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Clonal hematopoiesis and platelet traits
continued from the previous page
Gene Gene Protein Overall role in Germline/ name (OMIM) function hematopoiesis somatic
Inherited disease Somatic Mutation
Mutation Thrombosis Bleeding Predisposition Ref.
risk tomalignancy platelet traits
regulator
and differentiation of HSC and megakaryocytes
size ↑, function ↓ (m)
Yes AMKL 88,91 (in Down syndrome)
No MPN (including 93 ET, PV), AMKL
(in non-Down syndrome)
n.d. AML, CMML, 55 MDS
n.d. CML 56
classification (OMIM, PMID)
Bleeding disorder platelet-type 21 (617443)
Anemia X-linked with/without platelet abnormalities (300835); Thrombocytopenia (314050, 300367)
Emberger syndrome (614038); Immunodeficiency 21 (614172)
Bleeding disorder platelet-type 17, Gray platelet syndrome (187900)
D-20 hydroxyglutaric aciduria 2 (613657)
Thrombocythemia 3 (614521)
phenotype (OMIM, PMID)
Ewing sarcoma (29977059)
Leukemia megakaryoblastic with/without Down syndrome somatic (190685)
effect on protein
Loss-of- function Gain-of- function
Loss-of- function
Gain-of- function
effect on risk platelet traits
FLI1
GATA1
GATA2
GFI1B
IDH2
JAK2
193067
305371
137295
604383
147650
147796
Transcription Development regulator andmaintenance
of HSC
Transcription Development
G,S
G,S
G,S
G,S
G,S
G,S
Count ↓, No size ↑,
Yes Solid cancers
No Lymphoblastic leukemia, lymphoma
82,85 87
function ↓ n.d. Count ↑,
function ↑
Count ↓, Yes
Transcription Development regulator and survival
of HSC
Transcription Development regulator andmobilization
of HSC and megakaryocytes
Epigenetic Development regulator and
(indirect) differentiation of HSC
Signaling Proliferation
Acute myeloid Loss-of- leukemia function (601626); Gain-of- Myelodysplastic function syndrome (614286); Predisposition to
infection and chronic myelomonocytic leukemia
(25359990)
Count ↑ Yes Count ↓ n.d.
n.d. n.d.
Acute myeloid leukemia (26851695)
Myeloproliferative neoplasm (20428194);
Aucte myeloid leukemia (20884716)
Loss-of- function
Gain-of- function
Count ↓, no size ↑,
Yes Various leukemias
63,65
function ↓
Count ↑/= n.d.
Yes AML, solid 31 cancers
SF3B1
SH2B3
605590
605093
Splicing Development factor of HSC
Signaling Development of regulator megakaryocytes
and platelet production
Transcription Tumor regulator suppression
S
G,S
G,S
Undefined
B-precursor
acute lymphoblastic Leukemia (23908464)
Hemorrhagic telangiectasia syndrome (175050); Myhre syndrome (139210); Polyposis
juvenile intestinal
(h, m)
Count ↑ Yes (h, m)
Count ↑, Yes function ↑
(m)
No ET, MDS, MPD 40
regulator
and survival of HSC
Erythrocytosis somatic (133100); Acute myeloid leukemia somatic (601626); Myelofibrosis somatic (254450), Polycythemia vera somatic (263300); Thrombocythemia 3 (614521); Budd-Chiari syndrome somatic; (600880)
Myelodysplastic Unclear syndrome somatic (614286)
Erythrocytosis Loss-of- somatic function (133100);
Myelofibrosis
somatic (254450); Thrombocythemia somatic (187950)
Pancreatic Loss-of- cancer somatic function (260350)
Count ↑, Yes size ↑/=,
function ↑
Gain-of- function
No MPN (including ET, PV)
36,38
SMAD4 600993
Count ↓, No size =,
Yes AML,solidcancers 67
function ↓ (m)
No MPN
44,45
(174900)
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haematologica | 2020; 105(8)
2023