 10.90
- Q43K (p.Gln43Lys), Ensembl rs2118631054
- Q43Q (p.Gln43Gln), rs35758162, gnomAD 9-90844027-G-A, CADD 9.94
- S44G (p.Ser44Gly), cosmic curated COSV65325
- S44I (p.Ser44Ile), cosmic curated COSV65327
- S44N (p.Ser44Asn), Ensembl rs2118631166
- S44T (p.Ser44Thr), Ensembl rs2118631166
- S44S (p.Ser44Ser), rs2118631223, gnomAD 9-90844030-C-T, CADD 9.38
- S44R (p.Ser44Arg), gnomAD 9-90844030-C-A, REVEL 0.81, CADD 20.80
- R45C (p.Arg45Cys), cosmic curated COSV10100, TOPMed rs1235073402, gnomAD rs1235073402, REVEL 0.78, CADD 29.50
- R45H (p.Arg45His), rs16906862, cosmic curated COSV65327, UniProt VAR 033838, ExAC rs16906862, REVEL 0.51, CADD 27.80
- R45L (p.Arg45Leu), ExAC rs16906862, gnomAD rs16906862, REVEL 0.64, CADD 23.30
- R45P (p.Arg45Pro), ExAC rs16906862, gnomAD rs16906862, REVEL 0.71, CADD 28.20
- R45R (p.Arg45Arg), rs201774526, gnomAD 9-90844033-C-A, CADD 11.30
- N46I (p.Asn46Ile), gnomAD rs1205743055
- N46S (p.Asn46Ser), gnomAD rs1205743055, REVEL 0.05, CADD 17.90
- N46T (p.Asn46Thr), gnomAD rs1205743055
- Y47* (p.Tyr47Ter), Ensembl rs2118631586
- Y47C (p.Tyr47Cys), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- Y47N (p.Tyr47Asn), cosmic curated COSV65330
- L48L (p.Leu48Leu), rs2118631650, gnomAD 9-90844040-C-T, CADD 9.93
- G49S (p.Gly49Ser), rs2118631757, ClinGen CA373790003, ClinVar RCV003425704, NCI-TCGA TCGA novel, REVEL 0.90, CADD 28.00, Uncertain significance, not provided
- G49C (p.Gly49Cys), gnomAD 9-90844043-G-T, REVEL 0.98, CADD 29.30
Public SYK analysis runs
- SYK analysis run — SYK (1,221 variants) — completed 2026-08-19