POU2AF1

protein-coding

POU class 2 homeobox associating factor 1

Gene summary

Enables transcription coactivator activity. Involved in positive regulation of transcription by RNA polymerase II. Part of RNA polymerase II transcription regulator complex. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_006235.3

Inheritance

ClinVar variants

U:26B:7

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.18

Max pathogenic AF

—

Genomic locus

chr11:111,352,255-111,455,630

External References & Databases

Ensembl (ENSG00000110777)

Transcript & Mutation Effects

hg38 • Region Span ~103.4 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

agammaglobulinemiaMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0015977

Submitter: PanelApp Australia

agammaglobulinemiaLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0015977

Submitter: ClinGen

*POU2AF1*, encoding the Bob1 protein, was first reported in relation to autosomal recessive agammaglobulinemia in 2021 by Kury et al (PMID: 33571536). This is the only report of a patient with a Bob1 deficiency caused by a homozygous *POU2AF1* null mutation (NM_006235.3:c.233del) resulting in a severe B-cell–intrinsic defect. B-cell receptor signaling was reduced and plasmablast development and immunoglobulin secretion seemed abrogated in the patient. This gene-disease relationship is supported by experimental evidence; the highly B lymphocyte-specific pattern of *POU2AF1* expression in lymphocytes, together with its selective stimulatory effect on immunoglobulin promoters strongly indicates that *POU2AF1*is a critical determinant of immunoglobulin transcription in lymphoid cells (PMID: 7859290), which is deficient in patient cells but can be rescued by lentiviral reconstitution (PMID: 33571536). The immunologic manifestations in the patient showed some overlap with the Bob1 knockout mice (PMIDs: 8977324, 8849727, 8849728, 35603192). Patient T cells were normal in terms of distribution and activation except for a reduction in circulating T-follicular helper (TFH) cells (PMID: 33571536). While it has been shown that *POU2AF1* does not act as a transcriptional coactivator for T cells (PMID: 35285071) the observed defect in T follicular helper differentiation is likely related to its functional impact in B cells, however, in a mouse model, it was shown that *POU2AF1* is expressed in activated (not naïve) T cells, and when deleted in T cells had a positive regulatory impact on autoimmune diabetes, suggesting that it has a role to play in T-cell-driven autoimmunity, and facilitates polarization of activated T helper cells to a TH17 phenotype (PMID: 33295943). In summary, there is limited evidence to support this gene-disease relationship. While more evidence is needed to establish this relationship definitively, no convincing contradictory evidence has emerged. This classification was approved by the ClinGen Antibody Deficiencies GCEP on 09/20/2022 (SOP Version 9). Of note, in B cells, CD19 and *POU2AF1* may also serve as diagnostic and prognostic biomarkers of chronic obstructive pulmonary disease (PMID: 35479834). Additionally, expression of *POU2AF1* in non-lymphocytes, specifically in airway epithelium appears to contribute to regulation of host immunity (PMID: 26927796).

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to POU2AF1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 32

not providedTotal: 7

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_006235.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				4 clinvar	1 clinvar	5
missense			23 clinvar	2 clinvar		25
nonsense						0
start loss						0
frameshift			2 clinvar			2
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	26	6	1	33

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 8 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_006235.3	RefSeq	NP_006226.2	5	MANE Select
ENST00000393067.8	Ensembl	ENSP00000376786.3	5	MANE Select
ENST00000531398.1	Ensembl	ENSP00000433527.1	4	Standard
XM_005271593.3	RefSeq	XP_005271650.1	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

transcription by RNA polymerase II
humoral immune response
positive regulation of transcription by RNA polymerase II

Molecular Function

RNA polymerase II proximal promoter sequence-specific DNA binding
RNA polymerase II core promoter sequence-specific DNA binding
transcription coregulator activity
transcription coactivator activity
protein binding

Cellular Component

RNA polymerase II transcription factor complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000393067
Coding exons: 5
Length: 103379
Individuals with no LoFs: 125691
Homozygous LoFs: 0
Heterozygous LoFs: 4
Defined: 125695
p: 0.0000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.949	120	153	0.784	0.00000898	1595
Missense (PolyPhen)		32	55.318	0.57847		628
Synonymous	-1.14	84	71.7	1.17	0.00000480	564
Loss of Function	2.53	2	11.1	0.180	5.45e-7	119

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000026	0.000026	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Transcriptional coactivator that specifically associates with either OCT1 or OCT2. It boosts the OCT1 mediated promoter activity and to a lesser extent, that of OCT2. It has no intrinsic DNA-binding activity. It recognizes the POU domains of OCT1 and OCT2. It is essential for the response of B-cells to antigens and required for the formation of germinal centers.;
Disease: DISEASE: Note=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. {ECO:0000269|PubMed:8574789}.;

Recessive Scores

pRec: 0.276

Intolerance Scores

LoFtool: 0.0796
RVIS EVS: -0.32
RVIS percentile EVS: 31.69

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.263

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium