Familial myelofibrosis

Summary

Familial myelofibrosis (MONDO:0023119) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	familial myelofibrosis
Mondo ID	MONDO:0023119
MeSH	C536848
UMLS	C2931351
MedGen	444034
GARD	0008516
Is cancer (heuristic)	no

Data availability: 1 ClinVar variant.

Disease family

Classification path: disease › human disease › disease by body system or component › hematologic disorder › anemia › aplastic anemia › acquired aplastic anemia › primary myelofibrosis › familial myelofibrosis

Related subtypes (3): cellular phase chronic idiopathic myelofibrosis, panostotic fibrous dysplasia, myelofibrosis with myeloid metaplasia

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

1 retrieved; paginated sample, class counts are floors:

1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
2428765	NM_005475.3(SH2B3):c.89G>A (p.Cys30Tyr)	SH2B3	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SH2B3	Orphanet:3318	Essential thrombocythemia
SH2B3	Orphanet:391366	Growth retardation-mild developmental delay-chronic hepatitis syndrome

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
SH2B3	HGNC:29605	ENSG00000111252	Q9UQQ2	SH2B adapter protein 3	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SH2B3	SH2B adapter protein 3	Links T-cell receptor activation signal to phospholipase C-gamma-1, GRB2 and phosphatidylinositol 3-kinase.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · 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
Scaffold/PPI	1	17.3×	0.058

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SH2B3	Scaffold/PPI	no		SH2, PH_domain, PH-like_dom_sf

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
leukocyte	1
monocyte	1
mononuclear cell	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SH2B3	260	ubiquitous	marker	monocyte, mononuclear cell, leukocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SH2B3	1,617

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
SH2B3	Q9UQQ2	63.45

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 10. 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
Negative regulation of FLT3	1	713.8×	0.008	SH2B3
Regulation of KIT signaling	1	601.0×	0.008	SH2B3
FLT3 Signaling	1	346.1×	0.010	SH2B3
Signaling by SCF-KIT	1	248.3×	0.010	SH2B3
Factors involved in megakaryocyte development and platelet production	1	66.4×	0.030	SH2B3
Signaling by Receptor Tyrosine Kinases	1	51.7×	0.032	SH2B3
Cytokine Signaling in Immune system	1	40.8×	0.035	SH2B3
Hemostasis	1	36.0×	0.035	SH2B3
Immune System	1	13.0×	0.086	SH2B3
Signal Transduction	1	10.2×	0.098	SH2B3

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
negative regulation of Kit signaling pathway	1	8426.0×	0.001	SH2B3
monocyte homeostasis	1	5617.3×	0.001	SH2B3
negative regulation of receptor signaling pathway via STAT	1	3370.4×	0.001	SH2B3
cellular response to interleukin-3	1	2808.7×	0.001	SH2B3
negative regulation of response to cytokine stimulus	1	2808.7×	0.001	SH2B3
negative regulation of chemokine-mediated signaling pathway	1	2407.4×	0.001	SH2B3
thrombopoietin-mediated signaling pathway	1	2106.5×	0.001	SH2B3
neutrophil homeostasis	1	1532.0×	0.002	SH2B3
negative regulation of platelet aggregation	1	1404.3×	0.002	SH2B3
embryonic hemopoiesis	1	991.3×	0.002	SH2B3
cellular response to chemokine	1	991.3×	0.002	SH2B3
negative regulation of receptor signaling pathway via JAK-STAT	1	887.0×	0.002	SH2B3
hematopoietic stem cell differentiation	1	766.0×	0.002	SH2B3
megakaryocyte development	1	702.2×	0.002	SH2B3
erythrocyte development	1	526.6×	0.002	SH2B3
negative regulation of MAPK cascade	1	300.9×	0.004	SH2B3
negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	1	263.3×	0.004	SH2B3
negative regulation of cell population proliferation	1	42.1×	0.025	SH2B3
intracellular signal transduction	1	38.1×	0.026	SH2B3

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SH2B3	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

0 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.

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
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	1	SH2B3

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
SH2B3	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.