IRF2BP2

Summary

IRF2BP2 (interferon regulatory factor 2 binding protein 2, HGNC:21729) is a protein-coding gene on chromosome 1q42.3, encoding Interferon regulatory factor 2-binding protein 2 (Q7Z5L9). Acts as a transcriptional corepressor in a IRF2-dependent manner; this repression is not mediated by histone deacetylase activities. It is a selective cancer dependency (DepMap: 14.1% of cell lines).

This gene encodes an interferon regulatory factor-2 (IRF2) binding protein that interacts with the C-terminal transcriptional repression domain of IRF2. Alternative splicing results in multiple transcript variants encoding distinct isoforms.

Source: NCBI Gene 359948 — RefSeq curated summary.

At a glance

• Gene–disease (curated): immunodeficiency, common variable, 14 (Strong, GenCC)
• GWAS associations: 27
• Clinical variants (ClinVar): 787 total — 3 likely-pathogenic
• Phenotypes (HPO): 47
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 14.1% of screened cell lines
• MANE Select transcript: NM_182972

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21729
Approved symbol	IRF2BP2
Name	interferon regulatory factor 2 binding protein 2
Location	1q42.3
Locus type	gene with protein product
Status	Approved
Aliases	LRIR2, IRF-2BP2
Ensembl gene	ENSG00000168264
Ensembl biotype	protein_coding
OMIM	615332
Entrez	359948

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 4 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000366609, ENST00000366610, ENST00000491430, ENST00000947260, ENST00000947261

RefSeq mRNA: 2 — MANE Select: NM_182972 NM_001077397, NM_182972

CCDS: CCDS1602, CCDS41475

Canonical transcript exons

ENST00000366609 — 2 exons

Exon	Start	End
ENSE00001442169	234608447	234610178
ENSE00004034711	234604269	234607852

Expression profiles

Bgee: expression breadth ubiquitous, 256 present calls, max score 99.72.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 108.0371 / max 5235.9331, expressed in 1822 samples.

FANTOM5 promoters (19 alternative TSS)

Promoter ID	TPM avg	Samples expressed
18067	62.9288	1818
18066	26.6017	1803
18063	3.0225	904
18065	2.5451	1298
18057	2.3511	697
18059	2.0702	927
18053	1.7998	1014
18064	1.6019	940
18051	1.5392	993
18062	0.9525	200

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mammary duct	UBERON:0001765	99.72	gold quality
epithelium of mammary gland	UBERON:0003244	99.72	gold quality
trachea	UBERON:0003126	99.65	gold quality
epithelial cell of pancreas	CL:0000083	99.64	gold quality
mucosa of paranasal sinus	UBERON:0005030	99.61	gold quality
superior surface of tongue	UBERON:0007371	99.56	gold quality
pylorus	UBERON:0001166	99.55	gold quality
trigeminal ganglion	UBERON:0001675	99.51	gold quality
cauda epididymis	UBERON:0004360	99.46	gold quality
caput epididymis	UBERON:0004358	99.43	gold quality
tongue	UBERON:0001723	99.39	gold quality
nipple	UBERON:0002030	99.39	gold quality
pericardium	UBERON:0002407	99.37	gold quality
adult organism	UBERON:0007023	99.37	gold quality
kidney epithelium	UBERON:0004819	99.36	gold quality
cardia of stomach	UBERON:0001162	99.35	gold quality
trabecular bone tissue	UBERON:0002483	99.35	gold quality
pharyngeal mucosa	UBERON:0000355	99.33	gold quality
body of tongue	UBERON:0011876	99.30	gold quality
superficial temporal artery	UBERON:0001614	99.29	gold quality
vena cava	UBERON:0004087	99.29	gold quality
upper arm skin	UBERON:0004263	99.28	gold quality
medulla oblongata	UBERON:0001896	99.24	gold quality
skin of hip	UBERON:0001554	99.23	gold quality
penis	UBERON:0000989	99.21	gold quality
parotid gland	UBERON:0001831	99.21	gold quality
pancreatic ductal cell	CL:0002079	99.20	gold quality
visceral pleura	UBERON:0002401	99.15	gold quality
lower lobe of lung	UBERON:0008949	99.15	gold quality
superior vestibular nucleus	UBERON:0007227	99.09	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-HCAD-4	yes	35.10
E-CURD-122	yes	13.74
E-CURD-46	yes	9.29
E-MTAB-7381	no	451.93
E-HCAD-31	no	2.45
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CDX1

miRNA regulators (miRDB)

199 targeting IRF2BP2, 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-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-548N	99.98	71.94	4170
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-4666A-3P	99.96	71.71	3434

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 14.1% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 18)

• Identification of IRF-2 binding protein 1 and IRF-2 binding protein 2 as co-repressor molecules for interferon regulatory factor-2. (PMID:12799427)
• results indicate that DIF-1 plays a key role in breast cancer cell survival (PMID:19190336)
• IRF2BP2 is a novel ischemia-induced coactivator of VEGFA expression that may contribute to revascularization of ischemic cardiac and skeletal muscles. (PMID:20702774)
• IRF2BP2 works with TEAD transcription factors to upregulate the expression of VEGFA in skeletal and cardiac muscle. IRF2BP2 protein levels are increased in response to tissue ischemia. (PMID:20702774)
• Data demonstrate that IRF-2BP2 is a negative regulator of the NFAT1 transcription factor and suggest that NFAT1 repression occurs at the transcriptional level. (PMID:21576369)
• Nuclear localization of IRF2BP2 depends on phosphorylation near a conserved NLS. Changes in phosphorylation status likely control nucleocytoplasmic localization of IRF2BP2 during muscle differentiation. (PMID:21887377)
• analysis of an IRF2BP2-CDX1 fusion gene brought about by translocation t(1;5)(q42;q32) in mesenchymal chondrosarcoma (PMID:23185413)
• A deletion variant that lowers IRF2BP2 expression predisposes to coronary artery disease in humans. (PMID:26195219)
• ETO2 and IRF2BP2 interacting with the NCOR1/SMRT co-repressor complex, suppresses the expression of erythroid genes until erythroid differentiation. (PMID:26593974)
• A novel IRFBP2 mutation was identified in a family with autosomal dominant CVID. Transduction experiments suggest that the mutant protein has an effect on B-cell differentiation and is likely a monogenic cause of the family’s CVID phenotype. (PMID:27016798)
• findings showed that the IRF2BP2-RARalpha fusion has the capacity to transform primary hematopoietic stem/progenitor cells and induced an ATRA-responsive acute promyelocytic leukemia (APL); this provides further evidence that formation of RARA fusion genes represent disease-defining mutations in APL pathogenesis (PMID:27872498)
• The expression of interferon regulatory protein 2-binding protein 2 (IRF2BP2), a regulator of KLF2, suppressed osteoclast differentiation and enhanced osteoblast differentiation and function. (PMID:31186082)
• Down-regulation of interferon regulatory factor 2 binding protein 2 suppresses gastric cancer progression by negatively regulating connective tissue growth factor. (PMID:31559693)
• LncRNA ATP1A1-AS1 inhibits cell proliferation and promotes cell apoptosis in thyroid carcinoma by regulating the miR-620/IRF2BP2 axis. (PMID:36002076)
• A novel IRF2BP2::CDX2 Gene fusion in digital intravascular myoepithelioma of soft tissue: An enigma! (PMID:36448218)
• Novel frameshift variants expand the map of the genetic defects in IRF2BP2. (PMID:37876937)
• Super-enhancer-driven IRF2BP2 enhances ALK activity and promotes neuroblastoma cell proliferation. (PMID:38864832)
• Novel hypermorphic variants in IRF2BP2 identified in patients with common variable immunodeficiency and autoimmunity. (PMID:39059757)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	irf2bp2a	ENSDARG00000004702
danio_rerio	irf2bp2b	ENSDARG00000098635
mus_musculus	Irf2bp2	ENSMUSG00000051495
rattus_norvegicus	Irf2bp2	ENSRNOG00000070206
drosophila_melanogaster	Pits	FBGN0030400
caenorhabditis_elegans	ztf-11	WBGENE00009939
caenorhabditis_elegans		WBGENE00010867

Paralogs (5): IRF2BPL (ENSG00000119669), ST18 (ENSG00000147488), IRF2BP1 (ENSG00000170604), MYT1L (ENSG00000186487), MYT1 (ENSG00000196132)

Protein

Protein identifiers

Interferon regulatory factor 2-binding protein 2 — Q7Z5L9 (reviewed: Q7Z5L9)

All UniProt accessions (1): Q7Z5L9

UniProt curated annotations — full annotation on UniProt →

Function. Acts as a transcriptional corepressor in a IRF2-dependent manner; this repression is not mediated by histone deacetylase activities. Represses the NFAT1-dependent transactivation of NFAT-responsive promoters. Acts as a coactivator of VEGFA expression in cardiac and skeletal muscles. Plays a role in immature B-cell differentiation.

Subunit / interactions. Interacts with IRF2. Part of a corepressor complex containing IRF2 and IRF2BP1. Interacts with VGLL4.

Subcellular location. Cytoplasm. Nucleus.

Post-translational modifications. Phosphorylation at Ser-360 is required for nuclear targeting.

Disease relevance. Immunodeficiency, common variable, 14 (CVID14) [MIM:617765] A primary immunodeficiency resulting in recurrent sinopulmonary infections since early childhood, and characterized by hypogammaglobulinemia with undetectable IgG and IgA, poor response to vaccination, and decreased levels of switched memory B cells. CVID14 inheritance is autosomal dominant. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The C-terminal RING-type zinc finger domain is sufficient for interaction with IRF2.

Similarity. Belongs to the IRF2BP family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q7Z5L9-1	1, IRF-2BP2A	yes
Q7Z5L9-2	2, IRF-2BP2B
Q7Z5L9-3	3

RefSeq proteins (2): NP_001070865, NP_892017* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR022750	IRF-2BP1_2-like_Znf	Domain
IPR044882	I2BP1/2_C3HC4-RING_sf	Homologous_superfamily
IPR057414	Zf-C3HC4_IRF-2BP1_2	Domain
IPR058682	IRF-2BP1/2-like_M	Domain

Pfam: PF11261, PF25454, PF25457

UniProt features (44 total): modified residue 11, cross-link 6, region of interest 5, compositionally biased region 4, strand 4, sequence conflict 3, splice variant 2, sequence variant 2, helix 2, initiator methionine 1, chain 1, zinc finger region 1, turn 1, short sequence motif 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
8YTG	X-RAY DIFFRACTION	1.45
8YTF	X-RAY DIFFRACTION	1.59
8YTH	X-RAY DIFFRACTION	2.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7Z5L9-F1	56.84	0.20

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 (17): 2, 71, 175, 240, 318, 360, 406, 423, 455, 457, 460, 289, 303, 324, 326, 348, 326

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 320 (showing top): GOBP_B_CELL_ACTIVATION, PATIL_LIVER_CANCER, SCHAEFFER_PROSTATE_DEVELOPMENT_6HR_DN, SCHAEFFER_PROSTATE_DEVELOPMENT_AND_CANCER_BOX4_UP, BASAKI_YBX1_TARGETS_DN, CUI_TCF21_TARGETS_2_DN, NUYTTEN_EZH2_TARGETS_DN, GARY_CD5_TARGETS_UP, GOBP_LYMPHOCYTE_DIFFERENTIATION, CHANDRAN_METASTASIS_TOP50_UP, GOMF_TRANSCRIPTION_COREPRESSOR_ACTIVITY, MARTENS_BOUND_BY_PML_RARA_FUSION, MARTENS_TRETINOIN_RESPONSE_DN, GOBP_NEGATIVE_REGULATION_OF_TRANSCRIPTION_BY_RNA_POLYMERASE_II, GOBP_IMMATURE_B_CELL_DIFFERENTIATION

GO Biological Process (3): negative regulation of transcription by RNA polymerase II (GO:0000122), immature B cell differentiation (GO:0002327), regulation of transcription by RNA polymerase II (GO:0006357)

GO Molecular Function (3): transcription corepressor activity (GO:0003714), zinc ion binding (GO:0008270), metal ion binding (GO:0046872)

GO Cellular Component (3): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transcription by RNA polymerase II	2
negative regulation of DNA-templated transcription	2
cellular anatomical structure	2
regulation of transcription by RNA polymerase II	1
B cell differentiation	1
regulation of DNA-templated transcription	1
transcription coregulator activity	1
transition metal ion binding	1
cation binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

929 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IRF2BP2	IRF2	P14316	920
IRF2BP2	NCOR1	O75376	793
IRF2BP2	VGLL4	Q14135	711
IRF2BP2	IRF2BP1	Q8IU81	685
IRF2BP2	ITGB3BP	Q13352	586
IRF2BP2	NTRK1	P04629	518
IRF2BP2	ETV6	P41212	517
IRF2BP2	TEAD1	P28347	508
IRF2BP2	NABP1	Q96AH0	507
IRF2BP2	NTRK3	Q16288	502
IRF2BP2	STAT1	P42224	486
IRF2BP2	EIF2S2	P20042	477
IRF2BP2	RELA	Q04206	467
IRF2BP2	LRBA	P50851	460
IRF2BP2	NCOR2	Q9Y618	451

IntAct

67 interactions, top by confidence:

A	B	Type	Score
BAG2	HGS	psi-mi:“MI:0914”(association)	0.530
FOSL2	ZZEF1	psi-mi:“MI:0914”(association)	0.530
CCNL2	ZBTB43	psi-mi:“MI:0914”(association)	0.530
IRF2	CTSS	psi-mi:“MI:0914”(association)	0.530
UPRT	SERPINB4	psi-mi:“MI:0914”(association)	0.530
IRF2BP1	SCRIB	psi-mi:“MI:0914”(association)	0.530
IRF2BP1	VGLL4	psi-mi:“MI:0914”(association)	0.530
VGLL4	IRF2BP2	psi-mi:“MI:0914”(association)	0.530
GPS1	PXDNL	psi-mi:“MI:0914”(association)	0.530
HSPA2	DNAJC13	psi-mi:“MI:0914”(association)	0.530
SIRT6	TRIM27	psi-mi:“MI:0914”(association)	0.530
VGLL4	YAP1	psi-mi:“MI:0914”(association)	0.530
VGLL4	TEAD1	psi-mi:“MI:0914”(association)	0.480
RBM45	HNRNPDL	psi-mi:“MI:0914”(association)	0.460
MTNR1B	IRF2BP2	psi-mi:“MI:0915”(physical association)	0.370
ERBB2	IRF2BP2	psi-mi:“MI:0915”(physical association)	0.370
ERBB3	IRF2BP2	psi-mi:“MI:0915”(physical association)	0.370
ERBB4	IRF2BP2	psi-mi:“MI:0915”(physical association)	0.370
IRF2	VWA8	psi-mi:“MI:0914”(association)	0.350
ATG16L1	ESYT2	psi-mi:“MI:0914”(association)	0.350
hspa1a_hspa1b_human-1	SHTN1	psi-mi:“MI:0914”(association)	0.350
SCRIB	C1orf226	psi-mi:“MI:0914”(association)	0.350
BAG1	PSMD11	psi-mi:“MI:0914”(association)	0.350
HSPA2	HGS	psi-mi:“MI:0914”(association)	0.350
PIAS4	TRIM24	psi-mi:“MI:0914”(association)	0.350
LMO2	POLR2D	psi-mi:“MI:0914”(association)	0.350
GCHFR	OBSL1	psi-mi:“MI:0914”(association)	0.350
SIRT6	MACROH2A1	psi-mi:“MI:0914”(association)	0.350
CHRNA10	ANO6	psi-mi:“MI:0914”(association)	0.350

BioGRID (166): IRF2BP2 (Affinity Capture-MS), IRF2BP2 (Affinity Capture-MS), IRF2BP2 (Affinity Capture-MS), IRF2BP2 (Affinity Capture-MS), IRF2BP2 (Affinity Capture-MS), EIF4H (Co-fractionation), IRF2BP2 (Co-fractionation), IRF2BP2 (Affinity Capture-MS), IRF2BP2 (Affinity Capture-MS), IRF2BP2 (Affinity Capture-MS), IRF2BP2 (Affinity Capture-MS), IRF2BP2 (Affinity Capture-MS), IRF2BP2 (Affinity Capture-MS), IRF2BP2 (Affinity Capture-MS), IRF2BP2 (Affinity Capture-MS)

ESM2 similar proteins: A4IHR5, A6H7J1, A6NKL6, A6NL88, A7UKY7, A7YY54, B8ZZ34, C9J069, C9JLR9, E9Q1P8, O15209, O35615, O35779, P04198, P15066, P17535, P39881, P52909, Q01101, Q0PHV7, Q14526, Q14934, Q15742, Q32KV8, Q4VA45, Q52KG4, Q5TJE2, Q61976, Q63ZV0, Q6NUJ5, Q6P0F9, Q7T3H2, Q7Z5L9, Q7Z6J2, Q8C3Q5, Q8IX07, Q8R4T5, Q8TF61, Q8VCG9, Q96B18

Diamond homologs: E9Q1P8, Q1LV17, Q2MJS2, Q5EIC4, Q66IY8, Q6DIH5, Q6NZT6, Q6PCG7, Q7T2G1, Q7Z5L9, Q7ZXS3, Q8IU81, Q8K3X4, Q8R3Y8, Q9H1B7

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
IRF2BP2	“up-regulates activity”	IRF2	binding
Ub:E2	“up-regulates activity”	IRF2BP2	ubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 91 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.

GO biological processes:

GO term	Partners	Fold	FDR
epidermal growth factor receptor signaling pathway	5	14.6×	4e-03
wound healing	5	13.4×	5e-03
glucose homeostasis	6	9.2×	6e-03
transcription by RNA polymerase II	8	6.6×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	3
Uncertain significance	491
Likely benign	260
Benign	18

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
2577020	NM_182972.3(IRF2BP2):c.314_324del (p.Glu105fs)	Likely pathogenic
2577035	NM_182972.3(IRF2BP2):c.217_244del (p.Pro73fs)	Likely pathogenic
3362908	NM_182972.3(IRF2BP2):c.1137G>A (p.Trp379Ter)	Likely pathogenic

SpliceAI

183 predictions. Top by Δscore:

Variant	Effect	Δscore
1:234607848:TGCAA:T	acceptor_gain	1.0000
1:234607849:GCAA:G	acceptor_gain	1.0000
1:234607850:CAA:C	acceptor_gain	1.0000
1:234607850:CAAC:C	acceptor_gain	1.0000
1:234607851:AA:A	acceptor_gain	1.0000
1:234607853:C:CC	acceptor_gain	1.0000
1:234607860:C:CT	acceptor_gain	1.0000
1:234607862:C:CT	acceptor_gain	1.0000
1:234607863:A:T	acceptor_gain	1.0000
1:234607869:A:C	acceptor_gain	0.9900
1:234607869:A:AC	acceptor_gain	0.9800
1:234608526:G:A	donor_gain	0.9800
1:234607847:TTGCA:T	acceptor_gain	0.9700
1:234607849:GCAAC:G	acceptor_gain	0.9700
1:234607850:CAACT:C	acceptor_gain	0.9600
1:234607851:AAC:A	acceptor_gain	0.9600
1:234607852:ACT:A	acceptor_gain	0.9600
1:234607853:CTGGA:C	acceptor_gain	0.9600
1:234607854:T:G	acceptor_gain	0.9600
1:234607861:A:T	acceptor_gain	0.9600
1:234608452:TTAG:T	donor_gain	0.9600
1:234608446:CCTG:C	donor_gain	0.9300
1:234607851:A:T	acceptor_gain	0.9200
1:234608442:CCTA:C	donor_loss	0.9200
1:234608443:CTACC:C	donor_loss	0.9200
1:234608444:TACCT:T	donor_loss	0.9200
1:234608446:C:G	donor_loss	0.9200
1:234608516:T:TA	donor_gain	0.9200
1:234608519:TAA:T	donor_gain	0.9100
1:234608520:AAA:A	donor_gain	0.9100

AlphaMissense

3769 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:234607177:A:G	L575P	1.000
1:234607180:A:C	I574S	1.000
1:234607180:A:G	I574T	1.000
1:234607180:A:T	I574N	1.000
1:234607189:A:C	I571S	1.000
1:234607189:A:T	I571N	1.000
1:234607192:T:A	E570V	1.000
1:234607192:T:C	E570G	1.000
1:234607193:C:T	E570K	1.000
1:234607200:C:A	M567I	1.000
1:234607200:C:G	M567I	1.000
1:234607200:C:T	M567I	1.000
1:234607201:A:G	M567T	1.000
1:234607203:A:C	F566L	1.000
1:234607203:A:T	F566L	1.000
1:234607204:A:C	F566C	1.000
1:234607204:A:G	F566S	1.000
1:234607205:A:C	F566V	1.000
1:234607205:A:G	F566L	1.000
1:234607205:A:T	F566I	1.000
1:234607209:C:A	W564C	1.000
1:234607209:C:G	W564C	1.000
1:234607210:C:G	W564S	1.000
1:234607211:A:G	W564R	1.000
1:234607211:A:T	W564R	1.000
1:234607231:A:G	L557P	1.000
1:234607231:A:T	L557H	1.000
1:234607236:G:C	C555W	1.000
1:234607237:C:A	C555F	1.000
1:234607237:C:G	C555S	1.000

dbSNP variants (sampled 300 via entrez): RS1000034637 (1:234610678 TAC>T), RS1000478741 (1:234609222 G>A,T), RS1000513602 (1:234610549 G>A), RS1000766976 (1:234608184 C>T), RS1001220608 (1:234608349 C>G,T), RS1001589233 (1:234605590 T>C), RS1001909997 (1:234609399 G>A), RS1001941373 (1:234609230 T>C,G), RS1002034303 (1:234608701 G>A), RS1002547649 (1:234603889 G>A,C), RS1002646233 (1:234611360 A>C,G), RS1002697225 (1:234611632 G>A,T), RS1002735045 (1:234606746 C>A,T), RS1002809822 (1:234605827 A>T), RS1003217104 (1:234606469 A>C)

Disease associations

OMIM: gene MIM:615332 | disease phenotypes: MIM:617765, MIM:600670, MIM:146830

GenCC curated gene-disease

Disease	Classification	Inheritance
immunodeficiency, common variable, 14	Strong	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
immunodeficiency, common variable, 14	Limited	AD

Mondo (4): immunodeficiency, common variable, 14 (MONDO:0054691), varicella, severe recurrent (MONDO:0010919), inborn error of immunity (MONDO:0003778), immune deficiency, familial variable (MONDO:0007814)

Orphanet (3): Common variable immunodeficiency phenotype due to IRF2BP2 deficiency (Orphanet:696904), Primary immunodeficiency (Orphanet:101997), OBSOLETE: Common variable immunodeficiency (Orphanet:1572)

HPO phenotypes

47 total (30 of 47 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000212	Gingival overgrowth
HP:0000225	Gingival bleeding
HP:0000421	Epistaxis
HP:0000790	Hematuria
HP:0000967	Petechiae
HP:0000978	Bruising susceptibility
HP:0000979	Purpura
HP:0001324	Muscle weakness
HP:0001824	Weight loss
HP:0001873	Thrombocytopenia
HP:0001875	Decreased total neutrophil count
HP:0001876	Pancytopenia
HP:0001882	Decreased total leukocyte count
HP:0001892	Abnormal bleeding
HP:0001903	Anemia
HP:0001945	Fever
HP:0001974	Increased total leukocyte count
HP:0002027	Abdominal pain
HP:0002028	Chronic diarrhea
HP:0002039	Anorexia
HP:0002321	Vertigo
HP:0002653	Bone pain
HP:0002716	Lymphadenopathy
HP:0002720	Decreased circulating IgA concentration
HP:0002850	Decreased circulating total IgM
HP:0002875	Exertional dyspnea
HP:0003765	Psoriasiform dermatitis
HP:0004315	Decreased circulating IgG concentration
HP:0005357	Defective B cell differentiation

GWAS associations

27 associations (top):

Study	Trait	p-value
GCST000759_2	LDL cholesterol	9.000000e-12
GCST000760_1	Cholesterol, total	5.000000e-14
GCST001376_2	Life threatening arrhythmia	6.000000e-06
GCST001569_3	Bipolar disorder	5.000000e-06
GCST002221_60	Cholesterol, total	5.000000e-14
GCST002222_31	LDL cholesterol	9.000000e-12
GCST002896_32	Cholesterol, total	2.000000e-16
GCST002898_27	LDL cholesterol	1.000000e-11
GCST003678_11	C-reactive protein levels or total cholesterol levels (pleiotropy)	2.000000e-14
GCST003679_2	C-reactive protein levels or LDL-cholesterol levels (pleiotropy)	3.000000e-12
GCST004135_5	White blood cell count (eosinophil)	6.000000e-09
GCST004233_43	LDL cholesterol levels	2.000000e-23
GCST004235_28	Total cholesterol levels	5.000000e-27
GCST006979_904	Heel bone mineral density	2.000000e-11
GCST010241_136	Apolipoprotein A1 levels	3.000000e-22
GCST010242_33	HDL cholesterol levels	1.000000e-15
GCST010243_169	Apolipoprotein B levels	8.000000e-67
GCST010243_99	Apolipoprotein B levels	4.000000e-11
GCST010245_19	LDL cholesterol levels	4.000000e-09
GCST010245_225	LDL cholesterol levels	8.000000e-64
GCST90000047_23	Age at first sexual intercourse	3.000000e-08
GCST90002390_342	Mean corpuscular hemoglobin	8.000000e-10
GCST90002392_258	Mean corpuscular volume	6.000000e-12
GCST90002397_757	Mean spheric corpuscular volume	9.000000e-13
GCST90002403_71	Red blood cell count	5.000000e-16
GCST90011900_35	Serum alkaline phosphatase levels	3.000000e-14
GCST90016667_36	Spleen volume	4.000000e-08

EFO canonical traits (13, from GWAS)

EFO ID	Trait name
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004574	total cholesterol measurement
EFO:0004269	cardiac arrhythmia
EFO:0004458	C-reactive protein measurement
EFO:0004842	eosinophil count
EFO:0009270	heel bone mineral density
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004615	apolipoprotein B measurement
EFO:0009749	age at first sexual intercourse measurement
EFO:0004527	mean corpuscular hemoglobin
EFO:0004305	erythrocyte count
EFO:0004533	alkaline phosphatase measurement

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D007153	Immunologic Deficiency Syndromes	C20.673
C564136	Immune Deficiency, Familial Variable (supp.)
C563458	Varicella, Severe Recurrent (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067201 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.08	Kd	84.2	nM	CHEMBL5653589
7.08	ED50	84.2	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 2 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
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148604: Binding affinity to human IRF2BP2 incubated for 45 mins by Kinobead based pull down assay	kd	0.0842	uM

CTD chemical–gene interactions

57 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, increases methylation	6
methylmercuric chloride	increases expression, affects cotreatment	4
trichostatin A	affects cotreatment, increases expression, affects expression	4
Phenylmercuric Acetate	increases expression, affects cotreatment	2
Aflatoxin B1	decreases methylation, increases methylation	2
aristolochic acid I	increases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
FR900359	affects phosphorylation	1
TAK-243	affects sumoylation	1
bisphenol A	affects expression	1
deoxynivalenol	increases expression	1
quercitrin	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	affects cotreatment, increases expression	1
butyraldehyde	decreases expression	1
beta-methylcholine	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
pentabromodiphenyl ether	increases expression	1
K 7174	increases expression	1
motexafin gadolinium	increases expression, affects cotreatment	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	1
ICG 001	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine	increases expression, increases response to substance	1
Resveratrol	affects cotreatment, decreases expression	1
Sunitinib	increases expression	1
Vorinostat	decreases expression	1
Leflunomide	increases expression	1
Acetaminophen	decreases 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
CHEMBL5651646	Binding	Binding affinity to human IRF2BP2 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

3 cell lines: 3 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A3F3	SEES3-1V human IRF2BP2, clone1	Embryonic stem cell	Male
CVCL_A3F4	SEES3-1V human IRF2BP2, clone2	Embryonic stem cell	Male
CVCL_A3F5	SEES3-1V human IRF2BP2, clone3	Embryonic stem cell	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03677557	PHASE4	UNKNOWN	Safety, Tolerability, Patient Satisfaction and Cost of 16.5% Subcutaneous Immunoglobulin (Cutaquig®) Treatment
NCT00001646	PHASE3	COMPLETED	Voriconazole vs. Amphotericin B in the Treatment of Invasive Aspergillosis
NCT00220766	PHASE3	COMPLETED	Rapid Infusion of Immune Globulin Intravenous (Human) In Primary Immunodeficiency Patients
NCT00468273	PHASE3	COMPLETED	A Clinical Study of Intravenous Immunoglobulin
NCT00811174	PHASE3	TERMINATED	Efficacy, Safety and Kinetics Study of Octagam 10% in Primary Immunodeficiency Diseases
NCT01012323	PHASE3	COMPLETED	A Study of NewGam, Human Immunoglobulin 10%, in Patients With Primary Immunodeficiency Diseases
NCT01313507	PHASE3	COMPLETED	High Infusion Rate Study of Immunoglobulin Intravenous (Human) 10% (NewGam)
NCT01406470	PHASE3	COMPLETED	Phase 3 Study of Immune Globulin Intravenous (Human)IVIG-SN™ in Subjects With Primary Immunodeficiency
NCT02783482	PHASE3	COMPLETED	Study of Immune Globulin Intravenous (Human) GC5107 in Subjects With Primary Humoral Immunodeficiency
NCT02810444	PHASE3	COMPLETED	Study to Investigate Efficacy, Safety and Pharmacokinetics of BT595 in Subjects With PID
NCT03961009	PHASE3	COMPLETED	Clinical Assessment of Pharmacokinetics, Efficacy, and Safety of 10% IVIg in PID Patients
NCT04842643	PHASE3	COMPLETED	An Extension Study of TAK-664 for Japanese People With Primary Immunodeficiency Disease
NCT04944979	PHASE3	ACTIVE_NOT_RECRUITING	Clinical Assessment of Pharmacokinetics, Efficacy, and Safety of 10% IVIg in Pediatric PID Patients (KIDCARES10)
NCT06089122	PHASE3	UNKNOWN	Efficacy, Safety, and Pharmacokinetics of Shu Yang IVIG
NCT06150833	PHASE3	UNKNOWN	Efficacy and Safety and Pharmacokinetics of Boya IVIG
NCT07346859	PHASE3	RECRUITING	Study of BP-SCIG 20% in Patients With Primary Immunodeficiency (PID)
NCT00001438	PHASE2	COMPLETED	A Pilot Study of the Combination of Retinoic Acid and Interferon-Alpha2a for the Treatment of Lymphoproliferative Disorders in Children With Immunodeficiency Syndromes
NCT00176865	PHASE2	COMPLETED	Stem Cell Transplant for Immunologic or Histiocytic Disorders
NCT00389324	PHASE2	COMPLETED	A Trial of the Pharmacokinetics, Safety, and Tolerability of Subcutaneous Gamunex® in Primary Immunodeficiency
NCT00598481	PHASE2	COMPLETED	ADA Gene Transfer Into Hematopoietic Stem/Progenitor Cells for the Treatment of ADA-SCID
NCT01856582	PHASE2	TERMINATED	CD34+ Stem Cell Infusion to Augment Graft Function
NCT06199427	PHASE2	RECRUITING	PTCy and and Ruxolitinib for GVHD Prophylaxis After HSCT With Thymoglobulin in Conditioning Regimen in Patients With Inborn Errors of Immunity
NCT00001158	Not specified	COMPLETED	Studies of the Immune Response in Normal Subjects and Patients With Disorders of the Immune System
NCT00001336	Not specified	COMPLETED	In Vitro Studies of Immunological and Stem Cell Function in Peripheral Blood Mononuclear Cells in Patients
NCT00001788	Not specified	TERMINATED	Genetic Basis of Primary Immunodeficiencies
NCT00006054	Not specified	TERMINATED	Allogeneic Bone Marrow Transplantation in Patients With Primary Immunodeficiencies
NCT00006131	Not specified	COMPLETED	Randomized Study of Two Doses of Oral Valacyclovir in Immunocompromised Patients With Uncomplicated Herpes Zoster
NCT01150240	Not specified	UNKNOWN	Clinical and Laboratory Online Patient- and Research Database for Primary Immunodeficiencies in Switzerland
NCT01727895	Not specified	COMPLETED	Effects of Orally Administered Beta-glucan on Leukocyte Function in Humans
NCT02176239	Not specified	COMPLETED	Monitoring of 5% Treatment Naïve Intravenous Immunoglobulin (IVIg) Primary Immunodeficiency Disease (PIDD) Patients Using the CareExchange® System: A Pilot Study Using 5% Gammaplex® IVIg in the Home Setting
NCT02417740	Not specified	RECRUITING	Natural History of Noncirrhotic Portal Hypertension
NCT02554630	Not specified	COMPLETED	Novel Mechanisms and Approaches to Treat Neonatal Sepsis
NCT02630082	Not specified	COMPLETED	Feasibility of Measuring Immune Resp, Activation in Foreskin/Mucosa in HIV-, Uncircumcised High-HIV-risk MSM, Lima Peru
NCT02735824	Not specified	RECRUITING	Genetic Study of Immunodeficiency: Search for New Genetic Causes for Primary Immunodeficiencies
NCT03252548	Not specified	UNKNOWN	Pediatric Primary Immunodeficiency Disease (PID) in China
NCT03478670	Not specified	ENROLLING_BY_INVITATION	Strimvelis Registry Study to Follow-up Patients With Adenosine Deaminase Severe Combined Immunodeficiency (ADA-SCID)
NCT03835312	Not specified	RECRUITING	Sequential Transplantation of UCBSCs and Islet Cells in Children and Adolescents With Monogenic Immunodeficiency T1DM
NCT03920735	Not specified	UNKNOWN	Retrospective Non-interventional Analysis of Opportunistic Infections in Immunocompromised and Frail Patients
NCT04798677	Not specified	COMPLETED	Efficacy and Tolerability of ABBC1 in Volunteers Receiving the Influenza or Covid-19 Vaccine
NCT05236764	Not specified	ACTIVE_NOT_RECRUITING	Haploidentical Hematopoietic Cell Transplantation Using TCR Alpha/Beta and CD19 Depletion