THPO

thrombopoietin, the group of Receptor ligands

Basic information

Region (hg38): 3:184371934-184381968

Previous symbols: [ "MGDF" ]

Links

ENSG00000090534 ∙ NCBI:7066 ∙ OMIM:600044 ∙ HGNC:11795 ∙ Uniprot:P40225 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• 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: CGD

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 ClinVar and linked to the THPO gene.

• not provided (73 variants)
• Thrombocythemia 1 (40 variants)
• Inborn genetic diseases (19 variants)
• Thrombocytopenia 9 (4 variants)
• Amegakaryocytic thrombocytopenia, congenital, 2 (4 variants)
• Thrombocytopenia (3 variants)
• not specified (3 variants)
• Macrothrombocytopenia (2 variants)
• Abnormal bleeding;Thrombocytopenia (1 variants)
• Stroke disorder (1 variants)
• THPO-related condition (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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	10		11
missense	2	2	33	5	1	43
nonsense	1	1	2			4
start loss						0
frameshift			4			4
inframe indel						0
splice donor/acceptor (+/-2bp)		1				1
splice region			1			1
non coding	1	1	20	9	11	42
Total	4	5	60	24	12

Highest pathogenic variant AF is 0.00000658

Variants in THPO

This is a list of pathogenic ClinVar variants found in the THPO region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
3-184372013-T-C		Thrombocythemia 1	Uncertain significance (Jan 12, 2018)
3-184372031-T-A		Thrombocythemia 1	Benign (Jan 12, 2018)
3-184372033-C-T		Thrombocythemia 1	Uncertain significance (Jan 13, 2018)
3-184372109-C-T		Thrombocythemia 1	Uncertain significance (Jan 13, 2018)
3-184372147-C-G		Thrombocythemia 1	Uncertain significance (Jan 12, 2018)
3-184372322-A-C		Thrombocythemia 1	Uncertain significance (Jan 13, 2018)
3-184372405-G-A		Thrombocythemia 1	Uncertain significance (Jan 13, 2018)
3-184372454-C-T		Thrombocythemia 1	Benign (Nov 27, 2018)
3-184372478-C-T		Thrombocythemia 1	Benign (Sep 10, 2021)
3-184372486-T-C		Thrombocythemia 1	Uncertain significance (Jan 13, 2018)
3-184372495-C-T		Thrombocythemia 1	Conflicting classifications of pathogenicity (Jan 13, 2018)
3-184372527-A-G			Uncertain significance (Aug 24, 2023)
3-184372543-G-A			Likely benign (Sep 20, 2021)
3-184372545-T-C		not specified • Thrombocythemia 1	Benign/Likely benign (Jan 23, 2024)
3-184372577-G-C		Inborn genetic diseases	Uncertain significance (Jul 14, 2021)
3-184372581-G-A		Inborn genetic diseases	Uncertain significance (Jan 23, 2024)
3-184372582-C-T			Likely benign (Feb 22, 2023)
3-184372583-G-T			Uncertain significance (Oct 29, 2023)
3-184372588-A-G			Likely benign (Jul 09, 2023)
3-184372592-G-T		THPO-related disorder	Uncertain significance (Jul 27, 2023)
3-184372602-G-A			Uncertain significance (Oct 04, 2023)
3-184372612-G-A		Thrombocythemia 1 • THPO-related disorder	Conflicting classifications of pathogenicity (Jun 21, 2019)
3-184372618-C-G		Inborn genetic diseases • not specified	Uncertain significance (Dec 18, 2023)
3-184372622-A-G			Uncertain significance (Oct 24, 2022)
3-184372642-G-A			Likely benign (Dec 11, 2023)

GnomAD

Source: gnomAD

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: dbNSFP

• 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