International Society of Thrombosis and Haemostasis tier 1 genes for numerical platelet disorders
| Gene . | Location . | MoI . | Disorder (OMIM accession no.) . | Common additional features . |
|---|---|---|---|---|
| ABCG8, ABCG5 | 2p21, 2p21 | AR | Sitosterolemia 1 and 2 (21025) | Large PLTs, high circulating plant sterols, xanthomas, and accelerated atherosclerosis |
| ACTB | 7p22.1 | AD | Baraitser-Winter syndrome 1 (243310) | Dysmorphia, hearing loss, myopathy, multiple malformations, neurodevelopmental delay, and epilepsy |
| ACTN1 | 14q24.1 | AD | Platelet-type bleeding disorder 15 (615193) | Large PLTs |
| ANKRD26 | 10p12.1 | AD | Thrombocytopenia 2 (188800) | Large PLTs, risk of myeloid malignancy |
| ARPC1B | 7q22.1 | AR | Immunodeficiency 71 with inflammatory disease and congenital thrombocytopenia (617718) | Small PLTs, PLT dysfunction, immunodeficiency, hepato-splenomegaly, and inflammatory disease |
| CDC42 | 1p36.12 | AD | Takenouchi-Kosaki syndrome (616737) | Large PLTs, developmental delay, lymphedema, dysmorphia, and multiple malformations |
| CYCS | 7p15.3 | AD | Thrombocytopenia 4 (612004) | Normal sized PLTs |
| DIAPH1 | 5q31.3 | AD | Autosomal dominant deafness 1, with/without thrombocytopenia (124900) | Large PLTs, hearing loss, and neutropenia |
| ETV6 | 12p13.2 | AD | Thrombocytopenia 5 (616216) | Large PLTs and risk of lymphoid malignancy |
| FLI1 | 11q24.3 | AR, AD | Platelet-type bleeding disorder 21 (Paris-Trousseau thrombocytopathy; 617443) | Large PLTs and PLT dysfunction |
| FLNA | Xq28 | XD | Periventricular heterotopia 1 (300049) | Large PLTs, variable intellectual disability, epilepsy, and cardiac malformation in females |
| FYB1 | 5p13.1 | AR | Thrombocytopenia 3 (273900) | Small PLTs |
| G6B | 6p21.33 | AR | Thrombocytopenia, anemia, and myelofibrosis (617441) | Large PLTs, anemia, myelofibrosis, and splenomegaly |
| GATA1 | Xp11.23 | XR | X-linked thrombocytopenia with beta thalassemia (314050) X-linked thrombocytopenia with/without dyserythropoietic anemia (300367) | Large PLTs, defective red cells |
| GFI1B | 9q34.13 | AD and AR | Platelet-type bleeding disorder17 (187900) | Large pale platelets, PLT dysfunction, myelofibrosis |
| GNE | 9p13.3 | AR | Nonaka myopathy (605820) | Large PLTs and distal myopathy |
| GP1BA, GPIBB, GP9 | 17p13.2, 22q11.21, 3q21.3 | AR and AD | Bernard-Soulier syndrome (231200; 153670) | Large PLTs and PLT dysfunction (AR); mild thrombocytopenia AD) |
| GP1BA | 22q11.21 | AR and AD | Platelet-type von Willebrand disease (177820) | Reduced von Willebrand factor activity |
| HOXA11 | 7p15.2 | AD | Radioulnar synostosis with amegakaryocytic thrombocytopenia 1 (605432) | Proximal fusion of radius and ulna, other skeletal defects, and pancytopenia |
| IKZF5 | 10q26.13 | AD | Thrombocytopenia 7 (619130) | Normal sized PLTs |
| ITGA2B | 17q21.31 | AD | Platelet-type bleeding disorder 16 (187800) | Large PLTs |
| ITGB3 | 17q21.32 | AD | Platelet-type bleeding disorder 24 (619271) | Large PLTs |
| KDSR | 18q21.33 | AR | Erythrokeratodermia variabilis et progressiva 4 (617526) | Thickened, red, scaly skin |
| MECOM | 3q26.2 | AD | Radioulnar synostosis with amegakaryocytic thrombocytopenia 2 (616738) | Proximal fusion of radius and ulna, other skeletal defects, and pancytopenia |
| MPL | 1p34.2 | AR | Congenital amegakaryocytic thrombocytopenia (604498) | Thrombocytopenia progressing to pancytopenia |
| MYH9 | 22q12.3 | AD | Macrothrombocytopenia and granulocyte inclusions with/without nephritis or sensorineural hearing loss (MYH9-related disorder 155100) | Giant PLTs, nephritis, hearing loss, and cataracts |
| NBEAL2 | 3p21.31 | AR | Gray platelet syndrome (139090) | Large pale PLTs, myelofibrosis, and splenomegaly |
| RAP1B | 12q15 | AD | RAP1B-related disorder | Multiple congenital malformations, intellectual disability, dysmorphia, and pancytopenia |
| RBM8A | 1q21.1 | AR | Thrombocytopenia-absent radius syndrome (274000) | Radial aplasia, other skeletal, cardiac and renal defects, and dysmorphia |
| RNU4ATAC | 2q14.2 | AR | Roifman syndrome | Growth retardation, microcephaly, retinopathy, skeletal defects, immunodeficiency, and dysmorphia |
| RUNX1 | 21q22.12 | AD | FPDMM | PLT dysfunction and risk of myeloid malignancy |
| SLFN14 | 17q12 | AD | Platelet bleeding disorder 20 (616913) | PLT dysfunction |
| SRC | 20q11.23 | AD | Thrombocytopenia 6 (616937) | Large PLTs, myelofibrosis, skeletal defect, and dysmorphia |
| STIM1 | 11p15.4 | AD | Stormorken syndrome (185070) | Myopathy, ocular and skin defects, and immunodeficiency |
| THPO | 3q27.1 | AR and AD | THPO-related disorder | Trilineage marrow failure (AR); mild thrombocytopenia (AD) |
| TPM4 | 19p13.12 | AD | TPM4-related disorder | Large PLTs |
| TUBB1 | 20q13.32 | AD | Isolated autosomal dominant macrothrombocytopenia 1 (613112) | Large PLTs |
| VWF | 12p13.31 | AD | Von Willebrand disease type 2 (Type 2B; 613554) | Reduced von Willebrand factor activity |
| WAS | Xp11.23 | XLR | Wiskott-Aldrich syndrome (301000), X-linked thrombocytopenia (313900) | Small PLTs, immunodeficiency, and eczema |
| Gene . | Location . | MoI . | Disorder (OMIM accession no.) . | Common additional features . |
|---|---|---|---|---|
| ABCG8, ABCG5 | 2p21, 2p21 | AR | Sitosterolemia 1 and 2 (21025) | Large PLTs, high circulating plant sterols, xanthomas, and accelerated atherosclerosis |
| ACTB | 7p22.1 | AD | Baraitser-Winter syndrome 1 (243310) | Dysmorphia, hearing loss, myopathy, multiple malformations, neurodevelopmental delay, and epilepsy |
| ACTN1 | 14q24.1 | AD | Platelet-type bleeding disorder 15 (615193) | Large PLTs |
| ANKRD26 | 10p12.1 | AD | Thrombocytopenia 2 (188800) | Large PLTs, risk of myeloid malignancy |
| ARPC1B | 7q22.1 | AR | Immunodeficiency 71 with inflammatory disease and congenital thrombocytopenia (617718) | Small PLTs, PLT dysfunction, immunodeficiency, hepato-splenomegaly, and inflammatory disease |
| CDC42 | 1p36.12 | AD | Takenouchi-Kosaki syndrome (616737) | Large PLTs, developmental delay, lymphedema, dysmorphia, and multiple malformations |
| CYCS | 7p15.3 | AD | Thrombocytopenia 4 (612004) | Normal sized PLTs |
| DIAPH1 | 5q31.3 | AD | Autosomal dominant deafness 1, with/without thrombocytopenia (124900) | Large PLTs, hearing loss, and neutropenia |
| ETV6 | 12p13.2 | AD | Thrombocytopenia 5 (616216) | Large PLTs and risk of lymphoid malignancy |
| FLI1 | 11q24.3 | AR, AD | Platelet-type bleeding disorder 21 (Paris-Trousseau thrombocytopathy; 617443) | Large PLTs and PLT dysfunction |
| FLNA | Xq28 | XD | Periventricular heterotopia 1 (300049) | Large PLTs, variable intellectual disability, epilepsy, and cardiac malformation in females |
| FYB1 | 5p13.1 | AR | Thrombocytopenia 3 (273900) | Small PLTs |
| G6B | 6p21.33 | AR | Thrombocytopenia, anemia, and myelofibrosis (617441) | Large PLTs, anemia, myelofibrosis, and splenomegaly |
| GATA1 | Xp11.23 | XR | X-linked thrombocytopenia with beta thalassemia (314050) X-linked thrombocytopenia with/without dyserythropoietic anemia (300367) | Large PLTs, defective red cells |
| GFI1B | 9q34.13 | AD and AR | Platelet-type bleeding disorder17 (187900) | Large pale platelets, PLT dysfunction, myelofibrosis |
| GNE | 9p13.3 | AR | Nonaka myopathy (605820) | Large PLTs and distal myopathy |
| GP1BA, GPIBB, GP9 | 17p13.2, 22q11.21, 3q21.3 | AR and AD | Bernard-Soulier syndrome (231200; 153670) | Large PLTs and PLT dysfunction (AR); mild thrombocytopenia AD) |
| GP1BA | 22q11.21 | AR and AD | Platelet-type von Willebrand disease (177820) | Reduced von Willebrand factor activity |
| HOXA11 | 7p15.2 | AD | Radioulnar synostosis with amegakaryocytic thrombocytopenia 1 (605432) | Proximal fusion of radius and ulna, other skeletal defects, and pancytopenia |
| IKZF5 | 10q26.13 | AD | Thrombocytopenia 7 (619130) | Normal sized PLTs |
| ITGA2B | 17q21.31 | AD | Platelet-type bleeding disorder 16 (187800) | Large PLTs |
| ITGB3 | 17q21.32 | AD | Platelet-type bleeding disorder 24 (619271) | Large PLTs |
| KDSR | 18q21.33 | AR | Erythrokeratodermia variabilis et progressiva 4 (617526) | Thickened, red, scaly skin |
| MECOM | 3q26.2 | AD | Radioulnar synostosis with amegakaryocytic thrombocytopenia 2 (616738) | Proximal fusion of radius and ulna, other skeletal defects, and pancytopenia |
| MPL | 1p34.2 | AR | Congenital amegakaryocytic thrombocytopenia (604498) | Thrombocytopenia progressing to pancytopenia |
| MYH9 | 22q12.3 | AD | Macrothrombocytopenia and granulocyte inclusions with/without nephritis or sensorineural hearing loss (MYH9-related disorder 155100) | Giant PLTs, nephritis, hearing loss, and cataracts |
| NBEAL2 | 3p21.31 | AR | Gray platelet syndrome (139090) | Large pale PLTs, myelofibrosis, and splenomegaly |
| RAP1B | 12q15 | AD | RAP1B-related disorder | Multiple congenital malformations, intellectual disability, dysmorphia, and pancytopenia |
| RBM8A | 1q21.1 | AR | Thrombocytopenia-absent radius syndrome (274000) | Radial aplasia, other skeletal, cardiac and renal defects, and dysmorphia |
| RNU4ATAC | 2q14.2 | AR | Roifman syndrome | Growth retardation, microcephaly, retinopathy, skeletal defects, immunodeficiency, and dysmorphia |
| RUNX1 | 21q22.12 | AD | FPDMM | PLT dysfunction and risk of myeloid malignancy |
| SLFN14 | 17q12 | AD | Platelet bleeding disorder 20 (616913) | PLT dysfunction |
| SRC | 20q11.23 | AD | Thrombocytopenia 6 (616937) | Large PLTs, myelofibrosis, skeletal defect, and dysmorphia |
| STIM1 | 11p15.4 | AD | Stormorken syndrome (185070) | Myopathy, ocular and skin defects, and immunodeficiency |
| THPO | 3q27.1 | AR and AD | THPO-related disorder | Trilineage marrow failure (AR); mild thrombocytopenia (AD) |
| TPM4 | 19p13.12 | AD | TPM4-related disorder | Large PLTs |
| TUBB1 | 20q13.32 | AD | Isolated autosomal dominant macrothrombocytopenia 1 (613112) | Large PLTs |
| VWF | 12p13.31 | AD | Von Willebrand disease type 2 (Type 2B; 613554) | Reduced von Willebrand factor activity |
| WAS | Xp11.23 | XLR | Wiskott-Aldrich syndrome (301000), X-linked thrombocytopenia (313900) | Small PLTs, immunodeficiency, and eczema |
International Society of Thrombosis and Haemostasis tier 1 genes for numerical platelet disorders.58 Disorder names are as listed in Online Inheritance in Man with accession numbers59,60 or identified using common synonyms.
AD, autosomal dominant; AR, autosomal recessive; MoI, mode of inheritance; PLT, platelet; XD, X-linked dominant; XR, X-linked recessive.