CD79B

Summary

CD79B (CD79b molecule, HGNC:1699) is a protein-coding gene on chromosome 17q23.3, encoding B-cell antigen receptor complex-associated protein beta chain (P40259). 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 presentation.

The B lymphocyte antigen receptor is a multimeric complex that includes the antigen-specific component, surface immunoglobulin (Ig). Surface Ig non-covalently associates with two other proteins, Ig-alpha and Ig-beta, which are necessary for expression and function of the B-cell antigen receptor. This gene encodes the Ig-beta protein of the B-cell antigen component. Alternatively spliced transcript variants encoding different isoforms have been described.

Source: NCBI Gene 974 — RefSeq curated summary.

At a glance

• Gene–disease (curated): agammaglobulinemia 6, autosomal recessive (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 2
• Clinical variants (ClinVar): 191 total — 2 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 41
• Druggable target: yes
• Cancer driver (intOGen): activating (oncogene-like) across 3 cancer types
• MANE Select transcript: NM_000626

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1699
Approved symbol	CD79B
Name	CD79b molecule
Location	17q23.3
Locus type	gene with protein product
Status	Approved
Aliases	B29, Ig-beta, Igbeta
Ensembl gene	ENSG00000007312
Ensembl biotype	protein_coding
OMIM	147245
Entrez	974

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 5 protein_coding, 4 retained_intron

ENST00000006750, ENST00000349817, ENST00000392795, ENST00000558969, ENST00000559358, ENST00000583260, ENST00000698624, ENST00000903736, ENST00000920712

RefSeq mRNA: 4 — MANE Select: NM_000626 NM_000626, NM_001039933, NM_001329050, NM_021602

CCDS: CCDS11655, CCDS11656, CCDS42372

Canonical transcript exons

ENST00000006750 — 6 exons

Exon	Start	End
ENSE00000857852	63930074	63930385
ENSE00000857853	63931335	63931385
ENSE00001331113	63932195	63932331
ENSE00003501045	63929770	63929888
ENSE00003602262	63929434	63929475
ENSE00003903376	63928740	63929324

Expression profiles

Bgee: expression breadth ubiquitous, 210 present calls, max score 97.51.

FANTOM5 (CAGE): breadth broad, TPM avg 8.2512 / max 1320.9225, expressed in 262 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
167534	7.8423	233
167535	0.3700	106
167532	0.0389	20

Top tissues by expression

267 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	97.51	gold quality
spleen	UBERON:0002106	97.49	gold quality
lymph node	UBERON:0000029	95.70	gold quality
vermiform appendix	UBERON:0001154	94.40	gold quality
apex of heart	UBERON:0002098	89.70	gold quality
blood	UBERON:0000178	89.59	gold quality
caecum	UBERON:0001153	88.81	gold quality
leukocyte	CL:0000738	88.66	gold quality
monocyte	CL:0000576	88.09	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	88.03	gold quality
bone marrow	UBERON:0002371	87.93	gold quality
mononuclear cell	CL:0000842	87.87	gold quality
adenohypophysis	UBERON:0002196	87.37	gold quality
bone marrow cell	CL:0002092	86.72	gold quality
pituitary gland	UBERON:0000007	86.48	gold quality
tendon of biceps brachii	UBERON:0008188	86.43	gold quality
small intestine Peyer’s patch	UBERON:0003454	84.96	gold quality
buccal mucosa cell	CL:0002336	83.78	gold quality
tonsil	UBERON:0002372	83.42	gold quality
minor salivary gland	UBERON:0001830	81.34	gold quality
small intestine	UBERON:0002108	80.90	gold quality
gall bladder	UBERON:0002110	80.63	gold quality
epithelium of nasopharynx	UBERON:0001951	80.35	gold quality
mucosa of transverse colon	UBERON:0004991	80.30	gold quality
trabecular bone tissue	UBERON:0002483	79.73	gold quality
saliva-secreting gland	UBERON:0001044	79.63	gold quality
mouth mucosa	UBERON:0003729	78.90	gold quality
superficial temporal artery	UBERON:0001614	78.51	gold quality
omental fat pad	UBERON:0010414	78.31	gold quality
peritoneum	UBERON:0002358	78.27	gold quality

Single-cell (SCXA)

Detected in 35 experiment(s), a significant marker in 33.

Experiment	Marker?	Max mean expression
E-MTAB-6505	yes	4883.10
E-HCAD-4	yes	4558.60
E-MTAB-9801	yes	4318.02
E-CURD-112	yes	3903.12
E-MTAB-9906	yes	3504.44
E-HCAD-6	yes	3426.74
E-MTAB-9067	yes	3163.86
E-MTAB-7407	yes	3019.45
E-MTAB-10042	yes	2975.82
E-MTAB-8221	yes	2828.49
E-GEOD-130473	yes	2784.88
E-CURD-122	yes	2503.76
E-GEOD-139324	yes	2086.19
E-HCAD-10	yes	1772.31
E-CURD-6	yes	1710.35

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): EBF1, MYC, NFKB, TCF3

miRNA regulators (miRDB)

11 targeting CD79B, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-361-3P	99.19	66.45	1381
HSA-MIR-4660	97.79	67.44	1328
HSA-MIR-3144-5P	97.64	65.45	646
HSA-MIR-4640-5P	97.42	66.33	1543
HSA-MIR-6508-3P	96.73	65.48	576
HSA-MIR-6851-3P	95.73	65.11	688

Literature-anchored findings (GeneRIF, showing 38)

• The B cell-specific B29 gene promoter is transactivated in B and non-B cells by cotransfection with the B cell-specific octamer cofactor gene, Bob1 (OCA-B/OBF-1). (PMID:11907094)
• The alternative splicing variant DeltaCD79b may be a powerful modulator of BCR signaling that may play an important role in normal and malignant B cell (PMID:12384401)
• There is a somatic hypermutation of this gene in B-cell lymphoma and multiple myeloma. (PMID:12651942)
• Following B cell receptor cross-linking, a significant amount of the transgenic Ig beta pool (together with Ig alpha) remains on the B cell surface independent of surface immunoglobulin internalization. (PMID:15661909)
• Results reveal tissue-specific patterns of chromatin structures and transcriptional controls at the CD79b/GH locus in B cells distinct from those in the pituitary gland and placenta. (PMID:16847312)
• establish a strong linkage between Igbeta mRNA expression and somatic hypermutation in chronic lymphocytic leukaemia and highlight the complex relationships between biochemical parameters and clinical status in this disease (PMID:17315213)
• Anti-CD79b antibodies downregulated surface B-cell receptor and were trafficked to the lysosomal-like major histocompatibility complex class II-positive compartment of a mouse xenograft model of non-Hodgkin lymphoma. (PMID:17374736)
• Ig-beta was phosphorylated in about 20% of myeloma IgG BCR isolates, but not in normal B-cell controls. (PMID:17701175)
• These results indicate that mutations in Igbeta can cause agammaglobulinemia in man. (PMID:17709424)
• mutations responsible for agammaglobulinemia in humans (PMID:18978465)
• STN produced significant antitumor effects in a mouse xenograft model of CD79A/B-mutated DLBCL. (PMID:21324920)
• Expression of CD79b is downregulated in both plasma cells and plasma cell myeloma. (PMID:21355953)
• The present study failed to find any mut-ation in MYD88, CARD11 or CD79B in ocular MALT lymphoma. (PMID:22808296)
• CD79B point mutation is associated with B-cell non-Hodgkin lymphomas. (PMID:23361872)
• Data indicate a secondary promoter located within exon 2 maintained full levels and specificity of hCD79b transcription. (PMID:23649625)
• results suggest that MYD88 mutations, and to a lesser extent CD79B mutations, are important drivers of lymphomagenesis in PTL (PMID:24253023)
• CD79B and MYD88 mutations are associated with an older age at onset in diffuse large b-cell lymphoma with a significant overlap, which did not affect the outcome of the disease. (PMID:24444466)
• Phosphorylation of CD79a causes a decrease in helical propensity in the C-terminal region, for CD79b, the opposite was observed and phosphorylation resulted in an increase of helical propensity in the C-terminal part. (PMID:24769851)
• Oncogenic CD79B mutation is associated with primary diffuse large B-cell lymphomas of central nervous system. (PMID:25347427)
• Abberant expression of CD79b in non-B cells caused unwanted reactivity, rendering CD79b unsuitable for T-cell receptor - based immunotherapies. (PMID:25414443)
• Diffuse large B cell lymphomas relapsing in the CNS lack oncogenic MYD88 and CD79B mutations. (PMID:25501023)
• hotspot mutations of CD79B Y196 and MYD88 L265 may serve as a genetic hallmark for primary central nervous system lymphoma (PMID:26111727)
• CD79B overexpression leading to activation of AKT/MAPK is a potential mechanism underlying primary ibrutinib resistance in ABC-DLBCL, and support its utility as an effective biomarker to predict therapeutic response to ibrutinib. (PMID:26699656)
• MYD88 L265P and CD79B mutations were frequently detected in primary breast diffuse large B-cell lymphoma. (PMID:26752547)
• Novel CD79B variations in mature B-cell non-Hodgkin’s lymphoma patients were detected. (PMID:27010137)
• Patients with primary breast and primary female genital tract diffuse large B cell lymphoma have a high frequency of CD79B mutations. (PMID:28803429)
• CD79B mutations were found in six of 19 cases (31.6%) of primary CNS diffuse large B-cell lymphoma , all in the Y196 mutation hotspot (PMID:28856744)
• mutational frequencies in CD79B and MYD88 greatly varied with respect to tissue distribution (PMID:28868954)
• CD79B Y196 mutation occurs in 26% of patients with intravascular large B-cell lymphoma (IVLBCL) in Dutch study. (PMID:29514783)
• MYD88, CARD11, and CD79B Oncogenic Mutations are Rare Events in the Indian Cohort of De Novo Nodal Diffuse Large B-Cell Lymphoma. (PMID:29734251)
• Detecting CD79B(Y196) in vitreous DNA may contribute to the confirmation of the diagnosis and may have a prognostic potential for patients with PVRL. (PMID:30390359)
• Genetically, primary adrenal diffuse large B-cell lymphoma harbor a high prevalence of MYD88 L265P (24%) and CD79B mutations (52%) which may be involved in lymphomagenesis. (PMID:31609782)
• primary vitreoretinal lymphoma had unique genetic features: an expression pattern different from activated B-cell type and relatively close to germinal center B-cell-type diffuse large B-cell lymphoma. CD79B mutations showed potential to serve as prognostic markers for CNS progression (PMID:32056332)
• A New Missense Mutation in CD79B Leads to Autosomal Recessive Agammaglobulinemia in Two Siblings. (PMID:33733381)
• Prevalence and prognostic value of MYD88 and CD79B mutations in ocular adnexal large B-cell lymphoma: a reclassification of ocular adnexal large B-cell lymphoma. (PMID:34706861)
• The Prognostic Significance of CD79B Mutation in Diffuse Large B-Cell Lymphoma: A Meta-analysis and Systematic Literature Review. (PMID:36182550)
• Mechanism of CD79A and CD79B Support for IgM+ B Cell Fitness through B Cell Receptor Surface Expression. (PMID:36426942)
• CD79B Y196 mutation is a potent predictive marker for favorable response to R-MPV in primary central nervous system lymphoma. (PMID:36478416)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	cd79b	ENSDARG00000104691
mus_musculus	Cd79b	ENSMUSG00000040592
rattus_norvegicus	Cd79b	ENSRNOG00000011917

Paralogs (1): CD79A (ENSG00000105369)

Protein

Protein identifiers

B-cell antigen receptor complex-associated protein beta chain — P40259 (reviewed: P40259)

Alternative names: B-cell-specific glycoprotein B29, Ig-beta, Immunoglobulin-associated B29 protein

All UniProt accessions (1): P40259

UniProt curated annotations — full annotation on UniProt →

Function. 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 presentation. Enhances phosphorylation of CD79A, possibly by recruiting kinases which phosphorylate CD79A or by recruiting proteins which bind to CD79A and protect it from dephosphorylation.

Subunit / interactions. Heterodimer of alpha and beta chains; disulfide-linked. Part of the B-cell antigen receptor complex where the alpha/beta chain heterodimer is non-covalently associated with an antigen-specific membrane-bound surface immunoglobulin of two heavy chains and two light chains. Interacts with LYN.

Subcellular location. Cell membrane.

Tissue specificity. B-cells.

Post-translational modifications. Phosphorylated on tyrosine upon B-cell activation by SRC-type Tyr-kinases such as BLK, LYN and SYK.

Disease relevance. Agammaglobulinemia 6, autosomal recessive (AGM6) [MIM:612692] A primary immunodeficiency characterized by profoundly low or absent serum antibodies and low or absent circulating B-cells due to an early block of B-cell development. Affected individuals develop severe infections in the first years of life. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The transmembrane helices of CD79A and CD79B chains and two IgM heavy chains assembly in a four-helix bundle structure that appears to be conserved among different BCR isotypes.

Isoforms (3)

UniProt ID	Names	Canonical?
P40259-1	Long	yes
P40259-2	Short
P40259-3	3

RefSeq proteins (4): NP_000617, NP_001035022, NP_001315979, NP_067613 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003110	Phos_immunorcpt_sig_ITAM	Repeat
IPR003599	Ig_sub	Domain
IPR007110	Ig-like_dom	Domain
IPR013106	Ig_V-set	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily

Pfam: PF07686

UniProt features (38 total): strand 11, glycosylation site 4, disulfide bond 3, sequence conflict 3, splice variant 2, mutagenesis site 2, topological domain 2, helix 2, domain 2, modified residue 2, signal peptide 1, chain 1, sequence variant 1, turn 1, transmembrane region 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
7WSO	ELECTRON MICROSCOPY	3.03
3KG5	X-RAY DIFFRACTION	3.2
7XQ8	ELECTRON MICROSCOPY	3.3
7XT6	ELECTRON MICROSCOPY	3.63
7WSP	ELECTRON MICROSCOPY	4.09

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P40259-F1	76.02	0.36

Antibody-complex structures (SAbDab): 1 — 7XQ8

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (2): 196, 207

Disulfide bonds (3): 43–126, 65–122, 136

Glycosylation sites (4): 101, 127, 128, 73

Mutagenesis-validated functional residues (2):

Position	Phenotype
55–57	blocks igm bcr assembly.
161	blocks igm bcr assembly.

Function

Pathways and Gene Ontology

Reactome pathways

10 pathways

ID	Pathway
R-HSA-5690714	CD22 mediated BCR regulation
R-HSA-9679191	Potential therapeutics for SARS
R-HSA-983695	Antigen activates B Cell Receptor (BCR) leading to generation of second messengers
R-HSA-1280218	Adaptive Immune System
R-HSA-1643685	Disease
R-HSA-168256	Immune System
R-HSA-5663205	Infectious disease
R-HSA-9679506	SARS-CoV Infections
R-HSA-9824446	Viral Infection Pathways
R-HSA-983705	Signaling by the B Cell Receptor (BCR)

MSigDB gene sets: 405 (showing top): PID_BCR_5PATHWAY, RNGTGGGC_UNKNOWN, LU_IL4_SIGNALING, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_B_CELL_ACTIVATION, MODULE_64, GOBP_ANTIGEN_RECEPTOR_MEDIATED_SIGNALING_PATHWAY, GOCC_CELL_SURFACE, BIOCARTA_CTCF_PATHWAY, TAL1ALPHAE47_01, GGGTGGRR_PAX4_03, CAGCTG_AP4_Q5, PUJANA_CHEK2_PCC_NETWORK, TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_ERYTHROCYTE_UP, GOBP_REGULATION_OF_IMMUNE_RESPONSE

GO Biological Process (8): adaptive immune response (GO:0002250), immune response (GO:0006955), signal transduction (GO:0007165), response to bacterium (GO:0009617), B cell differentiation (GO:0030183), B cell receptor signaling pathway (GO:0050853), immune system process (GO:0002376), cell surface receptor signaling pathway (GO:0007166)

GO Molecular Function (3): transmembrane signaling receptor activity (GO:0004888), identical protein binding (GO:0042802), protein binding (GO:0005515)

GO Cellular Component (6): plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), B cell receptor complex (GO:0019815), extracellular exosome (GO:0070062), IgM B cell receptor complex (GO:0071755), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-7 pathways:

Category	Pathways
Signaling by the B Cell Receptor (BCR)	2
SARS-CoV Infections	1
Immune System	1
Disease	1
Viral Infection Pathways	1
Infectious disease	1
Adaptive Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
immune response	1
immune system process	1
response to stimulus	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
response to other organism	1
lymphocyte differentiation	1
B cell activation	1
antigen receptor-mediated signaling pathway	1
biological_process	1
signal transduction	1
signaling receptor activity	1
protein binding	1
binding	1
membrane	1
cell periphery	1
plasma membrane	1
cell surface	1
side of membrane	1
immunoglobulin complex	1
plasma membrane signaling receptor complex	1
extracellular vesicle	1
B cell receptor complex	1
IgM immunoglobulin complex	1
cellular anatomical structure	1

Protein interactions and networks

STRING

2156 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CD79B	CD79A	P11912	993
CD79B	SYK	P43405	993
CD79B	VPREB1	P12018	993
CD79B	IGLL1	P15814	991
CD79B	CXCL9	Q07325	989
CD79B	LYN	P07948	975
CD79B	BTK	Q06187	927
CD79B	BLNK	Q8WV28	925
CD79B	CD19	P15391	893
CD79B	IGHV4-38-2	P0DP08	891
CD79B	CD22	P20273	860
CD79B	IGLL5	B9A064	857
CD79B	CARD11	Q9BXL7	855
CD79B	CANX	P27824	825
CD79B	PAX5	Q02548	811

IntAct

36 interactions, top by confidence:

A	B	Type	Score
CD79B	SGTA	psi-mi:“MI:0915”(physical association)	0.720
SGTA	CD79B	psi-mi:“MI:0915”(physical association)	0.720
CD79B	SGTB	psi-mi:“MI:0915”(physical association)	0.560
CD79B	BRAF	psi-mi:“MI:0915”(physical association)	0.550
CD79B	BRAF	psi-mi:“MI:2364”(proximity)	0.550
CD79B	GOLIM4	psi-mi:“MI:0914”(association)	0.350
AKT1	CD79B	psi-mi:“MI:2364”(proximity)	0.270
FBXW7	CD79B	psi-mi:“MI:2364”(proximity)	0.270
SMAD4	CD79B	psi-mi:“MI:2364”(proximity)	0.270
CD79B	SMARCA4	psi-mi:“MI:2364”(proximity)	0.270
SMARCA4	CD79B	psi-mi:“MI:2364”(proximity)	0.270
SPOP	CD79B	psi-mi:“MI:2364”(proximity)	0.270
CD79B	SPOP	psi-mi:“MI:2364”(proximity)	0.270
EGFR	CD79B	psi-mi:“MI:2364”(proximity)	0.270
CD79B	PTPN11	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (190): SGTA (Two-hybrid), SGTA (Two-hybrid), TBRG4 (Affinity Capture-MS), NF1 (Affinity Capture-MS), SLC12A6 (Affinity Capture-MS), TRPM4 (Affinity Capture-MS), TSC2 (Affinity Capture-MS), C17orf62 (Affinity Capture-MS), ENTPD4 (Affinity Capture-MS), TMTC4 (Affinity Capture-MS), MANEA (Affinity Capture-MS), TMUB2 (Affinity Capture-MS), C3orf52 (Affinity Capture-MS), ZRANB3 (Affinity Capture-MS), GOLIM4 (Affinity Capture-MS)

ESM2 similar proteins: A2A7V7, A2TGX5, A5D7B2, G3X8R9, O88875, O95944, P0DMS9, P11912, P12318, P15530, P16410, P22273, P31785, P31994, P31995, P34902, P40259, P50283, Q02242, Q1ERP8, Q2LA85, Q2YFS1, Q2YFS2, Q2YFS3, Q3LRV9, Q3U497, Q566E6, Q5T2D2, Q60513, Q6SJQ0, Q6SJQ5, Q6SJQ7, Q6TYI6, Q6UXG3, Q6UXN2, Q7TSN2, Q86YW5, Q8K558, Q8SPV8, Q8TDQ1

Diamond homologs: P15530, P40259, P01693, P11912

SIGNOR signaling

9 interactions.

A	Effect	B	Mechanism
CD79B	“form complex”	BCR-Mk	binding
CD79B	“form complex”	BCR-Ml	binding
CD79B	“form complex”	BCR-Dk	binding
CD79B	“form complex”	BCR-Dl	binding
SH2B1	“down-regulates activity”	CD79B	dephosphorylation
CD79B	up-regulates	TP53
FYN	“up-regulates activity”	CD79B	phosphorylation
LYN	“up-regulates activity”	CD79B	phosphorylation

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 3 cancer types — DLBCLNOS, MLYM, NHL.

Clinical variants and AI predictions

ClinVar

191 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	1
Uncertain significance	62
Likely benign	99
Benign	14

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
14802	NM_000626.4(CD79B):c.409G>A (p.Gly137Ser)	Pathogenic
14803	NM_000626.4(CD79B):c.238C>T (p.Gln80Ter)	Pathogenic
2573989	NM_000626.4(CD79B):c.586T>C (p.Tyr196His)	Likely pathogenic

SpliceAI

864 predictions. Top by Δscore:

Variant	Effect	Δscore
17:63929428:CCTTA:C	donor_loss	1.0000
17:63929429:CTTA:C	donor_loss	1.0000
17:63929430:TTACC:T	donor_loss	1.0000
17:63929431:TA:T	donor_loss	1.0000
17:63929432:A:AC	donor_gain	1.0000
17:63929432:A:AG	donor_loss	1.0000
17:63929433:C:CC	donor_gain	1.0000
17:63929433:CCT:C	donor_gain	1.0000
17:63929471:TCATC:T	acceptor_gain	1.0000
17:63929472:CATC:C	acceptor_gain	1.0000
17:63929472:CATCC:C	acceptor_gain	1.0000
17:63929473:ATC:A	acceptor_gain	1.0000
17:63929474:TC:T	acceptor_gain	1.0000
17:63929475:CC:C	acceptor_gain	1.0000
17:63929475:CCTG:C	acceptor_loss	1.0000
17:63929476:C:CC	acceptor_gain	1.0000
17:63929477:T:A	acceptor_loss	1.0000
17:63929483:C:CT	acceptor_gain	1.0000
17:63929484:G:T	acceptor_gain	1.0000
17:63929766:TCAC:T	donor_loss	1.0000
17:63929767:CACCT:C	donor_loss	1.0000
17:63929769:C:CA	donor_loss	1.0000
17:63929884:GAATC:G	acceptor_gain	1.0000
17:63929885:AATC:A	acceptor_gain	1.0000
17:63929886:ATC:A	acceptor_gain	1.0000
17:63929887:TC:T	acceptor_gain	1.0000
17:63929888:CC:C	acceptor_gain	1.0000
17:63929889:C:CC	acceptor_gain	1.0000
17:63929889:CTG:C	acceptor_loss	1.0000
17:63930072:AC:A	donor_gain	1.0000

AlphaMissense

1510 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:63929845:C:A	K158N	0.998
17:63929845:C:G	K158N	0.998
17:63929290:T:A	D209V	0.997
17:63929291:C:G	D209H	0.997
17:63929293:T:A	E208V	0.997
17:63929287:A:T	I210K	0.996
17:63929290:T:G	D209A	0.996
17:63929320:A:G	L199P	0.996
17:63930146:A:C	Y120D	0.996
17:63930348:G:C	F52L	0.996
17:63930348:G:T	F52L	0.996
17:63930350:A:G	F52L	0.996
17:63929256:C:A	W220C	0.995
17:63929256:C:G	W220C	0.995
17:63929297:A:G	Y207H	0.995
17:63929324:C:G	G198R	0.995
17:63930276:C:A	W76C	0.995
17:63930276:C:G	W76C	0.995
17:63929258:A:G	W220R	0.994
17:63929258:A:T	W220R	0.994
17:63929792:G:C	P176R	0.994
17:63930085:A:G	L140P	0.994
17:63930139:C:G	C122S	0.994
17:63930140:A:T	C122S	0.994
17:63930310:C:G	C65S	0.994
17:63930311:A:T	C65S	0.994
17:63929287:A:C	I210R	0.993
17:63929320:A:T	L199Q	0.993
17:63929792:G:T	P176H	0.993
17:63929292:C:A	E208D	0.992

dbSNP variants (sampled 300 via entrez): RS1001293257 (17:63928357 G>A), RS1001376465 (17:63929608 T>G), RS1001472006 (17:63929131 G>A,C), RS1001771089 (17:63933886 G>A), RS1003428765 (17:63932410 G>A), RS1003748043 (17:63931870 C>T), RS1004423787 (17:63931039 A>G), RS1005413031 (17:63929651 G>A), RS1005589265 (17:63934163 G>A,T), RS1005759979 (17:63929146 G>A,T), RS1005909992 (17:63933013 T>C), RS1006206922 (17:63928951 T>C,G), RS1006416067 (17:63928476 T>C), RS1006667688 (17:63933660 T>A), RS1007552216 (17:63932163 A>C,T)

Disease associations

OMIM: gene MIM:147245 | disease phenotypes: MIM:612692, MIM:170500

GenCC curated gene-disease

Disease	Classification	Inheritance
agammaglobulinemia 6, autosomal recessive	Strong	Autosomal recessive
autosomal agammaglobulinemia	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
agammaglobulinemia 6, autosomal recessive	Definitive	AR

Mondo (4): agammaglobulinemia 6, autosomal recessive (MONDO:0012987), hyperkalemic periodic paralysis (MONDO:0008224), diffuse large B-cell lymphoma (MONDO:0018905), autosomal agammaglobulinemia (MONDO:0011096)

Orphanet (2): Hyperkalemic periodic paralysis (Orphanet:682), Diffuse large B-cell lymphoma (Orphanet:544)

HPO phenotypes

41 total (30 of 41 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000218	High palate
HP:0000246	Sinusitis
HP:0000286	Epicanthus
HP:0000316	Hypertelorism
HP:0000377	Abnormal pinna morphology
HP:0000389	Chronic otitis media
HP:0000403	Recurrent otitis media
HP:0000509	Conjunctivitis
HP:0000988	Skin rash
HP:0001287	Meningitis
HP:0001369	Arthritis
HP:0001508	Failure to thrive
HP:0001581	Recurrent skin infections
HP:0001875	Decreased total neutrophil count
HP:0001944	Dehydration
HP:0001945	Fever
HP:0002014	Diarrhea
HP:0002024	Malabsorption
HP:0002110	Bronchiectasis
HP:0002205	Recurrent respiratory infections
HP:0002718	Recurrent bacterial infections
HP:0002719	Recurrent infections
HP:0002720	Decreased circulating IgA concentration
HP:0002721	Immunodeficiency
HP:0002754	Osteomyelitis
HP:0002837	Recurrent bronchitis
HP:0002843	Abnormal T cell morphology
HP:0002850	Decreased circulating total IgM
HP:0003593	Infantile onset

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST002647_155	Height	6.000000e-41
GCST90020028_1585	Hip circumference adjusted for BMI	3.000000e-17

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0008039	BMI-adjusted hip circumference

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D016403	Lymphoma, Large B-Cell, Diffuse	C04.557.386.480.150.585; C15.604.515.569.480.150.585; C20.683.515.761.480.150.585
D020513	Paralysis, Hyperkalemic Periodic	C05.651.701.600; C10.668.491.650.600; C16.320.565.618.711.600; C18.452.648.618.711.600
C538056	Agammaglobulinemia, non-Bruton type (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3712852 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: other protein — CD molecules

ChEMBL bioactivities

1 potent at pChembl≥5 of 1 total, top 1 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.01	Ki	97	nM	CHEMBL5630968

PubChem BioAssay actives

1 with measured affinity, of 1 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
[dibromo-[[[(2R,3S,4R,5R)-5-[2-chloro-6-(diethylamino)purin-9-yl]-3,4-dihydroxyoxolan-2-yl]methoxymethyl-hydroxyphosphoryl]oxy-hydroxyphosphoryl]methyl]phosphonic acid	2132862: Binding affinity to human recombinant CD79 expressed in Sf9 cells assessed as inhibition constant by malachite green based spectrophotometer assay	ki	0.0970	uM

CTD chemical–gene interactions

22 total (human), top 22 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases methylation	2
propionaldehyde	increases expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
butyraldehyde	increases expression	1
perfluorooctanoic acid	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	decreases expression, decreases reaction	1
pentanal	increases expression	1
di-n-butylphosphoric acid	affects expression	1
nutlin 3	affects cotreatment, increases expression	1
gardiquimod	decreases reaction, decreases expression	1
(+)-JQ1 compound	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Aldehydes	increases expression	1
Benzo(a)pyrene	increases methylation	1
Dactinomycin	affects cotreatment, increases expression	1
Lipopolysaccharides	decreases expression, decreases reaction	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	decreases expression	1
Aflatoxin B1	increases methylation	1
Asbestos, Serpentine	increases expression	1
Protein Kinase Inhibitors	decreases expression, decreases reaction	1
Particulate Matter	increases abundance, increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5622052	Binding	Binding affinity to human recombinant CD79 expressed in Sf9 cells assessed as inhibition constant by malachite green based spectrophotometer assay	Advances in CD73 inhibitors for immunotherapy: Antibodies, synthetic small molecule compounds, and natural compounds. — Eur J Med Chem

Cellosaurus cell lines

19 cell lines: 18 cancer cell line, 1 spontaneously immortalized cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_4213	HBL-1 [Human diffuse large B-cell lymphoma]	Cancer cell line	Male
CVCL_A442	TMD8	Cancer cell line	Male
CVCL_D3X9	ARSI	Cancer cell line	Female
CVCL_D5KS	TMD12	Cancer cell line	Male
CVCL_E6PR	Genomeditech CHO-K1 H_CD79B	Spontaneously immortalized cell line	Female
CVCL_E8GT	TMD8-Luc2	Cancer cell line	Male
CVCL_E8IZ	TMD8-BTK-A428D-KI-1B4	Cancer cell line	Male
CVCL_E8J0	TMD8-BTK-C481F-KI	Cancer cell line	Male
CVCL_E8J1	TMD8-BTK-C481S-KI-1B3	Cancer cell line	Male
CVCL_E8J2	TMD8-BTK-C481S-KI-1C6	Cancer cell line	Male

Clinical trials (associated diseases)

300 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00466258	PHASE4	COMPLETED	LINFOTARGAM: Treatment With Chemotherapy Plus Rituximab and Highly Active Antiretroviral Therapy in Patients With Diffuse Large B Cell Lymphoma and Infection With the Human Immunodeficiency Virus (HIV)
NCT01949818	PHASE4	UNKNOWN	Treatment of Diffuse Large B Cell Lymphoma
NCT02752815	PHASE4	UNKNOWN	Reduced Chemotherapy in Low Risk DLBCL
NCT03376958	PHASE4	COMPLETED	Apatinib for Relapsed and Refractory Diffuse Large B Cell Lymphoma
NCT03513601	PHASE4	UNKNOWN	Treatment of Elderly Patients With Diffuse Large B-cell Lymphoma
NCT03579082	PHASE4	UNKNOWN	A Clinical Trial of Decitabine in Relapse and Refractory Diffuse Large B Cell Lymphoma
NCT05108805	PHASE4	COMPLETED	Chimeric Antigen Receptor (CAR) T Cell Therapy With YESCARTA in the Outpatient Setting
NCT05518383	PHASE4	RECRUITING	B-cell Mature Non-Hodgkin’s Lymphoma Treatment Protocol in Children and Adolescents 2021
NCT00494507	PHASE3	COMPLETED	Hyper- and Hypokalemic Periodic Paralysis Study
NCT01939561	PHASE3	COMPLETED	Lamotrigine as Treatment of Myotonia
NCT00075478	PHASE3	COMPLETED	Total-Body Irradiation With or Without Fludarabine Phosphate Followed By Donor Stem Cell Transplant in Treating Patients With Hematologic Cancer
NCT00355199	PHASE3	COMPLETED	Comparison of HD Chemotherapy Followed by Auto-transplant and R-CHOP in High Risk Patients With DLBCL.
NCT00400478	PHASE3	COMPLETED	A Multicentre, Randomized Phase III Study of Rituximab as Maintenance Treatment Versus Observation in Patients With Aggressive B-cell Lymphoma: NHL-13
NCT00499018	PHASE3	UNKNOWN	Dose Dense Chemotherapy + Rituximab +/-Intensified High Dose Chemoimmunotherapy With Support of Peripheral Autologous Stem Cell in Diffuse Large B-Cell Lymphoma
NCT00790036	PHASE3	COMPLETED	Phase III Study of RAD001 Adjuvant Therapy in Poor Risk Patients With Diffuse Large B-Cell Lymphoma (DLBCL) of RAD001 Versus Matching Placebo After Patients Have Achieved Complete Response With First-line Rituximab-chemotherapy
NCT00846157	PHASE3	UNKNOWN	Biocell Natural Killer Mixture in Diffuse Large B Cell Lymphoma (DLBCL) Patients
NCT01122472	PHASE3	COMPLETED	Study of Lenalidomide Maintenance Versus Placebo in Responding Elderly Patients With DLBCL and Treated With R-CHOP
NCT01148446	PHASE3	COMPLETED	R-CHOP Versus R-mini-CEOP in Elderly Patients(>65)With DLBCL
NCT01231412	PHASE3	COMPLETED	Graft-Versus-Host Disease Prophylaxis in Treating Patients With Hematologic Malignancies Undergoing Unrelated Donor Peripheral Blood Stem Cell Transplant
NCT01285765	PHASE3	COMPLETED	Evaluate a Treatment Adapted to the PET Response Compared to a Standard Treatment, for Low Risk DLBCL CD 20+ Patients
NCT01287741	PHASE3	TERMINATED	A Study of Obinutuzumab in Combination With CHOP Chemotherapy Versus Rituximab With CHOP in Participants With CD20-Positive Diffuse Large B-Cell Lymphoma (GOYA)
NCT01321541	PHASE3	COMPLETED	Comparison of Pixantrone + Rituximab With Gemcitabine + Rituximab in Patients With Aggressive B-cell Non-Hodgkin Lymphoma or Follicular Grade 3 Lymphoma Who Have Relapsed After Therapy and Are Not Eligible for Stem Cell Transplant
NCT01459887	PHASE3	COMPLETED	Study of Recombinant Human-Mouse Chimeric Anti-CD20 Monoclonal Antibody to Treat Non-hodgkin’s Lymphoma
NCT01510184	PHASE3	TERMINATED	Study of Zevalin Versus Observation in Participants at Least 60 Years Old With Newly Diagnosed Diffuse Large B-cell Lymphoma in Positron Emission Tomography (PET)-Negative Complete Remission After Rituximab-Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (R-CHOP) or R-CHOP-like Therapy
NCT01804686	PHASE3	RECRUITING	A Long-term Extension Study of PCI-32765 (Ibrutinib)
NCT01852435	PHASE3	UNKNOWN	R-CEOP-90/R-CEOP-70 Versus R-CHOP-50 in the Treatment of Diffuse Large B-cell Lymphoma and Follicular Lymphoma Grade 3B
NCT02054559	PHASE3	WITHDRAWN	R-CHOP Alone vs. R-CHOP Plus Radiotherapy for Localized CD20+ DLBCL
NCT02128061	PHASE3	COMPLETED	Efficacy of Lenalidomide in Combination With Subcutaneous Rituximab + miniCHOP in DLBCL Patients of 80 y/o or+
NCT02268045	PHASE3	COMPLETED	Study of RTXM83 Plus CHOP Chemotherapy Versus a Rituximab Plus CHOP Therapy in Patients With Non Hodgkin’s Lymphoma
NCT02366663	PHASE3	TERMINATED	BEAM vs. 90-Yttrium Ibritumomab Tiuxetan (Zevalin®)/BEAM With ASCT for Relapsed DLBCL
NCT02449265	PHASE3	UNKNOWN	Efficacy of Consolidative Involved-site Radiotherapy for Patients With Limited-stage Diffuse Large B-cell Lymphoma
NCT02449278	PHASE3	UNKNOWN	The Palliative Benefit of Involved-site Radiotherapy for Patients With Advanced-stage Diffuse Large B-cell Lymphoma
NCT02531841	PHASE3	UNKNOWN	High-dose Chemotherapy and ASCT or Consolidating Conventional Chemotherapy in Primary CNS Lymphoma
NCT02617485	PHASE3	COMPLETED	MabionCD20 Compared to MabThera in Lymphoma Patients
NCT02767674	PHASE3	UNKNOWN	Trial of R-GemOx Versus R-miniCHOP Regimen in First-line Treatment of Elderly Diffuse Large B Cell Lymphoma
NCT02772822	PHASE3	UNKNOWN	A Study Comparing the Efficiency and Safety of S-CHOP(Cyclophosphamide, Hydroxydaunomycin, Oncovin, and Prednisone) Versus R-CHOP in Untreated CD20(Cluster of Differentiation Antigen 20)-Positive DLBCL Patients
NCT02777736	PHASE3	UNKNOWN	CNS Prophylaxis in Diffuse Large B-cell Lymphoma
NCT02842931	PHASE3	UNKNOWN	R-Dose-adjusted (DA) - EPOCH-21 Versus R-modified Non-Hodgkin Lymphoma (NHL)-Berlin-Frankfurt-Munster (BFM)-90 Program (mNHL-BFM-90) and Autologous Stem Cells Transplantation (Auto-SCT) in DLBCL With Poor Prognosis
NCT02951156	PHASE3	TERMINATED	Avelumab In Combination Regimens That Include An Immune Agonist, Epigenetic Modulator, CD20 Antagonist and/or Conventional Chemotherapy in Patients With Relapsed or Refractory Diffuse Large B-cell Lymphoma (R/R DLBCL)
NCT03123718	PHASE3	UNKNOWN	High-dose Intravenous Methotrexate Versus Intrathecal Methotrexate for Central Nervous System Prophylaxis in DLBCL