Kawasaki disease

Summary

Kawasaki disease (MONDO:0012727) is a disease with 44 cohort genes (63 GWAS associations across 13 studies) and 60 clinical trials. Top therapeutic interventions include aspirin, anakinra, and canakinumab.

At a glance

• Prevalence: Unknown (Worldwide)
• Cohort genes: 44
• GWAS associations: 63
• Phenotypes (HPO): 46
• Clinical trials: 60

Clinical features

Signs & symptoms

Clinical features (HPO)

46 HPO clinical features (Orphanet curated; top 46 by frequency):

HPO ID	Term	Frequency
HP:0000093	Proteinuria	Very frequent (80-99%)
HP:0000509	Conjunctivitis	Very frequent (80-99%)
HP:0000988	Skin rash	Very frequent (80-99%)
HP:0002633	Vasculitis	Very frequent (80-99%)
HP:0025289	Cervical lymphadenopathy	Very frequent (80-99%)
HP:0025493	Palmoplantar erythema	Very frequent (80-99%)
HP:0100776	Recurrent pharyngitis	Very frequent (80-99%)
HP:0100825	Cheilitis	Very frequent (80-99%)
HP:0001369	Arthritis	Frequent (30-79%)
HP:0001654	Abnormal heart valve morphology	Frequent (30-79%)
HP:0001701	Pericarditis	Frequent (30-79%)
HP:0001894	Thrombocytosis	Frequent (30-79%)
HP:0001945	Fever	Frequent (30-79%)
HP:0001974	Leukocytosis	Frequent (30-79%)
HP:0002014	Diarrhea	Frequent (30-79%)
HP:0002027	Abdominal pain	Frequent (30-79%)
HP:0003073	Hypoalbuminemia	Frequent (30-79%)
HP:0003565	Elevated erythrocyte sedimentation rate	Frequent (30-79%)
HP:0011227	Elevated circulating C-reactive protein concentration	Frequent (30-79%)
HP:0012378	Fatigue	Frequent (30-79%)
HP:0025525	Scaling skin on fingertip	Frequent (30-79%)
HP:0025537	Plantar edema	Frequent (30-79%)
HP:0025538	Palmar edema	Frequent (30-79%)
HP:0030953	Conjunctival hyperemia	Frequent (30-79%)
HP:0031042	Strawberry tongue	Frequent (30-79%)
HP:0031250	Lip fissure	Frequent (30-79%)
HP:0100643	Abnormality of nail color	Frequent (30-79%)
HP:0000206	Glossitis	Frequent (30-79%)
HP:0000969	Edema	Frequent (30-79%)
HP:0000508	Ptosis	Occasional (5-29%)
HP:0000737	Irritability	Occasional (5-29%)
HP:0000952	Jaundice	Occasional (5-29%)
HP:0001082	Cholecystitis	Occasional (5-29%)
HP:0001287	Meningitis	Occasional (5-29%)
HP:0001635	Congestive heart failure	Occasional (5-29%)
HP:0002017	Nausea and vomiting	Occasional (5-29%)
HP:0002076	Migraine	Occasional (5-29%)
HP:0002829	Arthralgia	Occasional (5-29%)
HP:0004970	Ascending tubular aorta aneurysm	Occasional (5-29%)
HP:0006530	Abnormal pulmonary interstitial morphology	Occasional (5-29%)
HP:0006824	Cranial nerve paralysis	Occasional (5-29%)
HP:0011658	Double outlet right ventricle with subpulmonary ventricular septal defect without pulmonary stenosis	Occasional (5-29%)
HP:0011675	Arrhythmia	Occasional (5-29%)
HP:0012115	Hepatitis	Occasional (5-29%)
HP:0012819	Myocarditis	Occasional (5-29%)
HP:0100586	Sterile pyuria	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	Kawasaki disease
Mondo ID	MONDO:0012727
EFO	EFO:0004246
MeSH	D009080
OMIM	611775
Orphanet	2331
DOID	DOID:13378
ICD-10-CM	M30.3
ICD-11	540285662
NCIT	C34825
SNOMED CT	75053002
UMLS	C0026691
MedGen	10118
GARD	0006816
MedDRA	10023320
Is cancer (heuristic)	no

Also known as: acute febrile mucocutaneous lymph node syndrome · acute febrile mucocutaneous lymph node syndrome [MCLS] · infantile polyarteritis nodosa · Kawasaki syndrome · mucocutaneous lymph node syndrome

Data availability: 63 GWAS associations (13 studies) · 1 cell line.

Disease family

Classification path: disease › human disease › disease by body system or component › immune system disorder › lymphoid system disorder › lymphatic system disorder › lymph node disorder › lymphadenitis › Kawasaki disease

Related subtypes (9): mesenteric lymphadenitis, cervical lymphadenitis, postauricular lymphadenitis, suppurative lymphadenitis, axillary lymphadenitis, cat-scratch disease, sialadenitis, Kimura disease, Kikuchi-Fujimoto disease

Genetics & variants

GWAS landscape

63 GWAS associations across 13 studies. Top hits map to 36 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs2736340	7e-33	FAM167A - BLK	T	1.55
rs2254546	8e-21	FAM167A - BLK	G	1.85
rs2857602	3e-15	NFKBIL1 - LTA	A	0.78
rs2849322	1e-14	OR5AK1P - OR5BQ1P	C	1.41
rs1883832	2e-13	CD40	C	1.28
rs35393613	5e-13	FAM167A - BLK	T	1.51
rs3129960	7e-13	TSBP1-AS1, TSBP1	G	0.73
rs7775228	7e-13	HLA-DQB1 - MTCO3P1	C	1.26
rs2071473	7e-13	HLA-DOB	T	1.26
rs28493229	2e-12	ITPKC, COQ8B	?	1.52
rs1264516	4e-11	MICC - TMPOP1	A	1.24
rs2857151	5e-11	HLA-DQB2 - HLA-DOB	G	1.47
rs1801274	7e-11	FCGR2A	A	1.32
rs2720378	1e-10	CASP3	G	0.74
rs1873212	2e-10	RNU7-26P - OR2B2	T	1.27
rs2233152	4e-10	MIA, MIA-RAB4B	A	1.52
rs1778477	7e-10	ZSCAN26 - PGBD1	T	0.77
rs3743841	8e-10	NAGPA	T
rs3745213	1e-09	ACTMAP	T	1.6
rs79523539	2e-09	PTPRC, PTPRC-AS1	?
rs6671847	3e-09	FCGR2A	A	0.7
rs12037447	5e-09	PLXNA2 - LINC01735	G	8.7
rs1569723	6e-09	RPL13P2 - CD40	A	1.42
rs4774175	6e-09	IGHVIII-67-4 - IGHV1-68	A	1.2
rs2130392	3e-08	CENPU	A	1.42
rs146732504	4e-08	KIF25	A	11.42
rs4813003	5e-08	CD40 - CDH22	C	1.41
rs73379591	7e-08	EPB41L3	C
rs111487401	8e-08	TPD52	T	2.4
rs10508313	1e-07	LINP1	C

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST010979	Johnson TA	2020	1,276	5,086	Association of an IGHV3-66 gene variant with Kawasaki disease.
GCST001456	Lee YC	2012	622	1,107	Two new susceptibility loci for Kawasaki disease identified through genome-wide association analysis.
GCST001455	Onouchi Y	2012	428	3,379	A genome-wide association study identifies three new risk loci for Kawasaki disease.
GCST001322	Khor CC	2011	405	6,252	Genome-wide association study identifies FCGR2A as a susceptibility locus for Kawasaki disease.
GCST90095078	Carmona EG	2021	402	7,538	Identification of a shared genetic risk locus for Kawasaki disease and IgA vasculitis by a cross-phenotype meta-analysis.
GCST90013537	Hoggart C	2021	400	6,101	Identification of novel locus associated with coronary artery aneurysms and validation of loci for susceptibility to Kawasaki disease.
GCST006809	Kim HJ	2018	296	1,000	Identification of LEF1 as a Susceptibility Locus for Kawasaki Disease in Patients Younger than 6 Months of Age.
GCST000962	Tsai FJ	2011	250	0	Identification of novel susceptibility Loci for kawasaki disease in a Han chinese population by a genome-wide association study.
GCST90651339	Liu TY	2025	244	228,546	Diversity and longitudinal records: Genetic architecture of disease associations and polygenic risk in the Taiwanese Han population.
GCST000939	Kim JJ	2011	186	0	A genome-wide association analysis reveals 1p31 and 2p13.3 as susceptibility loci for Kawasaki disease.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	8
Tier 2: splice/UTR	2
Tier 3: regulatory	1
Tier 4: intronic/intergenic	39

MAF distribution

Bucket	Variants
common (>=0.05)	34
low_freq (0.01-0.05)	5
rare (<0.01)	9
unknown	2

Functional consequences

Consequence	Count
intron_variant	26
intergenic_variant	12
missense_variant	8
5_prime_UTR_variant	1
non_coding_transcript_exon_variant	1
3_prime_UTR_variant	1
TF_binding_site_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs2736340	8	11486464	C>A,G,T	0.05	intergenic_variant	FAM167A - BLK	7e-33	Tier 4: intronic/intergenic
rs2254546	8	11486171	A>G,T	0.28	intergenic_variant	FAM167A - BLK	8e-21	Tier 4: intronic/intergenic
rs2857602	6	31565601	G>A,C,T	0.05	intron_variant	NFKBIL1 - LTA	3e-15	Tier 4: intronic/intergenic
rs2849322	11	57020853			intergenic_variant	OR5AK1P - OR5BQ1P	1e-14	Tier 4: intronic/intergenic
rs1883832	20	46118343	T>A,C,G	0.05	5_prime_UTR_variant	CD40	2e-13	Tier 2: splice/UTR
rs35393613	8	11480957	C>A,G,T	0.05	intron_variant	FAM167A - BLK	5e-13	Tier 4: intronic/intergenic
rs3129960	6	32333032	A>C,G,T	0.05	intron_variant	TSBP1-AS1, TSBP1	7e-13	Tier 4: intronic/intergenic
rs7775228	6	32690302	T>A,C	0.05	non_coding_transcript_exon_variant	HLA-DQB1 - MTCO3P1	7e-13	Tier 4: intronic/intergenic
rs2071473	6	32814828	C>A,G,T	0.05	intron_variant	HLA-DOB	7e-13	Tier 4: intronic/intergenic
rs28493229	19	40718299	G>A,C	0.13	intron_variant	ITPKC, COQ8B	2e-12	Tier 4: intronic/intergenic
rs1264516	6	30444126	C>A,T	0.05	intergenic_variant	MICC - TMPOP1	4e-11	Tier 4: intronic/intergenic
rs2857151	6	32795737	A>C,G,T	0.24	intergenic_variant	HLA-DQB2 - HLA-DOB	5e-11	Tier 4: intronic/intergenic
rs1801274	1	161509955	A>C,G,T	0.47	missense_variant	FCGR2A	7e-11	Tier 1: coding
rs2720378	4	184646959	C>A,G,T	0.05	intron_variant	CASP3	1e-10	Tier 4: intronic/intergenic
rs1873212	6	27901853	C>T	0.05	intergenic_variant	RNU7-26P - OR2B2	2e-10	Tier 4: intronic/intergenic
rs2233152	19	40775111	G>A,T	0.158	intron_variant	MIA, MIA-RAB4B	4e-10	Tier 4: intronic/intergenic
rs1778477	6	28280817	A>T	0.05	intron_variant	ZSCAN26 - PGBD1	7e-10	Tier 4: intronic/intergenic
rs3743841	16	5030085	C>G,T	0.05	intron_variant	NAGPA	8e-10	Tier 4: intronic/intergenic
rs3745213	19	40742104	C>T	0.132	3_prime_UTR_variant	ACTMAP	1e-09	Tier 2: splice/UTR
rs79523539	1	198671171	AC>A	0.05	intron_variant	PTPRC, PTPRC-AS1	2e-09	Tier 4: intronic/intergenic
rs6671847	1	161509020	G>A	0.492	intron_variant	FCGR2A	3e-09	Tier 4: intronic/intergenic
rs12037447	1	208432248	A>G,T	0.003	intron_variant	PLXNA2 - LINC01735	5e-09	Tier 4: intronic/intergenic
rs1569723	20	46113425	C>A	0.452	intergenic_variant	RPL13P2 - CD40	6e-09	Tier 4: intronic/intergenic
rs4774175	14	106696010	G>A,T	0.05	intergenic_variant	IGHVIII-67-4 - IGHV1-68	6e-09	Tier 4: intronic/intergenic
rs2130392	4	184718015	G>A,C,T	0.358	intron_variant	CENPU	3e-08	Tier 4: intronic/intergenic
rs146732504	6	168034024	C>A	0.001	missense_variant	KIF25	4e-08	Tier 1: coding
rs4813003	20	46134645	C>A,T	0.33	TF_binding_site_variant	CD40 - CDH22	5e-08	Tier 3: regulatory
rs73379591	18	5503378	T>C	0.05	intron_variant	EPB41L3	7e-08	Tier 4: intronic/intergenic
rs111487401	8	80082059	C>T	0.019	intron_variant	TPD52	8e-08	Tier 4: intronic/intergenic
rs10508313	10	6791131	C>T	0.05	intron_variant	LINP1	1e-07	Tier 4: intronic/intergenic

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 15 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
BLK	Orphanet:536	Systemic lupus erythematosus
BLK	Orphanet:552	MODY
CD40	Orphanet:101090	Hyper-IgM syndrome type 3
COPB2	Orphanet:2512	Autosomal recessive primary microcephaly
DAB1	Orphanet:363710	Spinocerebellar ataxia type 37
TECRL	Orphanet:3286	Catecholaminergic polymorphic ventricular tachycardia
SPECC1L	Orphanet:141258	Tessier number 4 facial cleft
SPECC1L	Orphanet:141276	Tessier number 7 facial cleft
SPECC1L	Orphanet:1519	SPECC1L-related hypertelorism syndrome
EPG5	Orphanet:1493	Vici syndrome
HLA-DQB1	Orphanet:2073	Narcolepsy type 1
HLA-DQB1	Orphanet:477738	Pediatric multiple sclerosis
HLA-DQB1	Orphanet:703	Bullous pemphigoid
HLA-DQB1	Orphanet:83465	Narcolepsy type 2
HLA-DQB1	Orphanet:930	Idiopathic achalasia

Cohort genes → proteins

44 cohort genes, 42 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	44

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
RPN2	HGNC:10382	ENSG00000118705	P04844	Dolichyl-diphosphooligosaccharide–protein glycosyltransferase subunit 2	gwas
BLK	HGNC:1057	ENSG00000136573	P51451	Tyrosine-protein kinase Blk	gwas
SLC16A7	HGNC:10928	ENSG00000118596	O60669	Monocarboxylate transporter 2	gwas
BTBD1	HGNC:1120	ENSG00000064726	Q9H0C5	BTB/POZ domain-containing protein 1	gwas
CD40	HGNC:11919	ENSG00000101017	P25942	Tumor necrosis factor receptor superfamily member 5	gwas
TPD52	HGNC:12005	ENSG00000076554	P55327	Tumor protein D52	gwas
TSBP1	HGNC:13922	ENSG00000204296	Q5SRN2	Testis-expressed basic protein 1	gwas
SHANK2	HGNC:14295	ENSG00000162105	Q9UPX8	SH3 and multiple ankyrin repeat domains protein 2	gwas
OR13C4	HGNC:14722	ENSG00000148136	Q8NGS5	Olfactory receptor 13C4	gwas
ITPKC	HGNC:14897	ENSG00000086544	Q96DU7	Inositol-trisphosphate 3-kinase C	gwas
CASP3	HGNC:1504	ENSG00000164305	P42574	Caspase-3	gwas
FAM167A	HGNC:15549	ENSG00000154319	Q96KS9	Protein FAM167A	gwas
PPM1L	HGNC:16381	ENSG00000163590	Q5SGD2	Protein phosphatase 1L	gwas
PGBD1	HGNC:19398	ENSG00000137338	Q96JS3	PiggyBac transposable element-derived protein 1	gwas
CENPU	HGNC:21348	ENSG00000151725	Q71F23	Centromere protein U	gwas
CARMIL1	HGNC:21581	ENSG00000079691	Q5VZK9	F-actin-uncapping protein LRRC16A	gwas
COPB2	HGNC:2232	ENSG00000184432	P35606	Coatomer subunit beta'	gwas
MED30	HGNC:23032	ENSG00000164758	Q96HR3	Mediator of RNA polymerase II transcription subunit 30	gwas
RHBDD1	HGNC:23081	ENSG00000144468	Q8TEB9	Rhomboid-related protein 4	gwas
NAALADL2	HGNC:23219	ENSG00000177694	Q58DX5	Inactive N-acetylated-alpha-linked acidic dipeptidase-like protein 2	gwas
ENPP6	HGNC:23409	ENSG00000164303	Q6UWR7	Glycerophosphocholine cholinephosphodiesterase ENPP6	gwas
SARNP	HGNC:24432	ENSG00000205323	P82979	SAP domain-containing ribonucleoprotein	gwas
DAB1	HGNC:2661	ENSG00000173406	O75553	Disabled homolog 1	gwas
TECRL	HGNC:27365	ENSG00000205678	Q5HYJ1	Trans-2,3-enoyl-CoA reductase-like	gwas
TMEM263	HGNC:28281	ENSG00000151135	Q8WUH6	Transmembrane protein 263	gwas
SPECC1L	HGNC:29022	ENSG00000100014	Q69YQ0	Cytospin-A	gwas
EPG5	HGNC:29331	ENSG00000152223	Q9HCE0	Ectopic P granules protein 5 homolog	gwas
RMST	HGNC:29893	ENSG00000255794		rhabdomyosarcoma 2 associated transcript	gwas
GALNT18	HGNC:30488	ENSG00000110328	Q6P9A2	Polypeptide N-acetylgalactosaminyltransferase 18	gwas
TRX-CAT1-6	HGNC:34863			tRNA-iMet (anticodon CAT) 1-6	gwas
FCGR2A	HGNC:3616	ENSG00000143226	P12318	Low affinity immunoglobulin gamma Fc region receptor II-a	gwas
HLA-DOB	HGNC:4937	ENSG00000241106	P13765	HLA class II histocompatibility antigen, DO beta chain	gwas
HLA-DQB1	HGNC:4944	ENSG00000179344	P01920	HLA class II histocompatibility antigen, DQ beta 1 chain	gwas
HLA-DQB2	HGNC:4945	ENSG00000232629	P05538	HLA class II histocompatibility antigen, DQ beta 2 chain	gwas
IGHV1-69	HGNC:5558	ENSG00000211973	P01742	Immunoglobulin heavy variable 1-69	gwas
KIF25	HGNC:6390	ENSG00000125337	Q9UIL4	Kinesin-like protein KIF25	gwas
LTA	HGNC:6709	ENSG00000226979	P01374	Lymphotoxin-alpha	gwas
MIA	HGNC:7076	ENSG00000261857	Q16674	Melanoma-derived growth regulatory protein	gwas
MICB	HGNC:7091	ENSG00000204516	Q29980	MHC class I polypeptide-related sequence B	gwas
ZFHX3	HGNC:777	ENSG00000140836	Q15911	Zinc finger homeobox protein 3	gwas
NUMBL	HGNC:8061	ENSG00000105245	Q9Y6R0	Numb-like protein	gwas
PELI1	HGNC:8827	ENSG00000197329	Q96FA3	E3 ubiquitin-protein ligase pellino homolog 1	gwas
PTPRJ	HGNC:9673	ENSG00000149177	Q12913	Receptor-type tyrosine-protein phosphatase eta	gwas
RAB4B	HGNC:9782	ENSG00000167578	P61018	Ras-related protein Rab-4B	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RPN2	Dolichyl-diphosphooligosaccharide–protein glycosyltransferase subunit 2	Subunit of the oligosaccharyl transferase (OST) complex that catalyzes the initial transfer of a defined glycan (Glc(3)Man(9)GlcNAc(2) in eukaryotes) from the lipid carrier dolichol-pyrophosphate to an asparagine residue within an Asn-X-Se…
BLK	Tyrosine-protein kinase Blk	Non-receptor tyrosine kinase involved in B-lymphocyte development, differentiation and signaling.
SLC16A7	Monocarboxylate transporter 2	Proton-coupled monocarboxylate symporter.
BTBD1	BTB/POZ domain-containing protein 1	Probable substrate-specific adapter of an E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins.
CD40	Tumor necrosis factor receptor superfamily member 5	Receptor for TNFSF5/CD40LG.
SHANK2	SH3 and multiple ankyrin repeat domains protein 2	Seems to be an adapter protein in the postsynaptic density (PSD) of excitatory synapses that interconnects receptors of the postsynaptic membrane including NMDA-type and metabotropic glutamate receptors, and the actin-based cytoskeleton.
OR13C4	Olfactory receptor 13C4	Odorant receptor.
ITPKC	Inositol-trisphosphate 3-kinase C	Catalyzes the phosphorylation of 1D-myo-inositol 1,4,5-trisphosphate (InsP3) into 1D-myo-inositol 1,3,4,5-tetrakisphosphate and participates to the regulation of calcium homeostasis.
CASP3	Caspase-3	Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.
PPM1L	Protein phosphatase 1L	Acts as a suppressor of the SAPK signaling pathways by associating with and dephosphorylating MAP3K7/TAK1 and MAP3K5, and by attenuating the association between MAP3K7/TAK1 and MAP2K4 or MAP2K6.
PGBD1	PiggyBac transposable element-derived protein 1	Transposase-derived from PiggyBac DNA transposons.
CENPU	Centromere protein U	Component of the CENPA-NAC (nucleosome-associated) complex, a complex that plays a central role in assembly of kinetochore proteins, mitotic progression and chromosome segregation.
CARMIL1	F-actin-uncapping protein LRRC16A	Cell membrane-cytoskeleton-associated protein that plays a role in the regulation of actin polymerization at the barbed end of actin filaments.
COPB2	Coatomer subunit beta'	The coatomer is a cytosolic protein complex that binds to dilysine motifs and reversibly associates with Golgi non-clathrin-coated vesicles, which further mediate biosynthetic protein transport from the ER, via the Golgi up to the trans Go…
MED30	Mediator of RNA polymerase II transcription subunit 30	Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes.
RHBDD1	Rhomboid-related protein 4	Intramembrane-cleaving serine protease that cleaves single transmembrane or multi-pass membrane proteins in the hydrophobic plane of the membrane, luminal loops and juxtamembrane regions.
NAALADL2	Inactive N-acetylated-alpha-linked acidic dipeptidase-like protein 2	May be catalytically inactive.
ENPP6	Glycerophosphocholine cholinephosphodiesterase ENPP6	Choline-specific glycerophosphodiesterase that hydrolyzes glycerophosphocholine (GPC) and lysophosphatidylcholine (LPC) and contributes to supplying choline to the cells.
SARNP	SAP domain-containing ribonucleoprotein	Binds both single-stranded and double-stranded DNA with higher affinity for the single-stranded form.
DAB1	Disabled homolog 1	Signaling adapter of the reelin-mediated signaling pathway, which regulates the migration and differentiation of postmitotic neurons during brain development.
TMEM263	Transmembrane protein 263	May play a role in bone development.
SPECC1L	Cytospin-A	Involved in cytokinesis and spindle organization.
EPG5	Ectopic P granules protein 5 homolog	Involved in autophagy.
GALNT18	Polypeptide N-acetylgalactosaminyltransferase 18	Catalyzes the initial reaction in O-linked oligosaccharide biosynthesis, the transfer of an N-acetyl-D-galactosamine (GalNAc) residue from UDP-GalNAc to a serine or threonine residue on the protein receptor.
FCGR2A	Low affinity immunoglobulin gamma Fc region receptor II-a	Binds to the Fc region of immunoglobulins gamma.
HLA-DOB	HLA class II histocompatibility antigen, DO beta chain	Important modulator in the HLA class II restricted antigen presentation pathway by interaction with the HLA-DM molecule in B-cells.
HLA-DQB1	HLA class II histocompatibility antigen, DQ beta 1 chain	Binds peptides derived from antigens that access the endocytic route of antigen presenting cells (APC) and presents them on the cell surface for recognition by the CD4 T-cells.
HLA-DQB2	HLA class II histocompatibility antigen, DQ beta 2 chain	Binds peptides derived from antigens that access the endocytic route of antigen presenting cells (APC) and presents them on the cell surface for recognition by the CD4 T-cells.
IGHV1-69	Immunoglobulin heavy variable 1-69	V region of the variable domain of immunoglobulin heavy chains that participates in the antigen recognition.
KIF25	Kinesin-like protein KIF25	Minus-end microtubule-dependent motor protein.
LTA	Lymphotoxin-alpha	Cytokine that in its homotrimeric form binds to TNFRSF1A/TNFR1, TNFRSF1B/TNFBR and TNFRSF14/HVEM.
MIA	Melanoma-derived growth regulatory protein	Elicits growth inhibition on melanoma cells in vitro as well as some other neuroectodermal tumors, including gliomas.
MICB	MHC class I polypeptide-related sequence B	Widely expressed membrane-bound protein which acts as a ligand to stimulate an activating receptor KLRK1/NKG2D, expressed on the surface of essentially all human natural killer (NK), gammadelta T and CD8+ alphabeta T-cells.
ZFHX3	Zinc finger homeobox protein 3	Transcriptional regulator which can act as an activator or a repressor.
NUMBL	Numb-like protein	Plays a role in the process of neurogenesis.
PELI1	E3 ubiquitin-protein ligase pellino homolog 1	E3 ubiquitin ligase catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins.
PTPRJ	Receptor-type tyrosine-protein phosphatase eta	Tyrosine phosphatase which dephosphorylates or contributes to the dephosphorylation of CTNND1, FLT3, PDGFRB, MET, KDR, LYN, SRC, MAPK1, MAPK3, EGFR, TJP1, OCLN, PIK3R1 and PIK3R2.
RAB4B	Ras-related protein Rab-4B	The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes.

Protein-family classification

Druggable: 18 · Difficult: 4 · Unknown: 22 · Druggable fraction: 0.41

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
Antibody/Immunoglobulin	6	4.0×	0.037
Phosphatase	3	5.7×	0.077
Transporter	1	1.8×	0.843
Protease	2	1.7×	0.843
Scaffold/PPI	3	1.2×	0.843
Enzyme (other)	4	1.1×	0.843
Other/Unknown	22	0.9×	0.942
Kinase	1	0.6×	0.942
GPCR	1	0.5×	0.942
Transcription factor	1	0.2×	0.997

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
RPN2	Enzyme (other)	yes	2.4.99.18	Swp1, Ribophorin_II_N, Ribophorin_II_3rd
BLK	Kinase	yes	2.7.10.2	Prot_kinase_dom, SH2, Ser-Thr/Tyr_kinase_cat_dom
SLC16A7	Transporter	yes		MCT, MFS, MFS_dom
BTBD1	Other/Unknown	no		BTB/POZ_dom, SKP1/BTB/POZ_sf, BACK
CD40	Other/Unknown	no		TNFR/NGFR_Cys_rich_reg, TNFR_5, TNFRSF5_N
TPD52	Other/Unknown	no		TPD52
TSBP1	Other/Unknown	no		TSBP1
SHANK2	Scaffold/PPI	no		SH3_domain, PDZ, SAM
OR13C4	GPCR	yes		GPCR_Rhodpsn, Olfact_rcpt, GPCR_Rhodpsn_7TM
ITPKC	Enzyme (other)	yes	2.7.1.127	IPK, IPK_sf
CASP3	Enzyme (other)	yes	3.4.22.56	Pept_C14_p20, Pept_C14_p10, Pept_C14
FAM167A	Other/Unknown	no		FAM167, FAM167_domain
PPM1L	Phosphatase	yes	3.1.3.16	PP2C_BS, PPM-type_phosphatase-like_dom, PP2C
PGBD1	Other/Unknown	no		SRCR, SCAN_dom, PGBD
CENPU	Other/Unknown	no		CENP-U
CARMIL1	Other/Unknown	no		Leu-rich_rpt, PH-like_dom_sf, CARMIL_C
COPB2	Scaffold/PPI	no		WD40_rpt, Beta-prop_COPA/B_2nd, WD40/YVTN_repeat-like_dom_sf
MED30	Other/Unknown	no		Mediator_Med30_met
RHBDD1	Protease	yes	3.4.21.105	Peptidase_S54_rhomboid_dom, Rhomboid-like_sf
NAALADL2	Protease	yes		Peptidase_M28, TFR-like_dimer_dom_sf, Peptidase_M28B
ENPP6	Phosphatase	yes	3.1.4.3	Phosphodiest/P_Trfase, Alkaline_phosphatase_core_sf
SARNP	Other/Unknown	no		SAP_dom, SAP_dom_sf, SAP_domain_ribonucleoprotein
DAB1	Other/Unknown	no		PTB/PI_dom, PH-like_dom_sf, DAB1/2_SBM
TECRL	Other/Unknown	no		3-oxo-5_a-steroid_4-DH_C, SRD5A/TECR, TECRL_Ubl
TMEM263	Other/Unknown	no		UPF0444
SPECC1L	Other/Unknown	no		CH_dom, CH_dom_sf, F-actin_Monoox_Mical
EPG5	Other/Unknown	no		Autophagy-related_EPG5, TPR_Epg5, TPR_Epg5_mid
RMST	Other/Unknown	no
GALNT18	Enzyme (other)	yes	2.4.1.41	Ricin_B_lectin, Glyco_trans_2-like, Nucleotide-diphossugar_trans
TRX-CAT1-6	Other/Unknown	no
FCGR2A	Antibody/Immunoglobulin	yes		Ig_sub2, Ig_sub, Ig-like_dom
HLA-DOB	Antibody/Immunoglobulin	yes		MHC_II_b_N, Ig/MHC_CS, Ig_C1-set
HLA-DQB1	Antibody/Immunoglobulin	yes		MHC_II_b_N, Ig/MHC_CS, Ig_C1-set
HLA-DQB2	Antibody/Immunoglobulin	yes		MHC_II_b_N, Ig/MHC_CS, Ig_C1-set
IGHV1-69	Antibody/Immunoglobulin	yes		Ig-like_dom, Ig_V-set, Ig-like_fold
KIF25	Other/Unknown	no		Kinesin_motor_dom, Kinesin_motor_CS, P-loop_NTPase
LTA	Other/Unknown	no		TNF_beta, TNF_dom, TNF
MIA	Scaffold/PPI	no		SH3_domain, SH3-like_dom_sf, MIA
MICB	Antibody/Immunoglobulin	yes		Ig_C1-set, Ig-like_dom, MHC_I-like_Ag-recog
ZFHX3	Transcription factor	no		HD, Matrin/U1-like-C_Znf_C2H2, Homeodomain-like_sf
NUMBL	Other/Unknown	no		PTB/PI_dom, Numb_domain, PH-like_dom_sf
PELI1	Other/Unknown	no		Pellino_fam, Pellino_FHA, Pellino_RING
PTPRJ	Phosphatase	yes	3.1.3.48	PTP_cat, Tyr_Pase_dom, Tyr_Pase_cat
RAB4B	Other/Unknown	no		Small_GTPase, Small_GTP-bd, P-loop_NTPase

Expression context

Cohort genes with no expression data: 1.

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

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	1
moderate (6-20)	0
broad (>20)	42
unknown	1

Top tissues across cohort

Tissue	Cohort genes
lymph node	5
spleen	5
secondary oocyte	5
granulocyte	5
male germ line stem cell (sensu Vertebrata) in testis	4
calcaneal tendon	4
buccal mucosa cell	4
right lung	3
jejunal mucosa	3
bone marrow cell	3
stromal cell of endometrium	3
primordial germ cell in gonad	3
oocyte	3
leukocyte	3
monocyte	3
heart right ventricle	2
lateral nuclear group of thalamus	2
Brodmann (1909) area 23	2
colonic epithelium	2
cortical plate	2

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RPN2	303	ubiquitous	marker	corpus epididymis, pylorus, placenta
BLK	145	tissue_specific	marker	spleen, male germ line stem cell (sensu Vertebrata) in testis, lymph node
SLC16A7	286	ubiquitous	marker	heart right ventricle, renal medulla, vena cava
BTBD1	290	ubiquitous	marker	skeletal muscle tissue of rectus abdominis, vastus lateralis, quadriceps femoris
CD40	242	ubiquitous	marker	lymph node, right lung, spleen
TPD52	291	ubiquitous	marker	jejunal mucosa, lateral nuclear group of thalamus, secondary oocyte
TSBP1	58	tissue_specific	yes	left testis, testis, right testis
SHANK2	240	broad	marker	Brodmann (1909) area 23, bronchial epithelial cell, middle temporal gyrus
OR13C4	1		yes	granulocyte, bone marrow cell, colonic epithelium
ITPKC	255	ubiquitous	marker	lower esophagus mucosa, esophagus mucosa, skin of leg
CASP3	245	ubiquitous	marker	jejunal mucosa, rectum, epithelium of nasopharynx
FAM167A	207	broad	marker	stromal cell of endometrium, islet of Langerhans, secondary oocyte
PPM1L	253	ubiquitous	marker	Brodmann (1909) area 23, lateral nuclear group of thalamus, endothelial cell
PGBD1	177	ubiquitous	marker	primordial germ cell in gonad, cortical plate, ganglionic eminence
CENPU	242	ubiquitous	marker	sperm, male germ cell, oocyte
CARMIL1	230	ubiquitous	marker	oocyte, secondary oocyte, calcaneal tendon
COPB2	295	ubiquitous	marker	parotid gland, stromal cell of endometrium, type B pancreatic cell
MED30	255	ubiquitous	marker	oocyte, secondary oocyte, bone marrow
RHBDD1	248	ubiquitous	marker	bone marrow cell, calcaneal tendon, secondary oocyte
NAALADL2	183	ubiquitous	marker	calcaneal tendon, colonic epithelium, primordial germ cell in gonad
ENPP6	186	tissue_specific	marker	C1 segment of cervical spinal cord, spinal cord, corpus callosum
SARNP	219	ubiquitous	marker	ganglionic eminence, ventricular zone, tibial artery
DAB1	190	broad	marker	cortical plate, jejunal mucosa, sural nerve
TECRL	135	tissue_specific	yes	myocardium, heart right ventricle, left ventricle myocardium
TMEM263	262	ubiquitous	marker	tibia, cartilage tissue, stromal cell of endometrium
SPECC1L	274	ubiquitous	marker	calcaneal tendon, tendon, male germ line stem cell (sensu Vertebrata) in testis
EPG5	260	ubiquitous	marker	pancreatic ductal cell, buccal mucosa cell, bone marrow cell
RMST	130	broad	marker	right lobe of thyroid gland, left lobe of thyroid gland, thyroid gland
GALNT18	222	ubiquitous	marker	right lung, upper lobe of left lung, upper lobe of lung
TRX-CAT1-6

Protein interactions among cohort

Intra-cohort edges: 12.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CASP3	8,532
CD40	3,765
RPN2	3,035
COPB2	2,982
BLK	2,967
FCGR2A	2,618
NUMBL	2,438
CENPU	1,939
SHANK2	1,920
SARNP	1,825

Intra-cohort edges

A	B	Sources
BLK	FAM167A	string_interaction
BLK	FCGR2A	string_interaction
BLK	ITPKC	string_interaction
CASP3	ITPKC	string_interaction
CD40	EPG5	intact
CD40	ITPKC	string_interaction
FAM167A	ITPKC	string_interaction
FCGR2A	ITPKC	string_interaction
ITPKC	NAALADL2	string_interaction
NAALADL2	ZFHX3	string_interaction
OR13C4	RHBDD1	string_interaction
SPECC1L	ZFHX3	intact

Structural data

PDB: 24 · AlphaFold-only: 18 · No structure: 2

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CASP3	P42574	135
CENPU	Q71F23	18
CD40	P25942	14
MED30	Q96HR3	11
HLA-DQB1	P01920	10
FCGR2A	P12318	9
RPN2	P04844	6
PTPRJ	Q12913	5
MIA	Q16674	4
SLC16A7	O60669	3
CARMIL1	Q5VZK9	3
LTA	P01374	3
ZFHX3	Q15911	3
SHANK2	Q9UPX8	2
COPB2	P35606	2
MICB	Q29980	2
ITPKC	Q96DU7	1
RHBDD1	Q8TEB9	1
SARNP	P82979	1
EPG5	Q9HCE0	1
HLA-DOB	P13765	1
NUMBL	Q9Y6R0	1
PELI1	Q96FA3	1
RAB4B	P61018	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ENPP6	Q6UWR7	93.06
IGHV1-69	P01742	90.67
PPM1L	Q5SGD2	89.78
GALNT18	Q6P9A2	89.10
BTBD1	Q9H0C5	87.99
HLA-DQB2	P05538	86.87
TECRL	Q5HYJ1	84.32
OR13C4	Q8NGS5	83.89
BLK	P51451	81.89
NAALADL2	Q58DX5	78.78
FAM167A	Q96KS9	71.98
KIF25	Q9UIL4	71.90
TPD52	P55327	69.11
SPECC1L	Q69YQ0	67.07
PGBD1	Q96JS3	66.92
DAB1	O75553	59.20
TMEM263	Q8WUH6	51.62
TSBP1	Q5SRN2	45.58

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 165. Enrichment computed across 44 evidence-associated genes (32 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 32 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
FCGR activation	2	54.9×	0.083	FCGR2A, IGHV1-69
TNF receptor superfamily (TNFSF) members mediating non-canonical NF-kB pathway	2	42.0×	0.083	CD40, LTA
Phosphorylation of CD3 and TCR zeta chains	2	34.0×	0.085	HLA-DQB2, PTPRJ
Role of phospholipids in phagocytosis	2	28.6×	0.090	FCGR2A, IGHV1-69
Antigen activates B Cell Receptor (BCR) leading to generation of second messengers	2	22.3×	0.118	BLK, IGHV1-69
Stimulation of the cell death response by PAK-2p34	1	178.4×	0.118	CASP3
FCGR3A-mediated IL10 synthesis	2	18.3×	0.118	FCGR2A, IGHV1-69
Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell	3	8.2×	0.118	CD40, IGHV1-69, MICB
CD22 mediated BCR regulation	1	71.4×	0.134	IGHV1-69
CASP4-mediated substrate cleavage	1	71.4×	0.134	CASP3
CASP5-mediated substrate cleavage	1	71.4×	0.134	CASP3
Activation of caspases through apoptosome-mediated cleavage	1	59.5×	0.134	CASP3
Classical antibody-mediated complement activation	1	59.5×	0.134	IGHV1-69
NADE modulates death signalling	1	59.5×	0.134	CASP3
Proton-coupled monocarboxylate transport	1	59.5×	0.134	SLC16A7
Reelin signalling pathway	1	59.5×	0.134	DAB1
RUNX1 regulates transcription of genes involved in BCR signaling	1	59.5×	0.134	BLK
SMAC (DIABLO) binds to IAPs	1	51.0×	0.134	CASP3
SMAC(DIABLO)-mediated dissociation of IAP:caspase complexes	1	51.0×	0.134	CASP3
SMAC, XIAP-regulated apoptotic response	1	51.0×	0.134	CASP3
Glycerophospholipid catabolism	1	51.0×	0.134	ENPP6
RUNX3 regulates CDKN1A transcription	1	51.0×	0.134	ZFHX3
Regulation of actin dynamics for phagocytic cup formation	2	11.5×	0.134	FCGR2A, IGHV1-69
TNFR2 non-canonical NF-kB pathway	2	11.3×	0.134	CD40, LTA
Caspase activation via extrinsic apoptotic signalling pathway	1	44.6×	0.147	CASP3
Cytochrome c-mediated apoptotic response	1	39.6×	0.157	CASP3
Caspase activation via Dependence Receptors in the absence of ligand	1	35.7×	0.157	CASP3
MET receptor recycling	1	35.7×	0.157	RAB4B
Interferon gamma signaling	2	7.8×	0.157	HLA-DQB1, HLA-DQB2
Apoptotic cleavage of cell adhesion proteins	1	32.4×	0.167	CASP3

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 39 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
peptide antigen assembly with MHC class II protein complex	3	81.0×	0.002	HLA-DOB, HLA-DQB1, HLA-DQB2
anterior neural tube closure	2	216.1×	0.005	CASP3, SPECC1L
antigen processing and presentation of exogenous peptide antigen via MHC class II	3	41.8×	0.005	HLA-DOB, HLA-DQB1, HLA-DQB2
positive regulation of immune response	3	37.0×	0.006	HLA-DOB, HLA-DQB1, HLA-DQB2
positive regulation of T cell activation	3	34.1×	0.006	HLA-DOB, HLA-DQB1, HLA-DQB2
nucleotide transport	1	432.1×	0.048	EPG5
cell-cell adhesion involved in neuronal-glial interactions involved in cerebral cortex radial glia guided migration	1	432.1×	0.048	DAB1
neural crest cell delamination	1	432.1×	0.048	SPECC1L
negative regulation of mitotic centrosome separation	1	432.1×	0.048	KIF25
barbed-end actin filament uncapping	1	432.1×	0.048	CARMIL1
interferon-mediated signaling pathway	1	432.1×	0.048	EPG5
negative regulation of antigen processing and presentation of peptide antigen via MHC class II	1	216.1×	0.048	HLA-DOB
positive regulation of chronic inflammatory response to antigenic stimulus	1	216.1×	0.048	LTA
intrinsic apoptotic signaling pathway in response to osmotic stress	1	216.1×	0.048	CASP3
cerebellum structural organization	1	216.1×	0.048	DAB1
response to cobalamin	1	216.1×	0.048	CD40
lactate transmembrane transport	1	216.1×	0.048	SLC16A7
regulation of protein binding	1	216.1×	0.048	BTBD1
photoreceptor cell differentiation	1	216.1×	0.048	EPG5
inclusion body assembly	1	216.1×	0.048	EPG5
leukocyte apoptotic process	1	216.1×	0.048	CASP3
maintenance of protein complex location	1	216.1×	0.048	EPG5
protein aggregate center assembly	1	216.1×	0.048	EPG5
positive regulation of lamellipodium organization	1	216.1×	0.048	CARMIL1
regulation of locomotor rhythm	1	216.1×	0.048	ZFHX3
membrane protein proteolysis involved in retrograde protein transport, ER to cytosol	1	216.1×	0.048	RHBDD1
cellular response to dsDNA	1	216.1×	0.048	EPG5
immune response-activating cell surface receptor signaling pathway	1	144.0×	0.048	MICB
regulation of Toll signaling pathway	1	144.0×	0.048	PELI1
protein metabolic process	1	144.0×	0.048	NUMBL

Therapeutics

Drugs indicated for this disease

1 approved, 5 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Human Immunoglobulin G	Approved (phase 4)
Anakinra	Phase 3 (in late-stage trials)
Aspirin	Phase 3 (in late-stage trials)
Infliximab	Phase 3 (in late-stage trials)
Polyethylene Glycol	Phase 3 (in late-stage trials)
Prednisolone	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Canakinumab, Defibrotide, Etanercept, Pravastatin.

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 2 · Phased (≥1): 4 · Undrugged: 40

Druggability breadth: 14 of 44 evidence-associated genes (32%) 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

Top cohort targets by molecule count

Symbol	Molecules	Max phase
BLK	62	4
CASP3	5	3
SLC16A7	1	1
SPECC1L	1	2
RPN2	0	0
BTBD1	0	0
CD40	0	0
TPD52	0	0
TSBP1	0	0
SHANK2	0	0

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
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
SUNITINIB	4	BLK
DASATINIB	4	BLK
ERLOTINIB	4	BLK
QUIZARTINIB	4	BLK
CRIZOTINIB	4	BLK
MIDOSTAURIN	4	BLK
GEFITINIB	4	BLK
IMATINIB	4	BLK
MASITINIB	3	BLK
LINIFANIB	3	BLK
CANERTINIB	3	BLK

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 9.

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

Symbol	Assays	Type breakdown
BLK	483	Binding:477, ADMET:4, Functional:2
CASP3	349	Binding:327, Functional:16, Toxicity:4, ADMET:2
CD40	10	Binding:10
RPN2	7	Binding:7
ENPP6	7	Binding:7
SPECC1L	6	Binding:6
SLC16A7	5	Binding:3, Functional:2
PTPRJ	5	Binding:4, ADMET:1
LTA	3	Binding:3
PELI1	2	Binding:2
COPB2	1	Binding:1
SARNP	1	Binding:1
TMEM263	1	Binding:1
FCGR2A	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
RPN2	2.4.99.18	dolichyl-diphosphooligosaccharide-protein glycotransferase
BLK	2.7.10.2	non-specific protein-tyrosine kinase
ITPKC	2.7.1.127	inositol-trisphosphate 3-kinase
CASP3	3.4.22.56	caspase-3
PPM1L	3.1.3.16	protein-serine/threonine phosphatase
RHBDD1	3.4.21.105	rhomboid protease
ENPP6	3.1.4.3	phospholipase C
GALNT18	2.4.1.41	polypeptide N-acetylgalactosaminyltransferase
PTPRJ	3.1.3.48	protein-tyrosine-phosphatase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
BLK	483
CASP3	349

Pharmacogenomics

Cohort genes with a PharmGKB record: 43; 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
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
SUNITINIB	4	BLK
DASATINIB	4	BLK
ERLOTINIB	4	BLK
QUIZARTINIB	4	BLK
CRIZOTINIB	4	BLK
MIDOSTAURIN	4	BLK
GEFITINIB	4	BLK
IMATINIB	4	BLK
MASITINIB	3	BLK
LINIFANIB	3	BLK
CANERTINIB	3	BLK

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	BLK
B	Phased (≥1) drug, not yet approved	3	SLC16A7, CASP3, SPECC1L
C	Druggable family + PDB, no drug	8	RPN2, ITPKC, RHBDD1, FCGR2A, HLA-DOB, HLA-DQB1, MICB, PTPRJ
D	Druggable family + AlphaFold only, no drug	7	OR13C4, PPM1L, NAALADL2, ENPP6, GALNT18, HLA-DQB2, IGHV1-69
E	Difficult family or no structure, no drug	25	BTBD1, CD40, TPD52, TSBP1, SHANK2, FAM167A, PGBD1, CENPU, CARMIL1, COPB2 (+15 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
ITPKC	0	BLK, CASP3
FAM167A	0	BLK
RPN2	7	—
BTBD1	0	—
CD40	10	—
TPD52	0	—
TSBP1	0	—
SHANK2	0	—
OR13C4	0	—
PPM1L	0	—
PGBD1	0	—
CENPU	0	—
CARMIL1	0	—
COPB2	1	—
MED30	0	—
RHBDD1	0	—
NAALADL2	0	—
ENPP6	7	—
SARNP	1	—
DAB1	0	—
TECRL	0	—
TMEM263	1	—
EPG5	0	—
RMST	0	—
GALNT18	0	—
TRX-CAT1-6	0	—
FCGR2A	1	—
HLA-DOB	0	—
HLA-DQB1	0	—
HLA-DQB2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 60.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	31
PHASE3	10
PHASE2	8
PHASE4	5
PHASE1/PHASE2	3
PHASE1	2
EARLY_PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05643651	PHASE4	RECRUITING	Rivaroxaban for Children Aged Over 2 Years With Giant Coronary Artery Aneurysms After Kawasaki Disease
NCT06697431	PHASE4	NOT_YET_RECRUITING	Non Inferiority KawasakI Trial With Anakinra
NCT06978439	PHASE4	RECRUITING	Model-informed Dose Optimization for Rivaroxaban in Children With Giant Coronary Artery Aneurysm After Kawasaki Disease
NCT01524939	PHASE4	COMPLETED	Study of Combined Therapy of Aspirin and IVIG-SN in Kawasaki Disease
NCT04003844	PHASE4	COMPLETED	Study of Combined Therapy IVIG-SN 10% and Acetylsalicylic Acid in Kawasaki Disease
NCT04656184	PHASE3	RECRUITING	A Trial Comparing the Efficacy and Safety of Anakinra Versus Intravenous Immunoglobulin (IVIG) Retreatment, in Patients With Kawasaki Disease Who Failed to Respond to Initial Standard IVIG Treatment
NCT00157079	PHASE3	COMPLETED	Safety and Efficacy Study of a 10% Intravenous Immune Globulin Solution in Subjects With Primary Immunodeficiency Disorders
NCT00162032	PHASE3	COMPLETED	A Study to Evaluate the Use and Safety of CARDIOLITE® in Pediatric Patients With Kawasaki Disease
NCT00760435	PHASE3	COMPLETED	Infliximab Plus Intravenous Immunoglobulin for the Primary Treatment of Kawasaki Disease
NCT02298062	PHASE3	COMPLETED	Infliximab for Kawasaki Disease Patients Resistant to IVIG : a Multicentre, Prospective, Randomised Trial
NCT02439996	PHASE3	COMPLETED	Different Doses of IVIG for Kawasaki Disease
NCT03065244	PHASE3	COMPLETED	KIDCARE (Kawasaki Disease Comparative Effectiveness Trial)
NCT03200561	PHASE3	UNKNOWN	A Trial to Evaluate the Efficacy of Immunoglobulin Plus Steroid for Prevention of Coronary Artery Abnormalities in Taiwanese Refractory Kawasaki Disease (RAST Study)
NCT04078568	PHASE3	COMPLETED	Efficacy of Immunoglobulin Plus Prednisolone in Reducing Coronary Artery Lesion in Patients With Kawasaki Disease
NCT04535518	PHASE3	WITHDRAWN	Efficacy of Immunoglobulin Plus Infliximab for the Early Regression of Coronary Artery Lesion in Kawasaki Disease
NCT01917721	PHASE2	ACTIVE_NOT_RECRUITING	Doxycycline Treatment to Prevent Progressive Coronary Artery Dilation in Children With Kawasaki Disease
NCT00000520	PHASE2	COMPLETED	Prevention of Coronary Aneurysms in Kawasaki Syndrome
NCT00162045	PHASE1/PHASE2	COMPLETED	A Trial to Determine Radiation Exposure to Organs and Assess the Safety of CARDIOLITE® in Pediatric Subjects
NCT00305201	PHASE2	WITHDRAWN	Cardiovascular Risk Markers and Response to Statins After Kawasaki Disease
NCT00841789	PHASE2	COMPLETED	A Randomized, Double Blind, Placebo Controlled Study of Etanercept in Children With Kawasaki Disease
NCT01431105	PHASE1/PHASE2	COMPLETED	Pharmacokinetics (PK)/Safety Study of Atorvastatin in Children With Kawasaki Disease and Coronary Artery Abnormalities
NCT02114099	PHASE2	UNKNOWN	Trial of Atorvastatin on the Persistent Coronary Aneurysm in Children With Kawasaki Disease
NCT02179853	PHASE1/PHASE2	COMPLETED	Anakinra in Infants and Children With Coronary Artery Abnormalities in Acute Kawasaki Disease
NCT02390596	PHASE2	COMPLETED	Anakinra and Kawasaki Disease
NCT02980263	PHASE2	WITHDRAWN	Study of Efficacy and Safety of Canakinumab in Pediatric Patients With Kawasaki Disease
NCT04777422	PHASE2	UNKNOWN	Defibrotide in Children With High Risk Kawasaki Disease
NCT00271570	PHASE1	COMPLETED	Infliximab (Remicade) for Patients With Acute Kawasaki Disease
NCT04509219	PHASE1	UNKNOWN	Methylprednisolone Pulse Therapy for Coronary Artery Dilatation or Aneurysm Formation in Kawasaki Disease
NCT04747847	EARLY_PHASE1	COMPLETED	Pilot Study of Atorvastatin and Anakinra in Children With Coronary Artery Abnormalities Secondary to Kawasaki Disease
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
NCT04278404	Not specified	RECRUITING	Pharmacokinetics, Pharmacodynamics, and Safety Profile of Understudied Drugs Administered to Children Per Standard of Care (POPS)
NCT06305611	Not specified	RECRUITING	European and North Indian Cohort of KaWasaki dIsease
NCT06641817	Not specified	ENROLLING_BY_INVITATION	The Value of Cardiovascular Imaging in Kawasaki Disease
NCT06641843	Not specified	ENROLLING_BY_INVITATION	Magnetic Resonance Myocardial Stress Perfusion in Pediatric Patients with Cardiovascular Disease
NCT06775457	Not specified	RECRUITING	Genome Analysis of Human Endogenous Retroviruses (HERVs)(COVID19)
NCT06993636	Not specified	RECRUITING	Pharmacometrics Analysis of Rivaroxaban in Chinese Children Aged Over 2 Years
NCT07086989	Not specified	RECRUITING	Cardiovascular Risk in Children With Chronic Conditions Study
NCT07291245	Not specified	RECRUITING	Kawasaki MATCH Trial
NCT07405658	Not specified	NOT_YET_RECRUITING	Clinical Study on an Artificial Intelligence-Assisted Chest Radiograph Model Based on Big Data and Deep Learning for Early Detection of Kawasaki Disease
NCT07491926	Not specified	NOT_YET_RECRUITING	MASKd: a Study on Kawasaki Disease (KD) Complicated by Macrophage Activation Syndrome (MAS)

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
ASPIRIN	4	6
ANAKINRA	4	4
CANAKINUMAB	4	1
HUMAN IMMUNOGLOBULIN G	4	1
PRAVASTATIN	4	1
RIVAROXABAN	4	1
TECHNETIUM TC 99M SESTAMIBI	4	1
WARFARIN	4	1
BLOOD, WHOLE	3	1
DEFIBROTIDE	3	1
TECHNETIUM	3	1
CHEMBL5220618	0	4
CHEMBL3183768	0	1