IgA glomerulonephritis

Summary

IgA glomerulonephritis (MONDO:0005342) is a disease with 33 cohort genes (268 GWAS associations across 15 studies) and 173 clinical trials. The dominant Reactome pathway is Interferon gamma signaling (8 cohort genes). Top therapeutic interventions include hydroxychloroquine, rituximab, and aliskiren.

At a glance

• Cohort genes: 33
• GWAS associations: 268
• ClinVar variants: 1
• Phenotypes (HPO): 17
• Clinical trials: 173

Clinical features

Signs & symptoms

Clinical features (HPO)

17 HPO clinical features (Orphanet curated; top 17 by frequency):

HPO ID	Term	Frequency
HP:0000794	IgA deposition in the glomerulus	Frequent (30-79%)
HP:0001919	Acute kidney injury	Frequent (30-79%)
HP:0002907	Microscopic hematuria	Frequent (30-79%)
HP:0012587	Macroscopic hematuria	Frequent (30-79%)
HP:0012595	Mild proteinuria	Frequent (30-79%)
HP:0000083	Renal insufficiency	Occasional (5-29%)
HP:0000099	Glomerulonephritis	Occasional (5-29%)
HP:0000282	Facial edema	Occasional (5-29%)
HP:0000822	Hypertension	Occasional (5-29%)
HP:0001394	Cirrhosis	Occasional (5-29%)
HP:0001541	Ascites	Occasional (5-29%)
HP:0002608	Celiac disease	Occasional (5-29%)
HP:0003261	Increased circulating IgA level	Occasional (5-29%)
HP:0030830	Crackles	Occasional (5-29%)
HP:0031504	Foamy urine	Occasional (5-29%)
HP:0033316	Glomerular crescent formation	Occasional (5-29%)
HP:0012593	Nephrotic range proteinuria	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	IgA glomerulonephritis
Mondo ID	MONDO:0005342
EFO	EFO:0004194
MeSH	D005922
Orphanet	34145
DOID	DOID:2986
NCIT	C34643
SNOMED CT	68779003
UMLS	C0017661
MedGen	9032
GARD	0000863
NORD	1298
Is cancer (heuristic)	no

Also known as: Berger’s disease · IgA glomerulonephritis · IgA Nephropathy · IgA nephropathy

Data availability: 1 ClinVar variant · 268 GWAS associations (15 studies) · 19 cell lines.

Disease family

Classification path: disease › human disease › disease by body system or component › urinary system disorder › kidney disorder › nephritis › glomerulonephritis › IgA glomerulonephritis

Related subtypes (19): acute poststreptococcal glomerulonephritis, membranoproliferative glomerulonephritis, exudative glomerulonephritis, proliferative glomerulonephritis, focal embolic glomerulonephritis, anti-basement membrane glomerulonephritis, diffuse glomerulonephritis, subacute glomerulonephritis, mesangial proliferative glomerulonephritis, immune-complex glomerulonephritis, membranous glomerulonephritis, lupus nephritis, minimal change disease, granulomatosis with polyangiitis, rapidly progressive glomerulonephritis, primary membranoproliferative glomerulonephritis, Pauci-immune glomerulonephritis, immunotactoid glomerulopathy, autoimmune glomerulonephritis

Genetics & variants

GWAS landscape

268 GWAS associations across 15 studies. Top hits map to 32 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs9268557	5e-47	TSBP1-AS1 - HLA-DRA	C	1.24
rs5828672	1e-46	ZNF787	?
rs35591339	1e-46	TENM3	?
rs143409664	5e-41	PRAG1	?
rs7763262	2e-38	HLA-DRA - HLA-DRB9	C	1.41
rs9275596	3e-31	MTCO3P1 - HLA-DQB3	T	1.44
rs9275224	6e-30	HLA-DQB1 - MTCO3P1	G	1.36
rs9270599	4e-28	HLA-DRB1 - HLA-DQA1	A	1.55
rs2738058	2e-27	DEFA9P - DEFA10P	T	1.27
rs34527214	2e-27	CYTH2	?
rs9266216	5e-27	HLA-B	T	0.13
rs767448033	3e-24	TRBV5-4	?
rs4803184	6e-24	FBXO27	?
chr6:37138023	2e-23		?
rs9314614	5e-22	GS1-24F4.2; DEFA9P - DEFA10P; DEFA7P - DEFA5	T	1.26
rs660895	4e-20	HLA-DRB1 - HLA-DQA1	G	1.34
rs7190997	2e-19	ITGAX	C	1.22
rs12716641	1e-18	DEFA7P - DEFA5	T	1.23
rs35666756	1e-18	MISP3	?
chr3:27763427	2e-18		?
rs954638	5e-18	MDN1	?
rs6677604	2e-17	CFH	G	1.21
rs11137085	3e-17	DEFA3 - DEFA11P	C	1.33
rs56254331	2e-16	CCDC97, TGFB1	C	0.13
rs2348459	4e-16	PKD1L1, PKD1L1-AS1	?
rs2466264	7e-16	TRMT9B	?
rs2856717	1e-15	HLA-DQB1 - MTCO3P1	G	1.27
rs7944434	3e-15	OR10G6	?
rs10533306	4e-15	SH3PXD2A	?
chr15:78913067	7e-15		?

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90018866	Sakaue S	2021	15,587	462,197	A cross-population atlas of genetic associations for 220 human phenotypes.
GCST90308722	Kiryluk K	2023	5,556	21,178	Genome-wide association analyses define pathogenic signaling pathways and prioritize drug targets for IgA nephropathy.
GCST90308723	Kiryluk K	2023	5,556	21,178	Genome-wide association analyses define pathogenic signaling pathways and prioritize drug targets for IgA nephropathy.
GCST90308724	Kiryluk K	2023	4,590	7,573	Genome-wide association analyses define pathogenic signaling pathways and prioritize drug targets for IgA nephropathy.
GCST90454539	Li M	2024	3,616	10,417	Identification of susceptibility loci and relevant cell type for IgA nephropathy in Han Chinese by integrative genome-wide analysis.
GCST90308721	Kiryluk K	2023	3,549	10,140	Genome-wide association analyses define pathogenic signaling pathways and prioritize drug targets for IgA nephropathy.
GCST011781	Li M	2020	2,628	11,563	Genome-Wide Meta-Analysis Identifies Three Novel Susceptibility Loci and Reveals Ethnic Heterogeneity of Genetic Susceptibility for IgA Nephropathy.
GCST90428872	Li M	2023	2,378	15,642	Genome-Wide Association Analysis of Protein-Coding Variants in IgA Nephropathy.
GCST002943	Li M	2015	1,434	10,661	Identification of new susceptibility loci for IgA nephropathy in Han Chinese.
GCST001364	Yu XQ	2011	1,434	4,270	A genome-wide association study in Han Chinese identifies multiple susceptibility loci for IgA nephropathy.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	2
Tier 2: splice/UTR	4
Tier 3: regulatory	2
Tier 4: intronic/intergenic	42

MAF distribution

Bucket	Variants
common (>=0.05)	44
low_freq (0.01-0.05)	0
rare (<0.01)	0
unknown	6

Functional consequences

Consequence	Count
intron_variant	20
intergenic_variant	12
non_coding_transcript_exon_variant	4
unknown	4
inframe_insertion	2
regulatory_region_variant	2
3_prime_UTR_variant	2
5_prime_UTR_variant	2
intron_variant; intergenic_variant; intergenic_variant	1
synonymous_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs9268557	6	32421528	T>A,C,G	0.05	intron_variant	TSBP1-AS1 - HLA-DRA	5e-47	Tier 4: intronic/intergenic
rs5828672	19	56088072	CTCGTCGTCG>C,CTCG,CTCGTCG,CTCGTCGTCGTCG,CTCGTCGTCGTCGTCG,CTCGTCGTCGTCGTCGTCG,CTCGTCGTCGTCGTCGTCGTCG	0.05	inframe_insertion	ZNF787	1e-46	Tier 1: coding
rs35591339	4	182449092	AGCGGCGGCGGCG>A,AGCG,AGCGGCG,AGCGGCGGCG,AGCGGCGGCGGCGGCG,AGCGGCGGCGGCGGCGGCG	0.05	intron_variant	TENM3	1e-46	Tier 4: intronic/intergenic
rs143409664	8	8318866	CGGGGCGGGGGCG>C,CGGGGCG,CGGGGCGGGGGCGGGGGCG,CGGGGCGGGGGCGGGGGCGGGGGCG	0.05	inframe_insertion	PRAG1	5e-41	Tier 1: coding
rs7763262	6	32457105	T>A,C,G	0.31	intron_variant	HLA-DRA - HLA-DRB9	2e-38	Tier 4: intronic/intergenic
rs9275596	6	32713854	C>A,G,T	0.35	intergenic_variant	MTCO3P1 - HLA-DQB3	3e-31	Tier 4: intronic/intergenic
rs9275224	6	32692101	A>C,G	0.49	regulatory_region_variant	HLA-DQB1 - MTCO3P1	6e-30	Tier 3: regulatory
rs9270599	6	32593879	G>A,C,T	0.428	intergenic_variant	HLA-DRB1 - HLA-DQA1	4e-28	Tier 4: intronic/intergenic
rs2738058	8	6964095	T>A,C,G	0.334	intergenic_variant	DEFA9P - DEFA10P	2e-27	Tier 4: intronic/intergenic
rs34527214	19	48481922	TA>T	0.05	3_prime_UTR_variant	CYTH2	2e-27	Tier 2: splice/UTR
rs9266216	6	31357313	C>G,T	0.05	non_coding_transcript_exon_variant	HLA-B	5e-27	Tier 4: intronic/intergenic
rs767448033	7	142463071	G>A	0.05	5_prime_UTR_variant	TRBV5-4	3e-24	Tier 2: splice/UTR
rs4803184	19	39014471	G>A,C,T	0.05	non_coding_transcript_exon_variant	FBXO27	6e-24	Tier 4: intronic/intergenic
chr6:37138023							2e-23	Tier 4: intronic/intergenic
rs9314614	8;8;8	6840209	C>G,T	0.246	intron_variant; intergenic_variant; intergenic_variant	GS1-24F4.2; DEFA9P - DEFA10P; DEFA7P - DEFA5	5e-22	Tier 4: intronic/intergenic
rs660895	6	32609603	A>G	0.24	regulatory_region_variant	HLA-DRB1 - HLA-DQA1	4e-20	Tier 3: regulatory
rs7190997	16	31356857	T>A,C,G	0.308	intron_variant	ITGAX	2e-19	Tier 4: intronic/intergenic
rs12716641	8	7041476	T>A,C	0.257	intergenic_variant	DEFA7P - DEFA5	1e-18	Tier 4: intronic/intergenic
rs35666756	19	14073902	C>CG,CGGG	0.05	intron_variant	MISP3	1e-18	Tier 4: intronic/intergenic
chr3:27763427							2e-18	Tier 4: intronic/intergenic
rs954638	6	89690573	C>A,G,T	0.05	intron_variant	MDN1	5e-18	Tier 4: intronic/intergenic
rs6677604	1	196717788	G>A	0.05	intron_variant	CFH	2e-17	Tier 4: intronic/intergenic
rs11137085	8	7019946	G>A,C,T	0.496	intergenic_variant	DEFA3 - DEFA11P	3e-17	Tier 4: intronic/intergenic
rs56254331	19	41320115	A>C,G,T	0.05	intron_variant	CCDC97, TGFB1	2e-16	Tier 4: intronic/intergenic
rs2348459	7	47795518	T>A,C,G	0.05	intron_variant	PKD1L1, PKD1L1-AS1	4e-16	Tier 4: intronic/intergenic
rs2466264	8	13012929	C>G	0.05	intron_variant	TRMT9B	7e-16	Tier 4: intronic/intergenic
rs2856717	6	32702531	A>C,G,T	0.38	intergenic_variant	HLA-DQB1 - MTCO3P1	1e-15	Tier 4: intronic/intergenic
rs7944434	11	123994379	A>C,G,T	0.05	synonymous_variant	OR10G6	3e-15	Tier 4: intronic/intergenic
rs10533306	10	103668696	CAG>C	0.05	intron_variant	SH3PXD2A	4e-15	Tier 4: intronic/intergenic
chr15:78913067							7e-15	Tier 4: intronic/intergenic

ClinVar germline variants

1 retrieved; paginated sample, class counts are floors:

1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
13526	NM_002644.4(PIGR):c.1739C>T (p.Ala580Val)	PIGR	Uncertain significance	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 42 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 2

Dual-evidence genes (GWAS + Mendelian — highest-confidence targets)

Gene	HGNC	Evidence routes
CFHR3	CFHR3	GWAS, Orphanet
CFHR1	CFHR1	GWAS, Orphanet

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CARD9	Orphanet:457088	Predisposition to invasive fungal disease due to CARD9 deficiency
CFHR3	Orphanet:329931	C3 glomerulonephritis
PADI3	Orphanet:1410	Uncombable hair syndrome
TAP1	Orphanet:34592	Immunodeficiency by defective expression of MHC class I
TAP2	Orphanet:34592	Immunodeficiency by defective expression of MHC class I
CFHR1	Orphanet:329931	C3 glomerulonephritis
CFHR1	Orphanet:93571	Dense deposit disease
HLA-A	Orphanet:179	Birdshot chorioretinopathy
HLA-B	Orphanet:117	Behçet disease
HLA-B	Orphanet:275798	Pulmonary arterial hypertension associated with connective tissue disease
HLA-B	Orphanet:29207	Reactive arthritis
HLA-B	Orphanet:3287	Takayasu arteritis
HLA-B	Orphanet:36426	Stevens-Johnson syndrome
HLA-B	Orphanet:397	Giant cell arteritis
HLA-DPA1	Orphanet:900	Granulomatosis with polyangiitis
HLA-DPB1	Orphanet:133	Chronic beryllium disease
HLA-DPB1	Orphanet:900	Granulomatosis with polyangiitis
HLA-DQA1	Orphanet:391490	Adult-onset myasthenia gravis
HLA-DQA1	Orphanet:930	Idiopathic achalasia
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
HLA-DRB1	Orphanet:2073	Narcolepsy type 1
HLA-DRB1	Orphanet:220393	Diffuse cutaneous systemic sclerosis
HLA-DRB1	Orphanet:220402	Limited cutaneous systemic sclerosis
HLA-DRB1	Orphanet:220407	Limited systemic sclerosis
HLA-DRB1	Orphanet:3437	Vogt-Koyanagi-Harada disease
HLA-DRB1	Orphanet:397	Giant cell arteritis
HLA-DRB1	Orphanet:477738	Pediatric multiple sclerosis
HLA-DRB1	Orphanet:536	Systemic lupus erythematosus
HLA-DRB1	Orphanet:545	Follicular lymphoma
HLA-DRB1	Orphanet:703	Bullous pemphigoid
HLA-DRB1	Orphanet:747	Autoimmune pulmonary alveolar proteinosis
HLA-DRB1	Orphanet:797	Sarcoidosis
HLA-DRB1	Orphanet:83465	Narcolepsy type 2
HLA-DRB1	Orphanet:85414	Systemic-onset juvenile idiopathic arthritis
IRF4	Orphanet:3452	Whipple disease
ITGAM	Orphanet:536	Systemic lupus erythematosus
MPDU1	Orphanet:79323	MPDU1-CDG
PSMB8	Orphanet:324977	Proteasome-associated autoinflammatory syndrome

Cohort genes → proteins

33 cohort genes, 32 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	32
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
ST6GAL1	HGNC:10860	ENSG00000073849	P15907	Beta-galactoside alpha-2,6-sialyltransferase 1	gwas
KLF10	HGNC:11810	ENSG00000155090	Q13118	Krueppel-like factor 10	gwas
TNFSF13	HGNC:11928	ENSG00000161955	O75888	Tumor necrosis factor ligand superfamily member 13	gwas
VAV3	HGNC:12659	ENSG00000134215	Q9UKW4	Guanine nucleotide exchange factor VAV3	gwas
CARD9	HGNC:16391	ENSG00000187796	Q9H257	Caspase recruitment domain-containing protein 9	gwas
CFHR3	HGNC:16980	ENSG00000116785	Q02985	Complement factor H-related protein 3	gwas
PADI3	HGNC:18337	ENSG00000142619	Q9ULW8	Protein-arginine deiminase type-3	gwas
PADI1	HGNC:18367	ENSG00000142623	Q9ULC6	Protein-arginine deiminase type-1	gwas
PADI4	HGNC:18368	ENSG00000159339	Q9UM07	Protein-arginine deiminase type-4	gwas
FCRL3	HGNC:18506	ENSG00000160856	Q96P31	Fc receptor-like protein 3	gwas
ACCS	HGNC:23989	ENSG00000110455	Q96QU6	1-aminocyclopropane-1-carboxylate synthase-like protein 1	gwas
ACOXL	HGNC:25621	ENSG00000153093	Q9NUZ1	Acyl-coenzyme A oxidase-like protein	gwas
HORMAD2	HGNC:28383	ENSG00000176635	Q8N7B1	HORMA domain-containing protein 2	gwas
TAP1	HGNC:43	ENSG00000168394	Q03518	Antigen peptide transporter 1	gwas
TAP2	HGNC:44	ENSG00000204267	Q03519	Antigen peptide transporter 2	gwas
CFHR1	HGNC:4888	ENSG00000244414	Q03591	Complement factor H-related protein 1	gwas
HLA-A	HGNC:4931	ENSG00000206503	P04439	HLA class I histocompatibility antigen, A alpha chain	gwas
HLA-B	HGNC:4932	ENSG00000234745	P01889	HLA class I histocompatibility antigen, B alpha chain	gwas
HLA-DPA1	HGNC:4938	ENSG00000231389	P20036	HLA class II histocompatibility antigen, DP alpha 1 chain	gwas
HLA-DPB1	HGNC:4940	ENSG00000223865	P04440	HLA class II histocompatibility antigen, DP beta 1 chain	gwas
HLA-DPB2	HGNC:4941	ENSG00000224557		major histocompatibility complex, class II, DP beta 2 (pseudogene)	gwas
HLA-DQA1	HGNC:4942	ENSG00000196735	P01909	HLA class II histocompatibility antigen, DQ alpha 1 chain	gwas
HLA-DQB1	HGNC:4944	ENSG00000179344	P01920	HLA class II histocompatibility antigen, DQ beta 1 chain	gwas
HLA-DRB1	HGNC:4948	ENSG00000196126	P01911	HLA class II histocompatibility antigen, DRB1 beta chain	gwas
IRF4	HGNC:6119	ENSG00000137265	Q15306	Interferon regulatory factor 4	gwas
ITGAM	HGNC:6149	ENSG00000169896	P11215	Integrin alpha-M	gwas
ITGAX	HGNC:6152	ENSG00000140678	P20702	Integrin alpha-X	gwas
MPDU1	HGNC:7207	ENSG00000129255	O75352	Mannose-P-dolichol utilization defect 1 protein	gwas
MTMR3	HGNC:7451	ENSG00000100330	Q13615	Phosphatidylinositol-3,5-bisphosphate 3-phosphatase MTMR3	gwas
ODF1	HGNC:8113	ENSG00000155087	Q14990	Outer dense fiber protein 1	gwas
PIGR	HGNC:8968	ENSG00000162896	P01833	Polymeric immunoglobulin receptor	clinvar
PSMB8	HGNC:9545	ENSG00000204264	P28062	Proteasome subunit beta type-8	gwas
PSMB9	HGNC:9546	ENSG00000240065	P28065	Proteasome subunit beta type-9	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ST6GAL1	Beta-galactoside alpha-2,6-sialyltransferase 1	Transfers sialic acid from CMP-sialic acid to galactose-containing acceptor substrates.
KLF10	Krueppel-like factor 10	Transcriptional repressor which binds to the consensus sequence 5’-GGTGTG-3'.
TNFSF13	Tumor necrosis factor ligand superfamily member 13	Cytokine that binds to TNFRSF13B/TACI and to TNFRSF17/BCMA.
VAV3	Guanine nucleotide exchange factor VAV3	Exchange factor for GTP-binding proteins RhoA, RhoG and, to a lesser extent, Rac1.
CARD9	Caspase recruitment domain-containing protein 9	Adapter protein that plays a key role in innate immune response against fungi by forming signaling complexes downstream of C-type lectin receptors.
CFHR3	Complement factor H-related protein 3	Might be involved in complement regulation.
PADI3	Protein-arginine deiminase type-3	Catalyzes the deimination of arginine residues of proteins.
PADI1	Protein-arginine deiminase type-1	Catalyzes the deimination of arginine residues of proteins.
PADI4	Protein-arginine deiminase type-4	Catalyzes the citrullination/deimination of arginine residues of proteins such as histones, thereby playing a key role in histone code and regulation of stem cell maintenance.
FCRL3	Fc receptor-like protein 3	Promotes TLR9-induced B-cell proliferation, activation and survival but inhibits antibody production and suppresses plasma cell differentiation.
ACCS	1-aminocyclopropane-1-carboxylate synthase-like protein 1	Does not catalyze the synthesis of 1-aminocyclopropane-1-carboxylate but is capable of catalyzing the deamination of L-vinylglycine.
HORMAD2	HORMA domain-containing protein 2	Essential for synapsis surveillance during meiotic prophase via the recruitment of ATR activity.
TAP1	Antigen peptide transporter 1	ABC transporter associated with antigen processing.
TAP2	Antigen peptide transporter 2	ABC transporter associated with antigen processing.
CFHR1	Complement factor H-related protein 1	Involved in complement regulation.
HLA-A	HLA class I histocompatibility antigen, A alpha chain	Antigen-presenting major histocompatibility complex class I (MHCI) molecule.
HLA-B	HLA class I histocompatibility antigen, B alpha chain	Antigen-presenting major histocompatibility complex class I (MHCI) molecule.
HLA-DPA1	HLA class II histocompatibility antigen, DP alpha 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-DPB1	HLA class II histocompatibility antigen, DP 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-DQA1	HLA class II histocompatibility antigen, DQ alpha 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-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-DRB1	HLA class II histocompatibility antigen, DRB1 beta chain	A beta chain of antigen-presenting major histocompatibility complex class II (MHCII) molecule.
IRF4	Interferon regulatory factor 4	Transcriptional activator.
ITGAM	Integrin alpha-M	Integrin ITGAM/ITGB2 is implicated in various adhesive interactions of monocytes, macrophages and granulocytes as well as in mediating the uptake of complement-coated particles and pathogens.
ITGAX	Integrin alpha-X	Integrin alpha-X/beta-2 is a receptor for fibrinogen.
MPDU1	Mannose-P-dolichol utilization defect 1 protein	Required for normal utilization of mannose-dolichol phosphate (Dol-P-Man) in the synthesis of N-linked and O-linked oligosaccharides and GPI anchors.
MTMR3	Phosphatidylinositol-3,5-bisphosphate 3-phosphatase MTMR3	Lipid phosphatase that specifically dephosphorylates the D-3 position of phosphatidylinositol 3-phosphate and phosphatidylinositol 3,5-bisphosphate, generating phosphatidylinositol and phosphatidylinositol 5-phosphate.
ODF1	Outer dense fiber protein 1	Component of the outer dense fibers (ODF) of spermatozoa.
PIGR	Polymeric immunoglobulin receptor	Mediates selective transcytosis of polymeric IgA and IgM across mucosal epithelial cells.
PSMB8	Proteasome subunit beta type-8	The proteasome is a multicatalytic proteinase complex which is characterized by its ability to cleave peptides with Arg, Phe, Tyr, Leu, and Glu adjacent to the leaving group at neutral or slightly basic pH.
PSMB9	Proteasome subunit beta type-9	The proteasome is a multicatalytic proteinase complex which is characterized by its ability to cleave peptides with Arg, Phe, Tyr, Leu, and Glu adjacent to the leaving group at neutral or slightly basic pH.

Protein-family classification

Druggable: 20 · Difficult: 2 · Unknown: 11 · Druggable fraction: 0.61

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	11	9.7×	5e-08
Complement	2	16.2×	0.027
Transporter	2	4.7×	0.179
Phosphatase	1	2.5×	0.523
Enzyme (other)	4	1.4×	0.523
Other/Unknown	11	0.6×	0.997
Scaffold/PPI	1	0.5×	0.997
Transcription factor	1	0.2×	0.997

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ST6GAL1	Enzyme (other)	yes	2.4.99.1	Glyco_trans_29, Sialyl_trans, GT29-like_sf
KLF10	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf
TNFSF13	Other/Unknown	no		TNF_dom, Tumour_necrosis_fac-like_dom, TNF_CS
VAV3	Scaffold/PPI	no		DH_dom, SH2, GDS_CDC24_CS
CARD9	Other/Unknown	no		CARD, DEATH-like_dom_sf, CARD_CARD9
CFHR3	Complement	yes		Sushi_SCR_CCP_dom, Sushi/SCR/CCP_sf, ComplSys_Reg/VirEntry_Med
PADI3	Enzyme (other)	yes	3.5.3.15	PAD, Cupredoxin, PAD_C
PADI1	Enzyme (other)	yes	3.5.3.15	PAD, Cupredoxin, PAD_C
PADI4	Enzyme (other)	yes	3.5.3.15	PAD, Cupredoxin, PAD_C
FCRL3	Antibody/Immunoglobulin	yes		Ig_sub2, Ig_sub, Ig-like_dom
ACCS	Other/Unknown	no		Aminotransferase_I/II_large, PyrdxlP-dep_Trfase_major, PyrdxlP-dep_Trfase_small
ACOXL	Other/Unknown	no		Acyl-CoA_oxidase_C, AcylCoA_DH/ox_M, AcylCoA_DH/oxidase_NM_dom_sf
HORMAD2	Other/Unknown	no		HORMA_dom, HORMA_dom_sf, HORMA_MeioticProgression
TAP1	Transporter	yes	7.4.2.14	ABC_transporter-like_ATP-bd, AAA+_ATPase, ABC1_TM_dom
TAP2	Transporter	yes	7.4.2.14	ABC_transporter-like_ATP-bd, AAA+_ATPase, Tap2/ABCB3
CFHR1	Complement	yes		Sushi_SCR_CCP_dom, Sushi/SCR/CCP_sf, ComplSys_Reg/VirEntry_Med
HLA-A	Antibody/Immunoglobulin	yes		MHC_I_a_a1/a2, Ig/MHC_CS, Ig_C1-set
HLA-B	Antibody/Immunoglobulin	yes		MHC_I_a_a1/a2, Ig/MHC_CS, Ig_C1-set
HLA-DPA1	Antibody/Immunoglobulin	yes		MHC_II_a_N, Ig/MHC_CS, Ig_C1-set
HLA-DPB1	Antibody/Immunoglobulin	yes		MHC_II_b_N, Ig/MHC_CS, Ig_C1-set
HLA-DPB2	Other/Unknown	no
HLA-DQA1	Antibody/Immunoglobulin	yes		MHC_II_a_N, Ig/MHC_CS, Ig_C1-set
HLA-DQB1	Antibody/Immunoglobulin	yes		MHC_II_b_N, Ig/MHC_CS, Ig_C1-set
HLA-DRB1	Antibody/Immunoglobulin	yes		MHC_II_b_N, Ig/MHC_CS, Ig_C1-set
IRF4	Other/Unknown	no		Interferon_reg_fact_DNA-bd_dom, SMAD_FHA_dom_sf, SMAD-like_dom_sf
ITGAM	Antibody/Immunoglobulin	yes		Integrin_alpha, VWF_A, FG-GAP
ITGAX	Antibody/Immunoglobulin	yes		Integrin_alpha, VWF_A, FG-GAP
MPDU1	Other/Unknown	no		PQ-loop_rpt, MannP-dilichol_defect-1
MTMR3	Phosphatase	yes	3.1.3.95	Znf_FYVE, Tyr_Pase_cat, Myotubularin-like_Pase_dom
ODF1	Other/Unknown	no		A-crystallin/Hsp20_dom, HSP20-like_chaperone, ODFP
PIGR	Antibody/Immunoglobulin	yes		Ig_sub, Ig-like_dom, Ig_V-set
PSMB8	Other/Unknown	no		Pept_T1A_subB, Proteasome_sua/b, Proteasome_bsu_CS
PSMB9	Other/Unknown	no		Pept_T1A_subB, Proteasome_sua/b, Proteasome_bsu_CS

Expression context

Cohort genes with no expression data: 0.

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

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	33
unknown	0

Top tissues across cohort

Tissue	Cohort genes
granulocyte	13
monocyte	8
leukocyte	6
lymph node	6
vermiform appendix	5
male germ line stem cell (sensu Vertebrata) in testis	4
blood	4
liver	3
right lobe of liver	3
mononuclear cell	3
spleen	3
renal medulla	2
esophagus mucosa	2
lower esophagus mucosa	2
right testis	2
rectum	2
right lung	2
mucosa of transverse colon	2
mucosa of paranasal sinus	1
skin of hip	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ST6GAL1	294	ubiquitous	marker	liver, right lobe of liver, renal medulla
KLF10	288	ubiquitous	marker	mucosa of paranasal sinus, skin of hip, upper leg skin
TNFSF13	134	ubiquitous	marker	monocyte, leukocyte, granulocyte
VAV3	258	ubiquitous	marker	tongue squamous epithelium, renal medulla, esophagus squamous epithelium
CARD9	172	broad	marker	monocyte, mononuclear cell, leukocyte
CFHR3	127	tissue_specific	marker	right lobe of liver, liver, male germ line stem cell (sensu Vertebrata) in testis
PADI3	43	tissue_specific	marker	lower esophagus mucosa, esophagus mucosa, urinary bladder
PADI1	97	tissue_specific	yes	lower esophagus mucosa, esophagus mucosa, vagina
PADI4	123	tissue_specific	marker	blood, bone marrow, bone marrow cell
FCRL3	167	tissue_specific	marker	ileal mucosa, granulocyte, lymph node
ACCS	188	ubiquitous	marker	right uterine tube, right adrenal gland cortex, granulocyte
ACOXL	168	broad	marker	primordial germ cell in gonad, male germ line stem cell (sensu Vertebrata) in testis, buccal mucosa cell
HORMAD2	66	tissue_specific	marker	right testis, left testis, testis
TAP1	134	ubiquitous	marker	granulocyte, vermiform appendix, lymph node
TAP2	134	ubiquitous	yes	vermiform appendix, lymph node, monocyte
CFHR1	125		marker	right lobe of liver, liver, male germ line stem cell (sensu Vertebrata) in testis
HLA-A	134	ubiquitous	marker	blood, granulocyte, stromal cell of endometrium
HLA-B	134	ubiquitous	marker	blood, spleen, granulocyte
HLA-DPA1	133	ubiquitous	marker	monocyte, leukocyte, granulocyte
HLA-DPB1	135	ubiquitous	marker	granulocyte, lymph node, vermiform appendix
HLA-DPB2	121	tissue_specific	marker	male germ line stem cell (sensu Vertebrata) in testis, lymph node, granulocyte
HLA-DQA1	244	broad	marker	gall bladder, rectum, monocyte
HLA-DQB1	268	broad	marker	right lung, spleen, upper lobe of left lung
HLA-DRB1	131	tissue_specific	marker	vermiform appendix, granulocyte, right lung
IRF4	180	broad	marker	lymph node, endocervix, vermiform appendix
ITGAM	236	broad	marker	monocyte, mononuclear cell, leukocyte
ITGAX	174	broad	marker	granulocyte, monocyte, mononuclear cell
MPDU1	234	ubiquitous	marker	rectum, mucosa of transverse colon, islet of Langerhans
MTMR3	282	ubiquitous	marker	oocyte, secondary oocyte, blood
ODF1	130	tissue_specific	yes	sperm, male germ cell, right testis

Protein interactions among cohort

Intra-cohort edges: 22.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ITGAM	4,816
CARD9	3,636
IRF4	3,450
HLA-DRB1	3,448
ITGAX	3,332
HLA-B	3,209
PSMB8	3,188
PSMB9	2,896
TAP1	2,139
PIGR	2,121

Intra-cohort edges

A	B	Sources
FCRL3	HLA-DRB1	string_interaction
FCRL3	PADI4	string_interaction
FCRL3	PIGR	string_interaction
HLA-A	HLA-B	biogrid_interaction, intact
HLA-A	HLA-DPA1	biogrid_interaction
HLA-A	HLA-DQA1	biogrid_interaction
HLA-A	HLA-DQB1	biogrid_interaction
HLA-B	ST6GAL1	biogrid_interaction, intact, string_interaction
HLA-B	TAP1	biogrid_interaction, string_interaction
HLA-B	TAP2	string_interaction
HLA-DPA1	HLA-DPB1	intact
HLA-DPA1	HLA-DQB1	intact
HLA-DQA1	HLA-DQB1	biogrid_interaction, intact
HORMAD2	MTMR3	string_interaction
PADI1	PADI3	biogrid_interaction, intact
PADI3	PADI4	biogrid_interaction, intact
PSMB8	PSMB9	intact, string_interaction
PSMB8	TAP1	intact, string_interaction
PSMB8	TAP2	intact, string_interaction
PSMB9	TAP1	string_interaction
PSMB9	TAP2	string_interaction
TAP1	TAP2	biogrid_interaction, intact, string_interaction

Structural data

PDB: 24 · AlphaFold-only: 8 · No structure: 1

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
HLA-A	P04439	403
HLA-B	P01889	237
HLA-DRB1	P01911	108
ITGAM	P11215	31
PADI4	Q9UM07	28
HLA-DQA1	P01909	28
TAP1	Q03518	22
PSMB8	P28062	22
TAP2	Q03519	21
IRF4	Q15306	19
PIGR	P01833	16
HLA-DPA1	P20036	10
HLA-DPB1	P04440	10
HLA-DQB1	P01920	10
ITGAX	P20702	9
CARD9	Q9H257	8
PADI3	Q9ULW8	7
PSMB9	P28065	7
ST6GAL1	P15907	4
CFHR1	Q03591	2
KLF10	Q13118	1
TNFSF13	O75888	1
VAV3	Q9UKW4	1
PADI1	Q9ULC6	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ACOXL	Q9NUZ1	92.00
CFHR3	Q02985	91.93
MPDU1	O75352	88.57
ACCS	Q96QU6	86.63
FCRL3	Q96P31	77.46
HORMAD2	Q8N7B1	72.61
MTMR3	Q13615	66.94
ODF1	Q14990	62.45

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 108. Enrichment computed across 33 evidence-associated genes (27 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 27 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Interferon gamma signaling	8	37.2×	3e-09	HLA-A, HLA-B, HLA-DPA1, HLA-DPB1, HLA-DQA1, HLA-DQB1, HLA-DRB1, IRF4
ER-Phagosome pathway	6	28.8×	2e-06	TAP1, TAP2, HLA-A, HLA-B, PSMB8, PSMB9
Translocation of ZAP-70 to Immunological synapse	4	94.0×	3e-06	HLA-DPA1, HLA-DPB1, HLA-DQA1, HLA-DRB1
Phosphorylation of CD3 and TCR zeta chains	4	80.6×	4e-06	HLA-DPA1, HLA-DPB1, HLA-DQA1, HLA-DRB1
Co-inhibition by PD-1	4	76.9×	4e-06	HLA-DPA1, HLA-DPB1, HLA-DQA1, HLA-DRB1
Antigen Presentation: Folding, assembly and peptide loading of class I MHC	4	58.3×	1e-05	TAP1, TAP2, HLA-A, HLA-B
Generation of second messenger molecules	4	51.3×	1e-05	HLA-DPA1, HLA-DPB1, HLA-DQA1, HLA-DRB1
Interferon alpha/beta signaling	4	22.6×	4e-04	HLA-A, HLA-B, IRF4, PSMB8
Downstream TCR signaling	4	19.0×	6e-04	HLA-DPA1, HLA-DPB1, HLA-DQA1, HLA-DRB1
MHC class II antigen presentation	4	13.2×	0.002	HLA-DPA1, HLA-DPB1, HLA-DQA1, HLA-DRB1
Endosomal/Vacuolar pathway	2	76.9×	0.003	HLA-A, HLA-B
Antigen processing: Ub, ATP-independent proteasomal degradation	2	42.3×	0.009	PSMB8, PSMB9
Defective MPDU1 causes CDG-1f	1	423.0×	0.018	MPDU1
Interleukin-4 and Interleukin-13 signaling	3	11.4×	0.018	IRF4, ITGAM, ITGAX
Antigen processing-Cross presentation	2	23.5×	0.023	TAP1, TAP2
Cross-presentation of soluble exogenous antigens (endosomes)	2	18.8×	0.034	PSMB8, PSMB9
Regulation of Complement cascade	2	17.3×	0.036	CFHR3, CFHR1
Chromatin modifying enzymes	3	8.0×	0.036	PADI3, PADI1, PADI4
Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein	2	15.4×	0.041	ST6GAL1, MPDU1
Proteasome assembly	2	15.1×	0.041	PSMB8, PSMB9
Signaling by Interleukins	3	7.1×	0.043	IRF4, ITGAM, ITGAX
Immune System	6	2.9×	0.074	CARD9, TAP1, TAP2, IRF4, ITGAM, ITGAX
Integrin cell surface interactions	2	9.9×	0.080	ITGAM, ITGAX
HuR (ELAVL1) binds and stabilizes mRNA	1	47.0×	0.088	TNFSF13
Maturation of protein 3a	1	47.0×	0.088	ST6GAL1
Nef mediated downregulation of MHC class I complex cell surface expression	1	42.3×	0.090	HLA-A
Beta-oxidation of pristanoyl-CoA	1	42.3×	0.090	ACOXL
Cytokine Signaling in Immune system	3	4.5×	0.100	IRF4, ITGAM, ITGAX
Neutrophil degranulation	4	3.4×	0.100	HLA-B, ITGAM, ITGAX, PIGR

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 30 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	5	175.5×	1e-08	HLA-DPA1, HLA-DPB1, HLA-DQA1, HLA-DQB1, HLA-DRB1
antigen processing and presentation of exogenous peptide antigen via MHC class II	5	90.6×	2e-07	HLA-DPA1, HLA-DPB1, HLA-DQA1, HLA-DQB1, HLA-DRB1
positive regulation of immune response	5	80.2×	3e-07	HLA-DPA1, HLA-DPB1, HLA-DQA1, HLA-DQB1, HLA-DRB1
positive regulation of T cell activation	5	73.9×	3e-07	HLA-DPA1, HLA-DPB1, HLA-DQA1, HLA-DQB1, HLA-DRB1
immune response	8	12.6×	7e-06	TNFSF13, FCRL3, HLA-A, HLA-B, HLA-DPA1, HLA-DQA1, HLA-DQB1, HLA-DRB1
antigen processing and presentation of endogenous peptide antigen via MHC class I	3	210.7×	1e-05	TAP1, TAP2, HLA-A
positive regulation of T cell mediated cytotoxicity	4	68.1×	1e-05	TAP2, HLA-A, HLA-B, HLA-DRB1
detection of bacterium	3	140.4×	3e-05	HLA-A, HLA-B, HLA-DRB1
adaptive immune response	6	16.9×	3e-05	TAP1, HLA-B, HLA-DPA1, HLA-DPB1, HLA-DQA1, HLA-DQB1
antigen processing and presentation of endogenous peptide antigen via MHC class I via ER pathway, TAP-dependent	2	561.7×	6e-05	TAP2, HLA-A
cytosol to endoplasmic reticulum transport	2	561.7×	6e-05	TAP1, TAP2
regulation of T-helper cell differentiation	2	280.9×	3e-04	HLA-DRB1, IRF4
protection from natural killer cell mediated cytotoxicity	2	187.2×	7e-04	HLA-A, HLA-B
T cell receptor signaling pathway	4	20.2×	7e-04	HLA-A, HLA-DPB1, HLA-DQB1, HLA-DRB1
positive regulation of B cell proliferation	3	34.4×	0.001	TNFSF13, VAV3, FCRL3
antigen processing and presentation of endogenous peptide antigen via MHC class Ib	2	86.4×	0.003	HLA-A, HLA-B
antigen processing and presentation of endogenous peptide antigen via MHC class I via ER pathway, TAP-independent	2	86.4×	0.003	HLA-A, HLA-B
T cell mediated cytotoxicity	2	74.9×	0.004	TAP2, HLA-A
positive regulation of type II interferon production	3	22.5×	0.004	HLA-A, HLA-DPA1, HLA-DPB1
integrin-mediated signaling pathway	3	16.1×	0.009	VAV3, ITGAM, ITGAX
complement activation	2	41.6×	0.011	CFHR3, CFHR1
heterotypic cell-cell adhesion	2	38.7×	0.012	ITGAM, ITGAX
antigen processing and presentation of endogenous peptide antigen via MHC class Ib via ER pathway, TAP-dependent	1	561.7×	0.016	TAP2
regulation of interleukin-4 production	1	561.7×	0.016	HLA-DRB1
regulation of toll-like receptor 9 signaling pathway	1	561.7×	0.016	FCRL3
immunoglobulin transcytosis in epithelial cells mediated by polymeric immunoglobulin receptor	1	280.9×	0.022	PIGR
antigen processing and presentation of exogenous protein antigen via MHC class Ib, TAP-dependent	1	280.9×	0.022	TAP2
antigen processing and presentation of endogenous peptide antigen via MHC class II	1	280.9×	0.022	HLA-DRB1
regulation of interleukin-10 production	1	280.9×	0.022	HLA-DRB1
regulation of interleukin-2 production	1	280.9×	0.022	CARD9

Therapeutics

Drugs indicated for this disease

2 approved, 19 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Budesonide	Approved (phase 4)
Sparsentan	Approved (phase 4)
Aliskiren	Phase 3 (in late-stage trials)
Atacicept	Phase 3 (in late-stage trials)
Atrasentan	Phase 3 (in late-stage trials)
Azathioprine	Phase 3 (in late-stage trials)
Blisibimod	Phase 3 (in late-stage trials)
Dapagliflozin	Phase 3 (in late-stage trials)
Icosapent	Phase 3 (in late-stage trials)
Iptacopan	Phase 3 (in late-stage trials)
Irbesartan	Phase 3 (in late-stage trials)
Losartan	Phase 3 (in late-stage trials)
Methylprednisolone	Phase 3 (in late-stage trials)
Mycophenolate Mofetil	Phase 3 (in late-stage trials)
Narsoplimab	Phase 3 (in late-stage trials)
Paricalcitol	Phase 3 (in late-stage trials)
Prednisolone	Phase 3 (in late-stage trials)
Prednisone	Phase 3 (in late-stage trials)
Ravulizumab	Phase 3 (in late-stage trials)
Telitacicept	Phase 3 (in late-stage trials)
Zigakibart	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Avacopan, Batiraxcept, Cemdisiran, Enalapril, Felzartamab, Fostamatinib, Hydroxychloroquine, OMEGA-3-ACID ETHYL ESTERS, Sirolimus, Tacrolimus Anhydrous.

Drug target analysis

Approved (phase 4): 5 · Phase ≥3: 5 · Phased (≥1): 7 · Undrugged: 26

Druggability breadth: 18 of 33 evidence-associated genes (55%) 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
KLF10	TOLCAPONE
PADI4	CHLORTETRACYCLINE
HLA-A	RALOXIFENE HYDROCHLORIDE
PSMB8	BORTEZOMIB
PSMB9	BORTEZOMIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
HLA-A	8	4
PSMB8	7	4
PSMB9	7	4
PADI4	3	4
KLF10	2	4
PADI3	1	2
PADI1	1	2
ST6GAL1	0	0
TNFSF13	0	0
VAV3	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
TOLCAPONE	4	KLF10
ATOMOXETINE	4	KLF10
CHLORTETRACYCLINE	4	PADI4
RALOXIFENE HYDROCHLORIDE	4	HLA-A
DOXAZOSIN MESYLATE	4	HLA-A
TRAZODONE HYDROCHLORIDE	4	HLA-A
ASTEMIZOLE	4	HLA-A
BORTEZOMIB	4	PSMB8, PSMB9
CARFILZOMIB	4	PSMB8, PSMB9
VATALANIB	3	HLA-A
IXAZOMIB	3	PSMB8, PSMB9
MARIZOMIB	3	PSMB8, PSMB9
STREPTONIGRIN	2	PADI1, PADI3, PADI4
PAPAVERINE HYDROCHLORIDE	2	PADI4
DISOMOTIDE	2	HLA-A
OVEMOTIDE	2	HLA-A
SPIPERONE	2	HLA-A
OPROZOMIB	2	PSMB8, PSMB9
DELANZOMIB	2	PSMB8, PSMB9
ZETOMIPZOMIB	2	PSMB8, PSMB9

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 7.

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

Symbol	Assays	Type breakdown
PSMB8	262	Binding:250, ADMET:9, Functional:3
PSMB9	220	Binding:210, ADMET:7, Functional:3
PADI4	86	Binding:84, Functional:2
PADI1	29	Binding:28, Functional:1
ST6GAL1	27	Binding:27
PADI3	27	Binding:27
HLA-DRB1	17	Binding:17
ITGAM	14	Binding:12, Functional:2
KLF10	10	Binding:10
TAP1	4	Binding:4
HLA-A	4	Binding:4
TAP2	3	Binding:3
IRF4	3	Binding:3
HLA-DQA1	2	Binding:2
HLA-B	1	Binding:1
MPDU1	1	Binding:1
PIGR	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ST6GAL1	2.4.99.1	beta-galactoside alpha-(2,6)-sialyltransferase
PADI3	3.5.3.15	protein-arginine deiminase
PADI1	3.5.3.15	protein-arginine deiminase
PADI4	3.5.3.15	protein-arginine deiminase
TAP1	7.4.2.14, 7.4.2.5	ABC-type antigen peptide transporter, bacterial ABC-type protein transporter
TAP2	7.4.2.14, 7.4.2.5	ABC-type antigen peptide transporter, bacterial ABC-type protein transporter
MTMR3	3.1.3.95	phosphatidylinositol-3,5-bisphosphate 3-phosphatase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
PSMB8	262
PSMB9	220

Pharmacogenomics

Cohort genes with a PharmGKB record: 33; with CPIC/DPWG dosing guidelines: 2.

Cohort genes with a CPIC/DPWG dosing guideline

Symbol	CPIC guidelines
HLA-A	1
HLA-B	1

Chemical tractability of cohort targets

19 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)
TOLCAPONE	4	KLF10
ATOMOXETINE	4	KLF10
CHLORTETRACYCLINE	4	PADI4
RALOXIFENE HYDROCHLORIDE	4	HLA-A
DOXAZOSIN MESYLATE	4	HLA-A
TRAZODONE HYDROCHLORIDE	4	HLA-A
ASTEMIZOLE	4	HLA-A
CARFILZOMIB	4	PSMB8, PSMB9
VATALANIB	3	HLA-A
IXAZOMIB	3	PSMB8, PSMB9
MARIZOMIB	3	PSMB8, PSMB9
STREPTONIGRIN	2	PADI1, PADI3, PADI4
PAPAVERINE HYDROCHLORIDE	2	PADI4
DISOMOTIDE	2	HLA-A
OVEMOTIDE	2	HLA-A
SPIPERONE	2	HLA-A
OPROZOMIB	2	PSMB8, PSMB9
DELANZOMIB	2	PSMB8, PSMB9
ZETOMIPZOMIB	2	PSMB8, PSMB9

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	5	KLF10, PADI4, HLA-A, PSMB8, PSMB9
B	Phased (≥1) drug, not yet approved	2	PADI3, PADI1
C	Druggable family + PDB, no drug	13	ST6GAL1, TAP1, TAP2, CFHR1, HLA-B, HLA-DPA1, HLA-DPB1, HLA-DQA1, HLA-DQB1, HLA-DRB1 (+3 more)
D	Druggable family + AlphaFold only, no drug	3	CFHR3, FCRL3, MTMR3
E	Difficult family or no structure, no drug	10	TNFSF13, VAV3, CARD9, ACCS, ACOXL, HORMAD2, HLA-DPB2, IRF4, MPDU1, ODF1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
TAP1	4	PSMB9, PSMB8
TAP2	3	PSMB9, PSMB8
ST6GAL1	27	—
TNFSF13	0	—
VAV3	0	—
CARD9	0	—
CFHR3	0	—
FCRL3	0	—
ACCS	0	—
ACOXL	0	—
HORMAD2	0	—
CFHR1	0	—
HLA-B	1	—
HLA-DPA1	0	—
HLA-DPB1	0	—
HLA-DPB2	0	—
HLA-DQA1	2	—
HLA-DQB1	0	—
HLA-DRB1	17	—
IRF4	3	—
ITGAM	14	—
ITGAX	0	—
MPDU1	1	—
MTMR3	0	—
ODF1	0	—
PIGR	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 173.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	53
PHASE2	44
PHASE3	29
PHASE4	24
PHASE1	10
EARLY_PHASE1	7
PHASE2/PHASE3	3
PHASE1/PHASE2	3

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06676384	PHASE4	RECRUITING	Which of the Commonly Available and Approved Drugs in Addition to Standard of Care Can Significantly Improve the Slope of Estimated Glomerular Filtration Rate at Two Years When Compared to Standard of Care Alone in South-Asian Kidney Biopsy-proven Adult (≥18 Years) Primary IgA Nephropathy?
NCT06712407	PHASE4	RECRUITING	Efficacy and Safety of Extended TARPEYO® Treatment Beyond 9 Months in Adult Patients With Primary IgA Nephropathy
NCT07030894	PHASE4	RECRUITING	Nefecon and Ambrisentan in IgA Nephropathy
NCT07604311	PHASE4	NOT_YET_RECRUITING	Efficacy and Safety of Nefecon on Prevention of Relapse of IgA Nephropathy: a Randomized, Double-blinded, Placebo-Controlled Trial
NCT00319761	PHASE4	COMPLETED	Calcitriol in the Treatment of Immunoglobulin A (IgA) Nephropathy
NCT00367562	PHASE4	COMPLETED	Inhibition of the Renin Angiotensin System Plus Corticosteroids for the Treatment of Proteinuria in IGA Nephropathy
NCT00426348	PHASE4	COMPLETED	A Study of the Antioxidant Probucol Combined With Valsartan in Patients With IgA Nephropathy
NCT00498368	PHASE4	COMPLETED	Rituximab in Progressive Immunoglobulin A (IgA) Nephropathy
NCT00755859	PHASE4	COMPLETED	Steroids and Azathioprine Versus Steroids Alone in IgAN
NCT00863252	PHASE4	COMPLETED	Mycophenolate Mofetil for IgA Nephropathy
NCT00922311	PHASE4	COMPLETED	Aliskiren for Proteinuric IgAN Despite Angiotensin Blockade
NCT01103778	PHASE4	COMPLETED	Pilot Study of Velcade® in IgA Nephropathy
NCT01115426	PHASE4	COMPLETED	Inhibitors of Angiotensin II in Proteinuric Mesangioproliferative Glomerulonephritis
NCT01129557	PHASE4	TERMINATED	Aldosterone Breakthrough During Diovan, Tekturna, and Combination Therapy in Patients With Proteinuric Kidney Disease
NCT01758120	PHASE4	UNKNOWN	Treatment of Prednisone Plus Cyclophosphamide in Patients With Advanced-stage IgA Nephropathy
NCT02231125	PHASE4	UNKNOWN	Efficacy and Safety of Abelmoschus Manihot for IgA Nephropathy
NCT02351752	PHASE4	COMPLETED	Hydroxychloroquine Sulfate for Reduction of Proteinuria in Patients With IgA Nephropathy: a Self- Controlled Study
NCT02382523	PHASE4	WITHDRAWN	Acthar on Proteinuria in IgA Nephropathy Patients
NCT02571842	PHASE4	UNKNOWN	Rituximab in Recurrent IgA Nephropathy
NCT02765594	PHASE4	UNKNOWN	Hydroxychloroquine Sulfate Alleviates Persistent Proteinuria in IgA Nephropathy
NCT02981212	PHASE4	UNKNOWN	Efficacy and Safety of a Combination of Mycophenolate Mofetil and Corticosteroid in Advanced IgA Nephropathy
NCT03218852	PHASE4	UNKNOWN	Extended Follow-up of Treatment of Prednisone Plus Cyclophosphamide in Patients With Advanced-stage IgA Nephropathy
NCT04525729	PHASE4	COMPLETED	Rituximab and RASi in Patients with IgAN
NCT05824390	PHASE4	UNKNOWN	A Randomized, Controlled Clinical Study of Rituximab in Treatment of Primary IgA Nephropathy
NCT04557462	PHASE3	RECRUITING	A Rollover Extension Program (REP) to Evaluate the Long-term Safety and Tolerability of Open Label Iptacopan/LNP023 in Participants With Primary IgA Nephropathy
NCT04573478	PHASE3	ACTIVE_NOT_RECRUITING	Atrasentan in Patients With IgA Nephropathy
NCT04716231	PHASE3	ACTIVE_NOT_RECRUITING	Atacicept in Subjects With IgA Nephropathy
NCT05596708	PHASE2/PHASE3	NOT_YET_RECRUITING	Study of Telitacicept in Patients With Refractory IgA Nephropathy
NCT05797610	PHASE3	RECRUITING	A Study to Evaluate the Efficacy and Safety of Sefaxersen (RO7434656) in Participants With Primary Immunoglobulin A (IgA) Nephropathy at High Risk of Progression
NCT05799287	PHASE3	ACTIVE_NOT_RECRUITING	A Study of Telitacicept for IgA Nephropathy (TELIGAN)
NCT05852938	PHASE3	ACTIVE_NOT_RECRUITING	A Study of Zigakibart in Adults With IgA Nephropathy
NCT06580288	PHASE3	NOT_YET_RECRUITING	Effect of Finerenone in IgA Nephropathy
NCT06819826	PHASE3	RECRUITING	A Study of SC0062 Capsule for the Treatment of IgA Nephropathy with Proteinuria
NCT07014826	PHASE3	RECRUITING	A Trial of HRS-5965 Capsule in Primary IgA Nephropathy
NCT07052981	PHASE3	NOT_YET_RECRUITING	Clinical Study on the Efficacy and Safety of Telitacicept in the Treatment of Pediatric IgA Nephropathy or IgA Vasculitis Nephritis
NCT07098897	PHASE3	ACTIVE_NOT_RECRUITING	To Evaluate the Effect and Safety of Telitacicept and Standard Treatment for 6months in IgA Nephropathy
NCT07390123	PHASE3	RECRUITING	Phase Ⅲ Study of Efficacy and Safety of HSK39297 Tablet in Treatment of Patients With Primary IgAN
NCT07498335	PHASE3	NOT_YET_RECRUITING	Study to Assess the Efficacy, Pharmacokinetics, Safety and Tolerability of Atrasentan in Pediatric Patients With Primary IgAN
NCT00318474	PHASE3	TERMINATED	Mycophenolate Mofetil (MMF) in Patients With IgA Nephropathy
NCT00549692	PHASE3	COMPLETED	Efficacy and Safety of Omega-3 Fatty Acids(Omacor®) for the Treatment of Immunoglobulin A Nephropathy

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
HYDROXYCHLOROQUINE	4	5
RITUXIMAB	4	4
ALISKIREN	4	3
CYCLOPHOSPHAMIDE ANHYDROUS	4	3
ENALAPRIL	4	3
FINERENONE	4	3
IPTACOPAN	4	3
VALSARTAN	4	3
CALCITRIOL	4	2
FOSTAMATINIB	4	2
LOSARTAN	4	2
MYCOPHENOLATE MOFETIL	4	2
PREDNISONE	4	2
ALLOPURINOL	4	1
AMBRISENTAN	4	1
AVACOPAN	4	1
AZATHIOPRINE	4	1
BORTEZOMIB	4	1
CORTICOTROPIN	4	1
DIPYRIDAMOLE	4	1
IRBESARTAN	4	1
PARICALCITOL	4	1
PEGCETACOPLAN	4	1
PROBUCOL	4	1
RASAGILINE	4	1
SPARSENTAN	4	1
TELITACICEPT	3	6
ATRASENTAN	3	5
ATACICEPT	3	4
BLISIBIMOD	3	2