Thrombocytopenia 6

Summary

Thrombocytopenia 6 (MONDO:0014837) is a disease caused by SRC (GenCC Strong), with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: SRC (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 4

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		9	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	thrombocytopenia 6
Mondo ID	MONDO:0014837
OMIM	616937
Orphanet	480851
UMLS	C4310789
MedGen	934756
GARD	0017870
Is cancer (heuristic)	no

Also known as: hereditary thrombocytopenia with early-onset myelofibrosis · THC6 · thrombocytopenia 6 · thrombocytopenia type 6

Data availability: 4 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › hematologic disorder › blood platelet disease › thrombocytopenia › inherited thrombocytopenia › syndromic constitutional thrombocytopenia › thrombocytopenia 6

Related subtypes (11): Jacobsen syndrome, platelet storage pool deficiency, Stormorken syndrome, thrombocytopenia-absent radius syndrome, radio-ulnar synostosis-amegakaryocytic thrombocytopenia syndrome, GNE myopathy, macrothrombocytopenia-lymphedema-developmental delay-facial dysmorphism-camptodactyly syndrome, macrothrombocytopenia and granulocyte inclusions with or without nephritis or sensorineural hearing loss, marcothrombocytopenia with mitral valve insufficiency, DIAPH1-related sensorineural hearing loss-thrombocytopenia syndrome, ACTB-associated syndromic thrombocytopenia

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

ClinVar germline variants

4 retrieved; paginated sample, class counts are floors:

3 uncertain significance, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
225689	NM_198291.3(SRC):c.1579G>A (p.Glu527Lys)	SRC	Likely pathogenic	criteria provided, single submitter
2572134	NM_198291.3(SRC):c.1585C>G (p.Gln529Glu)	SRC	Uncertain significance	criteria provided, single submitter
2584809	NM_198291.3(SRC):c.919C>T (p.Pro307Ser)	SRC	Uncertain significance	criteria provided, single submitter
3764601	NM_198291.3(SRC):c.1070C>T (p.Thr357Ile)	SRC	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 1 · 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
SRC	Strong	Autosomal dominant	thrombocytopenia 6	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SRC	Orphanet:480851	Hereditary thrombocytopenia with early-onset myelofibrosis

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
SRC	HGNC:11283	ENSG00000197122	P12931	Proto-oncogene tyrosine-protein kinase Src	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SRC	Proto-oncogene tyrosine-protein kinase Src	Non-receptor protein tyrosine kinase which is activated following engagement of many different classes of cellular receptors including immune response receptors, integrins and other adhesion receptors, receptor protein tyrosine kinases, G…

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Kinase	1	27.7×	0.036

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SRC	Kinase	yes	2.7.10.2	Prot_kinase_dom, SH2, Ser-Thr/Tyr_kinase_cat_dom

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

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
body of stomach	1
gall bladder	1
rectum	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SRC	236	ubiquitous	marker	body of stomach, gall bladder, rectum

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SRC	11,608

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SRC	P12931	79

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 121. 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
Regulation of gap junction activity	1	3806.7×	0.007	SRC
Activated NTRK2 signals through FYN	1	1903.3×	0.007	SRC
Activated NTRK3 signals through PI3K	1	1903.3×	0.007	SRC
Signaling by NTRK2 (TRKB)	1	1631.4×	0.007	SRC
Netrin mediated repulsion signals	1	1268.9×	0.007	SRC
InlA-mediated entry of Listeria monocytogenes into host cells	1	1268.9×	0.007	SRC
Downregulation of ERBB4 signaling	1	1142.0×	0.007	SRC
Signaling by NTRK3 (TRKC)	1	1142.0×	0.007	SRC
Listeria monocytogenes entry into host cells	1	1038.2×	0.007	SRC
Receptor Mediated Mitophagy	1	1038.2×	0.007	SRC
Regulation of commissural axon pathfinding by SLIT and ROBO	1	951.7×	0.007	SRC
GP1b-IX-V activation signalling	1	951.7×	0.007	SRC
p38MAPK events	1	878.5×	0.007	SRC
FCGR activation	1	878.5×	0.007	SRC
PECAM1 interactions	1	878.5×	0.007	SRC
RUNX2 regulates bone development	1	815.7×	0.007	SRC
p130Cas linkage to MAPK signaling for integrins	1	761.3×	0.007	SRC
Spry regulation of FGF signaling	1	713.8×	0.007	SRC
GRB2:SOS provides linkage to MAPK signaling for Integrins	1	713.8×	0.007	SRC
DCC mediated attractive signaling	1	713.8×	0.007	SRC
Signal regulatory protein family interactions	1	671.8×	0.007	SRC
Regulation of RUNX1 Expression and Activity	1	671.8×	0.007	SRC
GAB1 signalosome	1	634.4×	0.007	SRC
Regulation of KIT signaling	1	601.0×	0.007	SRC
MET promotes cell motility	1	601.0×	0.007	SRC
Signaling by ALK	1	571.0×	0.007	SRC
Ephrin signaling	1	571.0×	0.007	SRC
VEGFR2 mediated cell proliferation	1	571.0×	0.007	SRC
Co-inhibition by CTLA4	1	519.1×	0.007	SRC
Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants	1	519.1×	0.007	SRC

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
regulation of caveolin-mediated endocytosis	1	16852.0×	0.002	SRC
regulation of toll-like receptor 3 signaling pathway	1	8426.0×	0.002	SRC
positive regulation of dephosphorylation	1	8426.0×	0.002	SRC
positive regulation of platelet-derived growth factor receptor-beta signaling pathway	1	5617.3×	0.002	SRC
regulation of cell projection assembly	1	4213.0×	0.002	SRC
regulation of epithelial cell migration	1	2808.7×	0.002	SRC
negative regulation of telomere maintenance	1	2808.7×	0.002	SRC
cellular response to progesterone stimulus	1	2808.7×	0.002	SRC
negative regulation of neutrophil activation	1	2407.4×	0.002	SRC
signal complex assembly	1	2106.5×	0.002	SRC
osteoclast development	1	2106.5×	0.002	SRC
positive regulation of small GTPase mediated signal transduction	1	2106.5×	0.002	SRC
positive regulation of lamellipodium morphogenesis	1	2106.5×	0.002	SRC
regulation of early endosome to late endosome transport	1	2106.5×	0.002	SRC
regulation of intracellular estrogen receptor signaling pathway	1	1872.4×	0.002	SRC
positive regulation of integrin activation	1	1872.4×	0.002	SRC
ERBB2 signaling pathway	1	1872.4×	0.002	SRC
negative regulation of mitochondrial depolarization	1	1872.4×	0.002	SRC
positive regulation of podosome assembly	1	1872.4×	0.002	SRC
angiotensin-activated signaling pathway	1	1532.0×	0.002	SRC
regulation of bone resorption	1	1532.0×	0.002	SRC
intestinal epithelial cell development	1	1532.0×	0.002	SRC
branching involved in mammary gland duct morphogenesis	1	1404.3×	0.002	SRC
progesterone receptor signaling pathway	1	1296.3×	0.002	SRC
cellular response to fluid shear stress	1	1296.3×	0.002	SRC
positive regulation of protein processing	1	1203.7×	0.002	SRC
regulation of cell-cell adhesion	1	1203.7×	0.002	SRC
regulation of vascular permeability	1	1123.5×	0.002	SRC
interleukin-6-mediated signaling pathway	1	1123.5×	0.002	SRC
negative regulation of anoikis	1	887.0×	0.003	SRC

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
SRC	PONATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SRC	103	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
PONATINIB	4	SRC
AFATINIB	4	SRC
FEDRATINIB	4	SRC
TIVOZANIB	4	SRC
SORAFENIB	4	SRC
DASATINIB ANHYDROUS	4	SRC
NICLOSAMIDE	4	SRC
NERATINIB	4	SRC
INFIGRATINIB PHOSPHATE	4	SRC
INFIGRATINIB	4	SRC
IBRUTINIB	4	SRC
ENTRECTINIB	4	SRC
CABOZANTINIB	4	SRC
DACOMITINIB ANHYDROUS	4	SRC
CERITINIB	4	SRC
VANDETANIB	4	SRC
NILOTINIB	4	SRC
BOSUTINIB	4	SRC
BRIGATINIB	4	SRC
REPOTRECTINIB	4	SRC
PAZOPANIB	4	SRC
NINTEDANIB	4	SRC
SUNITINIB	4	SRC
DASATINIB	4	SRC
ERLOTINIB	4	SRC
LAPATINIB	4	SRC
TIRBANIBULIN	4	SRC
CRIZOTINIB	4	SRC
MIDOSTAURIN	4	SRC
ADENOSINE PHOSPHATE	4	SRC

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
SRC	1,917	Binding:1858, Functional:43, ADMET:16

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
SRC	2.7.10.2	non-specific protein-tyrosine kinase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
SRC	1,917

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)
PONATINIB	4	SRC
AFATINIB	4	SRC
FEDRATINIB	4	SRC
TIVOZANIB	4	SRC
SORAFENIB	4	SRC
DASATINIB ANHYDROUS	4	SRC
NICLOSAMIDE	4	SRC
NERATINIB	4	SRC
INFIGRATINIB PHOSPHATE	4	SRC
INFIGRATINIB	4	SRC
IBRUTINIB	4	SRC
ENTRECTINIB	4	SRC
CABOZANTINIB	4	SRC
DACOMITINIB ANHYDROUS	4	SRC
CERITINIB	4	SRC
VANDETANIB	4	SRC
NILOTINIB	4	SRC
BOSUTINIB	4	SRC
BRIGATINIB	4	SRC
REPOTRECTINIB	4	SRC
PAZOPANIB	4	SRC
NINTEDANIB	4	SRC
SUNITINIB	4	SRC
DASATINIB	4	SRC
ERLOTINIB	4	SRC
LAPATINIB	4	SRC
TIRBANIBULIN	4	SRC
CRIZOTINIB	4	SRC
MIDOSTAURIN	4	SRC
ADENOSINE PHOSPHATE	4	SRC

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	SRC
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.