Platelet storage pool deficiency

Summary

Platelet storage pool deficiency (MONDO:0008495) is a disease with 3 cohort genes and 3 clinical trials. Top therapeutic interventions include erythromycin, pirfenidone, and pravastatin.

At a glance

• Cohort genes: 3
• ClinVar variants: 5
• Clinical trials: 3

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	platelet storage pool deficiency
Mondo ID	MONDO:0008495
EFO	EFO:1001112
MeSH	D010981
OMIM	185050
Orphanet	734
DOID	DOID:2223
SNOMED CT	234474009
UMLS	C0032197
MedGen	19351
GARD	0005034
Is cancer (heuristic)	no

Also known as: alpha dense granule deficiency · combined alpha-delta platelet storage pool deficiency · platelet storage pool diseases

Data availability: 5 ClinVar variants · 1 GenCC gene-disease record.

Disease family

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

Related subtypes (11): Jacobsen syndrome, Stormorken syndrome, thrombocytopenia-absent radius syndrome, radio-ulnar synostosis-amegakaryocytic thrombocytopenia syndrome, GNE myopathy, macrothrombocytopenia-lymphedema-developmental delay-facial dysmorphism-camptodactyly syndrome, thrombocytopenia 6, 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

5 retrieved; paginated sample, class counts are floors:

3 pathogenic, 2 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
585291	NM_001377304.1(GFI1B):c.724del (p.His242fs)	GFI1B	Pathogenic	criteria provided, single submitter
627101	NM_001754.5(RUNX1):c.622C>T (p.Gln208Ter)	RUNX1	Pathogenic	reviewed by expert panel
627384	NM_001754.5(RUNX1):c.784C>T (p.Gln262Ter)	RUNX1	Pathogenic	reviewed by expert panel
626949	NM_024747.6(HPS6):c.1006G>T (p.Asp336Tyr)	HPS6	Uncertain significance	criteria provided, single submitter
627122	NM_024747.6(HPS6):c.692C>G (p.Pro231Arg)	HPS6	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 7 · 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
GFI1B	Strong	Autosomal dominant	platelet-type bleeding disorder 17	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
GFI1B	Orphanet:140957	Autosomal dominant macrothrombocytopenia
GFI1B	Orphanet:734	Alpha delta granule deficiency
RUNX1	Orphanet:102724	Acute myeloid leukemia with t(8;21)(q22;q22) translocation
RUNX1	Orphanet:521	Chronic myeloid leukemia
RUNX1	Orphanet:71290	Familial platelet disorder with associated myeloid malignancy
RUNX1	Orphanet:98850	Aggressive systemic mastocytosis
HPS6	Orphanet:231512	Hermansky-Pudlak syndrome due to BLOC-2 deficiency

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
GFI1B	HGNC:4238	ENSG00000165702	Q5VTD9	Zinc finger protein Gfi-1b	gencc,clinvar
RUNX1	HGNC:10471	ENSG00000159216	Q01196	Runt-related transcription factor 1	clinvar
HPS6	HGNC:18817	ENSG00000166189	Q86YV9	BLOC-2 complex member HPS6	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
GFI1B	Zinc finger protein Gfi-1b	Essential proto-oncogenic transcriptional regulator necessary for development and differentiation of erythroid and megakaryocytic lineages.
RUNX1	Runt-related transcription factor 1	Forms the heterodimeric complex core-binding factor (CBF) with CBFB.
HPS6	BLOC-2 complex member HPS6	May regulate the synthesis and function of lysosomes and of highly specialized organelles, such as melanosomes and platelet dense granules.

Protein-family classification

Druggable: 0 · Difficult: 2 · 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
Transcription factor	2	5.5×	0.081
Other/Unknown	1	0.6×	0.914

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
GFI1B	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf
RUNX1	Transcription factor	no		AML1_Runt, p53-like_TF_DNA-bd_sf, p53/RUNT-type_TF_DNA-bd_sf
HPS6	Other/Unknown	no		BLOC-2_complex_Hps6_subunit, HPS6_C, HPS6_N

Expression context

Cohort genes with no expression data: 0.

2 cohort genes 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)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
monocyte	1
sperm	1
trabecular bone tissue	1
epithelium of bronchus	1
mucosa of paranasal sinus	1
olfactory segment of nasal mucosa	1
gingival epithelium	1
granulocyte	1
stromal cell of endometrium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
GFI1B	126	tissue_specific	marker	sperm, trabecular bone tissue, monocyte
RUNX1	253	ubiquitous	marker	olfactory segment of nasal mucosa, epithelium of bronchus, mucosa of paranasal sinus
HPS6	216	ubiquitous	yes	granulocyte, gingival epithelium, stromal cell of endometrium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
RUNX1	4,994
GFI1B	1,554
HPS6	965

Structural data

PDB: 1 · AlphaFold-only: 2 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
RUNX1	Q01196	5

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
HPS6	Q86YV9	77.54
GFI1B	Q5VTD9	64.09

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 43. Enrichment computed across 3 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
RUNX3 regulates RUNX1-mediated transcription	1	3806.7×	0.003	RUNX1
RUNX1 regulates expression of components of tight junctions	1	2284.0×	0.003	RUNX1
RUNX1 regulates transcription of genes involved in interleukin signaling	1	2284.0×	0.003	RUNX1
RUNX2 regulates genes involved in differentiation of myeloid cells	1	2284.0×	0.003	RUNX1
RUNX1 regulates estrogen receptor mediated transcription	1	1903.3×	0.003	RUNX1
RUNX1 regulates transcription of genes involved in BCR signaling	1	1903.3×	0.003	RUNX1
RUNX1 regulates transcription of genes involved in WNT signaling	1	1903.3×	0.003	RUNX1
RUNX1 regulates transcription of genes involved in differentiation of myeloid cells	1	1427.5×	0.003	RUNX1
RUNX1 and FOXP3 control the development of regulatory T lymphocytes (Tregs)	1	1142.0×	0.003	RUNX1
RUNX1 regulates transcription of genes involved in differentiation of keratinocytes	1	1142.0×	0.003	RUNX1
RUNX3 regulates p14-ARF	1	1142.0×	0.003	RUNX1
Differentiation of naive CD4+ T cells to T helper 1 cells (Th1 cells)	1	878.5×	0.004	RUNX1
SLC-mediated transport of organic cations	1	761.3×	0.004	RUNX1
R-HSA-549132	1	761.3×	0.004	RUNX1
Regulation of RUNX1 Expression and Activity	1	671.8×	0.004	RUNX1
Pre-NOTCH Expression and Processing	1	368.4×	0.007	RUNX1
RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known	1	300.5×	0.008	RUNX1
Transcriptional regulation by RUNX3	1	271.9×	0.008	RUNX1
SARS-CoV-1 activates/modulates innate immune responses	1	271.9×	0.008	RUNX1
Transcriptional regulation by RUNX2	1	253.8×	0.008	RUNX1
R-HSA-425366	1	181.3×	0.011	RUNX1
Signaling by NOTCH	1	175.7×	0.011	RUNX1
SARS-CoV-1-host interactions	1	175.7×	0.011	RUNX1
Transcriptional regulation by RUNX1	1	146.4×	0.012	RUNX1
SARS-CoV-1 Infection	1	142.8×	0.012	RUNX1
ESR-mediated signaling	1	128.3×	0.012	RUNX1
Transcriptional regulation of granulopoiesis	1	125.5×	0.012	RUNX1
Pre-NOTCH Transcription and Translation	1	122.8×	0.012	RUNX1
RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function	1	120.2×	0.012	RUNX1
Signaling by Nuclear Receptors	1	102.0×	0.014	RUNX1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 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 connective tissue replacement	1	5617.3×	0.004	RUNX1
myeloid leukocyte differentiation	1	1872.4×	0.004	RUNX1
regulation of plasminogen activation	1	1872.4×	0.004	RUNX1
negative regulation of CD4-positive, alpha-beta T cell differentiation	1	1404.3×	0.004	RUNX1
cardiac muscle tissue regeneration	1	1404.3×	0.004	RUNX1
positive regulation of extracellular matrix organization	1	1404.3×	0.004	RUNX1
positive regulation of CD8-positive, alpha-beta T cell differentiation	1	1123.5×	0.004	RUNX1
regulation of cardiac muscle cell proliferation	1	1123.5×	0.004	RUNX1
positive regulation of granulocyte differentiation	1	936.2×	0.004	RUNX1
negative regulation of granulocyte differentiation	1	702.2×	0.005	RUNX1
peripheral nervous system neuron development	1	510.7×	0.006	RUNX1
regulation of hemopoiesis	1	510.7×	0.006	GFI1B
melanosome assembly	1	295.6×	0.009	HPS6
platelet dense granule organization	1	224.7×	0.010	HPS6
myeloid cell differentiation	1	216.1×	0.010	RUNX1
positive regulation of collagen biosynthetic process	1	216.1×	0.010	RUNX1
hematopoietic stem cell proliferation	1	216.1×	0.010	RUNX1
protein localization to membrane	1	200.6×	0.010	HPS6
lysosome localization	1	175.5×	0.011	HPS6
positive regulation of interleukin-2 production	1	156.0×	0.012	RUNX1
regulation of cell differentiation	1	144.0×	0.012	RUNX1
negative regulation of G1/S transition of mitotic cell cycle	1	119.5×	0.014	GFI1B
lipid homeostasis	1	112.3×	0.014	HPS6
negative regulation of transcription by RNA polymerase II	2	11.8×	0.014	GFI1B, RUNX1
chondrocyte differentiation	1	100.3×	0.014	RUNX1
hemopoiesis	1	89.2×	0.015	RUNX1
protein secretion	1	87.8×	0.015	HPS6
ossification	1	75.9×	0.017	RUNX1
blood coagulation	1	57.9×	0.021	HPS6
regulation of transcription by RNA polymerase II	2	7.8×	0.025	GFI1B, RUNX1

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 2

Druggability breadth: 2 of 3 evidence-associated genes (67%) 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
RUNX1	APOMORPHINE HYDROCHLORIDE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
RUNX1	2	4
GFI1B	0	0
HPS6	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
APOMORPHINE HYDROCHLORIDE	4	RUNX1
MOLIBRESIB	2	RUNX1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
RUNX1	20	Binding:17, Functional:3
HPS6	1	Binding:1

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

2 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)
APOMORPHINE HYDROCHLORIDE	4	RUNX1
MOLIBRESIB	2	RUNX1

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	RUNX1
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	2	GFI1B, HPS6

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
GFI1B	0	—
HPS6	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 3.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	1
PHASE1/PHASE2	1
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00001596	PHASE2	COMPLETED	Oral Pirfenidone for the Pulmonary Fibrosis of Hermansky-Pudlak Syndrome
NCT00467831	PHASE1/PHASE2	TERMINATED	Pilot Study of a Multi-Drug Regimen for Severe Pulmonary Fibrosis in Hermansky-Pudlak Syndrome
NCT05529394	Not specified	UNKNOWN	Effect of Storage Condition on CD47 Expression Level in Platelet Concentrate

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
ERYTHROMYCIN	4	1
PIRFENIDONE	4	1
PRAVASTATIN	4	1
ZILEUTON	4	1
CHEMBL5435500	0	1