THPO
thrombopoietin, the group of Receptor ligands
Basic information
Region (hg38): 3:184371935-184381968
Previous symbols: [ "MGDF" ]
Links
Phenotypes
GenCC
Source:
- thrombocythemia 1 (Strong), mode of inheritance: AD
- thrombocythemia 1 (Moderate), mode of inheritance: AD
- congenital amegakaryocytic thrombocytopenia (Supportive), mode of inheritance: AR
- familial thrombocytosis (Supportive), mode of inheritance: AD
- hereditary thrombocytosis with transverse limb defect (Supportive), mode of inheritance: AD
- hereditary isolated aplastic anemia (Supportive), mode of inheritance: AD
- thrombocythemia 1 (Strong), mode of inheritance: AD
- congenital amegakaryocytic thrombocytopenia (Moderate), mode of inheritance: AR
- thrombocythemia 1 (Moderate), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Thrombocythemia 1; Amegakaryocytic thrombocytopenia, congenital, 2 | AD/AR | Hematologic; Oncologic | Individuals with Thrombocythemia may have hemorrhagic or thrombotic tendencies, and preventive measures and prompt treatment may be beneficial; Surveillance for and early treatment of oncologic complications may also be beneficial; Individuals with Amegakaryocytic thrombocytopenia may have severe and recurrent infections, and awareness may allow early and aggressive treatment of infections; Medical management (with THPO receptor agonists) has been described as beneficial, though bone marrow transplant may not be effective | Hematologic; Oncologic | 8167182; 7772529; 9425899; 10583217; 18367486; 22453305; 24085763; 28559357; 29191945; 36226497 |
ClinVar
This is a list of variants' phenotypes submitted to
- not_provided (127 variants)
- Inborn_genetic_diseases (46 variants)
- Thrombocythemia_1 (27 variants)
- Thrombocytopenia_9 (9 variants)
- Amegakaryocytic_thrombocytopenia,_congenital,_2 (9 variants)
- Thrombocytopenia (5 variants)
- THPO-related_disorder (5 variants)
- not_specified (3 variants)
- Macrothrombocytopenia (2 variants)
- Abnormal_bleeding (1 variants)
- See_cases (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the THPO gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000460.4. Only rare variants are included in the table.
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.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 38 | 40 | ||||
| missense | 89 | 99 | ||||
| nonsense | 2 | |||||
| start loss | 0 | |||||
| frameshift | 8 | |||||
| splice donor/acceptor (+/-2bp) | 3 | |||||
| Total | 5 | 8 | 94 | 44 | 1 |
Highest pathogenic variant AF is 0.00000820869
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| THPO | protein_coding | protein_coding | ENST00000204615 | 5 | 6210 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.197 | 0.794 | 125734 | 0 | 14 | 125748 | 0.0000557 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.411 | 171 | 187 | 0.915 | 0.0000106 | 2199 |
| Missense in Polyphen | 39 | 59.373 | 0.65687 | 714 | ||
| Synonymous | -2.11 | 105 | 80.8 | 1.30 | 0.00000451 | 851 |
| Loss of Function | 2.25 | 3 | 11.1 | 0.271 | 6.66e-7 | 111 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000246 | 0.000246 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000704 | 0.0000615 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.0000653 | 0.0000653 |
| Other | 0.000163 | 0.000163 |
dbNSFP
Source:
- Function
- FUNCTION: Lineage-specific cytokine affecting the proliferation and maturation of megakaryocytes from their committed progenitor cells. It acts at a late stage of megakaryocyte development. It may be the major physiological regulator of circulating platelets.;
- Disease
- DISEASE: Thrombocythemia 1 (THCYT1) [MIM:187950]: A myeloproliferative disorder characterized by excessive platelet production, resulting in increased numbers of circulating platelets. It can be associated with spontaneous hemorrhages and thrombotic episodes. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Jak-STAT signaling pathway - Homo sapiens (human);Hematopoietic cell lineage - Homo sapiens (human);Cytokine-cytokine receptor interaction - Homo sapiens (human);JAK-STAT-Core;JAK STAT MolecularVariation 1;GPCR signaling-G alpha q;GPCR signaling-cholera toxin;GPCR signaling-pertussis toxin;GPCR signaling-G alpha s Epac and ERK;Platelet Aggregation (Plug Formation);Platelet activation, signaling and aggregation;GPCR signaling-G alpha s PKA and ERK;tpo signaling pathway;Hemostasis;JAK STAT pathway and regulation;GPCR signaling-G alpha i;TPO signaling
(Consensus)
Recessive Scores
- pRec
- 0.437
Intolerance Scores
- loftool
- 0.748
- rvis_EVS
- -0.29
- rvis_percentile_EVS
- 32.94
Haploinsufficiency Scores
- pHI
- 0.204
- hipred
- N
- hipred_score
- 0.153
- ghis
- 0.526
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- N
- gene_indispensability_score
- 0.354
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Thpo
- Phenotype
- homeostasis/metabolism phenotype; hematopoietic system phenotype; immune system phenotype;
Gene ontology
- Biological process
- positive regulation of protein phosphorylation;multicellular organism development;cell population proliferation;positive regulation of cell population proliferation;regulation of signaling receptor activity;myeloid cell differentiation;thrombopoietin-mediated signaling pathway;positive regulation of megakaryocyte differentiation;positive regulation of protein kinase B signaling;positive regulation of ERK1 and ERK2 cascade;positive regulation of hematopoietic stem cell proliferation
- Cellular component
- extracellular region;extracellular space
- Molecular function
- signaling receptor binding;cytokine activity;hormone activity;growth factor activity