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Periodontitis, aggressive 1

disease
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Also known as periodontitis 1, juvenileperiodontitis, aggressive, type 1

Summary

Periodontitis, aggressive 1 (MONDO:0008226) is a disease with 10 cohort genes (35 GWAS associations across 5 studies).

At a glance

  • Cohort genes: 10
  • GWAS associations: 35

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

FieldValue
Canonical nameperiodontitis, aggressive 1
Mondo IDMONDO:0008226
EFOEFO:0006342
MeSHD010520
OMIM170650
DOIDDOID:0061237, DOID:1474
GARD0024610
Is cancer (heuristic)no

Also known as: periodontitis 1, juvenile · periodontitis, aggressive, type 1

Data availability: 35 GWAS associations (5 studies) · 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › ectodermal dysplasia syndrome › CTSC-related disorder › periodontitis, aggressive 1

Related subtypes (2): Papillon-Lefevre disease, Haim-Munk syndrome

Genetics & variants

GWAS landscape

35 GWAS associations across 5 studies. Top hits map to 12 distinct genes (as reported by GWAS).

Top associations by p-value

rsIDp-valueGeneRisk alleleOdds ratio
chr1:1612178751e-09T0.32
rs109886636e-08HMCN2T1.2
rs110840941e-07SIGLEC5T0.24
chr3:52438141e-07A0.88
rs29789512e-07DEFA9P - DEFA10PA1.29
chr11:121538525e-07A0.63
rs562177536e-07CRYBB2P1T
rs111988986e-07GRK5A
rs109826176e-07DELEC1?
chr11:440664397e-07T0.35
rs11229008e-07SLC1A3-AS1A1.27
rs75520898e-07UBIAD1 - MTCYBP45?
rs49704691e-06OSTCP2G1.52
rs42847421e-06SIGLEC5G1.34
chr12:615290972e-06T0.24
chrX:1440043962e-06A0.64
chr2:98089722e-06T0.83
rs755270843e-06LINC00355 - LGMNP1T0.82
rs728322783e-06GPR179A0.46
chr1:2232594193e-06T0.21
rs1987124e-06RNA5SP228 - NPY?2.36
rs20709014e-06FCER1GT1.29
rs100293384e-06ABLIM2A
rs72246724e-06TUFMP1 - RPL34P31A0.26
rs1509560985e-06ZNF37CP - ZNF33CPA0.53
chr16:264782085e-06T0.28
chr1:193379175e-06C0.2
rs112439576e-06GFI1B?
chr18:715839166e-06T0.21
chr1:1876121336e-06A0.78

Top studies (by case count)

StudyLead authorYearCasesControlsTitle
GCST004303Munz M20178516,836A genome-wide association study identifies nucleotide variants at SIGLEC5 and DEFA1A3 as risk loci for periodontitis.
GCST009253Freitag-Wolf S20194990Smoking Modifies the Genetic Risk for Early-Onset Periodontitis.
GCST002635Freitag-Wolf S20143290Genome-wide exploration identifies sex-specific genetic effects of alleles upstream NPY to increase the risk of severe periodontitis in men.
GCST90454259De Almeida SD202300A genome-wide association study meta-analysis in a European sample of stage III/IV grade C periodontitis patients ≤35 years of age identifies new risk loci.
GCST90027904Freitag-Wolf S202100Sex-specific genetic factors affect the risk of early-onset periodontitis in Europeans.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

TierVariants
Tier 1: coding0
Tier 2: splice/UTR2
Tier 3: regulatory0
Tier 4: intronic/intergenic33

MAF distribution

BucketVariants
common (>=0.05)17
low_freq (0.01-0.05)0
rare (<0.01)0
unknown18

Functional consequences

ConsequenceCount
unknown16
intron_variant9
intergenic_variant7
5_prime_UTR_variant2
non_coding_transcript_exon_variant1

Top variants

rsIDChrPosAllelesMAFConsequenceGenep-valueTier
chr1:1612178751e-09Tier 4: intronic/intergenic
rs109886639130265816G>T5_prime_UTR_variantHMCN26e-08Tier 2: splice/UTR
rs110840941951616293T>C0.05intron_variantSIGLEC51e-07Tier 4: intronic/intergenic
chr3:52438141e-07Tier 4: intronic/intergenic
rs297895186965773A>G,T0.41intergenic_variantDEFA9P - DEFA10P2e-07Tier 4: intronic/intergenic
chr11:121538525e-07Tier 4: intronic/intergenic
rs562177532225517801T>A,C,G0.05intron_variantCRYBB2P16e-07Tier 4: intronic/intergenic
rs1119889810119358980A>C,T0.05intron_variantGRK56e-07Tier 4: intronic/intergenic
rs109826179115219960G>A0.05intron_variantDELEC16e-07Tier 4: intronic/intergenic
chr11:440664397e-07Tier 4: intronic/intergenic
rs1122900536689079A>C,G0.4intron_variantSLC1A3-AS18e-07Tier 4: intronic/intergenic
rs7552089111398960A>C,G,T0.05intergenic_variantUBIAD1 - MTCYBP458e-07Tier 4: intronic/intergenic
rs4970469126986325G>A,T0.1non_coding_transcript_exon_variantOSTCP21e-06Tier 4: intronic/intergenic
rs42847421951628480A>C,G,T0.24intron_variantSIGLEC51e-06Tier 4: intronic/intergenic
chr12:615290972e-06Tier 4: intronic/intergenic
chrX:1440043962e-06Tier 4: intronic/intergenic
chr2:98089722e-06Tier 4: intronic/intergenic
rs755270841364244614C>Tintergenic_variantLINC00355 - LGMNP13e-06Tier 4: intronic/intergenic
rs728322781738334544A>C,G0.05intron_variantGPR1793e-06Tier 4: intronic/intergenic
chr1:2232594193e-06Tier 4: intronic/intergenic
rs198712724141436G>A,T0.37intergenic_variantRNA5SP228 - NPY4e-06Tier 4: intronic/intergenic
rs20709011161215268G>C,T0.245_prime_UTR_variantFCER1G4e-06Tier 2: splice/UTR
rs1002933848048616G>A,C0.05intron_variantABLIM24e-06Tier 4: intronic/intergenic
rs72246721727221716A>C,G0.05intergenic_variantTUFMP1 - RPL34P314e-06Tier 4: intronic/intergenic
rs1509560981037884551A>G0.05intergenic_variantZNF37CP - ZNF33CP5e-06Tier 4: intronic/intergenic
chr16:264782085e-06Tier 4: intronic/intergenic
chr1:193379175e-06Tier 4: intronic/intergenic
rs112439579132968138A>G0.05intergenic_variantGFI1B6e-06Tier 4: intronic/intergenic
chr18:715839166e-06Tier 4: intronic/intergenic
chr1:1876121336e-06Tier 4: intronic/intergenic

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 10 · Orphanet: 2 · 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.

GeneClassificationInheritanceDiseaseRecords
CTSCLimitedUnknownperiodontitis, aggressive 110

Orphanet rare-disease linkage (cohort genes)

GeneOrphanet IDRare disease
CTSCOrphanet:2342Haim-Munk syndrome
CTSCOrphanet:678Papillon-Lefèvre syndrome

Cohort genes → proteins

10 cohort genes, 6 distinct canonical proteins.

Evidence partition

SubsetGenes
gwas_only9
multi_evidence1

Cohort genes (full)

SymbolHGNCEnsemblUniProtNameEvidence
CTSCHGNC:2528ENSG00000109861P53634Dipeptidyl peptidase 1gencc
SIGLEC5HGNC:10874ENSG00000105501O15389Sialic acid-binding Ig-like lectin 5gwas
ABLIM2HGNC:19195ENSG00000163995Q6H8Q1Actin-binding LIM protein 2gwas
CRYBB2P1HGNC:2399ENSG00000100058crystallin beta B2 pseudogene 1gwas
DEFA1A3HGNC:32231defensin alpha 1 and alpha 3, variable copy number locusgwas
FCER1GHGNC:3611ENSG00000158869P30273High affinity immunoglobulin epsilon receptor subunit gammagwas
OSTCP2HGNC:42864ENSG00000225294oligosaccharyltransferase complex subunit pseudogene 2gwas
GRK5HGNC:4544ENSG00000198873P34947G protein-coupled receptor kinase 5gwas
SLC1A3-AS1HGNC:56374ENSG00000250155SLC1A3 antisense RNA 1gwas
NPYHGNC:7955ENSG00000122585P01303Pro-neuropeptide Ygwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

SymbolProtein nameFunction (lead sentence)
CTSCDipeptidyl peptidase 1Thiol protease.
SIGLEC5Sialic acid-binding Ig-like lectin 5Putative adhesion molecule that mediates sialic-acid dependent binding to cells.
ABLIM2Actin-binding LIM protein 2May act as scaffold protein.
FCER1GHigh affinity immunoglobulin epsilon receptor subunit gammaAdapter protein containing an immunoreceptor tyrosine-based activation motif (ITAM) that transduces activation signals from various immunoreceptors.
GRK5G protein-coupled receptor kinase 5Serine/threonine kinase that phosphorylates preferentially the activated forms of a variety of G-protein-coupled receptors (GPCRs).
NPYPro-neuropeptide YNPY is implicated in the control of feeding and in secretion of gonadotrophin-release hormone.

Protein-family classification

Druggable: 3 · Difficult: 1 · Unknown: 6 · Druggable fraction: 0.3

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.

FamilyGenesFoldFDR
Protease13.7×0.513
Antibody/Immunoglobulin12.9×0.513
Kinase12.8×0.513
Other/Unknown61.1×0.657
Transcription factor10.8×0.725

Per-gene assignment

SymbolFamilyDruggable?ECInterPro (top 3)
CTSCProteaseyes3.4.14.1Pept_cys_AS, Peptidase_C1A_C, Peptidase_C1A
SIGLEC5Antibody/ImmunoglobulinyesIg_sub2, Ig_sub, Ig-like_dom
ABLIM2Transcription factornoZnf_LIM, Villin_headpiece, AbLIM_anchor
CRYBB2P1Other/Unknownno
DEFA1A3Other/Unknownno
FCER1GOther/UnknownnoPhos_immunorcpt_sig_ITAM, CD3_zeta/IgE_Fc_rcpt_gamma, FCER1G
OSTCP2Other/Unknownno
GRK5Kinaseyes2.7.11.16GPCR_kinase, Prot_kinase_dom, AGC-kinase_C
SLC1A3-AS1Other/Unknownno
NPYOther/UnknownnoPancreatic_hormone-like, Pancreatic_hormone-like_CS

Expression context

Cohort genes with no expression data: 1.

7 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

BucketGenes
narrow (1-5 tissues)0
moderate (6-20)0
broad (>20)9
unknown1

Top tissues across cohort

TissueCohort genes
leukocyte3
male germ line stem cell (sensu Vertebrata) in testis2
adenohypophysis2
monocyte2
epithelium of nasopharynx1
nasopharynx1
palpebral conjunctiva1
blood1
gastrocnemius1
hindlimb stylopod muscle1
tibialis anterior1
C1 segment of cervical spinal cord1
stromal cell of endometrium1
mononuclear cell1
right uterine tube1
pylorus1
saphenous vein1
synovial joint1
corpus callosum1
caudate nucleus1

Per-gene tissue summary (top 30)

SymbolBgee breadthFANTOM5 breadthSCXATop tissues
CTSC285ubiquitousmarkerpalpebral conjunctiva, epithelium of nasopharynx, nasopharynx
SIGLEC5120yesblood, male germ line stem cell (sensu Vertebrata) in testis, leukocyte
ABLIM2223broadmarkertibialis anterior, gastrocnemius, hindlimb stylopod muscle
CRYBB2P1226markerstromal cell of endometrium, C1 segment of cervical spinal cord, adenohypophysis
DEFA1A3
FCER1G251broadmarkermonocyte, mononuclear cell, leukocyte
OSTCP246markermale germ line stem cell (sensu Vertebrata) in testis, right uterine tube, adenohypophysis
GRK5270broadmarkersaphenous vein, pylorus, synovial joint
SLC1A3-AS1131yescorpus callosum, monocyte, leukocyte
NPY193broadmarkerganglionic eminence, putamen, caudate nucleus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

SymbolInteractor count
CTSC2,733
NPY2,707
FCER1G2,457
SIGLEC51,641
GRK51,566
ABLIM2782
CRYBB2P10
DEFA1A30
OSTCP20
SLC1A3-AS10

Structural data

PDB: 6 · AlphaFold-only: 0 · No structure: 4

Cohort genes with PDB structures (top 30)

SymbolUniProtPDB entries
GRK5P3494723
CTSCP5363418
NPYP0130310
SIGLEC5O153893
ABLIM2Q6H8Q13
FCER1GP302733

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 33. Enrichment computed across 10 evidence-associated genes (5 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 5 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

PathwayCohort genesFoldFDRSample cohort genes
DCC mediated attractive signaling1142.8×0.050ABLIM2
Platelet Adhesion to exposed collagen1134.3×0.050FCER1G
Role of LAT2/NTAL/LAB on calcium mobilization1120.2×0.050FCER1G
Netrin-1 signaling187.8×0.050ABLIM2
Dectin-2 family184.6×0.050FCER1G
FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes176.1×0.050NPY
FCERI mediated Ca+2 mobilization171.4×0.050FCER1G
FCERI mediated MAPK activation169.2×0.050FCER1G
Cargo concentration in the ER167.2×0.050CTSC
GPVI-mediated activation cascade161.7×0.050FCER1G
Fc epsilon receptor (FCERI) signaling154.4×0.050FCER1G
Neutrophil degranulation29.2×0.050CTSC, FCER1G
COPII-mediated vesicle transport132.6×0.074CTSC
FCERI mediated NF-kB activation131.3×0.074FCER1G
ER to Golgi Anterograde Transport126.6×0.082CTSC
Transport to the Golgi and subsequent modification120.6×0.098CTSC
Cell surface interactions at the vascular wall119.0×0.100FCER1G
MHC class II antigen presentation117.8×0.100CTSC
Peptide ligand-binding receptors114.8×0.110NPY
G alpha (s) signalling events114.6×0.110GRK5
Asparagine N-linked glycosylation112.0×0.126CTSC
G alpha (q) signalling events111.5×0.126GRK5
Axon guidance19.0×0.152ABLIM2
Nervous system development18.6×0.153ABLIM2
G alpha (i) signalling events17.8×0.161NPY
Membrane Trafficking17.4×0.162CTSC
Vesicle-mediated transport17.0×0.166CTSC
Adaptive Immune System16.0×0.185CTSC
Innate Immune System15.1×0.206CTSC
Post-translational protein modification13.8×0.258CTSC

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 6 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO termCohort genesFoldFDRSample cohort genes
regulation of nerve growth factor production12808.7×0.008NPY
short-day photoperiodism12808.7×0.008NPY
positive regulation of type I hypersensitivity11404.3×0.008FCER1G
Fc receptor mediated stimulatory signaling pathway11404.3×0.008FCER1G
positive regulation of type IIa hypersensitivity1936.2×0.008FCER1G
positive regulation of type III hypersensitivity1936.2×0.008FCER1G
T cell differentiation involved in immune response1936.2×0.008FCER1G
serotonin secretion by platelet1936.2×0.008FCER1G
positive regulation of appetite1936.2×0.008NPY
negative regulation of mast cell apoptotic process1936.2×0.008FCER1G
obsolete positive regulation of nitric oxide metabolic process1936.2×0.008NPY
negative regulation of acute inflammatory response to antigenic stimulus1702.2×0.008NPY
mast cell apoptotic process1702.2×0.008FCER1G
positive regulation of dopamine metabolic process1702.2×0.008NPY
obsolete positive regulation of proteolysis involved in protein catabolic process1702.2×0.008CTSC
positive regulation of mast cell cytokine production1561.7×0.009FCER1G
regulation of platelet activation1468.1×0.010FCER1G
interleukin-3-mediated signaling pathway1401.2×0.010FCER1G
antigen processing and presentation of exogenous peptide antigen via MHC class I1401.2×0.010FCER1G
positive regulation of eating behavior1401.2×0.010NPY
positive regulation of microglial cell activation1351.1×0.010CTSC
neutrophil activation involved in immune response1312.1×0.010FCER1G
tachykinin receptor signaling pathway1312.1×0.010GRK5
negative regulation of myelination1312.1×0.010CTSC
Fc-gamma receptor signaling pathway1312.1×0.010FCER1G
monocyte activation1312.1×0.010NPY
regulation of presynaptic cytosolic calcium ion concentration1312.1×0.010NPY
adult feeding behavior1280.9×0.010NPY
positive regulation of mast cell degranulation1255.3×0.010FCER1G
intestinal epithelial cell differentiation1255.3×0.010NPY

Therapeutics

Drug target analysis

Approved (phase 4): 2 · Phase ≥3: 2 · Phased (≥1): 2 · Undrugged: 8

Druggability breadth: 2 of 10 evidence-associated genes (20%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

SymbolExample approved molecule
CTSCOSIMERTINIB
GRK5ENTRECTINIB

Top cohort targets by molecule count

SymbolMoleculesMax phase
GRK584
CTSC34
SIGLEC500
ABLIM200
CRYBB2P100
DEFA1A300
FCER1G00
OSTCP200
SLC1A3-AS100
NPY00

Drugs targeting cohort genes (top 30)

MoleculeMax phaseTargets in cohort
OSIMERTINIB4CTSC
ENTRECTINIB4GRK5
UPADACITINIB4GRK5
SUNITINIB4GRK5
CANERTINIB3CTSC
BRENSOCATIB3CTSC
ALISERTIB3GRK5
SOTRASTAURIN2GRK5
PF-005622711GRK5
RG-15301GRK5
MLN-80541GRK5

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

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

SymbolAssaysType breakdown
GRK5172Binding:171, Functional:1
CTSC107Binding:106, ADMET:1

Cohort enzymes (BRENDA EC)

SymbolEC numbersNames
CTSC3.4.14.1dipeptidyl-peptidase I
GRK52.7.11.16G-protein-coupled receptor kinase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

SymbolChEMBL assays
CTSC107
GRK5172

Pharmacogenomics

Cohort genes with a PharmGKB record: 8; with CPIC/DPWG dosing guidelines: 1.

Cohort genes with a CPIC/DPWG dosing guideline

SymbolCPIC guidelines
GRK51

Chemical tractability of cohort targets

11 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.

CompoundMax phaseCohort target (bioactivity)
OSIMERTINIB4CTSC
ENTRECTINIB4GRK5
UPADACITINIB4GRK5
SUNITINIB4GRK5
CANERTINIB3CTSC
BRENSOCATIB3CTSC
ALISERTIB3GRK5
SOTRASTAURIN2GRK5
PF-005622711GRK5
RG-15301GRK5
MLN-80541GRK5

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

TierDefinitionGenesSymbols
AApproved (phase 4 drug)2CTSC, GRK5
BPhased (≥1) drug, not yet approved0
CDruggable family + PDB, no drug1SIGLEC5
DDruggable family + AlphaFold only, no drug0
EDifficult family or no structure, no drug7ABLIM2, CRYBB2P1, DEFA1A3, FCER1G, OSTCP2, SLC1A3-AS1, NPY

Undrugged target profiles

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

SymbolChEMBL assaysDrugged partners (top 3)
SIGLEC50—
ABLIM20—
CRYBB2P10—
DEFA1A30—
FCER1G0—
OSTCP20—
SLC1A3-AS10—
NPY0—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
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Sources 68

This page pulls from 68 datasets indexed by BioBTree:

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