Periodontitis

Summary

Periodontitis (MONDO:0005076) is a disease with 75 cohort genes (172 GWAS associations across 48 studies) and 882 clinical trials. Top therapeutic interventions include chlorhexidine, minocycline, and doxycycline anhydrous.

At a glance

• Cohort genes: 75
• GWAS associations: 172
• ClinVar variants: 11
• Clinical trials: 882

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	periodontitis
Mondo ID	MONDO:0005076
EFO	EFO:0000649
MeSH	D010518
DOID	DOID:824, DOID:9893
ICD-10-CM	K05.4
NCIT	C34918
SNOMED CT	41565005
UMLS	C0031099
MedGen	45815
Is cancer (heuristic)	no

Also known as: inflammation of periodontium · periodontium inflammation · periodontosis

Data availability: 11 ClinVar variants · 172 GWAS associations (48 studies).

Disease family

An umbrella term covering 4 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › musculoskeletal system disorder › skeletal system disorder › periodontal disorder › periodontitis

Related subtypes (3): gingival disorder, Papillon-Lefevre disease, regional odontodysplasia

Subtypes (4): acute pericementitis, periapical periodontitis, chronic periodontitis, pericoronitis

Genetics & variants

GWAS landscape

172 GWAS associations across 48 studies. Top hits map to 34 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs75933965	6e-13	TCF7L2	A	0.05
rs8047395	2e-12	FTO	A	0.03
rs12255678	6e-11	TCF7L2	T	0.02
rs149290349	3e-10	LINC01126, ZFP36L2	A	0.04
rs10770140	8e-10	TH - MIR4686	T	0.02
rs76895963	2e-09	CCND2-AS1, CCND2	T	0.08
rs4376068	2e-09	IGF2BP2	A	0.02
rs1537415	6e-09	GLT6D1	G	1.59
rs77464186	8e-09	ARAP1	A	0.03
rs80193913	9e-09	ZFHX3	?	1.15
rs3200401	9e-09	MALAT1, TALAM1	T	0.03
rs729876	1e-08	SHISA9 - TMF1P1	T	1.23
rs17522122	1e-08	AKAP6	T	0.02
rs242016	2e-08	CRACR2A	A	3.7
rs2010390	2e-08	PPP1R3B-DT	A	0.02
rs2546494	3e-08	SUMO2P17 - ATP5MC1	A	0.02
rs6711375	3e-08	ITGB6	A	0.02
rs1265758	3e-08	TSBP1, TSBP1-AS1	A	0.02
rs11084095	5e-08	SIGLEC5	A	1.17
rs665268	5e-08	MLX	A	0.02
rs7762544	8e-08	NCR2 - FOXP4-AS1	?	1.4
rs370522109	1e-07	SLC12A7	?
rs139915770	1e-07	LINC02763	?
rs13237474	2e-07	FAM180A - MTPN	T	3.05
rs188596802	2e-07	PKHD1 - MIR206	?
rs11800854	3e-07	RNU4-77P - KCNK1	G	12.3
rs6802315	3e-07	MFSD1	?	1.37
rs2521634	4e-07	NPY - RNU6-1103P	?	1.49
rs9979250	4e-07	ETS2-AS1	T	0.15
rs10760187	5e-07	DAB2IP - TTLL11	C	2.07

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90478260	Verma A	2024	34,270	396,445	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90478263	Verma A	2024	22,330	412,351	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90478259	Verma A	2024	17,928	94,012	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90480860	Verma A	2024	17,928	94,012	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST008296	Shungin D	2019	17,353	470,262	Genome-wide analysis of dental caries and periodontitis combining clinical and self-reported data.
GCST008300	Shungin D	2019	17,353	28,210	Genome-wide analysis of dental caries and periodontitis combining clinical and self-reported data.
GCST90269795	Saarentaus EC	2023	14,631	245,774	Inflammatory and infectious upper respiratory diseases associate with 41 genomic loci and type 2 inflammation.
GCST90478262	Verma A	2024	11,304	102,475	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90480835	Verma A	2024	11,304	102,475	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90018677	Sakaue S	2021	9,560	169,166	A cross-population atlas of genetic associations for 220 human phenotypes.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	3
Tier 2: splice/UTR	2
Tier 3: regulatory	1
Tier 4: intronic/intergenic	44

MAF distribution

Bucket	Variants
common (>=0.05)	43
low_freq (0.01-0.05)	5
rare (<0.01)	0
unknown	2

Functional consequences

Consequence	Count
intron_variant	26
intergenic_variant	13
non_coding_transcript_exon_variant	4
missense_variant	3
3_prime_UTR_variant	2
synonymous_variant	1
regulatory_region_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs75933965	10	112989662	G>A	0.07	intron_variant	TCF7L2	6e-13	Tier 4: intronic/intergenic
rs8047395	16	53764611	G>A,C	0.49	intron_variant	FTO	2e-12	Tier 4: intronic/intergenic
rs12255678	10	112969723	T>G	0.25	intron_variant	TCF7L2	6e-11	Tier 4: intronic/intergenic
rs149290349	2	43224818	G>A,C,T	0.07	missense_variant	LINC01126, ZFP36L2	3e-10	Tier 1: coding
rs10770140	11	2172367	C>A,G,T	0.39	non_coding_transcript_exon_variant	TH - MIR4686	8e-10	Tier 4: intronic/intergenic
rs76895963	12	4275678	T>C,G	0.02	non_coding_transcript_exon_variant	CCND2-AS1, CCND2	2e-09	Tier 4: intronic/intergenic
rs4376068	3	185779847	A>C,T	0.31	intron_variant	IGF2BP2	2e-09	Tier 4: intronic/intergenic
rs1537415	9	135637876	G>A,C,T	0.38	intron_variant	GLT6D1	6e-09	Tier 4: intronic/intergenic
rs77464186	11	72749353	A>C	0.16	intron_variant	ARAP1	8e-09	Tier 4: intronic/intergenic
rs80193913	16	73142018	C>A,T	0.05	intron_variant	ZFHX3	9e-09	Tier 4: intronic/intergenic
rs3200401	11	65504361	C>T	0.2	non_coding_transcript_exon_variant	MALAT1, TALAM1	9e-09	Tier 4: intronic/intergenic
rs729876	16	13294921	T>C	0.2	intron_variant	SHISA9 - TMF1P1	1e-08	Tier 4: intronic/intergenic
rs17522122	14	32833676	G>T	0.48	3_prime_UTR_variant	AKAP6	1e-08	Tier 2: splice/UTR
rs242016	12	3679094	G>A	0.21	synonymous_variant	CRACR2A	2e-08	Tier 4: intronic/intergenic
rs2010390	8	9189668	A>G,T	0.3	intergenic_variant	PPP1R3B-DT	2e-08	Tier 4: intronic/intergenic
rs2546494	17	48882163	G>A,C	0.49	intron_variant	SUMO2P17 - ATP5MC1	3e-08	Tier 4: intronic/intergenic
rs6711375	2	160234362	G>A,C,T	0.32	intergenic_variant	ITGB6	3e-08	Tier 4: intronic/intergenic
rs1265758	6	32355752	A>C,G,T	0.42	intron_variant	TSBP1, TSBP1-AS1	3e-08	Tier 4: intronic/intergenic
rs11084095	19	51623777	G>A	0.41	intron_variant	SIGLEC5	5e-08	Tier 4: intronic/intergenic
rs665268	17	42570011	A>C,G,T	0.28	missense_variant	MLX	5e-08	Tier 1: coding
rs7762544	6	41411577	G>A,C,T	0.05	intergenic_variant	NCR2 - FOXP4-AS1	8e-08	Tier 4: intronic/intergenic
rs370522109	5	1083297	G>A,T		intron_variant	SLC12A7	1e-07	Tier 4: intronic/intergenic
rs139915770	11	112532080	C>A,T	0.05	intron_variant	LINC02763	1e-07	Tier 4: intronic/intergenic
rs13237474	7	135816721	C>T	0.03	intron_variant	FAM180A - MTPN	2e-07	Tier 4: intronic/intergenic
rs188596802	6	52093172	T>A		intergenic_variant	PKHD1 - MIR206	2e-07	Tier 4: intronic/intergenic
rs11800854	1	233584238	G>A	0.053	intergenic_variant	RNU4-77P - KCNK1	3e-07	Tier 4: intronic/intergenic
rs6802315	3	158796571	T>A,G	0.45	intergenic_variant	MFSD1	3e-07	Tier 4: intronic/intergenic
rs2521634	7	24338421	G>A,C	0.05	intron_variant	NPY - RNU6-1103P	4e-07	Tier 4: intronic/intergenic
rs9979250	21	38911809	C>T	0.04	intron_variant	ETS2-AS1	4e-07	Tier 4: intronic/intergenic
rs10760187	9	121803541	T>A,C,G	0.498	intergenic_variant	DAB2IP - TTLL11	5e-07	Tier 4: intronic/intergenic

ClinVar germline variants

11 retrieved; paginated sample, class counts are floors:

6 benign, 2 conflicting classifications of pathogenicity, 2 uncertain significance, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
684727	NM_000396.4(CTSK):c.905G>A (p.Trp302Ter)	CTSK	Pathogenic	criteria provided, multiple submitters, no conflicts
1252227	NM_000376.3(VDR):c.1025-49G>T	VDR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
308887	NM_000376.3(VDR):c.2T>C (p.Met1Thr)	VDR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
831452	NC_000019.10:g.(?51745922)(51759909_?)dup	FPR1	Uncertain significance	criteria provided, single submitter
951604	NM_002029.4(FPR1):c.664G>A (p.Gly222Arg)	FPR1	Uncertain significance	criteria provided, single submitter
15987	NM_000583.4(GC):c.1296T>G (p.Asp432Glu)	GC	Benign	criteria provided, single submitter
1259287	NM_000376.3(VDR):c.1024+283G>A	VDR	Benign	criteria provided, single submitter
308841	NM_000376.3(VDR):c.*1906C>A	VDR	Benign	criteria provided, multiple submitters, no conflicts
308862	NM_000376.3(VDR):c.*461G>T	VDR	Benign	criteria provided, multiple submitters, no conflicts
308868	NM_000376.3(VDR):c.*308C>A	VDR	Benign	criteria provided, multiple submitters, no conflicts
308877	NM_000376.3(VDR):c.1056T>C (p.Ile352=)	VDR	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 46 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ROBO2	Orphanet:289365	Familial vesicoureteral reflux
RUNX2	Orphanet:1452	Cleidocranial dysplasia
RUNX2	Orphanet:2504	Metaphyseal dysplasia-maxillary hypoplasia-brachydacty syndrome
BLK	Orphanet:536	Systemic lupus erythematosus
BLK	Orphanet:552	MODY
SCN2A	Orphanet:140927	Self-limited neonatal-infantile epilepsy
SCN2A	Orphanet:1934	Early infantile developmental and epileptic encephalopathy
SCN2A	Orphanet:2131	Alternating hemiplegia of childhood
SCN2A	Orphanet:293181	Epilepsy of infancy with migrating focal seizures
SCN2A	Orphanet:306	Self-limited infantile epilepsy
SCN2A	Orphanet:33069	Dravet syndrome
SCN2A	Orphanet:36387	Genetic epilepsy with febrile seizure plus
SCN2A	Orphanet:697160	Infantile epileptic spasms syndrome
SNRPN	Orphanet:177901	Prader-Willi syndrome due to paternal deletion of 15q11q13 type 1
SNRPN	Orphanet:177904	Prader-Willi syndrome due to paternal deletion of 15q11q13 type 2
SNRPN	Orphanet:177907	Prader-Willi syndrome due to translocation
SNRPN	Orphanet:177910	Prader-Willi syndrome due to imprinting mutation
SNRPN	Orphanet:411515	Angelman syndrome due to imprinting defect in 15q11-q13
SNRPN	Orphanet:98754	Prader-Willi syndrome due to maternal uniparental disomy of chromosome 15
SOS2	Orphanet:648	Noonan syndrome
ATL1	Orphanet:100984	Autosomal dominant spastic paraplegia type 3
ATL1	Orphanet:36386	Hereditary sensory and autonomic neuropathy type 1
SS18	Orphanet:3273	Synovial sarcoma
TGIF1	Orphanet:220386	Semilobar holoprosencephaly
TGIF1	Orphanet:280195	Septopreoptic holoprosencephaly
TGIF1	Orphanet:280200	Microform holoprosencephaly
TGIF1	Orphanet:93924	Lobar holoprosencephaly
TGIF1	Orphanet:93925	Alobar holoprosencephaly
TGIF1	Orphanet:93926	Midline interhemispheric variant of holoprosencephaly
TRPS1	Orphanet:502	Trichorhinophalangeal syndrome type 2
TRPS1	Orphanet:77258	Trichorhinophalangeal syndrome type 1
VDR	Orphanet:93160	Hypocalcemic vitamin D-resistant rickets
NIN	Orphanet:319675	Microcephalic primordial dwarfism, Dauber type
NIN	Orphanet:808	Seckel syndrome
ACTN1	Orphanet:140957	Autosomal dominant macrothrombocytopenia
ACTN2	Orphanet:154	Familial isolated dilated cardiomyopathy
ACTN2	Orphanet:708129	Autosomal recessive ACTN2-related distal myopathy
ACTN2	Orphanet:708133	Autosomal dominant ACTN2-related distal myopathy
NME8	Orphanet:244	Primary ciliary dyskinesia
CDH2	Orphanet:293910	Inherited isolated arrhythmogenic cardiomyopathy, dominant-right variant
CAMTA1	Orphanet:157791	Epithelioid hemangioendothelioma
CAMTA1	Orphanet:314647	Non-progressive cerebellar ataxia with intellectual disability
CHD1	Orphanet:529965	Intellectual disability-autism-speech apraxia-craniofacial dysmorphism syndrome
L2HGDH	Orphanet:79314	L-2-hydroxyglutaric aciduria
ANTXR1	Orphanet:2067	GAPO syndrome
CNTN2	Orphanet:86814	Familial adult myoclonic epilepsy

Cohort genes → proteins

75 cohort genes, 74 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	74
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
RIT2	HGNC:10017	ENSG00000152214	Q99578	GTP-binding protein Rit2	gwas
ROBO2	HGNC:10250	ENSG00000185008	Q9HCK4	Roundabout homolog 2	gwas
RUNX2	HGNC:10472	ENSG00000124813	Q13950	Runt-related transcription factor 2	gwas
RYR3	HGNC:10485	ENSG00000198838	Q15413	Ryanodine receptor 3	gwas
BLK	HGNC:1057	ENSG00000136573	P51451	Tyrosine-protein kinase Blk	gwas
SCN2A	HGNC:10588	ENSG00000136531	Q99250	Sodium channel protein type 2 subunit alpha	gwas
SEL1L	HGNC:10717	ENSG00000071537	Q9UBV2	Protein sel-1 homolog 1	gwas
SEMA6A	HGNC:10738	ENSG00000092421	Q9H2E6	Semaphorin-6A	gwas
SETMAR	HGNC:10762	ENSG00000170364	Q53H47	Histone-lysine N-methyltransferase SETMAR	gwas
SIGLEC5	HGNC:10874	ENSG00000105501	O15389	Sialic acid-binding Ig-like lectin 5	gwas
SNRPN	HGNC:11164	ENSG00000128739	P63162	Small nuclear ribonucleoprotein-associated protein N	gwas
SNTB1	HGNC:11168	ENSG00000172164	Q13884	Beta-1-syntrophin	gwas
SOS2	HGNC:11188	ENSG00000100485	Q07890	Son of sevenless homolog 2	gwas
ATL1	HGNC:11231	ENSG00000198513	Q8WXF7	Atlastin-1	gwas
SS18	HGNC:11340	ENSG00000141380	Q15532	Protein SSXT	gwas
TBC1D1	HGNC:11578	ENSG00000065882	Q86TI0	TBC1 domain family member 1	gwas
TGIF1	HGNC:11776	ENSG00000177426	Q15583	Homeobox protein TGIF1	gwas
TIMP2	HGNC:11821	ENSG00000035862	P16035	Metalloproteinase inhibitor 2	gwas
NPAP1	HGNC:1190	ENSG00000185823	Q9NZP6	Nuclear pore-associated protein 1	gwas
TRPS1	HGNC:12340	ENSG00000104447	Q9UHF7	Zinc finger transcription factor Trps1	gwas
UHRF2	HGNC:12557	ENSG00000147854	Q96PU4	E3 ubiquitin-protein ligase UHRF2	gwas
VAMP3	HGNC:12644	ENSG00000049245	Q15836	Vesicle-associated membrane protein 3	gwas
VAV1	HGNC:12657	ENSG00000141968	P15498	Proto-oncogene vav	gwas
VDR	HGNC:12679	ENSG00000111424	P11473	Vitamin D3 receptor	clinvar
VPREB1	HGNC:12709	ENSG00000169575	P12018	Immunoglobulin iota chain	gwas
C5AR1	HGNC:1338	ENSG00000197405	P21730	C5a anaphylatoxin chemotactic receptor 1	gwas
PGPEP1	HGNC:13568	ENSG00000130517	Q9NXJ5	Pyroglutamyl-peptidase 1	gwas
CSMD1	HGNC:14026	ENSG00000183117	Q96PZ7	CUB and sushi domain-containing protein 1	gwas
NLGN1	HGNC:14291	ENSG00000169760	Q8N2Q7	Neuroligin-1	gwas
CAMK4	HGNC:1464	ENSG00000152495	Q16566	Calcium/calmodulin-dependent protein kinase type IV	gwas
NIN	HGNC:14906	ENSG00000100503	Q8N4C6	Ninein	gwas
LINC00208	HGNC:15535	ENSG00000170983	Q96KT6	Putative uncharacterized protein encoded by LINC00208	gwas
IL33	HGNC:16028	ENSG00000137033	O95760	Interleukin-33	gwas
ACTN1	HGNC:163	ENSG00000072110	P12814	Alpha-actinin-1	gwas
ADAMTS15	HGNC:16305	ENSG00000166106	Q8TE58	A disintegrin and metalloproteinase with thrombospondin motifs 15	gwas
OSBPL10	HGNC:16395	ENSG00000144645	Q9BXB5	Oxysterol-binding protein-related protein 10	gwas
ACTN2	HGNC:164	ENSG00000077522	P35609	Alpha-actinin-2	gwas
NKAIN2	HGNC:16443	ENSG00000188580	Q5VXU1	Sodium/potassium-transporting ATPase subunit beta-1-interacting protein 2	gwas
NMUR2	HGNC:16454	ENSG00000132911	Q9GZQ4	Neuromedin-U receptor 2	gwas
NME8	HGNC:16473	ENSG00000086288	Q8N427	Protein NME8	gwas
RAB6C	HGNC:16525	ENSG00000222014	Q9H0N0	Ras-related protein Rab-6C	gwas
MAPK6P2	HGNC:16756	ENSG00000223488		mitogen-activated protein kinase 6 pseudogene 2	gwas
SMURF2	HGNC:16809	ENSG00000108854	Q9HAU4	E3 ubiquitin-protein ligase SMURF2	gwas
GPN1	HGNC:17030	ENSG00000198522	Q9HCN4	GPN-loop GTPase 1	gwas
ANKRD30A	HGNC:17234	ENSG00000148513	Q9BXX3	Ankyrin repeat domain-containing protein 30A	gwas
DAB2IP	HGNC:17294	ENSG00000136848	Q5VWQ8	Disabled homolog 2-interacting protein	gwas
CDH13	HGNC:1753	ENSG00000140945	P55290	Cadherin-13	gwas
JDP2	HGNC:17546	ENSG00000140044	Q8WYK2	Jun dimerization protein 2	gwas
CDH2	HGNC:1759	ENSG00000170558	P19022	Cadherin-2	gwas
SAV1	HGNC:17795	ENSG00000151748	Q9H4B6	Protein salvador homolog 1	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RIT2	GTP-binding protein Rit2	Binds and exchanges GTP and GDP.
ROBO2	Roundabout homolog 2	Receptor for SLIT2, and probably SLIT1, which are thought to act as molecular guidance cue in cellular migration, including axonal navigation at the ventral midline of the neural tube and projection of axons to different regions during neu…
RUNX2	Runt-related transcription factor 2	Transcription factor involved in osteoblastic differentiation and skeletal morphogenesis.
RYR3	Ryanodine receptor 3	Cytosolic calcium-activated calcium channel that mediates the release of Ca(2+) from the sarcoplasmic reticulum into the cytoplasm in muscle and thereby plays a role in triggering muscle contraction.
BLK	Tyrosine-protein kinase Blk	Non-receptor tyrosine kinase involved in B-lymphocyte development, differentiation and signaling.
SCN2A	Sodium channel protein type 2 subunit alpha	Mediates the voltage-dependent sodium ion permeability of excitable membranes.
SEL1L	Protein sel-1 homolog 1	Plays a role in the endoplasmic reticulum quality control (ERQC) system also called ER-associated degradation (ERAD) involved in ubiquitin-dependent degradation of misfolded endoplasmic reticulum proteins.
SEMA6A	Semaphorin-6A	Cell surface receptor for PLXNA2 that plays an important role in cell-cell signaling.
SETMAR	Histone-lysine N-methyltransferase SETMAR	Protein derived from the fusion of a methylase with the transposase of an Hsmar1 transposon that plays a role in DNA double-strand break repair, stalled replication fork restart and DNA integration.
SIGLEC5	Sialic acid-binding Ig-like lectin 5	Putative adhesion molecule that mediates sialic-acid dependent binding to cells.
SNRPN	Small nuclear ribonucleoprotein-associated protein N	May be involved in tissue-specific alternative RNA processing events.
SNTB1	Beta-1-syntrophin	Adapter protein that binds to and probably organizes the subcellular localization of a variety of membrane proteins.
SOS2	Son of sevenless homolog 2	Acts as guanine nucleotide exchange factor (GEF) for RAS proteins.
ATL1	Atlastin-1	Atlastin-1 (ATL1) is a membrane-anchored GTPase that mediates the GTP-dependent fusion of endoplasmic reticulum (ER) membranes, maintaining the continuous ER network.
SS18	Protein SSXT	Appears to function synergistically with RBM14 as a transcriptional coactivator.
TBC1D1	TBC1 domain family member 1	May act as a GTPase-activating protein for Rab family protein(s).
TGIF1	Homeobox protein TGIF1	Binds to a retinoid X receptor (RXR) responsive element from the cellular retinol-binding protein II promoter (CRBPII-RXRE).
TIMP2	Metalloproteinase inhibitor 2	Complexes with metalloproteinases (such as collagenases) and irreversibly inactivates them by binding to their catalytic zinc cofactor.
NPAP1	Nuclear pore-associated protein 1	May be involved in spermatogenesis.
TRPS1	Zinc finger transcription factor Trps1	Transcriptional repressor.
UHRF2	E3 ubiquitin-protein ligase UHRF2	E3 ubiquitin ligase that plays important roles in DNA methylation, histone modifications, cell cycle and DNA repair.
VAMP3	Vesicle-associated membrane protein 3	SNARE involved in vesicular transport from the late endosomes to the trans-Golgi network.
VAV1	Proto-oncogene vav	Couples tyrosine kinase signals with the activation of the Rho/Rac GTPases, thus leading to cell differentiation and/or proliferation.
VDR	Vitamin D3 receptor	Nuclear receptor for calcitriol, the active form of vitamin D3 which mediates the action of this vitamin on cells.
VPREB1	Immunoglobulin iota chain	Associates with the Ig-mu chain to form a molecular complex that is expressed on the surface of pre-B-cells.
C5AR1	C5a anaphylatoxin chemotactic receptor 1	Receptor for the chemotactic and inflammatory peptide anaphylatoxin C5a, stimulating chemotaxis, granule enzyme release, intracellular calcium release and superoxide anion production.
PGPEP1	Pyroglutamyl-peptidase 1	Removes 5-oxoproline from various penultimate amino acid residues except L-proline.
CSMD1	CUB and sushi domain-containing protein 1	Potential suppressor of squamous cell carcinomas.
NLGN1	Neuroligin-1	Cell surface protein involved in cell-cell-interactions via its interactions with neurexin family members.
CAMK4	Calcium/calmodulin-dependent protein kinase type IV	Calcium/calmodulin-dependent protein kinase that operates in the calcium-triggered CaMKK-CaMK4 signaling cascade and regulates, mainly by phosphorylation, the activity of several transcription activators, such as CREB1, MEF2D, JUN and RORA…
NIN	Ninein	Centrosomal protein required in the positioning and anchorage of the microtubule minus-end in epithelial cells.
IL33	Interleukin-33	Cytokine that binds to and signals through the IL1RL1/ST2 receptor which in turn activates NF-kappa-B and MAPK signaling pathways in target cells.
ACTN1	Alpha-actinin-1	F-actin cross-linking protein which is thought to anchor actin to a variety of intracellular structures.
ADAMTS15	A disintegrin and metalloproteinase with thrombospondin motifs 15	Metalloprotease which has proteolytic activity against the proteoglycan VCAN, cleaving it at the ‘Glu-1428-|-1429-Ala’ site.
OSBPL10	Oxysterol-binding protein-related protein 10	Probable lipid transporter involved in lipid countertransport between the endoplasmic reticulum and the plasma membrane.
ACTN2	Alpha-actinin-2	F-actin cross-linking protein which is thought to anchor actin to a variety of intracellular structures.
NMUR2	Neuromedin-U receptor 2	Receptor for the neuromedin-U and neuromedin-S neuropeptides.
NME8	Protein NME8	Possesses an intrinsic kinase activity.
RAB6C	Ras-related protein Rab-6C	The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes.
SMURF2	E3 ubiquitin-protein ligase SMURF2	E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates.
GPN1	GPN-loop GTPase 1	Small GTPase involved in the correct assembly of RNA polymerase II (RNAPII) complex, ensuring proper nuclear import of RNAPII.
DAB2IP	Disabled homolog 2-interacting protein	Functions as a scaffold protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways.
CDH13	Cadherin-13	Cadherins are calcium-dependent cell adhesion proteins.
JDP2	Jun dimerization protein 2	Component of the AP-1 transcription factor that represses transactivation mediated by the Jun family of proteins.
CDH2	Cadherin-2	Calcium-dependent cell adhesion protein; preferentially mediates homotypic cell-cell adhesion by dimerization with a CDH2 chain from another cell.
SAV1	Protein salvador homolog 1	Regulator of STK3/MST2 and STK4/MST1 in the Hippo signaling pathway which plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis.
NRSN1	Neurensin-1	May play an important role in neural organelle transport, and in transduction of nerve signals or in nerve growth.
TTLL11	Tubulin polyglutamylase TTLL11	Polyglutamylase which modifies tubulin, generating polyglutamate side chains of variable lengths on the gamma-carboxyl group of specific glutamate residues within the C-terminal tail of tubulin.
RBFOX1	RNA binding protein fox-1 homolog 1	RNA-binding protein that regulates alternative splicing events by binding to 5’-UGCAUGU-3’ elements.
DMAC2L	ATP synthase subunit s, mitochondrial	Involved in regulation of mitochondrial membrane ATP synthase.

Protein-family classification

Druggable: 22 · Difficult: 14 · Unknown: 39 · Druggable fraction: 0.29

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
Complement	2	7.2×	0.176
Scaffold/PPI	9	2.1×	0.176
Nuclear receptor	1	5.2×	0.390
Ion channel	2	3.0×	0.390
Antibody/Immunoglobulin	5	1.9×	0.390
Kinase	4	1.5×	0.524
Protease	2	1.0×	0.841
GPCR	3	1.0×	0.841
Other/Unknown	39	0.9×	0.958
Transcription factor	5	0.6×	0.958
Enzyme (other)	3	0.5×	0.958

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
RIT2	Other/Unknown	no		Small_GTPase, Small_GTP-bd, Small_GTPase_Ras-type
ROBO2	Antibody/Immunoglobulin	yes		Ig_sub2, Ig_sub, FN3_dom
RUNX2	Transcription factor	no		AML1_Runt, p53-like_TF_DNA-bd_sf, p53/RUNT-type_TF_DNA-bd_sf
RYR3	Ion channel	yes		RIH_dom, B30.2/SPRY, EF_hand_dom
BLK	Kinase	yes	2.7.10.2	Prot_kinase_dom, SH2, Ser-Thr/Tyr_kinase_cat_dom
SCN2A	Ion channel	yes		IQ_motif_EF-hand-BS, Na_channel_asu, Ion_trans_dom
SEL1L	Other/Unknown	no		FN_type2_dom, Sel1-like, TPR-like_helical_dom_sf
SEMA6A	Scaffold/PPI	no		Semap_dom, Plexin_repeat, WD40/YVTN_repeat-like_dom_sf
SETMAR	Enzyme (other)	yes	2.1.1.357	SET_dom, Transposase_1, Post-SET_dom
SIGLEC5	Antibody/Immunoglobulin	yes		Ig_sub2, Ig_sub, Ig-like_dom
SNRPN	Other/Unknown	no		Sm_dom_euk/arc, LSM_dom_sf, snRNP-assoc_SmB/SmN
SNTB1	Scaffold/PPI	no		PDZ, PH_domain, PH-like_dom_sf
SOS2	Scaffold/PPI	no		DH_dom, Ras-like_Gua-exchang_fac_N, PH_domain
ATL1	Other/Unknown	no		Guanylate-bd_N, P-loop_NTPase, G_GB1_RHD3_dom
SS18	Other/Unknown	no		SS18_N
TBC1D1	Other/Unknown	no		Rab-GAP-TBC_dom, PTB/PI_dom, PH-like_dom_sf
TGIF1	Transcription factor	no		HD, KN_HD, Homeodomain-like_sf
TIMP2	Enzyme (other)	yes	3.4.24.22	Netrin_domain, TIMP, TIMP-like_OB-fold
NPAP1	Other/Unknown	no		Nucleoporin
TRPS1	Transcription factor	no		Znf_GATA, Znf_C2H2_type, Znf_NHR/GATA
UHRF2	Transcription factor	no		Ubiquitin-like_dom, Znf_RING, Znf_PHD
VAMP3	Other/Unknown	no		Synaptobrevin-like, Synaptobrevin/VAMP, V_SNARE_CC
VAV1	Scaffold/PPI	no		DH_dom, SH2, GDS_CDC24_CS
VDR	Nuclear receptor	yes		VitD_rcpt, Nucl_hrmn_rcpt_lig-bd, Znf_hrmn_rcpt
VPREB1	Antibody/Immunoglobulin	yes		Ig_sub, Ig-like_dom, Ig_V-set
C5AR1	GPCR	yes		GPCR_Rhodpsn, Formyl_rcpt-rel, Anphylx_rcpt_C3a/C5a1-2
PGPEP1	Protease	yes	3.4.19.3	Peptidase_C15, Peptidase_C15-like, PGPEP1_Glu_AS
CSMD1	Complement	yes		Sushi_SCR_CCP_dom, CUB_dom, Sperma_CUB_dom_sf
NLGN1	Other/Unknown	no		Nlgn, CarbesteraseB, Carboxylesterase_B_CS
CAMK4	Kinase	yes	2.7.11.17	Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
NIN	Other/Unknown	no		EF_hand_dom, EF-hand-dom_pair
LINC00208	Other/Unknown	no
IL33	Other/Unknown	no		IL-33, IL33_C
ACTN1	Other/Unknown	no		Actinin_actin-bd_CS, CH_dom, Spectrin_repeat
ADAMTS15	Protease	yes	3.4.24.B12	TSP1_rpt, Peptidase_M12B, Peptidase_M12B_N
OSBPL10	Scaffold/PPI	no		Oxysterol-bd, PH_domain, PH-like_dom_sf
ACTN2	Other/Unknown	no		Actinin_actin-bd_CS, CH_dom, Spectrin_repeat
NKAIN2	Other/Unknown	no		Na/K-Atpase_Interacting
NMUR2	GPCR	yes		GPCR_Rhodpsn, NeuromedU_rcpt, NeuromedU_rcpt_2
NME8	Other/Unknown	no		Thioredoxin_domain, Thioredoxin_CS, NDK-like_dom
RAB6C	Other/Unknown	no		Small_GTPase, Small_GTP-bd, P-loop_NTPase
MAPK6P2	Other/Unknown	no
SMURF2	Scaffold/PPI	no	2.3.2.26	C2_dom, HECT_dom, WW_dom
GPN1	Other/Unknown	no		AAA+_ATPase, Gpn, P-loop_NTPase
ANKRD30A	Scaffold/PPI	no		Ankyrin_rpt, Ankyrin_rpt-contain_sf, CC144C-like_CC_dom
DAB2IP	Scaffold/PPI	no		C2_dom, PH_domain, RasGAP_dom
CDH13	Other/Unknown	no		Cadherin-like_dom, Cadherin_pro_dom, Cadherin-like_sf
JDP2	Other/Unknown	no		AP-1, bZIP, bZIP_sf
CDH2	Other/Unknown	no		Cadherin_Y-type_LIR, Cadherin-like_dom, Cadherin_pro_dom
SAV1	Scaffold/PPI	no		WW_dom, SARAH_dom, Sav

Expression context

Cohort genes with no expression data: 0.

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

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	2
moderate (6-20)	2
broad (>20)	71
unknown	0

Top tissues across cohort

Tissue	Cohort genes
male germ line stem cell (sensu Vertebrata) in testis	10
Brodmann (1909) area 23	7
ventricular zone	6
middle temporal gyrus	6
right testis	6
secondary oocyte	6
left testis	6
endothelial cell	5
calcaneal tendon	5
sperm	5
buccal mucosa cell	4
stromal cell of endometrium	4
oocyte	4
monocyte	4
cerebellar cortex	3
cerebellar hemisphere	3
cortical plate	3
ganglionic eminence	3
colonic epithelium	3
adrenal tissue	3

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RIT2	128	tissue_specific	marker	cerebellar cortex, cerebellar hemisphere, cerebellum
ROBO2	192	broad	marker	ganglionic eminence, cortical plate, ventricular zone
RUNX2	241	ubiquitous	marker	tibia, mucosa of paranasal sinus, trabecular bone tissue
RYR3	233	broad	marker	diaphragm, sural nerve, right hemisphere of cerebellum
BLK	145	tissue_specific	marker	spleen, male germ line stem cell (sensu Vertebrata) in testis, lymph node
SCN2A	187	broad	marker	middle temporal gyrus, Brodmann (1909) area 23, cerebellar vermis
SEL1L	290	ubiquitous	marker	body of pancreas, pancreas, colonic epithelium
SEMA6A	266	ubiquitous	marker	inferior vagus X ganglion, adrenal tissue, lateral globus pallidus
SETMAR	250	ubiquitous	marker	body of uterus, popliteal artery, tibial artery
SIGLEC5	120		yes	blood, male germ line stem cell (sensu Vertebrata) in testis, leukocyte
SNRPN	134	broad	marker	superior frontal gyrus, prefrontal cortex, primary visual cortex
SNTB1	245	ubiquitous	marker	right adrenal gland, right adrenal gland cortex, left adrenal gland
SOS2	298	ubiquitous	marker	vastus lateralis, biceps brachii, buccal mucosa cell
ATL1	241	ubiquitous	marker	middle temporal gyrus, Brodmann (1909) area 23, endothelial cell
SS18	291	ubiquitous	marker	adrenal tissue, right adrenal gland cortex, right adrenal gland
TBC1D1	280	ubiquitous	marker	ventricular zone, body of uterus, muscle layer of sigmoid colon
TGIF1	267	ubiquitous	marker	stromal cell of endometrium, gall bladder, ventricular zone
TIMP2	292	ubiquitous	marker	tendon of biceps brachii, synovial joint, stromal cell of endometrium
NPAP1	40	tissue_specific	marker	male germ line stem cell (sensu Vertebrata) in testis, ileal mucosa, right testis
TRPS1	284	ubiquitous	marker	mammary duct, epithelium of mammary gland, calcaneal tendon
UHRF2	261	ubiquitous	marker	secondary oocyte, oocyte, epithelial cell of pancreas
VAMP3	302	ubiquitous	marker	inferior olivary complex, parietal pleura, visceral pleura
VAV1	188	broad	marker	granulocyte, monocyte, leukocyte
VDR	224	ubiquitous	marker	tibia, hair follicle, jejunal mucosa
VPREB1	25	tissue_specific	marker	male germ line stem cell (sensu Vertebrata) in testis, bone marrow, bone marrow cell
C5AR1	215	broad	marker	blood, monocyte, mononuclear cell
PGPEP1	263	ubiquitous	marker	cardia of stomach, renal medulla, tendon of biceps brachii
CSMD1	179	broad	marker	Brodmann (1909) area 23, middle temporal gyrus, primary visual cortex
NLGN1	216	broad	marker	cortical plate, ventricular zone, endothelial cell
CAMK4	205	ubiquitous	marker	cerebellar vermis, cerebellar cortex, cerebellar hemisphere

Protein interactions among cohort

Intra-cohort edges: 12.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
NME8	8,310
CDH2	5,623
CHD1	4,224
RUNX2	4,101
VAMP3	3,407
RIT2	3,234
ACTN1	3,220
CAMK4	3,127
VAV1	3,042
RBFOX1	2,990

Intra-cohort edges

A	B	Sources
ACTN1	ACTN2	biogrid_interaction
ATL1	LNPK	string_interaction
CSMD3	FAT3	string_interaction
CSMD3	TRPS1	string_interaction
DAB2IP	TTLL11	string_interaction
FAT3	SNTB1	intact
GLT6D1	SIGLEC5	string_interaction
HS6ST2	NRSN1	biogrid_interaction, intact
NRSN1	VAMP3	biogrid_interaction
RBFOX1	SNRPN	intact
RUNX2	SMURF2	string_interaction
RUNX2	TRPS1	string_interaction

Structural data

PDB: 41 · AlphaFold-only: 33 · No structure: 1

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
VDR	P11473	52
C5AR1	P21730	19
CHD1	O14646	18
ACTN2	P35609	16
ATL1	Q8WXF7	14
SOS2	Q07890	11
RYR3	Q15413	10
VAV1	P15498	10
UHRF2	Q96PU4	9
SMURF2	Q9HAU4	8
ROBO2	Q9HCK4	6
SCN2A	Q99250	5
SEL1L	Q9UBV2	5
SETMAR	Q53H47	5
IL33	O95760	5
ANTXR1	Q9H6X2	5
CNTN2	Q02246	5
RUNX2	Q13950	4
TIMP2	P16035	4
ACTN1	P12814	4
RBFOX1	Q9NWB1	4
SIGLEC5	O15389	3
TGIF1	Q15583	3
VPREB1	P12018	3
NMUR2	Q9GZQ4	3
WAPL	Q7Z5K2	3
SNRPN	P63162	2
SNTB1	Q13884	2
NLGN1	Q8N2Q7	2
SEMA6A	Q9H2E6	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
PGPEP1	Q9NXJ5	93.62
VAMP3	Q15836	91.56
DMAC2L	Q99766	91.27
GLT6D1	Q7Z4J2	91.00
RIT2	Q99578	88.46
L2HGDH	Q9H9P8	88.26
PSMA8	Q8TAA3	84.04
BLK	P51451	81.89
GPR141	Q7Z602	81.63
GPN1	Q9HCN4	79.83
NME8	Q8N427	79.81
CDH2	P19022	79.68
ADAMTS15	Q8TE58	77.87
CMTM8	Q8IZV2	77.37
JDP2	Q8WYK2	76.36
NKAIN2	Q5VXU1	76.15
ARHGAP18	Q8N392	75.05
OSBPL10	Q9BXB5	75.03
TPGS2	Q68CL5	74.51
HS6ST2	Q96MM7	74.28
RAB6C	Q9H0N0	73.09
TPD52L3	Q96J77	73.00
NRSN1	Q8IZ57	69.20
LNPK	Q9C0E8	68.98
DAB2IP	Q5VWQ8	65.74
NIN	Q8N4C6	64.47
CLIC6	Q96NY7	60.24
LINC00208	Q96KT6	51.52
TRPS1	Q9UHF7	49.12
DAOA	P59103	46.78

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 428. Enrichment computed across 170 evidence-associated genes (97 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 97 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Transfer of LPS from LBP carrier to CD14	1	58.9×	0.397	LBP
Activation of Na-permeable kainate receptors	1	58.9×	0.397	GRIK1
PTEN Loss of Function in Cancer	1	58.9×	0.397	PTEN
Defective ABCA1 causes TGD	1	58.9×	0.397	ABCA1
Potassium transport channels	1	39.2×	0.397	KCNJ16
Tandem of pore domain in a weak inwardly rectifying K+ channels (TWIK)	1	39.2×	0.397	KCNK1
Interconversion of 2-oxoglutarate and 2-hydroxyglutarate	1	39.2×	0.397	L2HGDH
Interleukin-33 signaling	1	39.2×	0.397	IL33
Loss of phosphorylation of MECP2 at T308	1	29.4×	0.397	CAMK4
Signalling to p38 via RIT and RIN	1	23.6×	0.397	RIT2
RUNX2 regulates chondrocyte maturation	1	23.6×	0.397	RUNX2
RUNX2 regulates genes involved in differentiation of myeloid cells	1	23.6×	0.397	RUNX2
Regulation of cortical dendrite branching	1	23.6×	0.397	ROBO2
MECP2 regulates transcription factors	1	23.6×	0.397	RBFOX1
Uptake and function of anthrax toxins	2	19.6×	0.397	ANTXR1, PDCD6IP
RUNX1 regulates transcription of genes involved in BCR signaling	1	19.6×	0.397	BLK
Vitamin D (calciferol) metabolism	2	18.1×	0.397	VDR, GC
Regulation of MITF-M-dependent genes involved in extracellular matrix, focal adhesion and epithelial-to-mesenchymal transition	2	18.1×	0.397	CDH2, STT3B
Kidney development	2	16.8×	0.397	ROBO2, ITGA8
NrCAM interactions	1	16.8×	0.397	CNTN2
Signaling by LRP5 mutants	1	16.8×	0.397	DKK1
Glycine degradation	1	16.8×	0.397	GLDC
CREB1 phosphorylation through the activation of CaMKII/CaMKK/CaMKIV cascasde	1	14.7×	0.397	CAMK4
Formyl peptide receptors bind formyl peptides and many other ligands	1	14.7×	0.397	FPR1
Regulation of cytoskeletal remodeling and cell spreading by IPP complex components	1	14.7×	0.397	ACTN1
Hh mutants abrogate ligand secretion	1	14.7×	0.397	SEL1L
RUNX1 regulates transcription of genes involved in differentiation of myeloid cells	1	14.7×	0.397	RUNX2
RUNX2 regulates genes involved in cell migration	1	14.7×	0.397	RUNX2
HDL assembly	1	14.7×	0.397	ABCA1
Loss of function of MECP2 in Rett syndrome	1	14.7×	0.397	CAMK4

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 152 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
mammary gland branching involved in pregnancy	2	55.4×	0.133	VDR, CSMD1
negative regulation of vascular endothelial growth factor signaling pathway	3	25.6×	0.133	SEMA6A, DAB2IP, ANGPT1
negative regulation of epithelial to mesenchymal transition	4	10.8×	0.133	DAB2IP, EPHA3, FOXA1, PTEN
cell morphogenesis	6	6.2×	0.133	SS18, VDR, CDH13, CDH2, DKK1, PLEC
folic acid-containing compound biosynthetic process	1	110.9×	0.140	MTHFS
positive regulation of cellular defense response	1	110.9×	0.140	IL33
regulation of nerve growth factor production	1	110.9×	0.140	NPY
ligamentous ossification	1	110.9×	0.140	RUNX2
response to methylamine	1	110.9×	0.140	GLDC
regulation of endodermal cell fate specification	1	110.9×	0.140	DKK1
protein-containing complex organization	1	110.9×	0.140	PLEC
small molecule metabolic process	1	110.9×	0.140	L2HGDH
mitotic DNA integrity checkpoint signaling	1	110.9×	0.140	SETMAR
positive regulation of Wnt signaling pathway, calcium modulating pathway	1	110.9×	0.140	DKK1
D-amino acid metabolic process	1	110.9×	0.140	DAOA
folic acid catabolic process	1	110.9×	0.140	MTHFS
short-day photoperiodism	1	110.9×	0.140	NPY
cytoskeletal matrix organization at active zone	1	110.9×	0.140	NLGN1
actin filament uncapping	1	110.9×	0.140	ACTN2
establishment of protein localization to juxtaparanode region of axon	1	110.9×	0.140	CNTN2
medium-term memory	1	110.9×	0.140	FOS
endocardial cushion to mesenchymal transition	1	110.9×	0.140	HAS2
presynaptic membrane organization	1	110.9×	0.140	CNTN2
neurexin clustering involved in presynaptic membrane assembly	1	110.9×	0.140	NLGN1
keratinocyte apoptotic process	1	110.9×	0.140	SAV1
presynapse organization	1	110.9×	0.140	C5AR1
negative regulation of cell adhesion involved in sprouting angiogenesis	1	110.9×	0.140	SEMA6A
negative regulation of macrophage proliferation	1	110.9×	0.140	IL33
large intestinal transit	1	110.9×	0.140	HTR4
dipeptide transmembrane transport from lysosomal lumen to cytosol	1	110.9×	0.140	MFSD1

Therapeutics

Drugs indicated for this disease

1 approved, 11 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Sodium Monofluorophosphate	Approved (phase 4)
Amoxicillin	Phase 3 (in late-stage trials)
Arginine	Phase 3 (in late-stage trials)
Calcium Hydroxide	Phase 3 (in late-stage trials)
Chlorhexidine	Phase 3 (in late-stage trials)
Curcumin	Phase 3 (in late-stage trials)
Metronidazole	Phase 3 (in late-stage trials)
Minocycline	Phase 3 (in late-stage trials)
Sodium Fluoride	Phase 3 (in late-stage trials)
Tetracycline	Phase 3 (in late-stage trials)
Trafermin	Phase 3 (in late-stage trials)
Triclosan	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Alendronic Acid, Aloe, Articaine, Aspirin, Atorvastatin, Azithromycin, Boric Acid, Clarithromycin, Cyclosporine, Fibrin, Flurbiprofen, Glutamine, Hyaluronic Acid, Ibuprofen, Ketoprofen, Ketorolac, Melatonin, Metformin, Nitazoxanide, OMEGA-3 FATTY ACIDS, OMEGA-3-ACID ETHYL ESTERS, Rosuvastatin, Simvastatin, Sodium Chloride.

Drug target analysis

Approved (phase 4): 8 · Phase ≥3: 10 · Phased (≥1): 11 · Undrugged: 64

Druggability breadth: 59 of 170 evidence-associated genes (35%) 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.

Symbol	Example approved molecule
BLK	AFATINIB
SCN2A	BEPRIDIL
SOS2	TACRINE
VDR	CHOLECALCIFEROL
C5AR1	LOPERAMIDE HYDROCHLORIDE
CAMK4	RUXOLITINIB
PSMA8	BORTEZOMIB
CSNK1G2	ALECTINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SCN2A	99	4
BLK	62	4
CSNK1G2	22	4
CAMK4	14	4
VDR	10	4
PSMA8	5	4
CDKL1	3	3
SOS2	1	4
C5AR1	1	4
NMUR2	1	3

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
AFATINIB	4	BLK
FEDRATINIB	4	BLK
AXITINIB	4	BLK
SORAFENIB	4	BLK
NERATINIB	4	BLK, CSNK1G2
IBRUTINIB	4	BLK
ENTRECTINIB	4	BLK
BELUMOSUDIL	4	BLK
AFATINIB DIMALEATE	4	BLK
VANDETANIB	4	BLK
NILOTINIB	4	BLK
BOSUTINIB	4	BLK
BRIGATINIB	4	BLK
ACALABRUTINIB	4	BLK
ZANUBRUTINIB	4	BLK
TIRABRUTINIB	4	BLK
RITLECITINIB	4	BLK
PAZOPANIB	4	BLK
NINTEDANIB	4	BLK, CAMK4
SUNITINIB	4	BLK, CAMK4, CSNK1G2
DASATINIB	4	BLK
ERLOTINIB	4	BLK
QUIZARTINIB	4	BLK
CRIZOTINIB	4	BLK
MIDOSTAURIN	4	BLK
GEFITINIB	4	BLK
IMATINIB	4	BLK
BEPRIDIL	4	SCN2A
DIBUCAINE	4	SCN2A
ARTICAINE	4	SCN2A

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 10.

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

Symbol	Assays	Type breakdown
VDR	561	Binding:459, Functional:99, ADMET:3
BLK	483	Binding:477, ADMET:4, Functional:2
CAMK4	342	Binding:342
CSNK1G2	316	Binding:315, Functional:1
SCN2A	203	Binding:172, Functional:20, ADMET:10, Toxicity:1
PSMA8	168	Binding:159, ADMET:6, Functional:3
C5AR1	139	Binding:81, Functional:58
CDKL1	94	Binding:94
NMUR2	46	Functional:33, Binding:8, ADMET:5
SOS2	10	Binding:10
DAB2IP	8	Binding:8
WAPL	6	Binding:6
CHD1	5	Binding:5
CDH2	4	Binding:3, Functional:1
RYR3	2	Binding:2
PGPEP1	2	Binding:2
SMURF2	2	Binding:2
GPR141	2	Binding:2
SETMAR	1	Binding:1
VAV1	1	Binding:1
IL33	1	Binding:1
ACTN1	1	Binding:1
SAV1	1	Binding:1
LNPK	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
BLK	2.7.10.2	non-specific protein-tyrosine kinase
SETMAR	2.1.1.357, 2.7.7.B22	[histone H3]-lysine36 N-dimethyltransferase,
TIMP2	3.4.24.22	stromelysin 2
PGPEP1	3.4.19.3	pyroglutamyl-peptidase I
CAMK4	2.7.11.17	Ca2+/calmodulin-dependent protein kinase
ADAMTS15	3.4.24.B12
SMURF2	2.3.2.26	HECT-type E3 ubiquitin transferase
CDKL1	2.7.11.22	cyclin-dependent kinase
L2HGDH	1.1.99.2	L-2-hydroxyglutarate dehydrogenase
CSNK1G2	2.7.11.1	non-specific serine/threonine protein kinase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
BLK	483
SCN2A	203
VDR	561
C5AR1	139
CAMK4	342
PSMA8	168
CSNK1G2	316

Pharmacogenomics

Cohort genes with a PharmGKB record: 74; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

30 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)
AFATINIB	4	BLK
FEDRATINIB	4	BLK
AXITINIB	4	BLK
SORAFENIB	4	BLK
NERATINIB	4	BLK, CSNK1G2
IBRUTINIB	4	BLK
ENTRECTINIB	4	BLK
BELUMOSUDIL	4	BLK
AFATINIB DIMALEATE	4	BLK
VANDETANIB	4	BLK
NILOTINIB	4	BLK
BOSUTINIB	4	BLK
BRIGATINIB	4	BLK
ACALABRUTINIB	4	BLK
ZANUBRUTINIB	4	BLK
TIRABRUTINIB	4	BLK
RITLECITINIB	4	BLK
PAZOPANIB	4	BLK
NINTEDANIB	4	BLK, CAMK4
SUNITINIB	4	BLK, CAMK4, CSNK1G2
DASATINIB	4	BLK
ERLOTINIB	4	BLK
QUIZARTINIB	4	BLK
CRIZOTINIB	4	BLK
MIDOSTAURIN	4	BLK
GEFITINIB	4	BLK
IMATINIB	4	BLK
BEPRIDIL	4	SCN2A
DIBUCAINE	4	SCN2A
ARTICAINE	4	SCN2A

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	8	BLK, SCN2A, SOS2, VDR, C5AR1, CAMK4, PSMA8, CSNK1G2
B	Phased (≥1) drug, not yet approved	3	NMUR2, CDKL1, WAPL
C	Druggable family + PDB, no drug	9	ROBO2, RYR3, SETMAR, SIGLEC5, TIMP2, VPREB1, CSMD1, CAMTA1, CNTN2
D	Druggable family + AlphaFold only, no drug	5	PGPEP1, ADAMTS15, CSMD3, GPR141, L2HGDH
E	Difficult family or no structure, no drug	50	RIT2, RUNX2, SEL1L, SEMA6A, SNRPN, SNTB1, ATL1, SS18, TBC1D1, TGIF1 (+40 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
RIT2	0	—
ROBO2	0	—
RUNX2	0	—
RYR3	2	—
SEL1L	0	—
SEMA6A	0	—
SETMAR	1	—
SIGLEC5	0	—
SNRPN	0	—
SNTB1	0	—
ATL1	0	—
SS18	0	—
TBC1D1	0	—
TGIF1	0	—
TIMP2	0	—
NPAP1	0	—
TRPS1	0	—
UHRF2	0	—
VAMP3	0	—
VAV1	1	—
VPREB1	0	—
PGPEP1	2	—
CSMD1	0	—
NLGN1	0	—
NIN	0	—
LINC00208	0	—
IL33	1	—
ACTN1	1	—
ADAMTS15	0	—
OSBPL10	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 882.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	725
PHASE4	46
PHASE2	37
PHASE3	24
EARLY_PHASE1	16
PHASE1	13
PHASE1/PHASE2	11
PHASE2/PHASE3	10

Top trials by phase / activity

NCT	Phase	Status	Title
NCT07316582	PHASE4	ENROLLING_BY_INVITATION	Melatonin Loaded in Injectable Platelet-Rich Fibrin in the Management Periodontitis
NCT07402694	PHASE4	NOT_YET_RECRUITING	Oral Health Outcomes With Amphion Mouthwash as an Adjunct to Non-Surgical Periodontal Therapy
NCT07459049	PHASE4	RECRUITING	Effect of Ibuprofen on Acute Inflammatory Response After One-Stage Periodontal Therapy
NCT00296881	PHASE4	UNKNOWN	SRP in Combination With PERIOWAVE in Comparison to SRP Alone in Chronic Periodontitis
NCT00297518	PHASE4	COMPLETED	Study of Scaling and Root Planing (SRP) With PerioWave vs. SRP Alone in Chronic Periodontitis
NCT00297531	PHASE4	UNKNOWN	Study of Scaling and Root Planing With PerioWave Versus Scaling and Root Planing Alone in Chronic Periodontitis
NCT00668746	PHASE4	COMPLETED	Long-term Safety of Minocycline in Patients With Gum Disease
NCT00707369	PHASE4	COMPLETED	Adjunctive Antimicrobial Therapy of Periodontitis: Long-Term Effects on Disease Progression and Oral Microbiological Colonization
NCT01030666	PHASE4	TERMINATED	Effect of Postsurgical Systemic Doxycycline After Regenerative Periodontal Therapy
NCT01538927	PHASE4	COMPLETED	Effect of Fibrin Sealant on Early Wound Healing
NCT01548469	PHASE4	COMPLETED	Study to Evaluate Clinical Efficacy and Safety of Bio Mineral Toothpaste in Patients With Mild Periodontitis
NCT01593540	PHASE4	COMPLETED	Clinical Examination of Metal Free Interdental Brushes
NCT01806974	PHASE4	TERMINATED	Consequences of Anti-interleukin 6 Immunotherapy Treatment for Rheumatoid Arthritis on Periodontium
NCT02030470	PHASE4	COMPLETED	Evaluation of Photodynamic Treatment FOTOSAN® Efficacy in Periodontology
NCT02062047	PHASE4	COMPLETED	Full-mouth and Partial-mouth Scaling and Root Planing in Type 2 Diabetic Subjects
NCT02124655	PHASE4	COMPLETED	Antiplaque Effect of Essential Oils and 0.2% Chlorhexidine on an in Situ Model of Oral Biofilm Growth.
NCT02135952	PHASE4	UNKNOWN	Metronidazole and Amoxicillin for the Treatment of Type 2 Diabetic Subjects With Periodontitis
NCT02149758	PHASE4	COMPLETED	EFFECT OF SELECTIVE COX-2 INHIBITOR (ETORICOXIB) ALONG WITH SCALING AND ROOT PLANING (SRP) ON CLINICAL PARAMETERS AND SALIVARY LEVEL OF SUPEROXIDE DISMUTASE IN CHRONIC GENERALIZED PERIODONTITIS A DOUBLE-BLIND, PLACEBO-CONTROLLED, DOUBLE-MASKED RANDOMIZED CONTROLLED TRIAL (RCT).
NCT02215460	PHASE4	COMPLETED	Treatment of Periodontitis by Conventional 4 Weekly Sections or Within 24 Hours
NCT02215473	PHASE4	COMPLETED	Bacteremia in Periodontal Patients
NCT02267239	PHASE4	UNKNOWN	Methodology Antiseptic Application, Influence on Oral Biofilm.
NCT02359721	PHASE4	COMPLETED	Clarithromycin is an Adjunct to Scaling and Root Planing
NCT02470611	PHASE4	COMPLETED	Sodium Alendronate in Non Surgical Periodontal Therapy
NCT02794506	PHASE4	COMPLETED	Propolis Improves Glycemic Control in Subjects With Type 2 Diabetes and Chronic Periodontitis
NCT02921165	PHASE4	COMPLETED	Comparison of Topical Analgesic With Saline Rinses in Post Extraction Healing
NCT02946801	PHASE4	UNKNOWN	Antiplaque Effect of Essential Oils With and Without Alcochol on an in Situ Model of Oral Biofilm Growth
NCT03103204	PHASE4	COMPLETED	Treatment of Periodontitis in Obese Individuals
NCT03146390	PHASE4	UNKNOWN	Essential Oils With and Without Alcohol: Substantivity and Antiplaque Effect
NCT03176537	PHASE4	WITHDRAWN	Periodontal Profile of Hypogonadic Men
NCT03311906	PHASE4	COMPLETED	Evaluation of the Efficacy of 0.8% Hyaluronic Acid Gel
NCT03354312	PHASE4	COMPLETED	Acceptance and Preference of Lidocaine Gel Compared to Injection Anesthesia After Non Surgical Periodontal Treatment
NCT04027179	PHASE4	UNKNOWN	Tongue Dysbiosis Effects on Arterial Pressure of Periodontitis Patients
NCT04032132	PHASE4	COMPLETED	Curcumin Paste as an Adjunctive Therapy in Periodontitis
NCT04036890	PHASE4	COMPLETED	Local Minocycline in Patients Under Supportive Periodontal Therapy
NCT04044417	PHASE4	COMPLETED	Curcumin-Simvastatin-EDTA in the Treatment of Periodontitis
NCT04149405	PHASE4	COMPLETED	Alterations of GCF Levels of Sclerostin and DKK-1 in Postmenopausal Osteoporosis
NCT04178590	PHASE4	COMPLETED	Effect of Injectable Platelet-Rich Fibrin (i-PRF) in Initial Treatment of Chronic Periodontitis
NCT04223076	PHASE4	UNKNOWN	Clinical Effect of Chlorhexidine Mouthwash After Periodontal Surgery
NCT04353362	PHASE4	COMPLETED	Alternative Antibiotic Regimen in Periodontitis Treatment
NCT04964167	PHASE4	COMPLETED	Indocyanine-green Mediated Photosensitizer VS Aloe Vera Gel: Adjunct Therapy to Scaling and Root Planing in Patients With Chronic Periodontitis

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
CHLORHEXIDINE	4	9
MINOCYCLINE	4	6
DOXYCYCLINE ANHYDROUS	4	5
CLINDAMYCIN	4	3
METRONIDAZOLE	4	3
WATER	4	3
INDOCYANINE GREEN ACID FORM	4	2
ALENDRONATE SODIUM	4	1
AMOXICILLIN	4	1
ARTICAINE HYDROCHLORIDE	4	1
ATORVASTATIN CALCIUM	4	1
BULEVIRTIDE	4	1
CALCIUM	4	1
CHOLECALCIFEROL	4	1
ESFLURBIPROFEN	4	1
ETORICOXIB	4	1
FLURBIPROFEN	4	1
GLUTAMINE	4	1
HYALURONIC ACID	4	1
HYDROGEN PEROXIDE	4	1
INULIN	4	1
MELATONIN	4	1
NITAZOXANIDE	4	1
OFLOXACIN	4	1
ORGOTEIN	4	1
PIPERACILLIN	4	1
SIMVASTATIN	4	1
TETRACYCLINE	4	1
TRAFERMIN	4	1
TRICLOSAN	4	1