Platelet-type bleeding disorder 20

Summary

Platelet-type bleeding disorder 20 (MONDO:0014830) is a disease caused by SLFN14 (GenCC Strong), with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: SLFN14 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 36

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		4	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	platelet-type bleeding disorder 20
Mondo ID	MONDO:0014830
OMIM	616913
Orphanet	466806
DOID	DOID:0111055
UMLS	C4310797
MedGen	934764
GARD	0018491
Is cancer (heuristic)	no

Also known as: autosomal dominant thrombocytopenia with platelet secretion defect · BDPLT20 · bleeding disorder, platelet-type, 20 · inherited bleeding disorder, platelet-type caused by mutation in SLFN14 · SLFN14 inherited bleeding disorder, platelet-type

Data availability: 36 ClinVar variants · 4 GenCC gene-disease records.

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 20

Related subtypes (27): gray platelet syndrome, primary release disorder of platelets, platelet-type von Willebrand disease, platelet-type bleeding disorder 16, platelet-type bleeding disorder 17, 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, 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

36 retrieved; paginated sample, class counts are floors:

22 uncertain significance, 7 benign, 2 likely benign, 2 conflicting classifications of pathogenicity, 1 pathogenic/likely pathogenic, 1 likely pathogenic, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
225533	NM_001129820.2(SLFN14):c.659T>A (p.Val220Asp)	SLFN14	Pathogenic/Likely pathogenic	no assertion criteria provided
225536	NM_001129820.2(SLFN14):c.667C>T (p.Arg223Trp)	SLFN14	Pathogenic	no assertion criteria provided
225535	NM_001129820.2(SLFN14):c.652A>G (p.Lys218Glu)	SLFN14	Likely pathogenic	criteria provided, multiple submitters, no conflicts
225534	NM_001129820.2(SLFN14):c.657A>T (p.Lys219Asn)	SLFN14	Conflicting classifications of pathogenicity	no assertion criteria provided
732258	NM_001129820.2(SLFN14):c.1456C>T (p.Arg486Ter)	SLFN14	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1275748	NM_001129820.2(SLFN14):c.1356G>T (p.Gln452His)	LOC107985033	Uncertain significance	criteria provided, single submitter
1339107	NM_001129820.2(SLFN14):c.1108G>A (p.Ala370Thr)	LOC107985033	Uncertain significance	criteria provided, multiple submitters, no conflicts
2664215	NM_001129820.2(SLFN14):c.1382T>A (p.Ile461Lys)	LOC107985033	Uncertain significance	criteria provided, single submitter
4292360	NM_001129820.2(SLFN14):c.1106C>G (p.Ser369Ter)	LOC107985033	Uncertain significance	criteria provided, single submitter
4846933	NM_001129820.2(SLFN14):c.1401_1406del (p.Val468_Leu469del)	LOC107985033	Uncertain significance	criteria provided, single submitter
1030178	NM_001129820.2(SLFN14):c.1904C>T (p.Thr635Ile)	SLFN14	Uncertain significance	criteria provided, single submitter
1033309	NM_001129820.2(SLFN14):c.2146C>T (p.Leu716Phe)	SLFN14	Uncertain significance	criteria provided, single submitter
1033310	NM_001129820.2(SLFN14):c.2153del (p.Pro718fs)	SLFN14	Uncertain significance	criteria provided, single submitter
1703796	NM_001129820.2(SLFN14):c.643T>C (p.Phe215Leu)	SLFN14	Uncertain significance	criteria provided, single submitter
1704375	NM_001129820.2(SLFN14):c.1759C>T (p.Arg587Cys)	SLFN14	Uncertain significance	criteria provided, multiple submitters, no conflicts
1803221	NM_001129820.2(SLFN14):c.2637del (p.Ser880fs)	SLFN14	Uncertain significance	criteria provided, single submitter
2389627	NM_001129820.2(SLFN14):c.1048G>C (p.Asp350His)	SLFN14	Uncertain significance	criteria provided, multiple submitters, no conflicts
2579302	NM_001129820.2(SLFN14):c.1840T>C (p.Phe614Leu)	SLFN14	Uncertain significance	criteria provided, multiple submitters, no conflicts
2584871	NM_001129820.2(SLFN14):c.574A>T (p.Lys192Ter)	SLFN14	Uncertain significance	criteria provided, single submitter
3391156	NM_001129820.2(SLFN14):c.2173C>T (p.Arg725Ter)	SLFN14	Uncertain significance	criteria provided, single submitter
3778834	NM_001129820.2(SLFN14):c.687del (p.His230fs)	SLFN14	Uncertain significance	criteria provided, single submitter
3780641	NM_001129820.2(SLFN14):c.2556dup (p.Thr853fs)	SLFN14	Uncertain significance	criteria provided, single submitter
3892502	NM_001129820.2(SLFN14):c.1576C>T (p.Pro526Ser)	SLFN14	Uncertain significance	criteria provided, multiple submitters, no conflicts
3892504	NM_001129820.2(SLFN14):c.1975A>G (p.Ile659Val)	SLFN14	Uncertain significance	criteria provided, multiple submitters, no conflicts
3892505	NM_001129820.2(SLFN14):c.2377C>T (p.Gln793Ter)	SLFN14	Uncertain significance	criteria provided, single submitter
3892507	NM_001129820.2(SLFN14):c.277C>T (p.Gln93Ter)	SLFN14	Uncertain significance	criteria provided, single submitter
3892508	NM_001129820.2(SLFN14):c.48A>G (p.Ile16Met)	SLFN14	Uncertain significance	criteria provided, single submitter
1244326	NM_001129820.2(SLFN14):c.1153A>G (p.Lys385Glu)	LOC107985033	Benign	criteria provided, multiple submitters, no conflicts
1246755	NM_001129820.2(SLFN14):c.1066C>T (p.Pro356Ser)	LOC107985033	Benign	criteria provided, multiple submitters, no conflicts
1333128	NM_001129820.2(SLFN14):c.1348A>G (p.Lys450Glu)	LOC107985033	Benign	criteria provided, multiple submitters, no conflicts

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
SLFN14	Strong	Autosomal dominant	platelet-type bleeding disorder 20	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SLFN14	Orphanet:466806	Autosomal dominant thrombocytopenia with platelet secretion defect

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
SLFN14	HGNC:32689	ENSG00000236320	P0C7P3	Protein SLFN14	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SLFN14	Protein SLFN14	Shows no ribosome-associated and endoribonuclease activities.

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)
SLFN14	Other/Unknown	no		Schlafen_AlbA_2_dom, P-loop_NTPase, Schlafen

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
bone marrow cell	1
leukocyte	1
monocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SLFN14	35	tissue_specific	yes	monocyte, leukocyte, bone marrow cell

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SLFN14	279

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SLFN14	P0C7P3	4

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
platelet maturation	1	16852.0×	3e-04	SLFN14
cellular response to magnesium ion	1	2407.4×	7e-04	SLFN14
cellular response to manganese ion	1	2407.4×	7e-04	SLFN14
rRNA catabolic process	1	991.3×	0.001	SLFN14
mRNA catabolic process	1	495.6×	0.002	SLFN14

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
SLFN14	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	SLFN14

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)
SLFN14	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.