Ehlers-Danlos syndrome, periodontitis type

Summary

Ehlers-Danlos syndrome, periodontitis type (MONDO:0007527) is a disease with 2 cohort genes.

At a glance

• Prevalence: Unknown (Worldwide) [Orphanet-validated]
• Cohort genes: 2
• Phenotypes (HPO): 12

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		62	Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

12 HPO clinical features (Orphanet curated; top 12 by frequency):

HPO ID	Term	Frequency
HP:0000704	Periodontitis	Very frequent (80-99%)
HP:0001034	Hypermelanotic macule	Very frequent (80-99%)
HP:0001075	Atrophic scars	Very frequent (80-99%)
HP:0004322	Short stature	Very frequent (80-99%)
HP:0001382	Joint hypermobility	Frequent (30-79%)
HP:0000212	Gingival overgrowth	Frequent (30-79%)
HP:0000691	Microdontia	Frequent (30-79%)
HP:0000974	Hyperextensible skin	Frequent (30-79%)
HP:0006308	Atrophy of alveolar ridges	Frequent (30-79%)
HP:0006349	Agenesis of permanent teeth	Frequent (30-79%)
HP:0000347	Micrognathia	Occasional (5-29%)
HP:0006323	Premature loss of primary teeth	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	Ehlers-Danlos syndrome, periodontitis type
Mondo ID	MONDO:0007527
MeSH	C562626
Orphanet	75392
ICD-11	893527307
SNOMED CT	50869007
UMLS	C0268347
MedGen	82791
GARD	0012474
Is cancer (heuristic)	no

Also known as: EDS VIII · EDS VIII (formerly) · EDS8 · EDS8 (formerly) · Ehlers-Danlos syndrome type 8 · Ehlers-Danlos syndrome type 8 (formerly) · Ehlers-Danlos syndrome, periodontitis type · Ehlers-Danlos syndrome, type VIII (formerly) · pEDS · periodontal EDS · periodontal Ehlers-Danlos syndrome

Data availability: 2 GenCC gene-disease records.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › syndromic disease › Ehlers-Danlos syndrome › Ehlers-Danlos syndrome, periodontitis type

Related subtypes (24): Ehlers-Danlos syndrome, classic type, Ehlers-Danlos syndrome, hypermobility type, Ehlers-Danlos syndrome, arthrochalasia type, Ehlers-Danlos syndrome, spondylodysplastic type, Ehlers-Danlos syndrome, autosomal dominant, type unspecified, joint laxity, familial, Ehlers-Danlos syndrome, fibronectinemic type, Ehlers-Danlos syndrome, dermatosparaxis type, brittle cornea syndrome, X-linked Ehlers-Danlos syndrome, Ehlers-Danlos syndrome, musculocontractural type, Ehlers-Danlos syndrome due to tenascin-X deficiency, Ehlers-Danlos syndrome, Beasley-Cohen type, Ehlers-Danlos syndrome, kyphoscoliotic type, 2, Ehlers-Danlos syndrome, kyphoscoliotic type 1, Ehlers-Danlos syndrome, vascular-like type, Ehlers-Danlos/osteogenesis imperfecta syndrome, Ehlers-Danlos syndrome, vascular type, spondylodysplastic Ehlers-Danlos syndrome, Bethlem myopathy 2, Ehlers-Danlos syndrome, classic-like, 2, COL1A1-related Ehlers-Danlos syndrome, COL1A2-related Ehlers-Danlos syndrome, Ehlers-Danlos syndrome, classic-like, 3

Subtypes (2): Ehlers-Danlos syndrome, periodontal type 2, Ehlers-Danlos syndrome, periodontal type 1

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

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 12 · Orphanet: 5 · 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
C1R	Definitive	Autosomal dominant	Ehlers-Danlos syndrome, periodontal type 1	5
C1S	Strong	Autosomal dominant	Ehlers-Danlos syndrome, periodontal type 2	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
C1R	Orphanet:169147	Immunodeficiency due to a classical component pathway complement deficiency
C1R	Orphanet:300345	Autosomal systemic lupus erythematosus
C1R	Orphanet:75392	Periodontal Ehlers-Danlos syndrome
C1S	Orphanet:169147	Immunodeficiency due to a classical component pathway complement deficiency
C1S	Orphanet:75392	Periodontal Ehlers-Danlos syndrome

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
C1R	HGNC:1246	ENSG00000159403	P00736	Complement C1r subcomponent	gencc
C1S	HGNC:1247	ENSG00000182326	P09871	Complement C1s subcomponent	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
C1R	Complement C1r subcomponent	Serine protease component of the complement C1 complex, a multiprotein complex that initiates the classical pathway of the complement system, a cascade of proteins that leads to phagocytosis and breakdown of pathogens and signaling that st…
C1S	Complement C1s subcomponent	Component of the complement C1 complex, a multiprotein complex that initiates the classical pathway of the complement system, a cascade of proteins that leads to phagocytosis and breakdown of pathogens and signaling that strengthens the ad…

Protein-family classification

Druggable: 2 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Protease	2	36.6×	7e-04

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
C1R	Protease	yes	3.4.21.41	Sushi_SCR_CCP_dom, EGF, CUB_dom
C1S	Protease	yes	3.4.21.42	EGF-type_Asp/Asn_hydroxyl_site, Sushi_SCR_CCP_dom, CUB_dom

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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
right lobe of liver	2
liver	1
right ovary	1
parietal pleura	1
pericardium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
C1R	134	ubiquitous	marker	right lobe of liver, liver, right ovary
C1S	287	ubiquitous	marker	pericardium, right lobe of liver, parietal pleura

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
C1S	2,304
C1R	2,153

Intra-cohort edges

A	B	Sources
C1R	C1S	biogrid_interaction, intact, string_interaction

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
C1S	P09871	14
C1R	P00736	12

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 8. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Classical antibody-mediated complement activation	2	1903.3×	2e-06	C1R, C1S
Initial triggering of complement	2	601.0×	1e-05	C1R, C1S
Regulation of Complement cascade	2	233.1×	5e-05	C1R, C1S
Creation of C4 and C2 activators	1	951.7×	0.002	C1S
Complement cascade	1	317.2×	0.005	C1S
Dengue virus activates/modulates innate and adaptive immune responses	1	167.9×	0.008	C1S
Innate Immune System	1	12.8×	0.088	C1S
Immune System	1	6.5×	0.148	C1S

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
complement activation, classical pathway	2	543.6×	2e-05	C1R, C1S
innate immune response	2	33.6×	0.002	C1R, C1S
zymogen activation	1	337.0×	0.005	C1R
immune response	1	23.5×	0.053	C1R
proteolysis	1	17.1×	0.058	C1S

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 2 · Phased (≥1): 2 · Undrugged: 0

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
C1R	1	3
C1S	1	3

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
NAFAMOSTAT	3	C1R, C1S

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

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

Symbol	Assays	Type breakdown
C1S	30	Binding:28, Functional:2
C1R	29	Binding:29

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
C1R	3.4.21.41	complement subcomponent C1r
C1S	3.4.21.42	complement subcomponent C1s

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

1 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)
NAFAMOSTAT	3	C1R, C1S

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	2	C1R, C1S
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 0.