Autosomal agammaglobulinemia

Summary

Autosomal agammaglobulinemia (MONDO:0011096) is a disease (an umbrella term covering 8 Mondo subtypes) with 9 cohort genes. The dominant Reactome pathway is Antigen activates B Cell Receptor (BCR) leading to generation of second messengers (5 cohort genes).

At a glance

• Prevalence: (Worldwide) [Orphanet-validated]
• Umbrella term: 8 Mondo subtypes
• Cohort genes: 9
• Phenotypes (HPO): 29

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		100	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Europe	Not yet validated

Signs & symptoms

Clinical features (HPO)

29 HPO clinical features (Orphanet curated; top 29 by frequency):

HPO ID	Term	Frequency
HP:0000246	Sinusitis	Very frequent (80-99%)
HP:0000389	Chronic otitis media	Very frequent (80-99%)
HP:0000509	Conjunctivitis	Very frequent (80-99%)
HP:0000988	Skin rash	Very frequent (80-99%)
HP:0001581	Recurrent skin infections	Very frequent (80-99%)
HP:0001945	Fever	Very frequent (80-99%)
HP:0002014	Diarrhea	Very frequent (80-99%)
HP:0002205	Recurrent respiratory infections	Very frequent (80-99%)
HP:0002719	Recurrent infections	Very frequent (80-99%)
HP:0002721	Immunodeficiency	Very frequent (80-99%)
HP:0004432	Agammaglobulinemia	Very frequent (80-99%)
HP:0012378	Fatigue	Very frequent (80-99%)
HP:0012735	Cough	Very frequent (80-99%)
HP:0001369	Arthritis	Frequent (30-79%)
HP:0001508	Failure to thrive	Frequent (30-79%)
HP:0002754	Osteomyelitis	Frequent (30-79%)
HP:0000218	High palate	Occasional (5-29%)
HP:0000286	Epicanthus	Occasional (5-29%)
HP:0000316	Hypertelorism	Occasional (5-29%)
HP:0001287	Meningitis	Occasional (5-29%)
HP:0001875	Decreased total neutrophil count	Occasional (5-29%)
HP:0001944	Dehydration	Occasional (5-29%)
HP:0002024	Malabsorption	Occasional (5-29%)
HP:0002110	Bronchiectasis	Occasional (5-29%)
HP:0012115	Hepatitis	Occasional (5-29%)
HP:0100658	Cellulitis	Occasional (5-29%)
HP:0100806	Sepsis	Occasional (5-29%)
HP:0200043	Verrucae	Occasional (5-29%)
HP:0000377	Abnormal pinna morphology	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	autosomal agammaglobulinemia
Mondo ID	MONDO:0011096
MeSH	C538056
Orphanet	33110
UMLS	C1832241
MedGen	316941
GARD	0009640
Is cancer (heuristic)	no

Also known as: agammaglobulinemia, non-Bruton type · AGM

Data availability: 8 GenCC gene-disease records.

Disease family

An umbrella term covering 8 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › immune system disorder › inborn error of immunity › B cell deficiency › agammaglobulinemia › isolated agammaglobulinemia › autosomal agammaglobulinemia

Related subtypes (1): Bruton-type agammaglobulinemia

Subtypes (8): agammaglobulinemia 6, autosomal recessive, agammaglobulinemia 2, autosomal recessive, agammaglobulinemia 3, autosomal recessive, agammaglobulinemia 4, autosomal recessive, agammaglobulinemia 5, autosomal dominant, agammaglobulinemia 7, autosomal recessive, agammaglobulinemia 8, autosomal dominant, autosomal recessive agammaglobulinemia 1

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 46 · Orphanet: 12 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

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

Gene	Classification	Inheritance	Disease	Records
CD79A	Definitive	Autosomal recessive	agammaglobulinemia 3, autosomal recessive	4
IGHM	Definitive	Autosomal recessive	autosomal recessive agammaglobulinemia 1	4
BLNK	Strong	Autosomal recessive	agammaglobulinemia 4, autosomal recessive	4
CD79B	Strong	Autosomal recessive	agammaglobulinemia 6, autosomal recessive	3
IGLL1	Strong	Autosomal recessive	agammaglobulinemia 2, autosomal recessive	5
PIK3R1	Strong	Autosomal recessive	agammaglobulinemia 7, autosomal recessive	13
TCF3	Strong	Autosomal dominant	agammaglobulinemia 8, autosomal dominant	5
TCF7L1	Strong	Autosomal dominant	agammaglobulinemia 8, autosomal dominant	6
LRRC8A	Supportive	Autosomal dominant	autosomal agammaglobulinemia	2

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TCF3	Orphanet:33110	Autosomal non-syndromic agammaglobulinemia
TCF3	Orphanet:585956	B-lymphoblastic leukemia/lymphoma with t(1;19)(q23;p13.3)
TCF3	Orphanet:641375	B-lymphoblastic leukemia/lymphoma with t(17;19)
BLNK	Orphanet:33110	Autosomal non-syndromic agammaglobulinemia
CD79A	Orphanet:33110	Autosomal non-syndromic agammaglobulinemia
CD79B	Orphanet:33110	Autosomal non-syndromic agammaglobulinemia
LRRC8A	Orphanet:33110	Autosomal non-syndromic agammaglobulinemia
IGHM	Orphanet:33110	Autosomal non-syndromic agammaglobulinemia
IGLL1	Orphanet:33110	Autosomal non-syndromic agammaglobulinemia
PIK3R1	Orphanet:3163	SHORT syndrome
PIK3R1	Orphanet:33110	Autosomal non-syndromic agammaglobulinemia
PIK3R1	Orphanet:693681	Activated PI3K-delta syndrome 2

Cohort genes → proteins

9 cohort genes, 9 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	9

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TCF3	HGNC:11633	ENSG00000071564	P15923	Transcription factor E2-alpha	gencc
TCF7L1	HGNC:11640	ENSG00000152284	Q9HCS4	Transcription factor 7-like 1	gencc
BLNK	HGNC:14211	ENSG00000095585	Q8WV28	B-cell linker protein	gencc
CD79A	HGNC:1698	ENSG00000105369	P11912	B-cell antigen receptor complex-associated protein alpha chain	gencc
CD79B	HGNC:1699	ENSG00000007312	P40259	B-cell antigen receptor complex-associated protein beta chain	gencc
LRRC8A	HGNC:19027	ENSG00000136802	Q8IWT6	Volume-regulated anion channel subunit LRRC8A	gencc
IGHM	HGNC:5541	ENSG00000211899	P01871	Immunoglobulin heavy constant mu	gencc
IGLL1	HGNC:5870	ENSG00000128322	P15814	Immunoglobulin lambda-like polypeptide 1	gencc
PIK3R1	HGNC:8979	ENSG00000145675	P27986	Phosphatidylinositol 3-kinase regulatory subunit alpha	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TCF3	Transcription factor E2-alpha	Transcriptional regulator involved in the initiation of neuronal differentiation and mesenchymal to epithelial transition.
TCF7L1	Transcription factor 7-like 1	Participates in the Wnt signaling pathway.
BLNK	B-cell linker protein	Functions as a central linker protein, downstream of the B-cell receptor (BCR), bridging the SYK kinase to a multitude of signaling pathways and regulating biological outcomes of B-cell function and development.
CD79A	B-cell antigen receptor complex-associated protein alpha chain	Required in cooperation with CD79B for initiation of the signal transduction cascade activated by binding of antigen to the B-cell antigen receptor complex (BCR) which leads to internalization of the complex, trafficking to late endosomes…
CD79B	B-cell antigen receptor complex-associated protein beta chain	Required in cooperation with CD79A for initiation of the signal transduction cascade activated by the B-cell antigen receptor complex (BCR) which leads to internalization of the complex, trafficking to late endosomes and antigen presentati…
LRRC8A	Volume-regulated anion channel subunit LRRC8A	Essential component of the volume-regulated anion channel (VRAC, also named VSOAC channel), an anion channel required to maintain a constant cell volume in response to extracellular or intracellular osmotic changes.
IGHM	Immunoglobulin heavy constant mu	Constant region of immunoglobulin heavy chains.
IGLL1	Immunoglobulin lambda-like polypeptide 1	Critical for B-cell development.
PIK3R1	Phosphatidylinositol 3-kinase regulatory subunit alpha	Binds to activated (phosphorylated) protein-Tyr kinases, through its SH2 domain, and acts as an adapter, mediating the association of the p110 catalytic unit to the plasma membrane.

Protein-family classification

Druggable: 5 · Difficult: 2 · Unknown: 2 · Druggable fraction: 0.56

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	4	13.0×	7e-04
Kinase	1	3.1×	0.692
Scaffold/PPI	1	1.9×	0.692
Transcription factor	1	0.9×	0.859
Other/Unknown	2	0.4×	0.992

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TCF3	Transcription factor	no		bHLH_dom, HLH_DNA-bd_sf, NeuroDiff_E-box_TFs
TCF7L1	Other/Unknown	no		HMG_box_dom, CTNNB1-bd_N, TCF/LEF
BLNK	Scaffold/PPI	no		SH2, SH2_dom_sf, Immunoreceptor_sig_adapters
CD79A	Antibody/Immunoglobulin	yes		Phos_immunorcpt_sig_ITAM, Ig_sub2, Ig_sub
CD79B	Antibody/Immunoglobulin	yes		Phos_immunorcpt_sig_ITAM, Ig_sub, Ig-like_dom
LRRC8A	Other/Unknown	no		Leu-rich_rpt, Leu-rich_rpt_typical-subtyp, LRRC8_Pannexin-like
IGHM	Antibody/Immunoglobulin	yes		Ig/MHC_CS, Ig_C1-set, Ig-like_dom
IGLL1	Antibody/Immunoglobulin	yes		Ig/MHC_CS, Ig_C1-set, Ig-like_dom
PIK3R1	Kinase	yes	2.7.1.153	RhoGAP_dom, SH2, SH3_domain

Expression context

Cohort genes with no expression data: 0.

9 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)	9
unknown	0

Top tissues across cohort

Tissue	Cohort genes
granulocyte	3
spleen	3
corpus epididymis	2
lymph node	2
embryo	1
ganglionic eminence	1
ventricular zone	1
aorta	1
popliteal artery	1
tibial artery	1
oral cavity	1
tongue squamous epithelium	1
gingiva	1
gingival epithelium	1
nasal cavity epithelium	1
vermiform appendix	1
bone marrow	1
bone marrow cell	1
male germ line stem cell (sensu Vertebrata) in testis	1
calcaneal tendon	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TCF3	294	ubiquitous	marker	ganglionic eminence, ventricular zone, embryo
TCF7L1	230	ubiquitous	marker	popliteal artery, tibial artery, aorta
BLNK	257	broad	marker	tongue squamous epithelium, oral cavity, corpus epididymis
CD79A	182	broad	marker	spleen, granulocyte, lymph node
CD79B	210	broad	marker	granulocyte, spleen, lymph node
LRRC8A	262	ubiquitous	marker	gingival epithelium, nasal cavity epithelium, gingiva
IGHM	180	tissue_specific	marker	spleen, granulocyte, vermiform appendix
IGLL1	112	tissue_specific	marker	bone marrow, bone marrow cell, male germ line stem cell (sensu Vertebrata) in testis
PIK3R1	294	ubiquitous	marker	calcaneal tendon, caput epididymis, corpus epididymis

Protein interactions among cohort

Intra-cohort edges: 10.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PIK3R1	5,168
CD79A	3,177
CD79B	2,382
TCF7L1	1,635
LRRC8A	1,554
BLNK	1,475
IGLL1	1,349
TCF3	457
IGHM	93

Intra-cohort edges

A	B	Sources
BLNK	CD79A	biogrid_interaction, string_interaction
BLNK	CD79B	string_interaction
BLNK	IGLL1	string_interaction
BLNK	LRRC8A	string_interaction
CD79A	CD79B	string_interaction
CD79A	IGLL1	string_interaction
CD79A	LRRC8A	string_interaction
CD79B	IGLL1	string_interaction
CD79B	LRRC8A	string_interaction
IGLL1	LRRC8A	string_interaction

Structural data

PDB: 8 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PIK3R1	P27986	105
IGHM	P01871	31
LRRC8A	Q8IWT6	9
TCF3	P15923	5
CD79A	P11912	5
CD79B	P40259	5
IGLL1	P15814	3
BLNK	Q8WV28	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
TCF7L1	Q9HCS4	52.59

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 122. Enrichment computed across 9 evidence-associated genes (9 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 9 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Antigen activates B Cell Receptor (BCR) leading to generation of second messengers	5	198.3×	2e-09	BLNK, CD79A, CD79B, IGHM, PIK3R1
CD22 mediated BCR regulation	3	761.3×	2e-07	CD79A, CD79B, IGHM
Potential therapeutics for SARS	4	50.8×	3e-05	BLNK, CD79A, CD79B, IGHM
Signaling by the B Cell Receptor (BCR)	3	115.3×	6e-05	BLNK, CD79A, CD79B
Regulation of signaling by CBL	2	110.3×	0.003	BLNK, PIK3R1
Interleukin-3, Interleukin-5 and GM-CSF signaling	2	70.5×	0.007	BLNK, PIK3R1
SARS-CoV Infections	3	18.5×	0.008	BLNK, CD79A, CD79B
Viral Infection Pathways	3	10.3×	0.037	BLNK, CD79A, CD79B
Adaptive Immune System	3	9.9×	0.037	BLNK, CD79A, CD79B
MET activates PI3K/AKT signaling	1	211.5×	0.044	PIK3R1
Activated NTRK3 signals through PI3K	1	211.5×	0.044	PIK3R1
Cell surface interactions at the vascular wall	2	21.1×	0.044	IGHM, IGLL1
Infectious disease	3	8.3×	0.044	BLNK, CD79A, CD79B
Activated NTRK2 signals through PI3K	1	181.3×	0.044	PIK3R1
Signaling by LTK in cancer	1	181.3×	0.044	PIK3R1
PI3K/AKT activation	1	141.0×	0.044	PIK3R1
Binding of TCF/LEF:CTNNB1 to target gene promoters	1	126.9×	0.044	TCF7L1
RUNX3 regulates WNT signaling	1	126.9×	0.044	TCF7L1
IRS-mediated signalling	1	115.3×	0.044	PIK3R1
PI3K events in ERBB4 signaling	1	115.3×	0.044	PIK3R1
Co-stimulation by ICOS	1	115.3×	0.044	PIK3R1
GP1b-IX-V activation signalling	1	105.7×	0.044	PIK3R1
Signaling by FGFR4 in disease	1	105.7×	0.044	PIK3R1
Erythropoietin activates Phosphoinositide-3-kinase (PI3K)	1	105.7×	0.044	PIK3R1
Signaling by PDGFRA transmembrane, juxtamembrane and kinase domain mutants	1	97.6×	0.044	PIK3R1
Signaling by PDGFRA extracellular domain mutants	1	97.6×	0.044	PIK3R1
Signaling by LTK	1	97.6×	0.044	PIK3R1
Signaling by FLT3 ITD and TKD mutants	1	84.6×	0.044	PIK3R1
Repression of WNT target genes	1	79.3×	0.044	TCF7L1
Constitutive Signaling by EGFRvIII	1	79.3×	0.044	PIK3R1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 9 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
B cell differentiation	5	121.6×	2e-08	TCF3, BLNK, CD79A, CD79B, PIK3R1
B cell receptor signaling pathway	4	178.3×	2e-07	BLNK, CD79A, CD79B, IGHM
intracellular glucose homeostasis	2	129.1×	0.003	LRRC8A, PIK3R1
adaptive immune response	3	28.1×	0.003	CD79A, CD79B, IGHM
pre-B cell differentiation	1	1872.4×	0.009	LRRC8A
immune response	3	15.7×	0.010	CD79B, IGLL1, PIK3R1
pre-B cell allelic exclusion	1	624.1×	0.015	IGHM
regulation of toll-like receptor 4 signaling pathway	1	624.1×	0.015	PIK3R1
positive regulation of endoplasmic reticulum unfolded protein response	1	624.1×	0.015	PIK3R1
myeloid leukocyte migration	1	468.1×	0.018	PIK3R1
B cell lineage commitment	1	374.5×	0.018	TCF3
taurine transmembrane transport	1	312.1×	0.018	LRRC8A
immunoglobulin V(D)J recombination	1	312.1×	0.018	TCF3
interleukin-18-mediated signaling pathway	1	312.1×	0.018	PIK3R1
monoatomic anion transmembrane transport	1	312.1×	0.018	LRRC8A
cyclic-GMP-AMP transmembrane import across plasma membrane	1	234.1×	0.023	LRRC8A
positive regulation of focal adhesion disassembly	1	208.1×	0.024	PIK3R1
response to osmotic stress	1	170.2×	0.025	LRRC8A
monoatomic anion transport	1	156.0×	0.025	LRRC8A
aspartate transmembrane transport	1	156.0×	0.025	LRRC8A
protein hexamerization	1	156.0×	0.025	LRRC8A
T follicular helper cell differentiation	1	156.0×	0.025	PIK3R1
growth hormone receptor signaling pathway	1	133.8×	0.028	PIK3R1
positive regulation of RNA splicing	1	117.0×	0.031	PIK3R1
positive regulation of leukocyte migration	1	110.1×	0.031	PIK3R1
negative regulation of cell-matrix adhesion	1	98.5×	0.032	PIK3R1
regulation of Wnt signaling pathway	1	98.5×	0.032	TCF7L1
immunoglobulin mediated immune response	1	78.0×	0.039	IGLL1
cell volume homeostasis	1	66.9×	0.041	LRRC8A
positive regulation of lamellipodium assembly	1	66.9×	0.041	PIK3R1

Therapeutics

Drug target analysis

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

Druggability breadth: 2 of 9 evidence-associated genes (22%) 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
PIK3R1	IDELALISIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PIK3R1	26	4
TCF3	0	0
TCF7L1	0	0
BLNK	0	0
CD79A	0	0
CD79B	0	0
LRRC8A	0	0
IGHM	0	0
IGLL1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
IDELALISIB	4	PIK3R1
ALPELISIB	4	PIK3R1
DUVELISIB	4	PIK3R1
COPANLISIB	4	PIK3R1
UMBRALISIB	4	PIK3R1
DACTOLISIB	3	PIK3R1
BUPARLISIB	3	PIK3R1
QUERCETIN	3	PIK3R1
OMIPALISIB	2	PIK3R1
VISTUSERTIB	2	PIK3R1
FIMEPINOSTAT	2	PIK3R1
EGANELISIB	2	PIK3R1
BERZOSERTIB	2	PIK3R1
BIMIRALISIB	2	PIK3R1
PICTILISIB	2	PIK3R1
ZSTK-474	2	PIK3R1
GSK-2636771	2	PIK3R1
AMDIZALISIB	2	PIK3R1
RISOVALISIB	2	PIK3R1
DEZAPELISIB	2	PIK3R1
ROGINOLISIB	2	PIK3R1
AZD-8055	1	PIK3R1
VS-5584	1	PIK3R1
AZD-8186	1	PIK3R1
GS-9901	1	PIK3R1
AZD-7648	1	PIK3R1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
PIK3R1	493	Binding:470, ADMET:23
CD79B	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
PIK3R1	2.7.1.153	phosphatidylinositol-4,5-bisphosphate 3-kinase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
PIK3R1	493

Pharmacogenomics

Cohort genes with a PharmGKB record: 9; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

26 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)
IDELALISIB	4	PIK3R1
ALPELISIB	4	PIK3R1
DUVELISIB	4	PIK3R1
COPANLISIB	4	PIK3R1
UMBRALISIB	4	PIK3R1
DACTOLISIB	3	PIK3R1
BUPARLISIB	3	PIK3R1
QUERCETIN	3	PIK3R1
OMIPALISIB	2	PIK3R1
VISTUSERTIB	2	PIK3R1
FIMEPINOSTAT	2	PIK3R1
EGANELISIB	2	PIK3R1
BERZOSERTIB	2	PIK3R1
BIMIRALISIB	2	PIK3R1
PICTILISIB	2	PIK3R1
ZSTK-474	2	PIK3R1
GSK-2636771	2	PIK3R1
AMDIZALISIB	2	PIK3R1
RISOVALISIB	2	PIK3R1
DEZAPELISIB	2	PIK3R1
ROGINOLISIB	2	PIK3R1
AZD-8055	1	PIK3R1
VS-5584	1	PIK3R1
AZD-8186	1	PIK3R1
GS-9901	1	PIK3R1
AZD-7648	1	PIK3R1

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	PIK3R1
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	4	CD79A, CD79B, IGHM, IGLL1
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	4	TCF3, TCF7L1, BLNK, LRRC8A

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
TCF3	0	—
TCF7L1	0	—
BLNK	0	—
CD79A	0	—
CD79B	1	—
LRRC8A	0	—
IGHM	0	—
IGLL1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.