Common variable immunodeficiency

Summary

Common variable immunodeficiency (MONDO:0015517) is a disease (an umbrella term covering 16 Mondo subtypes) with 65 cohort genes (52 GWAS associations across 3 studies) and 42 clinical trials. The dominant Reactome pathway is Interleukin-23 signaling (4 cohort genes). Top therapeutic interventions include human immunoglobulin g, dextrose, and leniolisib.

At a glance

• Umbrella term: 16 Mondo subtypes
• Cohort genes: 65
• GWAS associations: 52
• ClinVar variants: 294
• Clinical trials: 42

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	common variable immunodeficiency
Mondo ID	MONDO:0015517
MeSH	D017074
OMIM	607594
Orphanet	1572
DOID	DOID:12177
ICD-10-CM	D83
ICD-11	1908371517
NCIT	C26725
SNOMED CT	23238000
UMLS	C0009447
MedGen	40407
GARD	0006140
MedDRA	10021449
NORD	990
Is cancer (heuristic)	no

Also known as: common variable hypogamma-globulinemia · Common Variable Immune Deficiency · common variable immune deficiency · hypogamma-globulinemia, acquired · Immunoglobulin deficiency, late-onset · primary antibody deficiency · primary hypogammaglobulinemia · secondary hypogammaglobulinemia

Data availability: 294 ClinVar variants · 52 GWAS associations (3 studies) · 15 GenCC gene-disease records · 23 cell lines.

Disease family

An umbrella term covering 16 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › syndromic disease › syndromic agammaglobulinemia › common variable immunodeficiency

Related subtypes (2): transient hypogammaglobulinemia, agammaglobulinemia-microcephaly-craniosynostosis-severe dermatitis syndrome

Subtypes (16): immune deficiency, familial variable, immunodeficiency, common variable, 2, immunodeficiency, common variable, 1, immunodeficiency, common variable, 3, immunodeficiency, common variable, 4, immunodeficiency, common variable, 5, immunodeficiency, common variable, 6, immunodeficiency, common variable, 7, combined immunodeficiency due to LRBA deficiency, immunodeficiency, common variable, 10, IL21-related infantile inflammatory bowel disease, immunodeficiency, common variable, 12, pancytopenia due to IKZF1 mutations, immunodeficiency, common variable, 14, immunodeficiency, common variable, due to APRIL deficiency, immunodeficiency, common variable, 15

Genetics & variants

GWAS landscape

52 GWAS associations across 3 studies. Top hits map to 38 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs1049225	5e-16	HLA-DQB1-AS1, HLA-DQB1	A	0.56
rs11580078	8e-11	IL23R, C1orf141	G
rs7725052	8e-11	RNU1-150P - TTC33	C
rs6679677	8e-11	PHTF1 - RSBN1	A
rs10822050	8e-11	LINC02929 - ALDH7A1P4	C
rs17885785	8e-11	INS-IGF2, IGF2, IGF2-AS	T
rs72743477	8e-11	SMAD3	G
rs117372389	8e-11	NKD1	T
rs2066363	8e-11	ADGRL2	C
rs7660520	8e-11	TENM3 - DCTD	A
rs7100025	8e-11	LINC00993	G
rs36001488	8e-11	ATG16L1	C
rs4625	8e-11	BSN-DT, DAG1	G
rs1332099	9e-11	NKX2-3 - SLC25A28	T
rs7731626	1e-10	ANKRD55	A
rs755374	2e-10	IL12B-AS1	T
rs17466626	3e-10	LRRK2	G
rs11741255	2e-09	IRF1, CARINH	A
rs17806056	2e-09	CLEC16A	A	0.66
rs1689510	4e-09	SUOX	C
rs12598357	4e-09	SBK1 - NPIPB6	G
rs706778	6e-09	IL2RA	T
rs77150043	6e-09	ADCY7	T
rs4246905	1e-08	TNFSF15	T
rs1250563	1e-08	ZMIZ1	C
rs2807264	1e-08	RNU6-320P - LINC00892	C
rs62324212	3e-08	IL21-AS1	A
rs11145763	3e-08	CARD9	C
rs602662	5e-08	FUT2	G
rs2836882	5e-08	LINC02940 - RPL23AP12	A

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90301675	Li J	2015	778	10,999	Association of CLEC16A with human common variable immunodeficiency disorder and role in murine B cells.
GCST001039	Orange JS	2011	179	1,917	Genome-wide association identifies diverse causes of common variable immunodeficiency.
GCST003097	Li YR	2015	97	10,718	Meta-analysis of shared genetic architecture across ten pediatric autoimmune diseases.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

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

MAF distribution

Bucket	Variants
common (>=0.05)	46
low_freq (0.01-0.05)	4
rare (<0.01)	0
unknown	0

Functional consequences

Consequence	Count
intron_variant	29
intergenic_variant	15
3_prime_UTR_variant	3
missense_variant	1
regulatory_region_variant	1
splice_region_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs1049225	6	32659970	A>C,G,T	0.26	3_prime_UTR_variant	HLA-DQB1-AS1, HLA-DQB1	5e-16	Tier 2: splice/UTR
rs11580078	1	67203951	C>A,G,T	0.43	intron_variant	IL23R, C1orf141	8e-11	Tier 4: intronic/intergenic
rs7725052	5	40487168	C>T	0.43	intron_variant	RNU1-150P - TTC33	8e-11	Tier 4: intronic/intergenic
rs6679677	1	113761186	C>A,T	0.09	intergenic_variant	PHTF1 - RSBN1	8e-11	Tier 4: intronic/intergenic
rs10822050	10	62679011	T>C,G	0.39	intergenic_variant	LINC02929 - ALDH7A1P4	8e-11	Tier 4: intronic/intergenic
rs17885785	11	2146620	C>T	0.2	intron_variant	INS-IGF2, IGF2, IGF2-AS	8e-11	Tier 4: intronic/intergenic
rs72743477	15	67171953	A>C,G,T	0.21	intron_variant	SMAD3	8e-11	Tier 4: intronic/intergenic
rs117372389	16	50634166	G>T	0.02	3_prime_UTR_variant	NKD1	8e-11	Tier 2: splice/UTR
rs2066363	1	81771892	C>A,T	0.34	intron_variant	ADGRL2	8e-11	Tier 4: intronic/intergenic
rs7660520	4	182824168	G>A,C	0.26	intergenic_variant	TENM3 - DCTD	8e-11	Tier 4: intronic/intergenic
rs7100025	10	37303610	G>A	0.34	intron_variant	LINC00993	8e-11	Tier 4: intronic/intergenic
rs36001488	2	233276621	C>G,T	0.48	intron_variant	ATG16L1	8e-11	Tier 4: intronic/intergenic
rs4625	3	49534707	A>G	0.31	3_prime_UTR_variant	BSN-DT, DAG1	8e-11	Tier 2: splice/UTR
rs1332099	10	99538694	T>A,C,G	0.46	intergenic_variant	NKX2-3 - SLC25A28	9e-11	Tier 4: intronic/intergenic
rs7731626	5	56148856	G>A,C	0.39	intron_variant	ANKRD55	1e-10	Tier 4: intronic/intergenic
rs755374	5	159402286	C>A,G,T	0.32	intergenic_variant	IL12B-AS1	2e-10	Tier 4: intronic/intergenic
rs17466626	12	40366829	A>G	0.02	intron_variant	LRRK2	3e-10	Tier 4: intronic/intergenic
rs11741255	5	132475490	G>A	0.42	intron_variant	IRF1, CARINH	2e-09	Tier 4: intronic/intergenic
rs17806056	16	11098642	T>A	0.23	intron_variant	CLEC16A	2e-09	Tier 4: intronic/intergenic
rs1689510	12	56002984	G>A,C	0.31	intron_variant	SUOX	4e-09	Tier 4: intronic/intergenic
rs12598357	16	28329624	A>G,T	0.39	intergenic_variant	SBK1 - NPIPB6	4e-09	Tier 4: intronic/intergenic
rs706778	10	6056986	C>G,T	0.41	intron_variant	IL2RA	6e-09	Tier 4: intronic/intergenic
rs77150043	16	50270338	C>T	0.23	intron_variant	ADCY7	6e-09	Tier 4: intronic/intergenic
rs4246905	9	114790969	T>A,C	0.28	intron_variant	TNFSF15	1e-08	Tier 4: intronic/intergenic
rs1250563	10	79287626	G>C	0.29	intron_variant	ZMIZ1	1e-08	Tier 4: intronic/intergenic
rs2807264	X	136583619	C>A,G,T	0.21	intergenic_variant	RNU6-320P - LINC00892	1e-08	Tier 4: intronic/intergenic
rs62324212	4	122639784	C>A,G	0.42	intron_variant	IL21-AS1	3e-08	Tier 4: intronic/intergenic
rs11145763	9	136369144	A>C,G,T	0.4	intron_variant	CARD9	3e-08	Tier 4: intronic/intergenic
rs602662	19	48703728	G>A	0.49	missense_variant	FUT2	5e-08	Tier 1: coding
rs2836882	21	39094644	G>A	0.27	regulatory_region_variant	LINC02940 - RPL23AP12	5e-08	Tier 3: regulatory

ClinVar germline variants

294 retrieved; paginated sample, class counts are floors:

153 uncertain significance, 105 likely benign, 10 benign, 10 pathogenic, 5 conflicting classifications of pathogenicity, 4 benign/likely benign, 3 pathogenic/likely pathogenic, 3 likely pathogenic, 1 conflicting classifications of pathogenicity; risk factor

ClinVar	Variant (HGVS)	Gene	Classification	Review
636694	NM_003998.4(NFKB1):c.830dup (p.Lys278fs)	NFKB1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
827719	NM_003998.4(NFKB1):c.260T>G (p.Ile87Ser)	NFKB1	Pathogenic	criteria provided, single submitter
827720	NM_003998.4(NFKB1):c.293T>A (p.Val98Asp)	NFKB1	Pathogenic	criteria provided, single submitter
827721	NM_003998.4(NFKB1):c.843C>G (p.Ile281Met)	NFKB1	Pathogenic	criteria provided, single submitter
827723	NM_003998.4(NFKB1):c.1423del (p.Ala475fs)	NFKB1	Pathogenic	criteria provided, single submitter
827726	NM_003998.4(NFKB1):c.850C>T (p.Arg284Ter)	NFKB1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
827830	Single allele	NFKB1	Pathogenic	criteria provided, single submitter
827831	Single allele	NFKB1	Pathogenic	criteria provided, single submitter
65385	NM_001322934.2(NFKB2):c.2557C>T (p.Arg853Ter)	NFKB2	Pathogenic	criteria provided, multiple submitters, no conflicts
13138	NM_000536.4(RAG2):c.1352G>C (p.Gly451Ala)	RAG2	Pathogenic	reviewed by expert panel
827734	NM_000536.4(RAG2):c.629T>C (p.Ile210Thr)	RAG2	Pathogenic	criteria provided, single submitter
203368	NM_012452.3(TNFRSF13B):c.492C>G (p.Tyr164Ter)	TNFRSF13B	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
942527	NM_012452.3(TNFRSF13B):c.61+2T>A	TNFRSF13B	Pathogenic	criteria provided, single submitter
2574621	NM_000061.3(BTK):c.1787T>C (p.Met596Thr)	BTK	Likely pathogenic	criteria provided, single submitter
633147	NM_000074.3(CD40LG):c.288+1G>A	CD40LG	Likely pathogenic	criteria provided, single submitter
2827689	NM_003998.4(NFKB1):c.1753-1G>C	NFKB1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
5302	NM_012452.3(TNFRSF13B):c.310T>C (p.Cys104Arg)	TNFRSF13B	Conflicting classifications of pathogenicity; risk factor	criteria provided, conflicting classifications
5303	NM_012452.3(TNFRSF13B):c.542C>A (p.Ala181Glu)	TNFRSF13B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
618436	NM_012452.3(TNFRSF13B):c.260T>A (p.Ile87Asn)	TNFRSF13B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
624092	NM_003809.3(TNFSF12):c.674G>A (p.Arg225Gln)	TNFSF12	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
827747	NM_020458.4(TTC7A):c.1802+3G>C	TTC7A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
827752	NM_020458.4(TTC7A):c.793C>T (p.Arg265Trp)	TTC7A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2424768	NC_000017.10:g.(?7123304)(7606804_?)del	ACADVL	Uncertain significance	criteria provided, single submitter
827696	NM_000074.3(CD40LG):c.98T>A (p.Ile33Asn)	CD40LG	Uncertain significance	criteria provided, multiple submitters, no conflicts
1414300	NM_003809.3(TNFSF12):c.68C>T (p.Pro23Leu)	LOC130060153	Uncertain significance	criteria provided, single submitter
1435998	NM_003809.3(TNFSF12):c.88C>G (p.Leu30Val)	LOC130060153	Uncertain significance	criteria provided, single submitter
1436026	NM_003809.3(TNFSF12):c.46C>A (p.Pro16Thr)	LOC130060153	Uncertain significance	criteria provided, single submitter
1443273	NM_003809.3(TNFSF12):c.26G>A (p.Arg9Gln)	LOC130060153	Uncertain significance	criteria provided, single submitter
1495617	NM_003809.3(TNFSF12):c.35G>C (p.Arg12Pro)	LOC130060153	Uncertain significance	criteria provided, single submitter
1524145	NM_003809.3(TNFSF12):c.55G>A (p.Ala19Thr)	LOC130060153	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 52 · Orphanet: 80 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 3

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

Gene	HGNC	Evidence routes
CD40LG	CD40LG	GWAS, Orphanet
IKZF3	IKZF3	GWAS, Orphanet
IL2RA	IL2RA	GWAS, Orphanet

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
CD19	Definitive	Autosomal recessive	immunodeficiency, common variable, 3	3
CR2	Definitive	Autosomal recessive	immunodeficiency, common variable, 7	5
ICOS	Strong	Autosomal recessive	immunodeficiency, common variable, 1	5
NFKB1	Strong	Autosomal dominant	immunodeficiency, common variable, 12	3
NFKB2	Strong	Autosomal dominant	immunodeficiency, common variable, 10	5
TNFRSF13B	Strong	Autosomal recessive	immunodeficiency, common variable, 2	6
BLK	Moderate	Autosomal dominant	common variable immunodeficiency	5
MS4A1	Moderate	Autosomal recessive	immunodeficiency, common variable, 5	3
TNFRSF13C	Moderate	Autosomal recessive	immunodeficiency, common variable, 4	4
CD81	Supportive	Autosomal dominant	common variable immunodeficiency	2
PRKCD	Supportive	Autosomal dominant	common variable immunodeficiency	5
TNFSF12	Supportive	Autosomal dominant	common variable immunodeficiency	3
TNFSF13	Limited	Autosomal recessive	common variable immunodeficiency	2
VAV1	Limited	Autosomal dominant	common variable immunodeficiency

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TNFSF12	Orphanet:696931	Common variable immunodeficiency phenotype due to TWEAK deficiency
CD40LG	Orphanet:101088	X-linked hyper-IgM syndrome
TNFRSF13B	Orphanet:696907	Common variable immunodeficiency phenotype due to homozygous TACI deficiency
NFKB1	Orphanet:696874	NFKB1-related immune dysregulation
NFKB2	Orphanet:293978	Deficiency in anterior pituitary function-variable immunodeficiency syndrome
BLK	Orphanet:536	Systemic lupus erythematosus
BLK	Orphanet:552	MODY
CD19	Orphanet:696881	Common variable immunodeficiency phenotype due to CD19/CD81 deficiency
CD81	Orphanet:696881	Common variable immunodeficiency phenotype due to CD19/CD81 deficiency
TNFRSF13C	Orphanet:696925	Adult-onset common variable immunodeficiency due to BAFF-receptor deficiency
CR2	Orphanet:536	Systemic lupus erythematosus
CR2	Orphanet:696894	Common variable immunodeficiency phenotype due to CD21 deficiency
ICOS	Orphanet:695183	Late-onset combined immunodeficiency due to ICOS deficiency
PRKCD	Orphanet:664711	EBV-induced lymphoproliferative disease due to PRKCD deficiency
BTK	Orphanet:47	X-linked agammaglobulinemia
BTK	Orphanet:632	Short stature due to isolated growth hormone deficiency with X-linked hypogammaglobulinemia
SUOX	Orphanet:99731	Isolated sulfite oxidase deficiency
TNFSF15	Orphanet:186	Primary biliary cholangitis
TYK2	Orphanet:300865	Primary cutaneous anaplastic large cell lymphoma
TYK2	Orphanet:331226	Susceptibility to infection due to TYK2 deficiency
TYK2	Orphanet:98842	Lymphomatoid papulosis
IKZF3	Orphanet:67038	B-cell chronic lymphocytic leukemia
IKZF3	Orphanet:699590	Immune dysregulation with immunodeficiency due to AIOLOS haploinsufficiency
IKZF3	Orphanet:699593	Combined immunodeficiency-lymphopenia-cancer predisposing syndrome due to AIOLOS deficiency
CARD9	Orphanet:457088	Predisposition to invasive fungal disease due to CARD9 deficiency
ZMIZ1	Orphanet:528084	Non-specific syndromic intellectual disability
ZNF365	Orphanet:2073	Narcolepsy type 1
ZNF365	Orphanet:83465	Narcolepsy type 2
LRRK2	Orphanet:2828	Young-onset Parkinson disease
LRRK2	Orphanet:411602	Hereditary late-onset Parkinson disease
IL23R	Orphanet:117	Behçet disease
TTC7A	Orphanet:436252	Combined immunodeficiency-multiple intestinal atresia
CRB1	Orphanet:251295	Pigmented paravenous retinochoroidal atrophy
CRB1	Orphanet:35612	Nanophthalmos
CRB1	Orphanet:65	Leber congenital amaurosis
CRB1	Orphanet:791	Retinitis pigmentosa
ANKRD55	Orphanet:85408	Rheumatoid factor-negative polyarticular juvenile idiopathic arthritis
ANKRD55	Orphanet:85410	Oligoarticular juvenile idiopathic arthritis
DAG1	Orphanet:206599	Isolated asymptomatic elevation of creatine phosphokinase
DAG1	Orphanet:280333	Alpha-dystroglycan-related limb-girdle muscular dystrophy R16
DAG1	Orphanet:370997	Muscle-eye-brain disease with bilateral multicystic leucodystrophy
DAG1	Orphanet:899	Walker-Warburg syndrome
GPR35	Orphanet:171	Primary sclerosing cholangitis
NOD2	Orphanet:90340	Blau syndrome
IKBKG	Orphanet:464	Incontinentia pigmenti
IKBKG	Orphanet:69088	Hypohidrotic ectodermal dysplasia-immunodeficiency-osteopetrosis-lymphedema syndrome
IKBKG	Orphanet:699605	NEMO deleted exon 5 autoinflammatory syndrome
IKBKG	Orphanet:98813	Hypohidrotic ectodermal dysplasia with immunodeficiency
IL10	Orphanet:117	Behçet disease
IL10	Orphanet:238569	Immune dysregulation-inflammatory bowel disease-arthritis-recurrent infections syndrome

Cohort genes → proteins

65 cohort genes, 63 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	43
gwas_and_clinvar	1
multi_evidence	21

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TNFSF12	HGNC:11927	ENSG00000239697	O43508	Tumor necrosis factor ligand superfamily member 12	gencc,clinvar
CD40LG	HGNC:11935	ENSG00000102245	P29965	CD40 ligand	gwas,clinvar
TNFRSF13B	HGNC:18153	ENSG00000240505	O14836	Tumor necrosis factor receptor superfamily member 13B	gencc,clinvar
NFKB1	HGNC:7794	ENSG00000109320	P19838	Nuclear factor NF-kappa-B p105 subunit	gencc,clinvar
NFKB2	HGNC:7795	ENSG00000077150	Q00653	Nuclear factor NF-kappa-B p100 subunit	gencc,clinvar
BLK	HGNC:1057	ENSG00000136573	P51451	Tyrosine-protein kinase Blk	gencc
TNFSF13	HGNC:11928	ENSG00000161955	O75888	Tumor necrosis factor ligand superfamily member 13	gencc
VAV1	HGNC:12657	ENSG00000141968	P15498	Proto-oncogene vav	gencc
CD19	HGNC:1633	ENSG00000177455	P15391	B-lymphocyte antigen CD19	gencc
CD81	HGNC:1701	ENSG00000110651	P60033	CD81 antigen	gencc
TNFRSF13C	HGNC:17755	ENSG00000159958	Q96RJ3	Tumor necrosis factor receptor superfamily member 13C	gencc
CR2	HGNC:2336	ENSG00000117322	P20023	Complement receptor type 2	gencc
ICOS	HGNC:5351	ENSG00000163600	Q9Y6W8	Inducible T-cell costimulator	gencc
MS4A1	HGNC:7315	ENSG00000156738	P11836	B-lymphocyte antigen CD20	gencc
PRKCD	HGNC:9399	ENSG00000163932	Q05655	Protein kinase C delta type	gencc
BTK	HGNC:1133	ENSG00000010671	Q06187	Tyrosine-protein kinase BTK	clinvar
SUOX	HGNC:11460	ENSG00000139531	P51687	Sulfite oxidase, mitochondrial	gwas
TNFRSF6B	HGNC:11921	ENSG00000243509	O95407	Tumor necrosis factor receptor superfamily member 6B	gwas
TNFSF15	HGNC:11931	ENSG00000181634	O95150	Tumor necrosis factor ligand superfamily member 15	gwas
TNFSF18	HGNC:11932	ENSG00000120337	Q9UNG2	Tumor necrosis factor ligand superfamily member 18	gwas
TRG-GCC2-6	HGNC:12273			tRNA-Gly (anticodon GCC) 2-6	clinvar
EIPR1	HGNC:12383	ENSG00000032389	Q53HC9	EARP and GARP complex-interacting protein 1	gwas
TYK2	HGNC:12440	ENSG00000105397	P29597	Non-receptor tyrosine-protein kinase TYK2	gwas
IKZF3	HGNC:13178	ENSG00000161405	Q9UKT9	Zinc finger protein Aiolos	gwas
CARD9	HGNC:16391	ENSG00000187796	Q9H257	Caspase recruitment domain-containing protein 9	gwas
ZMIZ1	HGNC:16493	ENSG00000108175	Q9ULJ6	Zinc finger MIZ domain-containing protein 1	gwas
FNBP1	HGNC:17069	ENSG00000187239	Q96RU3	Formin-binding protein 1	gwas
ANKRD30A	HGNC:17234	ENSG00000148513	Q9BXX3	Ankyrin repeat domain-containing protein 30A	gwas
SBK1	HGNC:17699	ENSG00000188322	Q52WX2	Serine/threonine-protein kinase SBK1	gwas
ZNF365	HGNC:18194	ENSG00000138311	Q70YC4	Talanin	gwas
ADGRL2	HGNC:18582	ENSG00000117114	O95490	Adhesion G protein-coupled receptor L2	gwas
LRRK2	HGNC:18618	ENSG00000188906	Q5S007	Leucine-rich repeat serine/threonine-protein kinase 2	gwas
IL23R	HGNC:19100	ENSG00000162594	Q5VWK5	Interleukin-23 receptor	gwas
TTC7A	HGNC:19750	ENSG00000068724	Q9ULT0	Tetratricopeptide repeat protein 7A	clinvar
ATG16L1	HGNC:21498	ENSG00000085978	Q676U5	Autophagy-related protein 16-1	gwas
CRB1	HGNC:2343	ENSG00000134376	P82279	Protein crumbs homolog 1	gwas
ADCY7	HGNC:238	ENSG00000121281	P51828	Adenylate cyclase type 7	gwas
CYTL1	HGNC:24435	ENSG00000170891	Q9NRR1	Cytokine-like protein 1	gwas
ANKRD55	HGNC:25681	ENSG00000164512	Q3KP44	Ankyrin repeat domain-containing protein 55	gwas
DAG1	HGNC:2666	ENSG00000173402	Q14118	Dystroglycan 1	gwas
ERAP2	HGNC:29499	ENSG00000164308	Q6P179	Endoplasmic reticulum aminopeptidase 2	gwas
PSMG1	HGNC:3043	ENSG00000183527	O95456	Proteasome assembly chaperone 1	gwas
ATXN2L	HGNC:31326	ENSG00000168488	Q8WWM7	Ataxin-2-like protein	gwas
LURAP1L	HGNC:31452	ENSG00000153714	Q8IV03	Leucine rich adaptor protein 1-like	gwas
EFNB2	HGNC:3227	ENSG00000125266	P52799	Ephrin-B2	gwas
TNFSF12-TNFSF13	HGNC:33537	ENSG00000248871		TNFSF12-TNFSF13 readthrough	clinvar
FUT2	HGNC:4013	ENSG00000176920	Q10981	Galactoside alpha-(1,2)-fucosyltransferase 2	gwas
GPR35	HGNC:4492	ENSG00000178623	Q9HC97	G-protein coupled receptor 35	gwas
NOD2	HGNC:5331	ENSG00000167207	Q9HC29	Nucleotide-binding oligomerization domain-containing protein 2	gwas
IKBKG	HGNC:5961	ENSG00000269335	Q9Y6K9	NF-kappa-B essential modulator	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TNFSF12	Tumor necrosis factor ligand superfamily member 12	Binds to FN14 and possibly also to TNRFSF12/APO3.
CD40LG	CD40 ligand	Cytokine that acts as a ligand to CD40/TNFRSF5.
TNFRSF13B	Tumor necrosis factor receptor superfamily member 13B	Receptor for TNFSF13/APRIL and TNFSF13B/TALL1/BAFF/BLYS that binds both ligands with similar high affinity.
NFKB1	Nuclear factor NF-kappa-B p105 subunit	NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to many biological processes such as infl…
NFKB2	Nuclear factor NF-kappa-B p100 subunit	NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to many biological processes such as infl…
BLK	Tyrosine-protein kinase Blk	Non-receptor tyrosine kinase involved in B-lymphocyte development, differentiation and signaling.
TNFSF13	Tumor necrosis factor ligand superfamily member 13	Cytokine that binds to TNFRSF13B/TACI and to TNFRSF17/BCMA.
VAV1	Proto-oncogene vav	Couples tyrosine kinase signals with the activation of the Rho/Rac GTPases, thus leading to cell differentiation and/or proliferation.
CD19	B-lymphocyte antigen CD19	Functions as a coreceptor for the B-cell antigen receptor complex (BCR) on B-lymphocytes.
CD81	CD81 antigen	Structural component of specialized membrane microdomains known as tetraspanin-enriched microdomains (TERMs), which act as platforms for receptor clustering and signaling.
TNFRSF13C	Tumor necrosis factor receptor superfamily member 13C	B-cell receptor specific for TNFSF13B/TALL1/BAFF/BLyS.
CR2	Complement receptor type 2	Serves as a receptor for various ligands including complement component CD3d, HNRNPU OR IFNA1.
ICOS	Inducible T-cell costimulator	Stimulatory receptor expressed in activated or antigen-experienced T-cells that plays an important role in the immune response.
MS4A1	B-lymphocyte antigen CD20	B-lymphocyte-specific membrane protein that plays a role in the regulation of cellular calcium influx necessary for the development, differentiation, and activation of B-lymphocytes.
PRKCD	Protein kinase C delta type	Calcium-independent, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that plays contrasting roles in cell death and cell survival by functioning as a pro-apoptotic protein during DNA damage-induced apoptosi…
BTK	Tyrosine-protein kinase BTK	Non-receptor tyrosine kinase indispensable for B lymphocyte development, differentiation and signaling.
SUOX	Sulfite oxidase, mitochondrial	Catalyzes the oxidation of sulfite to sulfate, the terminal reaction in the oxidative degradation of sulfur-containing amino acids.
TNFRSF6B	Tumor necrosis factor receptor superfamily member 6B	Decoy receptor that can neutralize the cytotoxic ligands TNFS14/LIGHT, TNFSF15 and TNFSF6/FASL.
TNFSF15	Tumor necrosis factor ligand superfamily member 15	Receptor for TNFRSF25 and TNFRSF6B.
TNFSF18	Tumor necrosis factor ligand superfamily member 18	Cytokine that binds to TNFRSF18/AITR/GITR.
EIPR1	EARP and GARP complex-interacting protein 1	Acts as a component of endosomal retrieval machinery that is involved in protein transport from early endosomes to either recycling endosomes or the trans-Golgi network.
TYK2	Non-receptor tyrosine-protein kinase TYK2	Tyrosine kinase of the non-receptor type involved in numerous cytokines and interferons signaling, which regulates cell growth, development, cell migration, innate and adaptive immunity.
IKZF3	Zinc finger protein Aiolos	Transcription factor that plays an important role in the regulation of lymphocyte differentiation.
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.
ZMIZ1	Zinc finger MIZ domain-containing protein 1	Acts as a transcriptional coactivator.
FNBP1	Formin-binding protein 1	May act as a link between RND2 signaling and regulation of the actin cytoskeleton.
SBK1	Serine/threonine-protein kinase SBK1	May be involved in signal-transduction pathways related to the control of brain development.
ZNF365	Talanin	May play a role in uric acid excretion.
ADGRL2	Adhesion G protein-coupled receptor L2	Orphan adhesion G-protein coupled receptor (aGPCR), which mediates synapse specificity.
LRRK2	Leucine-rich repeat serine/threonine-protein kinase 2	Serine/threonine-protein kinase which phosphorylates a broad range of proteins involved in multiple processes such as neuronal plasticity, innate immunity, autophagy, and vesicle trafficking.
IL23R	Interleukin-23 receptor	Associates with IL12RB1 to form the interleukin-23 receptor.
TTC7A	Tetratricopeptide repeat protein 7A	Component of a complex required to localize phosphatidylinositol 4-kinase (PI4K) to the plasma membrane.
ATG16L1	Autophagy-related protein 16-1	Plays an essential role in both canonical and non-canonical autophagy: interacts with ATG12-ATG5 to mediate the lipidation to ATG8 family proteins (MAP1LC3A, MAP1LC3B, MAP1LC3C, GABARAPL1, GABARAPL2 and GABARAP).
CRB1	Protein crumbs homolog 1	Plays a role in photoreceptor morphogenesis in the retina.
ADCY7	Adenylate cyclase type 7	Adenylate cyclase that mediates formation of both cyclic AMP (cAMP) and cyclic di-AMP (c-di-AMP).
DAG1	Dystroglycan 1	The dystroglycan complex is involved in a number of signaling events and processes including laminin deposition and extracellular matrix assembly, acetylcholine receptor clustering, sarcolemmal stability, cell survival, peripheral nerve my…
ERAP2	Endoplasmic reticulum aminopeptidase 2	Aminopeptidase that plays a central role in peptide trimming, a step required for the generation of most HLA class I-binding peptides.
PSMG1	Proteasome assembly chaperone 1	Chaperone protein which promotes assembly of the 20S proteasome as part of a heterodimer with PSMG2.
ATXN2L	Ataxin-2-like protein	Involved in the regulation of stress granule and P-body formation.
EFNB2	Ephrin-B2	Cell surface transmembrane ligand for Eph receptors, a family of receptor tyrosine kinases which are crucial for migration, repulsion and adhesion during neuronal, vascular and epithelial development.
FUT2	Galactoside alpha-(1,2)-fucosyltransferase 2	Catalyzes the transfer of L-fucose, from a guanosine diphosphate-beta-L-fucose, to the terminal galactose on both O- and N-linked glycans chains of cell surface glycoproteins and glycolipids and the resulting epitope regulates several proc…
GPR35	G-protein coupled receptor 35	G-protein coupled receptor that binds to several ligands including the tryptophan metabolite kynurenic acid (KYNA), lysophosphatidic acid (LPA) or 5-hydroxyindoleacetic acid (5-HIAA) with high affinity, leading to rapid and transient activ…
NOD2	Nucleotide-binding oligomerization domain-containing protein 2	Pattern recognition receptor (PRR) that detects bacterial peptidoglycan fragments and other danger signals and plays an important role in gastrointestinal immunity.
IKBKG	NF-kappa-B essential modulator	Regulatory subunit of the IKK core complex which phosphorylates inhibitors of NF-kappa-B thus leading to the dissociation of the inhibitor/NF-kappa-B complex and ultimately the degradation of the inhibitor.
IL10	Interleukin-10	Major immune regulatory cytokine that acts on many cells of the immune system where it has profound anti-inflammatory functions, limiting excessive tissue disruption caused by inflammation.
IL12B	Interleukin-12 subunit beta	Cytokine that can act as a growth factor for activated T and NK cells, enhance the lytic activity of NK/lymphokine-activated killer cells, and stimulate the production of IFN-gamma by resting PBMC.
IL18R1	Interleukin-18 receptor 1	Within the IL18 receptor complex, responsible for the binding of the pro-inflammatory cytokine IL18, but not IL1A nor IL1B.
IL21	Interleukin-21	Cytokine with immunoregulatory activity.
IL2RA	Interleukin-2 receptor subunit alpha	Receptor for interleukin-2.
IL5	Interleukin-5	Homodimeric cytokine expressed predominantly by T-lymphocytes and NK cells that plays an important role in the survival, differentiation, and chemotaxis of eosinophils.

Protein-family classification

Druggable: 24 · Difficult: 13 · Unknown: 28 · Druggable fraction: 0.37

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	8.2×	0.082
Kinase	7	3.0×	0.082
Antibody/Immunoglobulin	6	2.7×	0.082
Scaffold/PPI	6	1.6×	0.432
Phosphatase	1	1.3×	0.903
GPCR	3	1.1×	0.903
Transcription factor	7	0.9×	0.928
Enzyme (other)	4	0.7×	0.928
Protease	1	0.6×	0.928
Other/Unknown	28	0.8×	0.986

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TNFSF12	Other/Unknown	no		TNF_dom, Tumour_necrosis_fac-like_dom, TNF_Ligand_Superfamily
CD40LG	Other/Unknown	no		CD40L, TNF_dom, Tumour_necrosis_fac-like_dom
TNFRSF13B	Other/Unknown	no		TACI_Cys-rich-dom, TNFR_13B
NFKB1	Transcription factor	no		NFkB/Dor, Death_dom, Ankyrin_rpt
NFKB2	Transcription factor	no		NFkB/Dor, Death_dom, Ankyrin_rpt
BLK	Kinase	yes	2.7.10.2	Prot_kinase_dom, SH2, Ser-Thr/Tyr_kinase_cat_dom
TNFSF13	Other/Unknown	no		TNF_dom, Tumour_necrosis_fac-like_dom, TNF_CS
VAV1	Scaffold/PPI	no		DH_dom, SH2, GDS_CDC24_CS
CD19	Antibody/Immunoglobulin	yes		Ig_sub, Ig-like_dom, Ig-like_fold
CD81	Other/Unknown	no		Tetraspanin_animals, Tetraspanin_EC2_sf, Tetraspanin/Peripherin
TNFRSF13C	Other/Unknown	no		TNFR_13C_TALL-1-bd, TNFR_13C, TNFR_13C/17
CR2	Complement	yes		Sushi_SCR_CCP_dom, Sushi/SCR/CCP_sf, SEZ6_CSMD_C4BPB_Regulators
ICOS	Antibody/Immunoglobulin	yes		Ig_V-set, Ig-like_fold, ICOS
MS4A1	Other/Unknown	no		CD20-like_TM, MS4A
PRKCD	Kinase	yes	2.7.11.13	C2_dom, Prot_kinase_dom, AGC-kinase_C
BTK	Kinase	yes	2.7.10.2	Prot_kinase_dom, SH2, Ser-Thr/Tyr_kinase_cat_dom
SUOX	Enzyme (other)	yes	1.8.3.1	OxRdtase_Mopterin-bd_dom, Cyt_B5-like_heme/steroid-bd, MoCF_OxRdtse_dimer
TNFRSF6B	Other/Unknown	no		TNFR/NGFR_Cys_rich_reg, TNFRSF6B_N, TNFRSF_decoy_receptor
TNFSF15	Other/Unknown	no		TNF_dom, TNF, Tumour_necrosis_fac-like_dom
TNFSF18	Other/Unknown	no		TNF_dom, Tumour_necrosis_fac-like_dom, TNFSF18
TRG-GCC2-6	Other/Unknown	no
EIPR1	Scaffold/PPI	no		WD40_rpt, WD40/YVTN_repeat-like_dom_sf, WD40_repeat_CS
TYK2	Kinase	yes	2.7.10.2	FERM_domain, Prot_kinase_dom, SH2
IKZF3	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf, Ikaros_C2H2-ZF
CARD9	Other/Unknown	no		CARD, DEATH-like_dom_sf, CARD_CARD9
ZMIZ1	Transcription factor	no		Znf_MIZ, Znf_RING/FYVE/PHD, ZMIZ1_N
FNBP1	Scaffold/PPI	no		FCH_dom, SH3_domain, HR1_rho-bd
ANKRD30A	Scaffold/PPI	no		Ankyrin_rpt, Ankyrin_rpt-contain_sf, CC144C-like_CC_dom
SBK1	Kinase	yes		Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
ZNF365	Transcription factor	no		GenomicStab_NeuMorph_Reg, FBX41/ZN365_Znf-C2H2
ADGRL2	GPCR	yes		GPS, GPCR_2_secretin-like, Lectin_gal-bd_dom
LRRK2	Kinase	yes		Prot_kinase_dom, Leu-rich_rpt, Leu-rich_rpt_typical-subtyp
IL23R	Antibody/Immunoglobulin	yes		FN3_dom, Ig-like_fold, FN3_sf
TTC7A	Other/Unknown	no		TPR-like_helical_dom_sf, TPR_rpt, TTC7_N
ATG16L1	Scaffold/PPI	no		WD40_rpt, Autophagy-rel_prot_16_dom, WD40/YVTN_repeat-like_dom_sf
CRB1	Other/Unknown	no		EGF-type_Asp/Asn_hydroxyl_site, EGF, Laminin_G
ADCY7	Enzyme (other)	yes	4.6.1.1	A/G_cyclase, Adcy_conserved_dom, A/G_cyclase_CS
CYTL1	Other/Unknown	no		CYTL1
ANKRD55	Scaffold/PPI	no		Ankyrin_rpt, Ankyrin_rpt-contain_sf
DAG1	Antibody/Immunoglobulin	yes		Cadg, DAG1_C, Ig-like_fold
ERAP2	Protease	yes	3.4.11.1	Peptidase_M1, Peptidase_M1_dom, ERAP1-like_C_dom
PSMG1	Other/Unknown	no		Proteasome_assmbl_chp_1
ATXN2L	Other/Unknown	no		LsmAD_domain, PAM2_motif, SM_dom_ATX
LURAP1L	Other/Unknown	no		LURAP1, LURA1/LRA25
EFNB2	Other/Unknown	no		Ephrin_RBD, Cupredoxin, Ephrin_CS
TNFSF12-TNFSF13	Other/Unknown	no
FUT2	Enzyme (other)	yes	2.4.1.344	Glyco_trans_11
GPR35	GPCR	yes		GPCR_Rhodpsn, GPCR_Rhodpsn_7TM, GPR35_7tmA
NOD2	Other/Unknown	no		CARD, Leu-rich_rpt, NACHT_NTPase
IKBKG	Other/Unknown	no		NEMO_N, CC2-LZ_dom, NEMO_ZF

Expression context

Cohort genes with no expression data: 1.

57 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)	64
unknown	1

Top tissues across cohort

Tissue	Cohort genes
granulocyte	10
spleen	10
monocyte	10
lymph node	9
leukocyte	7
male germ line stem cell (sensu Vertebrata) in testis	5
vermiform appendix	5
mononuclear cell	5
cartilage tissue	4
ganglionic eminence	4
left testis	4
right testis	4
blood	3
olfactory bulb	3
type B pancreatic cell	3
calcaneal tendon	3
olfactory segment of nasal mucosa	3
right hemisphere of cerebellum	3
right lung	3
ventricular zone	3

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TNFSF12	134	tissue_specific	marker	right coronary artery, thoracic aorta, ascending aorta
CD40LG	124	tissue_specific	marker	granulocyte, lymph node, blood
TNFRSF13B	158	tissue_specific	marker	type B pancreatic cell, olfactory bulb, spleen
NFKB1	252	ubiquitous	marker	endometrium epithelium, cartilage tissue, calcaneal tendon
NFKB2	221	ubiquitous	marker	granulocyte, muscle layer of sigmoid colon, spleen
BLK	145	tissue_specific	marker	spleen, male germ line stem cell (sensu Vertebrata) in testis, lymph node
TNFSF13	134	ubiquitous	marker	monocyte, leukocyte, granulocyte
VAV1	188	broad	marker	granulocyte, monocyte, leukocyte
CD19	164	tissue_specific	marker	spleen, lymph node, vermiform appendix
CD81	302	ubiquitous	marker	stromal cell of endometrium, seminal vesicle, body of uterus
TNFRSF13C	151	broad	marker	spleen, lymph node, vermiform appendix
CR2	150	broad	marker	secondary oocyte, oocyte, spleen
ICOS	110	tissue_specific	marker	lymph node, vermiform appendix, thymus
MS4A1	197	broad	marker	epithelium of nasopharynx, spleen, lymph node
PRKCD	229	ubiquitous	marker	monocyte, mononuclear cell, leukocyte
BTK	206	broad	marker	monocyte, mononuclear cell, leukocyte
SUOX	267	ubiquitous	marker	right lobe of liver, right adrenal gland, right adrenal gland cortex
TNFRSF6B	127	broad	yes	olfactory segment of nasal mucosa, spleen, subcutaneous adipose tissue
TNFSF15	149	broad	marker	cartilage tissue, jejunal mucosa, duodenum
TNFSF18	98	broad	yes	male germ line stem cell (sensu Vertebrata) in testis, gall bladder, stromal cell of endometrium
TRG-GCC2-6
EIPR1	249	ubiquitous	marker	prefrontal cortex, adenohypophysis, nucleus accumbens
TYK2	288	ubiquitous	marker	granulocyte, right hemisphere of cerebellum, adenohypophysis
IKZF3	155	broad	marker	granulocyte, lymph node, epithelium of nasopharynx
CARD9	172	broad	marker	monocyte, mononuclear cell, leukocyte
ZMIZ1	295	ubiquitous	marker	dorsal motor nucleus of vagus nerve, tibia, seminal vesicle
FNBP1	292	ubiquitous	marker	corpus callosum, mucosa of stomach, lower esophagus muscularis layer
ANKRD30A	69	tissue_specific	marker	epithelium of mammary gland, mammary duct, male germ line stem cell (sensu Vertebrata) in testis
SBK1	195	broad	yes	cortical plate, ganglionic eminence, cerebellar vermis
ZNF365	206	broad	yes	middle temporal gyrus, lateral nuclear group of thalamus, Brodmann (1909) area 23

Protein interactions among cohort

Intra-cohort edges: 57.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
INS	11,670
NFKB1	10,484
LRRK2	7,628
SMAD3	6,440
JAK2	6,197
IL10	6,185
IKBKG	4,981
BTK	4,467
RBMX	4,460
NFKB2	4,041

Intra-cohort edges

A	B	Sources
ADGRL2	ATG16L1	intact
ADGRL2	LURAP1L	string_interaction
ANKRD55	PTPN22	string_interaction
ATG16L1	NKX2-3	string_interaction
ATG16L1	NOD2	biogrid_interaction, string_interaction
ATG16L1	TNFSF15	string_interaction
BTK	CD19	intact
BTK	VAV1	string_interaction
CARD9	NKX2-3	string_interaction
CARD9	NOD2	string_interaction
CD19	CD81	biogrid_interaction
CD19	CR2	biogrid_interaction, string_interaction
CD19	IL21	string_interaction
CD19	TNFRSF13C	string_interaction
CD19	VAV1	biogrid_interaction
CD40LG	ICOS	string_interaction
CD40LG	IL21	string_interaction
CD40LG	TNFRSF13B	string_interaction
CD40LG	TNFRSF13C	string_interaction
CD81	CR2	biogrid_interaction
CD81	GPR35	biogrid_interaction, intact
CR2	TNFRSF13B	string_interaction
EFNB2	TYK2	biogrid_interaction
ICOS	IL21	string_interaction
ICOS	TNFRSF13B	string_interaction
IKBKG	NFKB1	string_interaction
IKBKG	NFKB2	string_interaction
IL10	IL12B	string_interaction
IL10	IL23R	string_interaction
IL10	IL2RA	string_interaction
IL10	IL5	string_interaction
IL10	NFKB2	biogrid_interaction
IL10	TNFSF13	string_interaction
IL12B	IL23R	string_interaction
IL12B	TYK2	string_interaction
IL18R1	NKX2-3	string_interaction
IL23R	JAK2	string_interaction
IL23R	NKX2-3	string_interaction
IL23R	NOD2	string_interaction
IL23R	TYK2	string_interaction
JAK2	TYK2	string_interaction
LURAP1L	NOD2	intact
NFKB1	NFKB2	intact, string_interaction
NFKB2	TNFRSF13C	string_interaction
NKX2-3	NOD2	string_interaction
NKX2-3	TNFSF15	string_interaction
NOD2	TNFSF15	string_interaction
PRKCD	PTPN22	intact
PSMG1	TNFRSF6B	string_interaction
PTPN22	VAV1	intact

Structural data

PDB: 49 · AlphaFold-only: 14 · No structure: 2

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
INS	P01308	382
JAK2	O60674	164
BTK	Q06187	156
TYK2	P29597	52
LRRK2	Q5S007	44
IL12B	P29460	20
IKBKG	Q9Y6K9	17
CD81	P60033	16
ATG16L1	Q676U5	16
NFKB1	P19838	15
ERAP2	Q6P179	14
PTPN22	Q9Y2R2	14
PSMG1	O95456	13
SMAD3	P84022	12
NFKB2	Q00653	11
VAV1	P15498	10
MS4A1	P11836	10
EFNB2	P52799	10
IL2RA	P01589	10
PTGER4	P35408	10
CR2	P20023	9
IL10	P22301	9
CD40LG	P29965	8
TNFRSF13C	Q96RJ3	8
TNFRSF6B	O95407	8
CARD9	Q9H257	8
DAG1	Q14118	8
TNFSF15	O95150	7
TNFSF18	Q9UNG2	7
IL5	P05113	5

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
FUT2	Q10981	90.65
EIPR1	Q53HC9	89.26
CYTL1	Q9NRR1	85.86
NOD2	Q9HC29	84.76
TTC7A	Q9ULT0	84.59
BLK	P51451	81.89
SBK1	Q52WX2	77.87
ADCY7	P51828	77.32
LURAP1L	Q8IV03	66.08
ANKRD55	Q3KP44	63.43
NKX2-3	Q8TAU0	60.75
ATXN2L	Q8WWM7	49.52
IKZF3	Q9UKT9	48.06
ZNF365	Q70YC4	30.21

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 401. Enrichment computed across 65 evidence-associated genes (50 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 50 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Interleukin-23 signaling	4	101.5×	2e-05	TYK2, IL23R, IL12B, JAK2
TNFs bind their physiological receptors	5	39.4×	3e-05	TNFRSF13B, TNFRSF6B, TNFSF13, TNFSF15, TNFSF18
IkBA variant leads to EDA-ID	3	97.9×	4e-04	NFKB1, NFKB2, IKBKG
Antigen activates B Cell Receptor (BCR) leading to generation of second messengers	4	28.6×	1e-03	BLK, BTK, VAV1, CD19
Signaling by the B Cell Receptor (BCR)	4	27.7×	1e-03	BLK, BTK, CD19, IKBKG
TAK1-dependent IKK and NF-kappa-B activation	4	24.0×	0.001	NFKB1, NFKB2, NOD2, IKBKG
RIP-mediated NFkB activation via ZBP1	3	40.3×	0.003	NFKB1, NFKB2, IKBKG
TNF receptor superfamily (TNFSF) members mediating non-canonical NF-kB pathway	3	40.3×	0.003	TNFSF12, CD40LG, TNFRSF13C
Interleukin-4 and Interleukin-13 signaling	5	10.3×	0.005	TYK2, IL23R, IL10, IL12B, JAK2
TRAF6 mediated NF-kB activation	3	27.4×	0.007	NFKB1, NFKB2, IKBKG
Interleukin-12 signaling	3	24.5×	0.008	TYK2, IL12B, JAK2
Interleukin receptor SHC signaling	3	24.5×	0.008	IL2RA, IL5, JAK2
DEx/H-box helicases activate type I IFN and inflammatory cytokines production	2	65.3×	0.012	NFKB1, NFKB2
CLEC7A (Dectin-1) signaling	4	11.4×	0.012	NFKB1, CARD9, IKBKG, PRKCD
NOD1/2 Signaling Pathway	3	19.0×	0.013	CARD9, NOD2, IKBKG
Interleukin-3, Interleukin-5 and GM-CSF signaling	3	19.0×	0.013	VAV1, IL5, JAK2
Interleukin-1 processing	2	50.8×	0.015	NFKB1, NFKB2
HuR (ELAVL1) binds and stabilizes mRNA	2	50.8×	0.015	TNFSF13, PRKCD
MAPK1 (ERK2) activation	2	45.7×	0.017	TYK2, JAK2
MAPK3 (ERK1) activation	2	41.5×	0.018	TYK2, JAK2
Interleukin-27 signaling	2	41.5×	0.018	TYK2, JAK2
Interleukin-6 signaling	2	38.1×	0.018	TYK2, JAK2
SUMOylation of immune response proteins	2	38.1×	0.018	NFKB2, IKBKG
Interleukin-35 Signalling	2	38.1×	0.018	TYK2, JAK2
C-type lectin receptors (CLRs)	3	14.3×	0.018	CARD9, IKBKG, PRKCD
Interleukin-10 signaling	3	14.0×	0.018	TYK2, IL10, IL12B
Regulation of Complement cascade	3	14.0×	0.018	CD19, CD81, CR2
Potential therapeutics for SARS	4	9.1×	0.018	BTK, TYK2, VAV1, JAK2
Diseases of Immune System	2	35.1×	0.019	BTK, IKBKG
Diseases associated with the TLR signaling cascade	2	35.1×	0.019	BTK, IKBKG

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 60 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
positive regulation of interleukin-17 production	7	70.2×	5e-09	TYK2, CARD9, IL23R, NOD2, IL12B, IL21, JAK2
B cell proliferation	7	56.2×	9e-09	CD40LG, VAV1, CD19, CR2, IL10, MS4A1, PRKCD
immune response	14	11.0×	9e-09	TNFSF12, TNFSF13, TNFSF15, TYK2, CR2, ICOS, IKBKG, IL10 (+6 more)
positive regulation of T-helper 17 type immune response	5	117.0×	8e-08	TYK2, CARD9, IL23R, IL12B, JAK2
positive regulation of T cell proliferation	7	30.2×	5e-07	CD40LG, TYK2, TNFRSF13C, IL23R, IL12B, IL21, JAK2
positive regulation of type II interferon production	7	26.2×	1e-06	TYK2, IL23R, IL12B, IL18R1, IL21, JAK2, PTPN22
obsolete positive regulation of NF-kappaB transcription factor activity	7	24.0×	2e-06	CD40LG, BTK, TNFSF18, CARD9, NOD2, IKBKG, IL18R1
positive regulation of B cell proliferation	6	34.4×	2e-06	BTK, TNFSF13, CD81, TNFRSF13C, IL21, IL5
positive regulation of natural killer cell proliferation	4	93.6×	7e-06	TYK2, IL23R, IL12B, JAK2
B cell differentiation	6	21.9×	3e-05	CD40LG, IKZF3, CR2, IL10, MS4A1, RAG2
B cell receptor signaling pathway	5	33.4×	3e-05	NFKB1, BLK, BTK, CD19, MS4A1
T cell costimulation	5	31.2×	3e-05	CD40LG, VAV1, TNFRSF13C, EFNB2, ICOS
adaptive immune response	8	11.2×	3e-05	TNFRSF13B, BTK, TNFSF18, TNFRSF13C, ERAP2, NOD2, IL18R1, JAK2
interleukin-23-mediated signaling pathway	3	140.4×	5e-05	TYK2, IL23R, JAK2
positive regulation of NK T cell proliferation	3	140.4×	5e-05	TYK2, IL12B, JAK2
positive regulation of canonical NF-kappaB signal transduction	8	9.7×	8e-05	CD40LG, BTK, TNFSF15, CARD9, LURAP1L, NOD2, IKBKG, INS
positive regulation of cytokine production	5	22.6×	1e-04	CARD9, IL10, IL21, INS, PTGER4
JNK cascade	5	22.6×	1e-04	NFKB1, CARD9, LRRK2, SMAD3, PTGER4
positive regulation of tumor necrosis factor production	6	15.3×	1e-04	BTK, CARD9, LRRK2, NOD2, IL12B, JAK2
interleukin-12-mediated signaling pathway	3	93.6×	1e-04	TYK2, IL12B, JAK2
negative regulation of inflammatory response	6	13.7×	2e-04	NFKB1, IL10, IL2RA, SMAD3, PRKCD, PTGER4
positive regulation of immunoglobulin production	4	32.1×	3e-04	BTK, IL10, IL21, IL5
positive regulation of receptor signaling pathway via JAK-STAT	4	28.8×	4e-04	TYK2, IL10, IL5, JAK2
cellular response to virus	5	16.7×	4e-04	NFKB1, TYK2, IL21, JAK2, SMAD3
positive regulation of interleukin-10 production	4	26.8×	5e-04	CD40LG, NOD2, IL12B, IL21
canonical NF-kappaB signal transduction	4	24.4×	7e-04	NFKB1, NFKB2, NOD2, IKBKG
positive regulation of granulocyte macrophage colony-stimulating factor production	3	49.6×	9e-04	CARD9, IL23R, IL12B
tumor necrosis factor-mediated signaling pathway	4	22.0×	1e-03	NFKB1, TNFSF18, TNFRSF13C, JAK2
negative regulation of B cell proliferation	3	46.8×	1e-03	TNFRSF13B, BTK, IL10
cell surface receptor signaling pathway via JAK-STAT	4	19.4×	0.001	TYK2, IL23R, IL12B, JAK2

Therapeutics

Drugs indicated for this disease

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

Drug	Development status
Human Immunoglobulin G	Phase 3 (in late-stage trials)

Drug target analysis

Approved (phase 4): 15 · Phase ≥3: 15 · Phased (≥1): 17 · Undrugged: 48

Druggability breadth: 42 of 65 evidence-associated genes (65%) 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
NFKB1	INDOPROFEN
NFKB2	INDOPROFEN
BLK	AFATINIB
PRKCD	INGENOL MEBUTATE
BTK	PONATINIB
TYK2	FEDRATINIB
IKZF3	POMALIDOMIDE
SBK1	AFATINIB
LRRK2	PONATINIB
GPR35	AMLEXANOX
NOD2	PACLITAXEL
IL5	BUDESONIDE
JAK2	FEDRATINIB
SMAD3	FLUORESCEIN
PTGER4	DINOPROSTONE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
NFKB1	152	4
JAK2	100	4
BTK	84	4
TYK2	72	4
BLK	62	4
PRKCD	49	4
LRRK2	42	4
GPR35	30	4
NFKB2	15	4
SBK1	14	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
INDOPROFEN	4	NFKB1, NFKB2
VAMOROLONE	4	NFKB1, NFKB2
BORTEZOMIB	4	NFKB1, NFKB2
DEXAMETHASONE	4	NFKB1, NFKB2
SULFASALAZINE	4	NFKB1, NFKB2
LEVOSALBUTAMOL	4	NFKB1
CLOTRIMAZOLE	4	NFKB1
GLIPIZIDE	4	NFKB1
SALMETEROL XINAFOATE	4	NFKB1
PHENELZINE	4	NFKB1
SULFAPHENAZOLE	4	NFKB1
AMOXAPINE	4	NFKB1
PROPANTHELINE	4	NFKB1
DECAMETHONIUM	4	NFKB1
NICARDIPINE HYDROCHLORIDE	4	NFKB1
PHENTOLAMINE MESYLATE	4	NFKB1
PHENYLEPHRINE	4	NFKB1
CARISOPRODOL	4	NFKB1
AZELAIC ACID	4	NFKB1
CARBETAPENTANE CITRATE	4	NFKB1
NIALAMIDE	4	NFKB1
EPINEPHRINE BITARTRATE	4	NFKB1
NILUTAMIDE	4	NFKB1
BUDESONIDE	4	IL5, NFKB1
ESTRONE	4	NFKB1
METHAPYRILENE	4	NFKB1
PIMOZIDE	4	NFKB1
TRIAMCINOLONE	4	NFKB1
BISOPROLOL FUMARATE	4	NFKB1
AZACITIDINE	4	NFKB1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 11.

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

Symbol	Assays	Type breakdown
JAK2	2,018	Binding:1911, Functional:51, ADMET:48, Unclassified:4, Toxicity:4
BTK	1,836	Binding:1810, Functional:23, ADMET:3
TYK2	1,083	Binding:1043, Functional:39, ADMET:1
LRRK2	809	Binding:799, ADMET:7, Functional:3
PRKCD	804	Binding:790, Functional:14
BLK	483	Binding:477, ADMET:4, Functional:2
PTGER4	288	Binding:207, Functional:80, ADMET:1
NFKB1	256	Binding:249, Functional:7
NFKB2	230	Binding:226, Functional:4
GPR35	162	Binding:84, Functional:78
PTPN22	137	Binding:122, Functional:10, ADMET:5
NOD2	126	Binding:121, Functional:5
IKZF3	101	Binding:100, Functional:1
SBK1	97	Binding:97
ERAP2	46	Binding:40, ADMET:4, Functional:2
IKBKG	38	Binding:30, Functional:8
SMAD3	24	Binding:18, Functional:6
ADCY7	16	Binding:14, Functional:2
IL23R	13	Binding:13
CD40LG	8	Binding:8
INS	8	Binding:7, ADMET:1
CD81	7	Binding:7
ICOS	7	Binding:7
RBMX	6	Binding:6
PSMG1	5	Binding:5
DAG1	4	Binding:4
IL5	4	Binding:4
FUT2	2	Binding:2
IL2RA	2	Binding:2
ACADVL	2	Binding:2
VAV1	1	Binding:1
ATXN2L	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
BLK	2.7.10.2	non-specific protein-tyrosine kinase
PRKCD	2.7.11.13	protein kinase C
BTK	2.7.10.2	non-specific protein-tyrosine kinase
SUOX	1.8.3.1	sulfite oxidase
TYK2	2.7.10.2	non-specific protein-tyrosine kinase
ADCY7	4.6.1.1	adenylate cyclase
ERAP2	3.4.11.1, 3.4.11.6	leucyl aminopeptidase, aminopeptidase B
FUT2	2.4.1.344, 2.4.1.69	type 2 galactoside alpha-(1,2)-fucosyltransferase, type 1 galactoside alpha-(1,2)-fucosyltransferase
JAK2	2.7.10.2	non-specific protein-tyrosine kinase
ACADVL	1.3.8.8, 1.3.8.9	long-chain acyl-CoA dehydrogenase, very-long-chain acyl-CoA dehydrogenase
PTPN22	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
NFKB1	256
NFKB2	230
BLK	483
PRKCD	804
BTK	1,836
TYK2	1,083
IKZF3	101
LRRK2	809
GPR35	162
NOD2	126
JAK2	2,018
PTGER4	288
PTPN22	137

Pharmacogenomics

Cohort genes with a PharmGKB record: 64; 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)
INDOPROFEN	4	NFKB1, NFKB2
VAMOROLONE	4	NFKB1, NFKB2
BORTEZOMIB	4	NFKB1, NFKB2
DEXAMETHASONE	4	NFKB1, NFKB2
SULFASALAZINE	4	NFKB1, NFKB2
LEVOSALBUTAMOL	4	NFKB1
CLOTRIMAZOLE	4	NFKB1
GLIPIZIDE	4	NFKB1
SALMETEROL XINAFOATE	4	NFKB1
PHENELZINE	4	NFKB1
SULFAPHENAZOLE	4	NFKB1
AMOXAPINE	4	NFKB1
PROPANTHELINE	4	NFKB1
DECAMETHONIUM	4	NFKB1
NICARDIPINE HYDROCHLORIDE	4	NFKB1
PHENTOLAMINE MESYLATE	4	NFKB1
PHENYLEPHRINE	4	NFKB1
CARISOPRODOL	4	NFKB1
AZELAIC ACID	4	NFKB1
CARBETAPENTANE CITRATE	4	NFKB1
NIALAMIDE	4	NFKB1
EPINEPHRINE BITARTRATE	4	NFKB1
NILUTAMIDE	4	NFKB1
BUDESONIDE	4	IL5, NFKB1
ESTRONE	4	NFKB1
METHAPYRILENE	4	NFKB1
PIMOZIDE	4	NFKB1
TRIAMCINOLONE	4	NFKB1
BISOPROLOL FUMARATE	4	NFKB1
AZACITIDINE	4	NFKB1

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	15	NFKB1, NFKB2, BLK, PRKCD, BTK, TYK2, IKZF3, SBK1, LRRK2, GPR35 (+5 more)
B	Phased (≥1) drug, not yet approved	2	ERAP2, ACADVL
C	Druggable family + PDB, no drug	11	CD19, CR2, ICOS, SUOX, ADGRL2, IL23R, DAG1, IL12B, IL18R1, IL2RA (+1 more)
D	Druggable family + AlphaFold only, no drug	2	ADCY7, FUT2
E	Difficult family or no structure, no drug	35	TNFSF12, CD40LG, TNFRSF13B, TNFSF13, VAV1, CD81, TNFRSF13C, MS4A1, TNFRSF6B, TNFSF15 (+25 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
CARD9	0	NOD2
IL23R	13	JAK2
ATG16L1	0	NOD2
NKX2-3	0	NOD2
PTPN22	137	—
TNFSF12	0	—
CD40LG	8	—
TNFRSF13B	0	—
TNFSF13	0	—
VAV1	1	—
CD19	0	—
CD81	7	—
TNFRSF13C	0	—
CR2	0	—
ICOS	7	—
MS4A1	0	—
SUOX	0	—
TNFRSF6B	0	—
TNFSF15	0	—
TNFSF18	0	—
TRG-GCC2-6	0	—
EIPR1	0	—
ZMIZ1	0	—
FNBP1	0	—
ANKRD30A	0	—
ZNF365	0	—
ADGRL2	0	—
TTC7A	0	—
CRB1	0	—
ADCY7	16	—

Clinical trials & evidence

Clinical trials

Clinical trials: 42.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	18
PHASE2	9
PHASE3	8
PHASE4	4
PHASE1/PHASE2	2
PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05193552	PHASE4	RECRUITING	Usage of Spirometry in Managing IgG Therapy in CVID With Airway Disease
NCT00520494	PHASE4	COMPLETED	Efficacy and Safety of Vivaglobin® in Previously Untreated Patients With Primary Immunodeficiency
NCT01289847	PHASE4	COMPLETED	A Study to Find Out How Safe and Effective Gammaplex® is in Young People With Primary Immunodeficiency
NCT01946906	PHASE4	COMPLETED	The Rifaximin Study in CVID
NCT00168012	PHASE3	COMPLETED	Efficacy and Safety of Intravenous Immunoglobulin IVIG-F10 in Patients With Primary Immunodeficiencies (PID)
NCT00168025	PHASE3	COMPLETED	Efficacy and Safety of Intravenous Immunoglobulin IgPro10 in Patients With Primary Immunodeficiencies (PID)
NCT00220766	PHASE3	COMPLETED	Rapid Infusion of Immune Globulin Intravenous (Human) In Primary Immunodeficiency Patients
NCT00322556	PHASE3	COMPLETED	Safety and Efficacy of Intravenous Immunoglobulin IgPro10 in Patients With Primary Immunodeficiencies (PID)
NCT00542997	PHASE3	COMPLETED	Study of Subcutaneous Immune Globulin in Patients Requiring IgG Replacement Therapy
NCT01884311	PHASE3	COMPLETED	Pharmacokinetics (PK) and Safety of Subgam-VF in Primary Immunodeficiency Diseases
NCT01963143	PHASE3	COMPLETED	Bioequivalence Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of Gammaplex® 10 and Gammaplex® 5% in Primary Immunodeficiency Diseases
NCT02247141	PHASE3	COMPLETED	A Multi-centre Open Study to Assess the Safety and Efficacy of Subgam®
NCT01821781	PHASE2	ACTIVE_NOT_RECRUITING	Immune Disorder HSCT Protocol
NCT01852370	PHASE1/PHASE2	ENROLLING_BY_INVITATION	Sequential Cadaveric Lung and Bone Marrow Transplant for Immune Deficiency Diseases
NCT02579967	PHASE2	RECRUITING	Pilot Trial of Allogeneic Blood or Marrow Transplantation for Primary Immunodeficiencies
NCT03663933	PHASE2	ACTIVE_NOT_RECRUITING	Allogeneic Hematopoietic Cell Transplantation for Disorders of T-cell Proliferation and/or Dysregulation
NCT04339777	PHASE2	RECRUITING	Allogeneic Hematopoietic Stem Cell Transplant for Patients With Inborn Errors of Immunity
NCT04925375	PHASE2	RECRUITING	Abatacept for the Treatment of Common Variable Immunodeficiency With Interstitial Lung Disease
NCT05593588	PHASE2	ENROLLING_BY_INVITATION	Senolytics Treatment of Interstitial Lung Disease in Common Variable Immunodeficiency
NCT06897358	PHASE2	ACTIVE_NOT_RECRUITING	Leniolisib for Immune Dysregulation in CVID
NCT07284641	PHASE2	RECRUITING	Hematopoietic Stem Cell Transplantation (HSCT) for Common Variable Immunodeficiency (CVID) and Other Autoimmune Manifestations of Primary Immune Regulatory Disorders (PIRD)
NCT01489618	PHASE2	TERMINATED	Prime Boost Vaccination Strategy Combining Conjugated Anti- Pneumococcal Vaccine (s0) and Polysaccharide Anti- Pneumococcal Vaccine (s4) Compared to Polysaccharide Anti- Pneumococcal Vaccine Alone (s4) In Patients With Common Variable Immunodeficiency
NCT03513328	PHASE1/PHASE2	COMPLETED	Conditioning Regimen for Allogeneic Hematopoietic Stem-Cell Transplantation
NCT00263237	PHASE1	COMPLETED	STA-5326 Meslylate to Treat Gut Inflammation Associated With Common Variable Immunodeficiency
NCT00943514	Not specified	RECRUITING	Natural History of Bronchiectasis
NCT01652092	Not specified	ACTIVE_NOT_RECRUITING	Allogeneic Hematopoietic Stem Cell Transplant for Patients With Primary Immune Deficiencies
NCT05321407	Not specified	ACTIVE_NOT_RECRUITING	COVID-19 Vaccine Responses in PIDD Subjects
NCT07255157	Not specified	NOT_YET_RECRUITING	Peripheral Helper T-cells in Common Variable ImmunoDeficiency
NCT00004695	Not specified	COMPLETED	Randomized Study of Polyethylene-Glycol-Conjugated Interleukin 2 in Patients With Common Variable Immunodeficiency
NCT00006054	Not specified	TERMINATED	Allogeneic Bone Marrow Transplantation in Patients With Primary Immunodeficiencies
NCT00015431	Not specified	COMPLETED	Immune System and Gut Abnormalities in Patients With Common Variable Immunodeficiency With and Without Gastrointestinal Symptoms
NCT00661401	Not specified	COMPLETED	Specific IgG Antibody in Patients With Primary Antibody Deficiencies Treated With Subcutaneous Immunoglobulin
NCT01196702	Not specified	COMPLETED	Lymphocyte Immunophenotyping in Common Variable Immunodeficiency
NCT01981785	Not specified	UNKNOWN	Investigation of Immune Disorders and Deficiencies
NCT02960399	Not specified	TERMINATED	Assessment of Immunogenicity of Zostavax® in Patients With Antibody Deficiency 60 Years of Age and Older
NCT03188419	Not specified	COMPLETED	Breadth of Donor Options for People With Inherited Diseases Requiring Allogeneic Hematopoietic Stem Cell Transplant in the Era of Alternative Donor Transplants Using Post-Transplantation Cyclophosphamide
NCT03211689	Not specified	COMPLETED	The Impact of Exercise on Stress, Fatigue, and Quality of Life in Individuals With Primary Immunodeficiency Disease
NCT03534479	Not specified	COMPLETED	Human IgGs and Endothelial Function in Vivo in Humans
NCT05310604	Not specified	COMPLETED	Early Detection of Primary Antibody Deficiencies in Primary Care Facilities by an Algorithm Driven Selection of Serologic Testing in Individuals at Risk.
NCT05481554	Not specified	UNKNOWN	Composition and Function of Gut Microbiota in Porto-sinusoidal Vascular Disease Associated With Variable Common Immunodeficiency

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
HUMAN IMMUNOGLOBULIN G	4	3
DEXTROSE	4	1
LENIOLISIB	4	1
PENTOSTATIN	4	1
RIFAXIMIN	4	1
APILIMOD	2	1
FISETIN	2	1
CHEMBL423707	0	1
CHEMBL3643409	0	1