St. Jude Research

SH2B3 Database

SH2B3 Visualization

The SH2B3 Database is a curated repository of germline SH2B3 variants identified in patients through published literature. Our goal is to provide a comprehensive knowledge base for understanding germline SH2B3 disorders, which have been recently recognized as novel bone marrow failure predispositions.

If you are interested in contributing variants, please contact wlodarskilab@stjude.org

SH2B3 transcript version is NM_005475.2. Curated by Lili Kotmayer, MD, PhD. Last updated: 07/29/2025.

Patient ID SH2B3 mutation (cDNA) SH2B3 mutation (Protein) Type of mutation Zygosity Mutation origin gnomAD (v4.1.0) population frequency Year of reporting PMID Patient also reported in (PMID) Original patient ID Disease Gender (M/F) Age at first presentation Peripheral blood at presentation Bone marrow at presentation Cytogenetics Organomegaly Autoimmunity Musculoskeletal changes Neurocognitive symptoms Other symptoms Co-occurring somatic mutations HSCT Outcome Notes
P001 c.671insGGCCCCG p.Asp231GlyfsX38 Frameshift Homozygous Germline Absent 2013 23908464   Sibling 1 (proband) Autoimmunity only M 6 years Anemia, thrombocytopenia, high WBC at birth Normocellular with 10-15% blasts, no megakaryocytes NA Hepatosplenomegaly Hashimoto thyroiditis, autoimmune hepatitis Growth retardation, developmental delay Speech delay       Alive and well Consanguineous parents, brother of Sibling 2
P002 c.671insGGCCCCG p.Asp231GlyfsX38 Frameshift Homozygous Germline Absent 2013 23908464   Sibling 2 B-precursor ALL + autoimmunity F 18 months     Normal   Hashimoto thyroiditis, autoimmune hepatitis Growth retardation, developmental delay   CDKN2A deletion     Consanguineous parents, sister of Sibling 1 (proband)
P003 c.1279insCTGTTGCCGTGTGC p.Gln427ProfsX40 Frameshift Homozygous Unknown Absent 2013 23908464   Cohort Case 1 B-precursor ALL NR NR     NA                 From screening of 167 ALL patients
P004 c.1670T>G p.Leu438Arg Missense Homozygous Germline Absent 2024 38152053 40481232 UPN3426 / P4.1 JMML-like, transient M 8 months Thrombocytopenia, leukocytosis, monocytosis, later thrombocytosis Normal Hepatosplenomegaly   IUGR, absence of one finger in the right hand Speech delay Intracranial and intrahepatic calcifications   Alive, spontaneous improvement Consanguineous parents
P005 c.1175G>A p.Arg392Gln Missense Homozygous Germline 0.00068% 2024 38152053 40481232 UPN3436 / P5.1 JMML F 4 months Leukocytosis, anemia, thrombocytopenia at 4 months Dysmegakaryopoiesis with 4% blasts NA     IUGR, growth retardation Speech and walking delay     yes Alive and well Consanguineous parents
P006 c.1108C>T p.Gln251X Nonsense Heterozygous Germline Absent 2024 38152053   UPN1744 JMML F 2 months Leukocytosis, thrombocytopenia   NA Splenomegaly           yes Alive 14 years post-HCT  
P007 NA p.Met211fsX57 Frameshift Heterozygous Germline + somatic LOH Absent 2024 38152053   UPN3160 JMML M 4 months Anemia, leukocytosis, peripheral monocytosis, 5% myeloblasts Myeloid hyperplasia Copy-neutral LOH 12q21.1-12q24.33             yes Alive, in remission 2 years post-HCT Responded to ruxolitinib
P008 c.441_468del p.Arg148ProfsX40 Frameshift Homozygous Germline 0.000067% 2023 37206266   Patient 1 Myeloproliferation + autoimmunity M 3 months Thrombocytosis, neutrophilia Myeloid hyperplasia with megakaryocytic hyperplasia and atypia NA Splenomegaly Alopecia areata, autoimmune hypothyroidism         Alive and well at age 18 years
P009 c.1204G>A p.Val402Met Missense Homozygous Germline 0.00074% 2023 37206266   Patient 2 Myeloproliferation + autoimmunity + thrombosis M Birth Persistent thrombocytosis Mildly hypercellular marrow with megakaryocytic hyperplasia and atypia NA Splenomegaly Autoimmune hypothyroidism, Raynaud syndrome, hepatitis, diabetes Stroke       Consanguineous parents
P010 c.1160G>C p.Gly387Ala Missense Homozygous Germline Absent 2024 37981895   Patient #79.1 JMML-like disorder M 15 days Monocytosis, thrombocytopenia, leukocytosis, 6% blasts Absent megakaryocytes Normal Hepatosplenomegaly   IUGR, microcephaly, short stature, growth retardation Cardiomegaly, tracheomalacia yes Alive Consanguineous parents, brother of #79.2
P011 c.1160G>C p.Gly387Ala Missense Homozygous Germline Absent 2024 37981895   Patient #79.2 JMML-like disorder M 36 days Monocytosis, thrombocytopenia, leukocytosis, 4% blasts Normal Splenomegaly Autoimmune hypothyroidism         Alive, spontaneous resolution Consanguineous parents, brother of #79.1
P012 c.1709dup p.Asp570LysfsX82 Frameshift Homozygous Germline Absent 2024 37981895   OPBG_2 Neonatal MPD → thrombocytosis M 30 days Initial thrombocytopenia, thrombocytosis at 8 years, 11% blasts Dysplastic megakaryocytes Normal Hepatosplenomegaly   Facial dysmorphic features, complex limb reduction defect Coronary heart disease     Alive, spontaneous resolution Consanguineous parents, brother of P2.1 / OPBG_1
P013 c.502G>T + c.1244G>A p.Glu168X + p.Arg415His Missense Compound heterozygous Germline p.Glu168X: Absent, p.Arg415His: 0.00037% 2024 37981895   Patient #201.1 JMML-like disorder F 22 days Thrombocytopenia, leukocytosis, monocytosis, persistent neutropenia Absent megakaryocytes Normal Hepatosplenomegaly             Alive at 9 years Sister of #201.2
P014 c.502G>T + c.1244G>A p.Glu168X + p.Arg415His Missense Compound heterozygous Germline p.Glu168X: Absent, p.Arg415His: 0.00037% 2024 37981895   Patient #201.2 JMML-like disorder M 11 days Erythrocytosis, thrombocytopenia, leukocytosis, monocytosis, persistent neutropenia Absent megakaryocytes NA Hepatosplenomegaly Liver cirrhosis     Liver transplant     Alive at 5 years Brother of #201.1
P015 c.685_691dupGGCCCCG p.Asp231GlyfsX39 Frameshift Homozygous Germline Absent (same AA change is in gnomAD) 2024 37981895   Patient #216 JMML-like disorder F 1 day Thrombocytopenia, leukocytosis, monocytosis Normal Hepatosplenomegaly             Alive at 5 years, spontaneous resolution Consanguineous parents
P016 c.1038dup p.Leu347AlafsX38  Frameshift Homozygous Germline Absent (same AA change is in gnomAD) 2024 37981895   Patient #244 JMML-like disorder F 22 days Thrombocytopenia, leukocytosis, monocytosis Absent megakaryocytes Normal Hepatosplenomegaly   IUGR, facial dysmorphic features Vermis hematoma and hemoperitoneum   Alive at 2 years with persistent hepatosplenomegaly Consanguineous parents
P017 c.1201T>C p.Tyr401His Missense Heterozygous Germline 0.0012% 2024 37981895   Patient #48 JMML-like disorder M 3.8 years Thrombocytopenia, monocytosis Absent megakaryocytes Normal Hepatosplenomegaly         PTPN11 yes Alive at 19 years  
P018 c.685_691dup p.Asp231GlyfsX39 Frameshift Heterozygous Germline Absent 2024 37981895   Patient #53 JMML-like disorder M 2.2 years Thrombocytopenia, leukocytosis, monocytosis Normal Hepatosplenomegaly       Xanthogranuloma PTPN11 yes Death at 17 years following veno-
occlusive disease
P019 c.1174C>T p.Arg392Trp Missense Homozygous Germline 0.00058% 2025 40481232   P1.1 Neonatal MPD F 0.1 years Leukocytosis, mild thrombocytopenia, 6% blasts NA Splenomegaly   IUGR, growth retardation, dysmorphic features (low-set and posteriorly rotated ears, prominent forehead with high hair line, mild hypertelorism) Speech and walking delay     yes   Consanguineous parents, sister of P1.2
P020 c.1174C>T p.Arg392Trp Missense Homozygous Germline 0.00058% 2025 40481232   P1.2 Neonatal MPD F Birth Leukocytosis, thrombocytopenia, 2% blasts NA Splenomegaly   IUGR, growth retardation, dysmorphic features (low-set and posteriorly rotated ears, prominent forehead with high hair line, mild hypertelorism) Speech and walking delay     yes   Consanguineous parents, sister of P1.1
P021 c.1709dup p.Asp570LysfsX82 Frameshift Homozygous Germline Absent 2025 40481232 37981895 P2.1 / OPBG_1 Neonatal MPD → thrombocytosis F 30 days Initial thrombocytopenia, thrombocytosis at 8 years, 11% blasts Absent megakaryocytes, dysplasia Normal Hepatosplenomegaly Multiple sclerosis, diabetes IUGR, growth retardation, facial dysmorphic features Speech and walking delay Coronary heart disease, persistent Botallo duct SETBP1 yes, for grade 3 myelofibrosis at age 10 years Alive, spontaneous resolution Consanguineous parents, sister of OPBG_2
P022 c.1A>G p.? Start loss Homozygous Germline Absent 2025 40481232   P3.1 Isolated thrombocytosis M 0.3 years Thrombocytosis   NA                  
P023 c.832A>T p.Lys278X Nonsense Homozygous Germline Absent 2025 40481232   P6.1 Neonatal MPD → thrombocytosis M 0.1 years Leukocytosis, initial thrombocytopenia, thrombocytosis at 0.2 years NA Hepato/splenomegaly Autoimmune hypothyroidism, localized scleroderma Microcephaly, IUGR, growth retardation Mild global developmental delay and cognitive impairment        
P024 c.1198G>A + c.1183G>A p.Glu400Lys + p.Glu395Lys Missense Compound heterozygous Germline p.Glu400Lys: 0.14%, p.Glu395Lys: 0.035% 2025 40481232   P7.1 Isolated thrombocytosis M 4.0 years Thrombocytosis at 4 years   NA                  
P025 c.833del p.Lys278ArgfsX2 Frameshift Heterozygous Germline + somatic LOH Absent 2025 40481232   P8.1 Neonatal MPD → thrombocytosis F 0.2 years Leukocytosis, thrombocytosis, 4% blasts NA Hepato/splenomegaly     Severe cognitive impairment, autism SH2B3 LOH      
P026 c.1159G>T p.Gly387X Nonsense Heterozygous Germline + somatic LOH Absent 2025 40481232   P9.1 Neonatal MPD F 0.7 years Leukocytosis, 2% blasts   NA Hepato/splenomegaly         SH2B3 LOH   Lost to follow up  
P027 c.1198G>A p.Glu400Lys Missense Heterozygous Germline 0.14% 2019 31173385   Patient 1 MDS/MPN-RS-T M Early 60s Progressive anemia, macrocytosis, and thrombocytosis MDS/MPN-overlap syndrome with RS Normal                 On aspirin
P028 c.1004_1005del p.Thr335ArgfsX4 Frameshift Heterozygous Germline Absent 2023 38024597   Patient 1 Erythrocytosis M 31 years Polycythemia, mild thrombocytopenia   Normal                 Smoker, mother is a carrier
P029 c.3G>A p.? Start loss Heterozygous Germline Absent 2022 35570682   #03 Primary myelofibrosis F 51 years     NA           JAK V617F, TET2, other JAK2     Mother of #01
P030 c.3G>A p.? Start loss Heterozygous Germline Absent 2022 35570682   #01 Essential thrombocytosis F 21 years     NA           JAK V617F     Daughter of #03
P031 c.1183G>A p.Glu395Lys Missense Heterozygous Germline 0.035% 2022 35281324   37-year-old Caucasian woman CMML without excess blasts F 37 years Initially leukocytosis, thrombocytosis   NA   Multiple sclerosis              
P032 c.622G>C p.Glu208Gln Missense Heterozygous Germline 0.066% 2016 27237057   F1 Primary myelofibrosis F 54 years     NA           JAK V617F, CALR, ASXL1, TET2, NRAS, KRAS   Mother of F2
P033 c.622G>C p.Glu208Gln Missense Heterozygous Germline 0.066% 2016 27237057   F2 Essential thrombocytosis F 37 years     NA                 Daughter of F1
P034 c.622G>C p.Glu208Gln Missense Heterozygous Germline 0.066% 2024 39672944   49-year-old woman Primary myelofibrosis F 49 years     NA Splenomegaly Psoriasis   Major depressive disorder Uterine fibroma JAK V617F yes   Responded to ruxolitinib

ALL: acute lymphoblastic leukemia, CMML: chronic myelomonocytic leukemia, HSCT: hematopoietic stem cell transplantation, IUGR: intrauterine growth retardation, JMML: juvenile myelomonocytic leukemia, LOH: loss of heterozygosity, MDS: myelodysplastic syndrome, MPD: myeloproliferative disorder, MDS/MPN-RS-T: myelodysplastic/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis, NA: not available, MPN: myeloproliferative neoplasm, RS: ring sideroblasts, WBC: white blood cell