Scott syndrome

Summary

Scott syndrome (MONDO:0009885) is a disease caused by ANO6 (GenCC Strong), with 1 cohort gene and 1 clinical trial.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: ANO6 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 14
• Phenotypes (HPO): 7
• Clinical trials: 1

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

Signs & symptoms

Clinical features (HPO)

7 HPO clinical features (Orphanet curated; top 7 by frequency):

HPO ID	Term	Frequency
HP:0004846	Prolonged bleeding after surgery	Very frequent (80-99%)
HP:0011891	Post-partum hemorrhage	Very frequent (80-99%)
HP:0000421	Epistaxis	Frequent (30-79%)
HP:0000978	Bruising susceptibility	Frequent (30-79%)
HP:0008151	Prolonged prothrombin time	Frequent (30-79%)
HP:0000132	Menorrhagia	Occasional (5-29%)
HP:0000225	Gingival bleeding	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	Scott syndrome
Mondo ID	MONDO:0009885
MeSH	C563120
OMIM	262890
Orphanet	806
DOID	DOID:0111052
ICD-11	186013982
SNOMED CT	128098009
UMLS	C0796149
MedGen	167107
GARD	0004777
Is cancer (heuristic)	no

Also known as: BDPLT7 · Platelet factor X receptor deficiency · prothrombin consumption deficiency · Scott syndrome · SCTS

Data availability: 14 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 › Scott syndrome

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, 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

14 retrieved; paginated sample, class counts are floors:

7 pathogenic, 3 likely pathogenic, 2 conflicting classifications of pathogenicity, 2 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
1323277	NM_001025356.3(ANO6):c.1308+2T>C	ANO6	Pathogenic	criteria provided, single submitter
2584644	NM_001025356.3(ANO6):c.826C>T (p.Arg276Ter)	ANO6	Pathogenic	no assertion criteria provided
2584645	NC_000012.12:g.(?45216094)(45367794_45378052)del	ANO6	Pathogenic	no assertion criteria provided
2584646	NM_001025356.3(ANO6):c.747+1G>A	ANO6	Pathogenic	no assertion criteria provided
2584647	NM_001025356.3(ANO6):c.1219dup (p.Trp407fs)	ANO6	Pathogenic	no assertion criteria provided
2626770	NM_001025356.3(ANO6):c.1255C>T (p.Arg419Ter)	ANO6	Pathogenic	criteria provided, single submitter
449565	NM_001025356.3(ANO6):c.1387-1G>T	ANO6	Pathogenic	criteria provided, multiple submitters, no conflicts
1323913	NM_001025356.3(ANO6):c.1914_1915del (p.Arg638fs)	ANO6	Likely pathogenic	criteria provided, single submitter
3779538	NM_001025356.3(ANO6):c.1073G>A (p.Trp358Ter)	ANO6	Likely pathogenic	criteria provided, single submitter
4845725	NM_001025356.3(ANO6):c.1516_1519del (p.Thr506fs)	ANO6	Likely pathogenic	criteria provided, single submitter
1323274	NM_001025356.3(ANO6):c.1880+1G>A	ANO6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3622420	NM_001025356.3(ANO6):c.2574T>C (p.Asp858=)	ANO6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2627032	NM_001025356.3(ANO6):c.2660C>T (p.Thr887Met)	ANO6	Uncertain significance	no assertion criteria provided
2664040	NM_001025356.3(ANO6):c.1622G>A (p.Arg541Lys)	ANO6	Uncertain significance	no assertion criteria provided

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
ANO6	Strong	Autosomal recessive	Scott syndrome	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ANO6	Orphanet:806	Scott 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
ANO6	HGNC:25240	ENSG00000177119	Q4KMQ2	Anoctamin-6	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ANO6	Anoctamin-6	Small-conductance calcium-activated nonselective cation (SCAN) channel which acts as a regulator of phospholipid scrambling in platelets and osteoblasts.

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)
ANO6	Other/Unknown	no		Anoctamin, Anoct_dimer, Anoctamin_TM

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
epithelial cell of pancreas	1
secondary oocyte	1
tibialis anterior	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ANO6	254	ubiquitous	marker	epithelial cell of pancreas, secondary oocyte, tibialis anterior

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ANO6	1,218

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ANO6	Q4KMQ2	82.00

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 16. 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
Defective ANO6 does not expose PS, PE on the platelet membrane	1	11420.0×	0.001	ANO6
Induction of Cell-Cell Fusion	1	878.5×	0.008	ANO6
Amplification and propagation of coagulation cascade	1	634.4×	0.008	ANO6
Late SARS-CoV-2 Infection Events	1	292.8×	0.014	ANO6
Regulation of clotting cascade	1	233.1×	0.014	ANO6
Stimuli-sensing channels	1	135.9×	0.020	ANO6
Ion channel transport	1	96.0×	0.024	ANO6
SARS-CoV-2 Infection	1	80.4×	0.025	ANO6
SARS-CoV Infections	1	55.4×	0.032	ANO6
Viral Infection Pathways	1	30.8×	0.050	ANO6
Innate Immune System	1	25.5×	0.050	ANO6
Transport of small molecules	1	25.1×	0.050	ANO6
Infectious disease	1	24.8×	0.050	ANO6
Neutrophil degranulation	1	23.1×	0.050	ANO6
Disease	1	13.1×	0.077	ANO6
Immune System	1	13.0×	0.077	ANO6

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
phosphatidylserine exposure on blood platelet	1	16852.0×	7e-04	ANO6
positive regulation of monoatomic ion transmembrane transport	1	8426.0×	7e-04	ANO6
activation of blood coagulation via clotting cascade	1	5617.3×	7e-04	ANO6
positive regulation of potassium ion export across plasma membrane	1	5617.3×	7e-04	ANO6
purinergic nucleotide receptor signaling pathway	1	4213.0×	7e-04	ANO6
calcium activated phosphatidylserine scrambling	1	4213.0×	7e-04	ANO6
negative regulation of cell volume	1	3370.4×	7e-04	ANO6
calcium activated phosphatidylcholine scrambling	1	3370.4×	7e-04	ANO6
pore complex assembly	1	1872.4×	0.001	ANO6
plasma membrane phospholipid scrambling	1	1532.0×	0.001	ANO6
bleb assembly	1	1532.0×	0.001	ANO6
positive regulation of phagocytosis, engulfment	1	1296.3×	0.001	ANO6
positive regulation of monocyte chemotaxis	1	802.5×	0.002	ANO6
positive regulation of bone mineralization	1	391.9×	0.004	ANO6
chloride transmembrane transport	1	237.3×	0.005	ANO6
calcium ion transmembrane transport	1	210.7×	0.005	ANO6
monoatomic ion transmembrane transport	1	208.1×	0.005	ANO6
sodium ion transmembrane transport	1	203.0×	0.005	ANO6
blood coagulation	1	173.7×	0.006	ANO6
positive regulation of apoptotic process	1	56.7×	0.018	ANO6

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
ANO6	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	ANO6

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)
ANO6	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00617721	Not specified	TERMINATED	Markers of Defective Membrane Remodelling in Scott-like Syndromes