Platelet-type bleeding disorder 17

Summary

Platelet-type bleeding disorder 17 (MONDO:0008553) is a disease caused by GFI1B (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: GFI1B (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 23

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	platelet-type bleeding disorder 17
Mondo ID	MONDO:0008553
MeSH	C566060
OMIM	187900
DOID	DOID:0111049
NCIT	C142084
UMLS	C1861194
MedGen	396078
GARD	0015117
Is cancer (heuristic)	no

Also known as: BDPLT17 · bleeding disorder, platelet-type 17 · bleeding disorder, platelet-type, 17 · GFI1B inherited bleeding disorder, platelet-type · inherited bleeding disorder, platelet-type caused by mutation in GFI1B · platelet-type bleeding disorder 17

Data availability: 23 ClinVar variants · 3 GenCC gene-disease records · 1 cell line.

Disease family

Classification path: disease › human disease › disease by body system or component › hematologic disorder › hemorrhagic disease › inherited bleeding disorder, platelet-type › platelet-type bleeding disorder 17

Related subtypes (27): gray platelet syndrome, primary release disorder of platelets, platelet-type von Willebrand disease, platelet-type bleeding disorder 16, Ehlers-Danlos syndrome, fibronectinemic type, Bernard-Soulier syndrome, Scott syndrome, congenital thrombotic thrombocytopenic purpura, Quebec platelet disorder, platelet-type bleeding disorder 12, platelet-type bleeding disorder 10, platelet-type bleeding disorder 8, platelet-type bleeding disorder 14, platelet-type bleeding disorder 9, platelet-type bleeding disorder 11, platelet-type bleeding disorder 15, platelet-type bleeding disorder 18, platelet-type bleeding disorder 19, platelet-type bleeding disorder 20, macrothrombocytopenia and granulocyte inclusions with or without nephritis or sensorineural hearing loss, cytosolic phospholipase-A2 alpha deficiency associated bleeding disorder, bleeding disorder, platelet-type, 24, bleeding disorder, platelet-type, 22, bleeding disorder, platelet-type, 21, Glanzmann thrombasthenia, bleeding diathesis due to thromboxane synthesis deficiency, bleeding disorder, platelet-type, 25

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

23 retrieved; paginated sample, class counts are floors:

14 uncertain significance, 5 pathogenic, 2 likely pathogenic, 1 conflicting classifications of pathogenicity, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
102428	NM_001377304.1(GFI1B):c.859C>T (p.Gln287Ter)	GFI1B	Pathogenic	criteria provided, multiple submitters, no conflicts
1703853	NM_001377304.1(GFI1B):c.520A>G (p.Thr174Ala)	GFI1B	Pathogenic	criteria provided, single submitter
1705843	NM_001377304.1(GFI1B):c.692G>T (p.Arg231Leu)	GFI1B	Pathogenic	criteria provided, single submitter
438346	NM_001377304.1(GFI1B):c.793A>T (p.Lys265Ter)	GFI1B	Pathogenic	no assertion criteria provided
88891	NM_001377304.1(GFI1B):c.880dup (p.His294fs)	GFI1B	Pathogenic	no assertion criteria provided
1684412	NM_001377304.1(GFI1B):c.521C>T (p.Thr174Ile)	GFI1B	Likely pathogenic	no assertion criteria provided
1684454	NM_001377304.1(GFI1B):c.551G>C (p.Arg184Pro)	GFI1B	Likely pathogenic	no assertion criteria provided
1695382	NM_001377304.1(GFI1B):c.503G>T (p.Cys168Phe)	GFI1B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1048772	NM_001377304.1(GFI1B):c.550C>T (p.Arg184Cys)	GFI1B	Uncertain significance	criteria provided, multiple submitters, no conflicts
1338724	NM_001377304.1(GFI1B):c.731del (p.Asp244fs)	GFI1B	Uncertain significance	criteria provided, single submitter
1677259	NM_001377304.1(GFI1B):c.981C>G (p.His327Gln)	GFI1B	Uncertain significance	criteria provided, multiple submitters, no conflicts
1684450	NM_001377304.1(GFI1B):c.758G>A (p.Cys253Tyr)	GFI1B	Uncertain significance	criteria provided, single submitter
1684451	NM_001377304.1(GFI1B):c.551G>A (p.Arg184His)	GFI1B	Uncertain significance	criteria provided, single submitter
2432114	NM_001377304.1(GFI1B):c.648G>C (p.Gln216His)	GFI1B	Uncertain significance	criteria provided, single submitter
2432115	NM_001377304.1(GFI1B):c.760G>A (p.Gly254Ser)	GFI1B	Uncertain significance	criteria provided, single submitter
2506299	NM_001377304.1(GFI1B):c.548G>A (p.Arg183Gln)	GFI1B	Uncertain significance	criteria provided, multiple submitters, no conflicts
2627763	NM_001377304.1(GFI1B):c.230C>T (p.Pro77Leu)	GFI1B	Uncertain significance	no assertion criteria provided
2664765	NM_001377304.1(GFI1B):c.649-5G>C	GFI1B	Uncertain significance	criteria provided, single submitter
2664801	NM_001377304.1(GFI1B):c.869A>G (p.Asn290Ser)	GFI1B	Uncertain significance	criteria provided, single submitter
417959	NM_001377304.1(GFI1B):c.568C>T (p.Arg190Trp)	GFI1B	Uncertain significance	criteria provided, single submitter
438347	NM_001377304.1(GFI1B):c.923T>C (p.Leu308Pro)	GFI1B	Uncertain significance	criteria provided, single submitter
627337	NM_001377304.1(GFI1B):c.581G>A (p.Cys194Tyr)	GFI1B	Uncertain significance	criteria provided, multiple submitters, no conflicts
2572114	NM_001377304.1(GFI1B):c.782C>G (p.Ser261Cys)	GFI1B	Likely benign	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 2 · 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

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
GFI1B	HGNC:4238	ENSG00000165702	Q5VTD9	Zinc finger protein Gfi-1b	gencc,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.

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
Transcription factor	1	8.3×	0.121

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
GFI1B	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_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
monocyte	1
sperm	1
trabecular bone tissue	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

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
GFI1B	1,554

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
GFI1B	Q5VTD9	64.09

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

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 hemopoiesis	1	1532.0×	0.003	GFI1B
negative regulation of G1/S transition of mitotic cell cycle	1	358.6×	0.007	GFI1B
chromatin organization	1	99.1×	0.017	GFI1B
negative regulation of transcription by RNA polymerase II	1	17.7×	0.071	GFI1B
regulation of transcription by RNA polymerase II	1	11.7×	0.086	GFI1B

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
GFI1B	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	GFI1B

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)
GFI1B	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.