Ehlers-Danlos syndrome, periodontal type 1

Summary

Ehlers-Danlos syndrome, periodontal type 1 (MONDO:0020684) is a disease caused by C1R (GenCC Definitive), with 2 cohort genes.

At a glance

• Causal gene: C1R (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 37

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Ehlers-Danlos syndrome, periodontal type 1
Mondo ID	MONDO:0020684
OMIM	130080
DOID	DOID:0080986
UMLS	C4551499
MedGen	1642148
GARD	0025210
Is cancer (heuristic)	no

Also known as: EDSPD1

Data availability: 37 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › Ehlers-Danlos syndrome › Ehlers-Danlos syndrome, periodontitis type › Ehlers-Danlos syndrome, periodontal type 1

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

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

37 retrieved; paginated sample, class counts are floors:

16 pathogenic, 9 uncertain significance, 5 conflicting classifications of pathogenicity, 3 likely pathogenic, 2 likely benign, 1 benign/likely benign, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
267351	NM_001733.7(C1R):c.1073G>T (p.Cys358Phe)	C1R	Pathogenic	criteria provided, single submitter
267352	NM_001733.7(C1R):c.902G>C (p.Arg301Pro)	C1R	Pathogenic	criteria provided, single submitter
267353	NM_001733.7(C1R):c.927C>G (p.Cys309Trp)	C1R	Pathogenic	criteria provided, single submitter
267354	NM_001733.7(C1R):c.899T>C (p.Leu300Pro)	C1R	Pathogenic	criteria provided, single submitter
267355	NM_001733.7(C1R):c.917_927delinsGGACA (p.Ile306_Cys309delinsArgThr)	C1R	Pathogenic	criteria provided, single submitter
267356	NM_001733.7(C1R):c.869A>G (p.Asp290Gly)	C1R	Pathogenic	criteria provided, single submitter
372129	NM_001733.7(C1R):c.890G>A (p.Gly297Asp)	C1R	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
372130	NM_001733.7(C1R):c.149_150delinsAT (p.Val50Asp)	C1R	Pathogenic	criteria provided, single submitter
375577	NM_001733.7(C1R):c.905A>G (p.Tyr302Cys)	C1R	Pathogenic	criteria provided, single submitter
375578	NM_001733.7(C1R):c.1012T>C (p.Cys338Arg)	C1R	Pathogenic	criteria provided, multiple submitters, no conflicts
375579	NM_001733.7(C1R):c.1092G>C (p.Trp364Cys)	C1R	Pathogenic	criteria provided, single submitter
375580	NM_001733.7(C1R):c.1113C>G (p.Cys371Trp)	C1R	Pathogenic	criteria provided, multiple submitters, no conflicts
375581	NM_001733.7(C1R):c.1200_1215delinsTCATGTAATA (p.Arg401_Tyr405delinsHisValIle)	C1R	Pathogenic	criteria provided, single submitter
375582	NM_001733.7(C1R):c.1303T>C (p.Trp435Arg)	C1R	Pathogenic	criteria provided, single submitter
973553	NM_001733.7(C1R):c.1427_1428dup (p.Trp477fs)	C1R	Pathogenic	criteria provided, single submitter
267348	NM_001734.5(C1S):c.945_947del (p.Asp315_Val316delinsGlu)	C1S	Pathogenic	criteria provided, single submitter
267349	NM_001734.5(C1S):c.880T>C (p.Cys294Arg)	C1S	Pathogenic	criteria provided, single submitter
2444516	NM_001733.7(C1R):c.1073G>A (p.Cys358Tyr)	C1R	Likely pathogenic	criteria provided, single submitter
3898059	NM_001733.7(C1R):c.925T>C (p.Cys309Arg)	C1R	Likely pathogenic	criteria provided, single submitter
4531436	NM_001733.7(C1R):c.1111T>C (p.Cys371Arg)	C1R	Likely pathogenic	criteria provided, single submitter
2439616	NM_001733.7(C1R):c.419C>T (p.Ala140Val)	C1R	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
597277	NM_001733.7(C1R):c.277G>T (p.Gly93Cys)	C1R	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
625897	NM_001733.7(C1R):c.336G>C (p.Met112Ile)	C1R	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
931271	NM_001733.7(C1R):c.646C>A (p.Pro216Thr)	C1R	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
992508	NM_001733.7(C1R):c.445C>T (p.Arg149Trp)	C1R	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1065580	NM_001733.7(C1R):c.646C>G (p.Pro216Ala)	C1R	Uncertain significance	criteria provided, single submitter
2439615	NM_001733.7(C1R):c.203C>T (p.Ser68Phe)	C1R	Uncertain significance	criteria provided, single submitter
2439617	NM_001733.7(C1R):c.450C>A (p.Ser150Arg)	C1R	Uncertain significance	criteria provided, single submitter
2499515	NM_001733.7(C1R):c.424+2T>C	C1R	Uncertain significance	criteria provided, single submitter
3235250	NM_001733.7(C1R):c.664T>A (p.Tyr222Asn)	C1R	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · 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

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,clinvar
C1S	HGNC:1247	ENSG00000182326	P09871	Complement C1s subcomponent	clinvar

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.