Hereditary thrombocytosis with transverse limb defect

Summary

Hereditary thrombocytosis with transverse limb defect (MONDO:0018000) is a disease with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 1

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		3	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	hereditary thrombocytosis with transverse limb defect
Mondo ID	MONDO:0018000
Orphanet	329319
UMLS	C4749944
MedGen	1653707
GARD	0021487
Is cancer (heuristic)	no

Also known as: familial thrombocytosis with transverse limb defect

Data availability: 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by body system or component › hematologic disorder › congenital hematological disorder › hereditary thrombocytosis with transverse limb defect

Related subtypes (20): congenital anemia, congenital agammaglobulinemia, sulfhemoglobinemia, congenital, congenital factor XII deficiency, leukocyte adhesion deficiency type II, thrombocytopenia-absent radius syndrome, congenital thrombotic thrombocytopenic purpura, radio-ulnar synostosis-amegakaryocytic thrombocytopenia syndrome, GNE myopathy, hypercoagulability syndrome due to glycosylphosphatidylinositol deficiency, congenital factor XI deficiency, congenital plasminogen activator inhibitor type 1 deficiency, congenital analbuminemia, macrothrombocytopenia-lymphedema-developmental delay-facial dysmorphism-camptodactyly syndrome, constitutional neutropenia, congenital vitamin K-dependent coagulation factors deficiency, congenital secondary polycythemia, congenital factor XIII deficiency, congenital progressive bone marrow failure-B-cell immunodeficiency-skeletal dysplasia syndrome, congenital amegakaryocytic thrombocytopenia 1

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 9 · Orphanet: 4 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
THPO	Supportive	Autosomal dominant	hereditary thrombocytosis with transverse limb defect	9

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
THPO	Orphanet:329319	Thrombocythemia with distal limb defects
THPO	Orphanet:3319	Congenital amegakaryocytic thrombocytopenia
THPO	Orphanet:397692	Hereditary isolated aplastic anemia
THPO	Orphanet:71493	Familial thrombocytosis

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
THPO	HGNC:11795	ENSG00000090534	P40225	Thrombopoietin	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
THPO	Thrombopoietin	Lineage-specific cytokine affecting the proliferation and maturation of megakaryocytes from their committed progenitor cells.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
THPO	Other/Unknown	no		EPO_TPO, Thrombopoietin, 4_helix_cytokine-like_core

Expression context

Cohort genes with no expression data: 0.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
liver	1
right hemisphere of cerebellum	1
right lobe of liver	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
THPO	157	tissue_specific	yes	right lobe of liver, liver, right hemisphere of cerebellum

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
THPO	1,375

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
THPO	P40225	3

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Platelet Aggregation (Plug Formation)	1	439.2×	0.002	THPO

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
thrombopoietin-mediated signaling pathway	1	2106.5×	0.002	THPO
positive regulation of hematopoietic stem cell proliferation	1	1872.4×	0.002	THPO
positive regulation of megakaryocyte differentiation	1	1404.3×	0.002	THPO
megakaryocyte differentiation	1	1203.7×	0.002	THPO
megakaryocyte development	1	702.2×	0.003	THPO
cell surface receptor signaling pathway via STAT	1	561.7×	0.004	THPO
positive regulation of protein phosphorylation	1	276.3×	0.006	THPO
cell population proliferation	1	102.8×	0.014	THPO
positive regulation of ERK1 and ERK2 cascade	1	85.1×	0.014	THPO
positive regulation of MAPK cascade	1	80.6×	0.014	THPO
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	1	78.4×	0.014	THPO
positive regulation of cell population proliferation	1	33.6×	0.030	THPO

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 0

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
THPO	PROGESTERONE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
THPO	103	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
PROGESTERONE	4	THPO
CLOTRIMAZOLE	4	THPO
COLCHICINE	4	THPO
SALMETEROL XINAFOATE	4	THPO
BRETYLIUM TOSYLATE	4	THPO
SULFAPHENAZOLE	4	THPO
AMOXAPINE	4	THPO
DICYCLOMINE	4	THPO
NICARDIPINE HYDROCHLORIDE	4	THPO
CARBIDOPA ANHYDROUS	4	THPO
EPINEPHRINE BITARTRATE	4	THPO
BUDESONIDE	4	THPO
CHLORZOXAZONE	4	THPO
PIMOZIDE	4	THPO
NICLOSAMIDE	4	THPO
AZACITIDINE	4	THPO
TRIFLUPERIDOL	4	THPO
CAPTOPRIL	4	THPO
KETOCONAZOLE	4	THPO
PSEUDOEPHEDRINE	4	THPO
CLEMASTINE	4	THPO
RIBAVIRIN	4	THPO
SERTRALINE HYDROCHLORIDE	4	THPO
TERFENADINE	4	THPO
FLUOROURACIL	4	THPO
NIFEDIPINE	4	THPO
PRAZOSIN	4	THPO
MAPROTILINE	4	THPO
MECAMYLAMINE	4	THPO
HYDRALAZINE	4	THPO

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
THPO	2	Functional:2

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

30 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Compound	Max phase	Cohort target (bioactivity)
PROGESTERONE	4	THPO
CLOTRIMAZOLE	4	THPO
COLCHICINE	4	THPO
SALMETEROL XINAFOATE	4	THPO
BRETYLIUM TOSYLATE	4	THPO
SULFAPHENAZOLE	4	THPO
AMOXAPINE	4	THPO
DICYCLOMINE	4	THPO
NICARDIPINE HYDROCHLORIDE	4	THPO
CARBIDOPA ANHYDROUS	4	THPO
EPINEPHRINE BITARTRATE	4	THPO
BUDESONIDE	4	THPO
CHLORZOXAZONE	4	THPO
PIMOZIDE	4	THPO
NICLOSAMIDE	4	THPO
AZACITIDINE	4	THPO
TRIFLUPERIDOL	4	THPO
CAPTOPRIL	4	THPO
KETOCONAZOLE	4	THPO
PSEUDOEPHEDRINE	4	THPO
CLEMASTINE	4	THPO
RIBAVIRIN	4	THPO
SERTRALINE HYDROCHLORIDE	4	THPO
TERFENADINE	4	THPO
FLUOROURACIL	4	THPO
NIFEDIPINE	4	THPO
PRAZOSIN	4	THPO
MAPROTILINE	4	THPO
MECAMYLAMINE	4	THPO
HYDRALAZINE	4	THPO

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	THPO
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

0 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Clinical trials & evidence

Clinical trials

Clinical trials: 0.