Cerebral cavernous malformation 3

Summary

Cerebral cavernous malformation 3 (MONDO:0011305) is a disease caused by PDCD10 (GenCC Definitive), with 1 cohort gene and 1 clinical trial.

At a glance

• Causal gene: PDCD10 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 150
• Clinical trials: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	cerebral cavernous malformation 3
Mondo ID	MONDO:0011305
MeSH	C566393
OMIM	603285
DOID	DOID:0060671
UMLS	C1864040
MedGen	355121
GARD	0018314
Is cancer (heuristic)	no

Also known as: CCM3 · cerebral cavernous malformation 3 · cerebral cavernous malformation type 3 · cerebral cavernous malformations 3 · cerebral cavernous malformations type 3 · cerebral cavernous malformations-3 · familial cerebral cavernous malformation caused by mutation in PDCD10 · PDCD10 familial cerebral cavernous malformation

Data availability: 150 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › congenital nervous system disorder › cerebral cavernous malformation › famililal cerebral cavernous malformations › cerebral cavernous malformation 3

Related subtypes (4): cerebral cavernous malformation 2, cerebral cavernous malformation 1, cerebral cavernous malformation 4, cerebral cavernous malformations 5

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

150 retrieved; paginated sample, class counts are floors:

67 pathogenic, 34 uncertain significance, 22 likely benign, 9 not provided, 6 pathogenic/likely pathogenic, 5 benign, 4 likely pathogenic, 2 conflicting classifications of pathogenicity, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
639871	NC_000003.12:g.(?167684288)(167720177_?)del	LOC129937855	Pathogenic	criteria provided, single submitter
1065419	NM_007217.4(PDCD10):c.333del (p.Lys111fs)	PDCD10	Pathogenic	criteria provided, single submitter
1075146	NM_007217.4(PDCD10):c.576_579del (p.Ser193fs)	PDCD10	Pathogenic	criteria provided, single submitter
1075385	NC_000003.11:g.(?167422610)(167437965_?)del	PDCD10	Pathogenic	criteria provided, single submitter
1075488	NM_007217.4(PDCD10):c.558-2A>G	PDCD10	Pathogenic	criteria provided, single submitter
1076520	NM_007217.4(PDCD10):c.211dup (p.Ser71fs)	PDCD10	Pathogenic	criteria provided, single submitter
1326560	NM_007217.4(PDCD10):c.557+1G>A	PDCD10	Pathogenic	criteria provided, multiple submitters, no conflicts
1358836	NM_007217.4(PDCD10):c.211del (p.Ser71fs)	PDCD10	Pathogenic	criteria provided, multiple submitters, no conflicts
1365315	NM_007217.4(PDCD10):c.442_443del (p.Val148fs)	PDCD10	Pathogenic	criteria provided, single submitter
1379108	NM_007217.4(PDCD10):c.131_132insTT (p.Leu44_Arg45insTer)	PDCD10	Pathogenic	criteria provided, single submitter
1393706	NM_007217.4(PDCD10):c.522_528del (p.Phe174fs)	PDCD10	Pathogenic	criteria provided, single submitter
1399974	NM_007217.4(PDCD10):c.160G>T (p.Glu54Ter)	PDCD10	Pathogenic	criteria provided, single submitter
1430959	NM_007217.4(PDCD10):c.160_161del (p.Glu54fs)	PDCD10	Pathogenic	criteria provided, single submitter
1453460	NM_007217.4(PDCD10):c.164del (p.Asn55fs)	PDCD10	Pathogenic	criteria provided, single submitter
1453765	NM_007217.4(PDCD10):c.334_337del (p.Gln112fs)	PDCD10	Pathogenic	criteria provided, multiple submitters, no conflicts
1456505	NM_007217.4(PDCD10):c.62_71del (p.Pro21fs)	PDCD10	Pathogenic	criteria provided, single submitter
1458726	NM_007217.4(PDCD10):c.456T>G (p.Tyr152Ter)	PDCD10	Pathogenic	criteria provided, single submitter
1459562	NC_000003.11:g.(?167437830)(167437945_?)del	PDCD10	Pathogenic	criteria provided, single submitter
1460202	NC_000003.11:g.(?167402096)(167405501_?)del	PDCD10	Pathogenic	criteria provided, single submitter
1460340	NC_000003.11:g.(?167413364)(167437945_?)del	PDCD10	Pathogenic	criteria provided, single submitter
1865	NM_007217.4(PDCD10):c.385C>T (p.Gln129Ter)	PDCD10	Pathogenic	no assertion criteria provided
1867	NM_007217.4(PDCD10):c.97_150del	PDCD10	Pathogenic	no assertion criteria provided
1869	NM_007217.4(PDCD10):c.475-1G>A	PDCD10	Pathogenic	criteria provided, single submitter
1870	NC_000003.12:g.(?167683298(167734892_?)del	PDCD10	Pathogenic	no assertion criteria provided
2023706	NM_007217.4(PDCD10):c.274_275del (p.Met92fs)	PDCD10	Pathogenic	criteria provided, single submitter
2092113	NM_007217.4(PDCD10):c.529dup (p.Thr177fs)	PDCD10	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2115676	NM_007217.4(PDCD10):c.97-1G>A	PDCD10	Pathogenic	criteria provided, single submitter
2124205	NM_007217.4(PDCD10):c.557+1G>T	PDCD10	Pathogenic	criteria provided, single submitter
2427340	NC_000003.11:g.(?167413364)(167413530_?)del	PDCD10	Pathogenic	criteria provided, single submitter
2427341	NC_000003.11:g.(?167405002)(167413530_?)del	PDCD10	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · 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
PDCD10	Definitive	Autosomal dominant	cerebral cavernous malformation 3	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PDCD10	Orphanet:221061	Familial cerebral cavernous malformation

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
PDCD10	HGNC:8761	ENSG00000114209	Q9BUL8	Programmed cell death protein 10	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PDCD10	Programmed cell death protein 10	Promotes cell proliferation.

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)
PDCD10	Other/Unknown	no		PDCD10, PDC10_dimerisation_sf, PDCD10_N

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
colonic mucosa	1
jejunal mucosa	1
mucosa of sigmoid colon	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PDCD10	295	ubiquitous	marker	jejunal mucosa, mucosa of sigmoid colon, colonic mucosa

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PDCD10	1,792

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PDCD10	Q9BUL8	10

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
intrinsic apoptotic signaling pathway in response to hydrogen peroxide	1	5617.3×	0.003	PDCD10
Golgi reassembly	1	3370.4×	0.003	PDCD10
negative regulation of blood vessel endothelial cell proliferation involved in sprouting angiogenesis	1	2106.5×	0.003	PDCD10
establishment of Golgi localization	1	1872.4×	0.003	PDCD10
endothelium development	1	1296.3×	0.003	PDCD10
positive regulation of protein serine/threonine kinase activity	1	1296.3×	0.003	PDCD10
wound healing, spreading of cells	1	1123.5×	0.003	PDCD10
negative regulation of cell migration involved in sprouting angiogenesis	1	991.3×	0.003	PDCD10
positive regulation of stress-activated MAPK cascade	1	802.5×	0.003	PDCD10
positive regulation of peptidyl-serine phosphorylation	1	766.0×	0.003	PDCD10
positive regulation of intracellular protein transport	1	674.1×	0.003	PDCD10
positive regulation of MAP kinase activity	1	648.1×	0.003	PDCD10
regulation of angiogenesis	1	421.3×	0.004	PDCD10
positive regulation of Notch signaling pathway	1	351.1×	0.005	PDCD10
cellular response to leukemia inhibitory factor	1	159.0×	0.010	PDCD10
negative regulation of gene expression	1	69.1×	0.020	PDCD10
protein stabilization	1	66.9×	0.020	PDCD10
angiogenesis	1	62.4×	0.020	PDCD10
positive regulation of cell migration	1	61.7×	0.020	PDCD10
positive regulation of gene expression	1	38.7×	0.029	PDCD10
intracellular signal transduction	1	38.1×	0.029	PDCD10
negative regulation of apoptotic process	1	34.8×	0.030	PDCD10
positive regulation of cell population proliferation	1	33.6×	0.030	PDCD10

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PDCD10	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
PDCD10	1	Binding:1

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	PDCD10

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)
PDCD10	1	—

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
NCT03652181	Not specified	COMPLETED	CASH (Cavernous Angiomas With Symptomatic Hemorrhage) Trial Readiness