POU2AF1

Summary

POU2AF1 (POU class 2 homeobox associating factor 1, HGNC:9211) is a protein-coding gene on chromosome 11q23.1, encoding POU domain class 2-associating factor 1 (Q16633). Transcriptional coactivator that specifically associates with either POU2F1/OCT1 or POU2F2/OCT2.

Enables transcription coactivator activity. Involved in positive regulation of transcription by RNA polymerase II. Part of RNA polymerase II transcription regulator complex.

Source: NCBI Gene 5450 — RefSeq curated summary.

At a glance

• Gene–disease (curated): agammaglobulinemia (Moderate, GenCC)
• GWAS associations: 15
• Clinical variants (ClinVar): 50 total
• Phenotypes (HPO): 41
• MANE Select transcript: NM_006235

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9211
Approved symbol	POU2AF1
Name	POU class 2 homeobox associating factor 1
Location	11q23.1
Locus type	gene with protein product
Status	Approved
Aliases	OBF1, BOB1, OCA-B
Ensembl gene	ENSG00000110777
Ensembl biotype	protein_coding
OMIM	601206
Entrez	5450

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 10 protein_coding_CDS_not_defined, 2 protein_coding

ENST00000393067, ENST00000515029, ENST00000525499, ENST00000525527, ENST00000525584, ENST00000525662, ENST00000525890, ENST00000526535, ENST00000529065, ENST00000530229, ENST00000530793, ENST00000531398

RefSeq mRNA: 1 — MANE Select: NM_006235 NM_006235

CCDS: CCDS31675

Canonical transcript exons

ENST00000393067 — 5 exons

Exon	Start	End
ENSE00002141635	111379162	111379275
ENSE00002175136	111352255	111354575
ENSE00003486273	111357445	111357710
ENSE00003524533	111358788	111358918
ENSE00003573322	111357795	111357837

Expression profiles

Bgee: expression breadth ubiquitous, 222 present calls, max score 97.90.

FANTOM5 (CAGE): breadth broad, TPM avg 6.7522 / max 770.3456, expressed in 204 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
122239	6.6770	161
122241	0.0593	40
122238	0.0102	6
122237	0.0057	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
epithelium of nasopharynx	UBERON:0001951	97.90	gold quality
pylorus	UBERON:0001166	97.47	gold quality
cardia of stomach	UBERON:0001162	96.63	gold quality
spleen	UBERON:0002106	96.20	gold quality
lymph node	UBERON:0000029	96.03	gold quality
vermiform appendix	UBERON:0001154	95.78	gold quality
bronchial epithelial cell	CL:0002328	95.25	gold quality
caecum	UBERON:0001153	94.94	gold quality
tonsil	UBERON:0002372	94.27	gold quality
bone marrow cell	CL:0002092	94.11	gold quality
ileal mucosa	UBERON:0000331	92.84	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	92.53	gold quality
epithelium of bronchus	UBERON:0002031	90.31	gold quality
bronchus	UBERON:0002185	90.26	gold quality
trabecular bone tissue	UBERON:0002483	90.17	gold quality
mucosa of sigmoid colon	UBERON:0004993	89.53	gold quality
colonic epithelium	UBERON:0000397	89.19	gold quality
duodenum	UBERON:0002114	88.26	gold quality
parotid gland	UBERON:0001831	88.02	gold quality
colonic mucosa	UBERON:0000317	87.72	gold quality
rectum	UBERON:0001052	87.57	gold quality
trachea	UBERON:0003126	87.55	gold quality
bone marrow	UBERON:0002371	87.03	gold quality
mucosa of paranasal sinus	UBERON:0005030	86.47	gold quality
superficial temporal artery	UBERON:0001614	86.23	gold quality
blood	UBERON:0000178	86.04	gold quality
mucosa of transverse colon	UBERON:0004991	85.93	gold quality
thymus	UBERON:0002370	84.99	gold quality
saliva-secreting gland	UBERON:0001044	84.95	gold quality
nasal cavity mucosa	UBERON:0001826	84.62	gold quality

Single-cell (SCXA)

Detected in 19 experiment(s), a significant marker in 17.

Experiment	Marker?	Max mean expression
E-CURD-122	yes	99.02
E-CURD-88	yes	94.72
E-GEOD-109979	yes	91.74
E-MTAB-9467	yes	54.81
E-HCAD-1	yes	50.34
E-CURD-46	yes	45.18
E-CURD-112	yes	42.08
E-MTAB-8410	yes	41.86
E-HCAD-4	yes	41.29
E-ANND-3	yes	32.78
E-HCAD-11	yes	22.96
E-HCAD-9	yes	18.82
E-MTAB-9067	yes	18.81
E-MTAB-8142	yes	17.12
E-MTAB-10553	yes	11.98

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

5 targets.

Target	Regulation
BCL2
ID2	Unknown
SPIB	Unknown
TK1	Activation
TNFRSF17	Activation

Upstream regulators (CollecTRI, top): CREB1, E2F1, GLI3, NCOR2, POU2F1, XBP1

miRNA regulators (miRDB)

100 targeting POU2AF1, 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-1252-5P	100.00	69.80	2774
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-515-5P	99.92	69.82	2343

Literature-anchored findings (GeneRIF, showing 25)

• The expression of the octamer cofactor gene OBF-1 (Bob1/OCA-B) is sufficient to override the silencing effects of the B29 silencer, indicating that OBF-1 plays a critical role in B cell-specific B29 promoter expression. (PMID:11907094)
• enhances transcriptional potential of Oct1 (PMID:12727885)
• OCA-B sustains expression of the immunoglobulin-secreting program when T lymphoma and plasmacytoma lines are fused, requiring Oct-2 coregulator for its function. (PMID:14662861)
• POU2AF1 was observed to be differentially expressed in the cells of patients with chronic lymphocytic leukemia. (PMID:15672409)
• Alteration of the BOB1 locus does not correlate with its suppressed expression in Hodgkin lymphoma. (PMID:15796964)
• Novel germ cell markers BOB1 were significantly upregulated in seminoma specimens, compared to normal testes. (PMID:17785371)
• Oct-2 and its cofactor Bob-1 have an important function in mediating the IgH enhancer-bcl-2 promoter region interactions (PMID:18695675)
• BOB.1 may be helpful marker in the differential diagnosis of classical Hodgkin’s lymphoma and primary mediastinal B-cell lymphoma (PMID:20102401)
• On multivariate analysis, co-expression of OCT-2/BOB.1 remained predictive for achievement of complete remission and increased risk of relapse. (PMID:20141429)
• Twenty-two cases of nodular lymphocyte predominant Hodgkin lymphoma were studied for the immunohistochemical expression of Pax-5, Oct-2, BOB.1, Bcl-6 protein and MUM1/IRF-4. (PMID:21424034)
• Data show that Igh 3’ enhancer-bound OCA-B and promoter-bound TFII-I mediate promoter-enhancer interactions, in both cis and trans, that are important for Igh transcription. (PMID:21549311)
• genetic polymorphism is associated with common variable immunodeficiency (PMID:21905497)
• Two significant susceptibility loci, TNFSF15 (rs4979462) and POU2AF1 (rs4938534) (combined odds ratio [OR] = 1.56, p = 2.84 x 10(-14) for rs4979462. (PMID:23000144)
• It has been identified as a new disease susceptibility gene among Japanese. Though different from Europeans, it is indicated that a B lymphocyte differentiation route shares a common disease developing process. [Review] (PMID:24005100)
• these findings suggest a novel function of POU2AF1 as a potential regulator of host defense genes in the human airway epithelium. (PMID:26927796)
• Oct2 and Bob1 are very reliable in determining B cell lineage in the absence of expression of other pan-B cell markers (PMID:27319306)
• These findings demonstrate for the first time that functional polymorphism in the 3’-UTR of POU2AF1 is associated with susceptibility, and that single-nucleotide polymorphisms interaction with hsa-miR-633 affects gene expression and increases the risk of lymphoma. (PMID:28345816)
• The number of follicular B2 lymphocytes and expression of the B-cell-specific transcriptional coactivator OcaB increase with age in spleen and in intra-abdominal epididymal white adipose tissue (eWAT), concomitantly with higher circulating levels of IgG and impaired glucose homeostasis. (PMID:29496744)
• The specific objective of this study was to measure the expression of SUMO1 and POU2AF1 on first-degree relatives of patients with rheumatoid arthritis. (PMID:30681271)
• Our findings demonstrate a novel role for BOB.1 in B cells during TD GC responses and suggest that its dysregulation may contribute to the pathogenesis of RA by disturbing the B cell-fate determination. (PMID:31053401)
• OBF1 and Oct factors control the germinal center transcriptional program. (PMID:33512466)
• POU2AF1 promotes MSCs adipogenesis by inhibiting HDAC1 expression. (PMID:33949290)
• Integrated single-cell transcriptomics and epigenomics reveals strong germinal center-associated etiology of autoimmune risk loci. (PMID:34623901)
• Four Genes Predictive for the Severity of Hematological Damage Reveal a Similar Response after X Irradiation and Chemotherapy. (PMID:36480042)
• Transcriptional Coactivator BOB1 (OBF1, OCA-B) Modulates the Specificity of DNA Recognition by the POU-Domain Factors OCT1 and OCT2 in a Monomeric Configuration. (PMID:38254723)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
mus_musculus	Pou2af1	ENSMUSG00000032053
rattus_norvegicus	Pou2af1	ENSRNOG00000011500
drosophila_melanogaster	CG11350	FBGN0035552
drosophila_melanogaster	CG31626	FBGN0051626
drosophila_melanogaster	CG32603	FBGN0052603

Protein

Protein identifiers

POU domain class 2-associating factor 1 — Q16633 (reviewed: Q16633)

Alternative names: B-cell-specific coactivator OBF-1, BOB-1, OCA-B, OCT-binding factor 1

All UniProt accessions (2): Q16633, E9PKH4

UniProt curated annotations — full annotation on UniProt →

Function. Transcriptional coactivator that specifically associates with either POU2F1/OCT1 or POU2F2/OCT2. It boosts the POU2F1/OCT1 mediated promoter activity and to a lesser extent, that of POU2F2/OCT2. It recognizes the POU domains of POU2F1/OCT1 and POU2F2/OCT2. It is essential for the response of B-cells to antigens and required for the formation of germinal centers. Regulates IL6 expression in B cells as POU2F2/OCT2 coactivator.

Subunit / interactions. Interacts with POU2F1/OCT1 and POU2F2/OCT2; the interaction increases POU2F1 and POU2F2 transactivation activity.

Subcellular location. Nucleus.

Tissue specificity. B-cell specific. Detected in mainly in spleen, but also in thymus, periphral blood leukocyte and small intestine.

Post-translational modifications. Ubiquitinated; mediated by SIAH1 or SIAH2 and leading to its subsequent proteasomal degradation.

Disease relevance. A chromosomal aberration involving POU2AF1/OBF1 may be a cause of a form of B-cell leukemia. Translocation t(3;11)(q27;q23) with BCL6.

Domain organisation. In the N-terminus possesses a conserved OCA domain for bivalent binding to class II POU domain-containing transcription factors and to an octamer DNA motif.

Similarity. Belongs to the POU2AF family.

RefSeq proteins (1): NP_006226* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR015389	PD-C2-AF1	Family
IPR047571	OCA	Domain

Pfam: PF09310

UniProt features (6 total): sequence variant 2, chain 1, domain 1, region of interest 1, helix 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
1CQT	X-RAY DIFFRACTION	3.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q16633-F1	57.15	0.09

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 429 (showing top): WALLACE_PROSTATE_CANCER_RACE_UP, GOBP_CELLULAR_RESPONSE_TO_VIRUS, MCLACHLAN_DENTAL_CARIES_UP, GOBP_B_CELL_ACTIVATION, GOBP_POSITIVE_REGULATION_OF_CYTOKINE_PRODUCTION, AAAYRNCTG_UNKNOWN, SREBP1_02, PUJANA_CHEK2_PCC_NETWORK, GOBP_CELL_ACTIVATION_INVOLVED_IN_IMMUNE_RESPONSE, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN, GATA6_01, GOBP_CYTOKINE_PRODUCTION, MYLLYKANGAS_AMPLIFICATION_HOT_SPOT_23, GOBP_HUMORAL_IMMUNE_RESPONSE, LIAO_METASTASIS

GO Biological Process (5): germinal center B cell differentiation (GO:0002314), humoral immune response (GO:0006959), positive regulation of interleukin-6 production (GO:0032755), positive regulation of transcription by RNA polymerase II (GO:0045944), cellular response to virus (GO:0098586)

GO Molecular Function (5): DNA binding (GO:0003677), transcription coregulator activity (GO:0003712), transcription coactivator activity (GO:0003713), POU domain binding (GO:0070974), protein binding (GO:0005515)

GO Cellular Component (2): RNA polymerase II transcription regulator complex (GO:0090575), nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
positive regulation of DNA-templated transcription	2
mature B cell differentiation involved in immune response	1
immune response	1
positive regulation of cytokine production	1
interleukin-6 production	1
regulation of interleukin-6 production	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
response to virus	1
nucleic acid binding	1
transcription regulator activity	1
transcription coregulator activity	1
protein domain specific binding	1
binding	1
transcription regulator complex	1
nuclear protein-containing complex	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1130 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
POU2AF1	POU2F1	P14859	843
POU2AF1	PAX5	Q02548	826
POU2AF1	SPIB	Q01892	815
POU2AF1	POU2F2	P09086	803
POU2AF1	SYK	P43405	755
POU2AF1	IKZF3	Q9UKT9	751
POU2AF1	EBF1	Q9UH73	690
POU2AF1	IGHV4-38-2	P0DP08	688
POU2AF1	CR2	P20023	627
POU2AF1	CD79A	P11912	625
POU2AF1	SPI1	P17947	617
POU2AF1	XBP1	P17861	614
POU2AF1	MS4A1	P08984	595
POU2AF1	CD22	P20273	592
POU2AF1	RHOH	Q15669	584

IntAct

151 interactions, top by confidence:

A	B	Type	Score
POU2AF1	ATE1	psi-mi:“MI:0915”(physical association)	0.590
VPS37C	POU2AF1	psi-mi:“MI:0915”(physical association)	0.560
POU2AF1	KLHL38	psi-mi:“MI:0915”(physical association)	0.560
POGZ	POU2AF1	psi-mi:“MI:0915”(physical association)	0.560
ROR2	POU2AF1	psi-mi:“MI:0915”(physical association)	0.560
HGS	POU2AF1	psi-mi:“MI:0915”(physical association)	0.560
FOXD2	POU2AF1	psi-mi:“MI:0915”(physical association)	0.560
KRTAP12-1	POU2AF1	psi-mi:“MI:0915”(physical association)	0.560
POU2AF1	KRTAP13-2	psi-mi:“MI:0915”(physical association)	0.560
POU2AF1	PITX2	psi-mi:“MI:0915”(physical association)	0.560
HOXC8	POU2AF1	psi-mi:“MI:0915”(physical association)	0.560
SCAND1	POU2AF1	psi-mi:“MI:0915”(physical association)	0.560
POU2AF1	TFG	psi-mi:“MI:0915”(physical association)	0.560
POU2AF1	KRTAP19-7	psi-mi:“MI:0915”(physical association)	0.560
POU2AF1	DGCR6L	psi-mi:“MI:0915”(physical association)	0.560
POU2AF1	ZNF581	psi-mi:“MI:0915”(physical association)	0.560
USP2	POU2AF1	psi-mi:“MI:0915”(physical association)	0.560
CIMIP2B	POU2AF1	psi-mi:“MI:0915”(physical association)	0.560
ITGB4	POU2AF1	psi-mi:“MI:0915”(physical association)	0.560
POU2AF1	HEMK1	psi-mi:“MI:0915”(physical association)	0.560
OTX1	POU2AF1	psi-mi:“MI:0915”(physical association)	0.560
MEIS2	POU2AF1	psi-mi:“MI:0915”(physical association)	0.560
POU2AF1	NDUFAF3	psi-mi:“MI:0915”(physical association)	0.560
TBX6	POU2AF1	psi-mi:“MI:0915”(physical association)	0.560
POU2AF1	CCDC120	psi-mi:“MI:0915”(physical association)	0.560
POU2AF1	RBM24	psi-mi:“MI:0915”(physical association)	0.560
TLX3	POU2AF1	psi-mi:“MI:0915”(physical association)	0.560
VGLL3	POU2AF1	psi-mi:“MI:0915”(physical association)	0.560
POU2AF1	TENT5B	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (63): ATE1 (Affinity Capture-MS), ATE1 (Affinity Capture-MS), POU2AF1 (Two-hybrid), POU2AF1 (Two-hybrid), POU2AF1 (Two-hybrid), POU2AF1 (Two-hybrid), POU2AF1 (Two-hybrid), RBM24 (Two-hybrid), TFG (Two-hybrid), HEMK1 (Two-hybrid), OTX1 (Two-hybrid), DGCR6L (Two-hybrid), ITGB4 (Two-hybrid), GPS2 (Two-hybrid), ZNF414 (Two-hybrid)

ESM2 similar proteins: A0PJS5, A1YG01, A2D4R4, A2D649, A2T6H5, A2T6Z0, A3KNJ3, A7Y7W3, A8K830, F6W2R2, F8VPY8, O15353, O42506, O43186, O54751, P14653, P17919, P28322, P31276, P32243, P40646, P43268, P57082, P70056, P80206, P83758, Q00288, Q06710, Q08820, Q16633, Q1KL10, Q28GC4, Q28IU6, Q2KJA4, Q4G112, Q503Z8, Q64693, Q66IK1, Q66IT9, Q7T1C0

Diamond homologs: Q16633, Q2KJA4, Q64693

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
POU2AF1	up-regulates	POU2F1	binding
POU2AF1	up-regulates	POU2F2	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 59 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Keratinization	6	8.8×	5e-03
Ub-specific processing proteases	6	8.4×	6e-03

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of miRNA transcription	6	35.6×	5e-06
anatomical structure morphogenesis	7	19.9×	1e-05
anterior/posterior pattern specification	5	18.5×	1e-03
positive regulation of gene expression	9	7.1×	7e-04
negative regulation of cell population proliferation	7	6.0×	8e-03

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	25
Likely benign	6
Benign	12

Top pathogenic / likely-pathogenic (0)

SpliceAI

1030 predictions. Top by Δscore:

Variant	Effect	Δscore
11:111356292:AACT:A	donor_gain	1.0000
11:111356304:T:C	donor_gain	1.0000
11:111357579:A:AC	donor_gain	1.0000
11:111357580:C:CC	donor_gain	1.0000
11:111357711:C:CC	acceptor_gain	1.0000
11:111357794:CCCA:C	donor_gain	1.0000
11:111357797:A:AC	donor_gain	1.0000
11:111357798:C:CC	donor_gain	1.0000
11:111354576:C:CC	acceptor_gain	0.9900
11:111356293:A:C	donor_gain	0.9900
11:111357706:AGGAC:A	acceptor_gain	0.9900
11:111357707:GGAC:G	acceptor_gain	0.9900
11:111357708:GAC:G	acceptor_gain	0.9900
11:111357709:AC:A	acceptor_gain	0.9900
11:111357710:CC:C	acceptor_gain	0.9900
11:111357790:CTTAC:C	donor_loss	0.9900
11:111357792:T:TA	donor_loss	0.9900
11:111357793:A:AA	donor_loss	0.9900
11:111357793:A:AC	donor_gain	0.9900
11:111357793:AC:A	donor_gain	0.9900
11:111357794:C:CC	donor_gain	0.9900
11:111357794:CC:C	donor_gain	0.9900
11:111357836:ACCTA:A	acceptor_loss	0.9900
11:111357837:CCT:C	acceptor_loss	0.9900
11:111357838:CTAG:C	acceptor_loss	0.9900
11:111357839:T:A	acceptor_loss	0.9900
11:111379157:CTTA:C	donor_loss	0.9900
11:111379158:TTA:T	donor_loss	0.9900
11:111379159:T:TG	donor_loss	0.9900
11:111379160:A:AC	donor_gain	0.9900

AlphaMissense

1615 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:111358830:C:A	K35N	0.999
11:111358830:C:G	K35N	0.999
11:111358840:A:G	L32P	0.999
11:111358843:A:G	L31P	0.999
11:111358848:C:A	K29N	0.999
11:111358848:C:G	K29N	0.999
11:111358874:C:G	G21R	0.999
11:111358860:C:A	K25N	0.998
11:111358860:C:G	K25N	0.998
11:111358865:C:T	V24M	0.998
11:111358874:C:A	G21C	0.998
11:111358840:A:T	L32Q	0.997
11:111358868:G:T	R23S	0.997
11:111358880:A:G	Y19H	0.997
11:111358831:T:A	K35M	0.996
11:111358833:C:A	R34S	0.996
11:111358833:C:G	R34S	0.996
11:111358834:C:A	R34M	0.996
11:111358847:C:T	E30K	0.996
11:111358852:A:T	V28E	0.996
11:111358853:C:T	V28M	0.996
11:111358864:A:G	V24A	0.996
11:111358832:T:C	K35E	0.995
11:111358843:A:T	L31Q	0.995
11:111358850:T:C	K29E	0.995
11:111358864:A:T	V24E	0.995
11:111358870:A:T	V22D	0.995
11:111358880:A:C	Y19D	0.995
11:111354497:A:G	W179R	0.994
11:111354497:A:T	W179R	0.994

dbSNP variants (sampled 300 via entrez): RS1000057523 (11:111369384 A>G,T), RS1000110229 (11:111375201 A>G), RS1000128859 (11:111370697 A>G), RS1000142836 (11:111375459 C>G,T), RS1000165755 (11:111354836 A>G), RS1000385906 (11:111361775 T>G), RS1000429987 (11:111369636 C>A,T), RS1000501184 (11:111353324 C>G,T), RS1000539816 (11:111372461 C>T), RS1000607638 (11:111353041 G>A,C), RS1000624832 (11:111374032 T>C), RS1000804225 (11:111364655 C>A), RS1000837025 (11:111364405 T>G), RS1000920606 (11:111369917 T>C), RS1001012402 (11:111358781 C>T)

Disease associations

OMIM: gene MIM:601206 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
agammaglobulinemia	Moderate	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
agammaglobulinemia	Limited	AR

Mondo (1): agammaglobulinemia (MONDO:0015977)

Orphanet (0):

HPO phenotypes

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

HPO	Term
HP:0000820	Abnormality of the thyroid gland
HP:0000939	Osteoporosis
HP:0000952	Jaundice
HP:0000953	Hyperpigmentation of the skin
HP:0000989	Pruritus
HP:0001114	Xanthelasma
HP:0001262	Excessive daytime somnolence
HP:0001278	Orthostatic hypotension
HP:0001394	Cirrhosis
HP:0001395	Hepatic fibrosis
HP:0001399	Hepatic failure
HP:0001402	Hepatocellular carcinoma
HP:0001409	Portal hypertension
HP:0001541	Ascites
HP:0001744	Splenomegaly
HP:0002040	Esophageal varix
HP:0002240	Hepatomegaly
HP:0002360	Sleep disturbance
HP:0002480	Hepatic encephalopathy
HP:0002570	Steatorrhea
HP:0002608	Celiac disease
HP:0002613	Biliary cirrhosis
HP:0002841	Recurrent fungal infections
HP:0002908	Conjugated hyperbilirubinemia
HP:0002960	Autoimmunity
HP:0003073	Hypoalbuminemia
HP:0003119	Abnormal circulating lipid concentration
HP:0003124	Hypercholesterolemia
HP:0003155	Elevated circulating alkaline phosphatase concentration
HP:0003261	Increased circulating IgA concentration

GWAS associations

15 associations (top):

Study	Trait	p-value
GCST001685_7	Primary biliary cholangitis	2.000000e-08
GCST001806_16	Corneal structure	4.000000e-09
GCST004145_6	Primary biliary cholangitis	1.000000e-08
GCST005523_29	Celiac disease	2.000000e-11
GCST006479_40	Diverticular disease	4.000000e-06
GCST007062_4	Hodgkin’s lymphoma	1.000000e-11
GCST007536_6	Serum urea levels	1.000000e-09
GCST008615_3	Low urine pH	2.000000e-14
GCST008616_3	Urine pH measurement	4.000000e-11
GCST009597_220	Multiple sclerosis	2.000000e-06
GCST009597_234	Multiple sclerosis	6.000000e-08
GCST010703_266	Brain morphology (MOSTest)	4.000000e-13
GCST90002381_521	Eosinophil count	2.000000e-10
GCST90002382_394	Eosinophil percentage of white cells	2.000000e-12
GCST90002389_370	Lymphocyte percentage of white cells	7.000000e-09

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0004267	biliary liver cirrhosis
EFO:0004345	corneal topography
EFO:0009959	diverticular disease
EFO:0010136	urinary pH measurement
EFO:0004346	neuroimaging measurement
EFO:0004842	eosinophil count
EFO:0007991	eosinophil percentage of leukocytes
EFO:0007993	lymphocyte percentage of leukocytes

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D000361	Agammaglobulinemia	C15.378.147.142; C15.604.515.032; C20.673.088

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, increases expression, affects methylation	5
(+)-JQ1 compound	affects binding, decreases reaction, decreases expression	3
Air Pollutants	affects methylation, increases abundance, increases expression	2
Nickel	increases expression	2
Tetrachlorodibenzodioxin	decreases expression	2
Tobacco Smoke Pollution	decreases expression	2
Particulate Matter	affects methylation, increases abundance, increases expression	2
OTX015	decreases expression	1
mivebresib	decreases expression	1
dicrotophos	increases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	increases expression	1
CGP 52608	affects binding, increases reaction	1
oligofectamine	increases expression	1
Leflunomide	increases expression	1
Arsenic	decreases expression	1
Calcitriol	decreases expression	1
Methyl Methanesulfonate	decreases expression	1
Nicotine	decreases expression	1
Quercetin	decreases expression	1
Testosterone	decreases expression	1
Tretinoin	decreases expression	1
Valproic Acid	increases methylation	1
Vincristine	decreases expression	1
Zinc	increases expression	1
2-Naphthylamine	decreases expression	1
Cyclosporine	decreases expression	1
Aflatoxin B1	increases methylation	1

Cellosaurus cell lines

4 cell lines: 3 embryonic stem cell, 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_1822	Karpas-231	Cancer cell line	Female
CVCL_A5L3	SEES3-1V human POU2AF1, clone1	Embryonic stem cell	Male
CVCL_A5L4	SEES3-1V human POU2AF1, clone2	Embryonic stem cell	Male
CVCL_A5L5	SEES3-1V human POU2AF1, clone3	Embryonic stem cell	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00520494	PHASE4	COMPLETED	Efficacy and Safety of Vivaglobin® in Previously Untreated Patients With Primary Immunodeficiency
NCT05612607	PHASE4	UNKNOWN	Switched Memory B-cells as a Marker for Humoral Immune System Recovery in Patients With Secondary Antibody Deficiency Due to Hematological Malignancies
NCT07135427	PHASE4	RECRUITING	Genetic Variation in IgG in Alpha 1 Antitrypsin Deficiency
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)
NCT01581593	PHASE3	COMPLETED	Efficacy and Safety Study of Kedrion IVIG 10% to Treat Subjects With Primary Immunodeficiency (PID)
NCT03578341	PHASE3	UNKNOWN	Oral Colostrum and Its Effect on Immune System
NCT06954441	PHASE3	RECRUITING	V-IMMUNE: A Novel Immunoglobulin Therapy for Immunodeficiency
NCT00161993	PHASE2	COMPLETED	Safety, Pharmacokinetic and Efficacy Study of a 10% Triple Virally Reduced Intravenous Immune Globulin Solution in Patients With Primary Immunodeficiency (Hypo- or Agammaglobulinemia)
NCT05584631	PHASE1	RECRUITING	IVIG vs SCIG in CIDP
NCT00661401	Not specified	COMPLETED	Specific IgG Antibody in Patients With Primary Antibody Deficiencies Treated With Subcutaneous Immunoglobulin
NCT02972281	Not specified	COMPLETED	Systematic Search for Primary Immunodeficiency in Adults With Infections