IRF2BP1

Summary

IRF2BP1 (interferon regulatory factor 2 binding protein 1, HGNC:21728) is a protein-coding gene on chromosome 19q13.32, encoding Interferon regulatory factor 2-binding protein 1 (Q8IU81). Acts as a transcriptional corepressor in a IRF2-dependent manner; this repression is not mediated by histone deacetylase activities.

Enables transcription corepressor activity and ubiquitin protein ligase activity. Involved in protein polyubiquitination. Acts upstream of or within negative regulation of transcription by RNA polymerase II. Located in nucleoplasm.

Source: NCBI Gene 26145 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 65 total
• MANE Select transcript: NM_015649

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21728
Approved symbol	IRF2BP1
Name	interferon regulatory factor 2 binding protein 1
Location	19q13.32
Locus type	gene with protein product
Status	Approved
Aliases	DKFZP434M154, IRF-2BP1
Ensembl gene	ENSG00000170604
Ensembl biotype	protein_coding
OMIM	615331
Entrez	26145

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000302165

RefSeq mRNA: 1 — MANE Select: NM_015649 NM_015649

CCDS: CCDS12678

Canonical transcript exons

ENST00000302165 — 1 exons

Exon	Start	End
ENSE00001156755	45883608	45886141

Expression profiles

Bgee: expression breadth ubiquitous, 216 present calls, max score 95.28.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 9.6800 / max 97.9314, expressed in 1757 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
181585	8.2697	1740
181584	1.4103	847

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
type B pancreatic cell	CL:0000169	95.28	gold quality
olfactory bulb	UBERON:0002264	93.82	silver quality
diaphragm	UBERON:0001103	92.92	gold quality
CA1 field of hippocampus	UBERON:0003881	89.45	silver quality
cardiac muscle of right atrium	UBERON:0003379	88.83	silver quality
apex of heart	UBERON:0002098	88.45	gold quality
hindlimb stylopod muscle	UBERON:0004252	87.89	gold quality
vena cava	UBERON:0004087	87.75	silver quality
nipple	UBERON:0002030	87.73	gold quality
right hemisphere of cerebellum	UBERON:0014890	87.62	gold quality
ventral tegmental area	UBERON:0002691	87.25	silver quality
mucosa of urinary bladder	UBERON:0001259	87.16	gold quality
ileal mucosa	UBERON:0000331	87.12	silver quality
cerebellar cortex	UBERON:0002129	86.84	gold quality
cerebellar hemisphere	UBERON:0002245	86.81	gold quality
cerebellum	UBERON:0002037	86.60	gold quality
prefrontal cortex	UBERON:0000451	86.59	gold quality
right frontal lobe	UBERON:0002810	86.58	gold quality
mammary duct	UBERON:0001765	86.37	gold quality
inferior vagus X ganglion	UBERON:0005363	86.21	gold quality
body of tongue	UBERON:0011876	86.19	silver quality
renal medulla	UBERON:0000362	85.98	gold quality
dorsal plus ventral thalamus	UBERON:0001897	85.94	silver quality
trachea	UBERON:0003126	85.84	silver quality
cerebellar vermis	UBERON:0004720	85.83	silver quality
subthalamic nucleus	UBERON:0001906	85.82	silver quality
tongue	UBERON:0001723	85.71	silver quality
Brodmann (1909) area 9	UBERON:0013540	85.71	gold quality
gastrocnemius	UBERON:0001388	85.59	gold quality
frontal cortex	UBERON:0001870	85.49	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.25

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

38 targeting IRF2BP1, 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-340-5P	100.00	72.50	4437
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-3140-3P	99.88	68.47	2069
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-6745	99.74	65.33	1321
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-6126	99.62	68.09	996
HSA-MIR-1249-5P	99.61	66.55	2049
HSA-MIR-6797-5P	99.61	66.55	2084
HSA-MIR-762	99.58	66.61	1994
HSA-MIR-514B-5P	99.50	68.19	1766
HSA-MIR-513C-5P	99.50	68.42	1730
HSA-MIR-4672	99.50	71.58	2893
HSA-MIR-6081	99.48	66.07	1446
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-363-5P	99.46	64.51	1015
HSA-MIR-1276	99.36	68.18	1642
HSA-MIR-4311	99.31	70.47	3041
HSA-MIR-7515	99.31	68.22	1795
HSA-MIR-4651	99.06	67.57	2002
HSA-MIR-5001-5P	99.05	66.76	1972
HSA-MIR-3154	98.94	66.55	1455
HSA-MIR-608	98.93	67.83	2013
HSA-MIR-583	98.71	67.44	1791
HSA-MIR-423-5P	98.69	67.48	1522
HSA-MIR-3184-5P	98.56	67.13	1491
HSA-MIR-6776-5P	98.54	67.43	1304

Literature-anchored findings (GeneRIF, showing 4)

• Identification of IRF-2 binding protein 1 and IRF-2 binding protein 2 as co-repressor molecules for interferon regulatory factor-2. (PMID:12799427)
• PCTA (IRF2BP1) defines a new component of the TGF-beta signalling pathway that functions to facilitate Smad2 phosphorylation through controlling the accumulation of cPML into the cytoplasm, and consequently, the assembly of Smad2-receptor complex. (PMID:18511908)
• IRF2-BP1 is a JDP2-binding protein enhancing the polyubiquitination of JDP2 and represses ATF2-mediated transcriptional activation from a CRE-containing promoter. (PMID:18671972)
• Transient deSUMOylation of IRF2BP proteins controls early transcription in EGFR signaling. (PMID:33480129)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	irf2bp1	ENSDARG00000005468
mus_musculus	Irf2bp1	ENSMUSG00000044030
rattus_norvegicus	Irf2bp1	ENSRNOG00000014252
drosophila_melanogaster	Pits	FBGN0030400
caenorhabditis_elegans	ztf-11	WBGENE00009939
caenorhabditis_elegans		WBGENE00010867

Paralogs (5): IRF2BPL (ENSG00000119669), ST18 (ENSG00000147488), IRF2BP2 (ENSG00000168264), MYT1L (ENSG00000186487), MYT1 (ENSG00000196132)

Protein

Protein identifiers

Interferon regulatory factor 2-binding protein 1 — Q8IU81 (reviewed: Q8IU81)

Alternative names: Probable E3 ubiquitin-protein ligase IRF2BP1, Probable RING-type E3 ubiquitin transferase IRF2BP1

All UniProt accessions (1): Q8IU81

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. May act as an E3 ligase towards JDP2, enhancing its polyubiquitination. Represses ATF2-dependent transcriptional activation.

Subunit / interactions. Interacts with IRF2. Part of a corepressor complex containing IRF2 and IRF2BP2. Interacts with JDP2.

Subcellular location. Nucleus.

Similarity. Belongs to the IRF2BP family.

RefSeq proteins (1): NP_056464* (*=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 (26 total): modified residue 10, region of interest 4, sequence conflict 4, cross-link 2, compositionally biased region 2, chain 1, zinc finger region 1, sequence variant 1, coiled-coil region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IU81-F1	66.17	0.35

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 (12): 125, 177, 186, 371, 384, 421, 436, 453, 457, 227, 438, 66

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 148 (showing top): MORF_RAGE, GGAMTNNNNNTCCY_UNKNOWN, SP1_Q2_01, MORF_FANCG, GOBP_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, GOBP_PROTEIN_POLYUBIQUITINATION, HIF1_Q3, AACTTT_UNKNOWN, MORF_PML, GFI1_01, ELK1_01, CREBP1_01, MORF_MT4, MORF_ORC1L, TCCCRNNRTGC_UNKNOWN

GO Biological Process (3): negative regulation of transcription by RNA polymerase II (GO:0000122), protein polyubiquitination (GO:0000209), regulation of transcription by RNA polymerase II (GO:0006357)

GO Molecular Function (6): transcription corepressor activity (GO:0003714), zinc ion binding (GO:0008270), ubiquitin protein ligase activity (GO:0061630), protein binding (GO:0005515), transferase activity (GO:0016740), metal ion binding (GO:0046872)

GO Cellular Component (2): nucleus (GO:0005634), nucleoplasm (GO:0005654)

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
regulation of transcription by RNA polymerase II	1
protein ubiquitination	1
regulation of DNA-templated transcription	1
transcription coregulator activity	1
transition metal ion binding	1
ubiquitin-protein transferase activity	1
ubiquitin-like protein ligase activity	1
binding	1
catalytic activity	1
cation binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1079 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IRF2BP1	IRF2	P14316	754
IRF2BP1	IRF2BP2	Q7Z5L9	685
IRF2BP1	ARL16	Q0P5N6	443
IRF2BP1	FASTKD2	Q9NYY8	441
IRF2BP1	STAT2	P52630	439
IRF2BP1	IRF2BPL	Q9H1B7	426
IRF2BP1	IFRD2	Q12894	421
IRF2BP1	STAT1	P42224	404
IRF2BP1	CCDC166	P0CW27	399
IRF2BP1	RELA	Q04206	393
IRF2BP1	SNX30	Q5VWJ9	392
IRF2BP1	ITGB3BP	Q13352	384
IRF2BP1	MRPS35	P82673	341
IRF2BP1	FAM228B	P0C875	310
IRF2BP1	IRGQ	Q8WZA9	309

IntAct

67 interactions, top by confidence:

A	B	Type	Score
RFXANK	RFXAP	psi-mi:“MI:0914”(association)	0.780
SCRIB	NOS1AP	psi-mi:“MI:0914”(association)	0.690
QPRT	PIK3C2A	psi-mi:“MI:0914”(association)	0.640
JDP2	IRF2BP1	psi-mi:“MI:0915”(physical association)	0.580
JDP2	JUNB	psi-mi:“MI:0914”(association)	0.550
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
BAG2	HGS	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
HSPA12B	EEF2K	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
ATF2	IRF2BP1	psi-mi:“MI:0915”(physical association)	0.400
IRF2BP1	PCBD2	psi-mi:“MI:0915”(physical association)	0.370
IRF2BP1	SMAD1	psi-mi:“MI:0915”(physical association)	0.370
MKI67	ARHGAP10	psi-mi:“MI:0914”(association)	0.350
IRF2	VWA8	psi-mi:“MI:0914”(association)	0.350
VGLL4	TEAD1	psi-mi:“MI:0914”(association)	0.350
IRF2BP1	IRF2BP2	psi-mi:“MI:0914”(association)	0.350
SOX2	SEC16A	psi-mi:“MI:0914”(association)	0.350
hspa1a_hspa1b_human-1	SHTN1	psi-mi:“MI:0914”(association)	0.350
PRKY	METTL15	psi-mi:“MI:0914”(association)	0.350

BioGRID (127): IRF2BP1 (Affinity Capture-MS), IRF2BP1 (Affinity Capture-MS), IRF2BP1 (Affinity Capture-MS), IRF2BP1 (Affinity Capture-MS), IRF2BP1 (Affinity Capture-MS), ARHGAP1 (Co-fractionation), FARSA (Co-fractionation), IRF2BP1 (Co-fractionation), IRF2BP1 (Co-fractionation), IRF2BP1 (Co-fractionation), IRF2BP1 (Affinity Capture-MS), IRF2BP1 (Affinity Capture-MS), IRF2BP1 (Affinity Capture-MS), IRF2BPL (Affinity Capture-MS), IRF2BP2 (Affinity Capture-MS)

ESM2 similar proteins: A0A8I6AGW3, A2A9A2, A6NMB9, A8MYZ6, E9PZZ1, J3QK54, O02755, O02756, O35392, O35767, O60548, O70220, P05554, P17676, P21272, P28033, P35713, P42582, P49715, P49716, P52952, P53566, P58012, Q12952, Q13461, Q14526, Q60843, Q61345, Q63244, Q63250, Q6BEB4, Q6VFT5, Q6VFT6, Q6ZQN5, Q70KY4, Q8IU81, Q8MIP2, Q8NDY6, Q8R2I0, Q98937

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
IRF2BP1	“up-regulates activity”	IRF2	binding
Ub:E2	“up-regulates activity”	IRF2BP1	ubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 80 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
TCF dependent signaling in response to WNT	5	13.4×	6e-03
Signaling by WNT	5	12.7×	6e-03

GO biological processes:

GO term	Partners	Fold	FDR
osteoblast differentiation	6	10.0×	5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	61
Likely benign	2
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

30 predictions. Top by Δscore:

Variant	Effect	Δscore
19:45885971:C:A	donor_gain	0.6700
19:45885964:C:CA	donor_gain	0.6500
19:45886130:T:TA	donor_gain	0.6300
19:45885961:A:AC	donor_gain	0.6100
19:45885962:C:CC	donor_gain	0.6100
19:45885947:AAG:A	donor_gain	0.5600
19:45886124:TCC:T	donor_gain	0.5400
19:45884346:CTT:C	donor_gain	0.4900
19:45885961:ACT:A	donor_gain	0.4600
19:45885962:CTC:C	donor_gain	0.4600
19:45886125:C:CT	donor_gain	0.4200
19:45884345:A:AC	donor_gain	0.4100
19:45884346:C:CC	donor_gain	0.4100
19:45885961:ACTC:A	donor_gain	0.4000
19:45885962:CTCC:C	donor_gain	0.4000
19:45884344:G:T	donor_gain	0.3800
19:45884348:T:TA	donor_gain	0.3800
19:45886126:C:CT	donor_gain	0.3700
19:45885962:CT:C	donor_gain	0.3400
19:45885948:AG:A	donor_gain	0.3200
19:45885198:C:CT	acceptor_gain	0.3100
19:45885970:T:TA	donor_gain	0.3100
19:45884997:C:CA	acceptor_gain	0.2700
19:45886082:C:CA	donor_gain	0.2700
19:45885199:G:T	acceptor_gain	0.2600
19:45884347:T:C	donor_gain	0.2300
19:45886037:CAG:C	donor_gain	0.2200
19:45885559:AAGGG:A	donor_gain	0.2100
19:45885954:T:A	donor_gain	0.2100
19:45885957:G:A	donor_gain	0.2100

AlphaMissense

3697 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:45884060:A:G	L572P	1.000
19:45884063:A:C	I571S	1.000
19:45884063:A:G	I571T	1.000
19:45884063:A:T	I571N	1.000
19:45884072:A:C	I568S	1.000
19:45884072:A:T	I568N	1.000
19:45884074:C:A	E567D	1.000
19:45884074:C:G	E567D	1.000
19:45884075:T:A	E567V	1.000
19:45884075:T:C	E567G	1.000
19:45884076:C:T	E567K	1.000
19:45884083:C:A	M564I	1.000
19:45884083:C:G	M564I	1.000
19:45884083:C:T	M564I	1.000
19:45884086:G:C	F563L	1.000
19:45884086:G:T	F563L	1.000
19:45884087:A:C	F563C	1.000
19:45884087:A:G	F563S	1.000
19:45884088:A:C	F563V	1.000
19:45884088:A:G	F563L	1.000
19:45884088:A:T	F563I	1.000
19:45884092:C:A	W561C	1.000
19:45884092:C:G	W561C	1.000
19:45884093:C:G	W561S	1.000
19:45884094:A:G	W561R	1.000
19:45884094:A:T	W561R	1.000
19:45884119:G:C	C552W	1.000
19:45884120:C:A	C552F	1.000
19:45884120:C:G	C552S	1.000
19:45884120:C:T	C552Y	1.000

dbSNP variants (sampled 300 via entrez): RS1000950546 (19:45885757 C>A,G), RS1001068744 (19:45883719 T>C), RS1001378441 (19:45887519 A>G), RS1001849374 (19:45887827 C>T), RS1001952552 (19:45883310 C>A,T), RS1003120682 (19:45886554 G>C), RS1003794312 (19:45886909 G>A,C), RS1005402175 (19:45884335 T>C), RS1005941935 (19:45887481 A>G,T), RS1005978545 (19:45883241 G>C), RS1006966664 (19:45886902 T>C,G), RS1008245011 (19:45885548 G>A,C), RS1009054134 (19:45885917 C>G), RS1009434112 (19:45887744 G>A), RS1010671138 (19:45885514 C>A,G,T)

Disease associations

OMIM: gene MIM:615331 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST007209_8	Gallstone disease	4.000000e-15
GCST009798_38	Asthma	2.000000e-10
GCST010241_73	Apolipoprotein A1 levels	7.000000e-14
GCST010242_14	HDL cholesterol levels	5.000000e-17
GCST90002390_660	Mean corpuscular hemoglobin	1.000000e-10

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004527	mean corpuscular hemoglobin

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	3
FR900359	affects phosphorylation	1
TAK-243	increases sumoylation	1
daidzein	affects cotreatment, increases expression	1
lead acetate	increases expression	1
cupric chloride	increases expression	1
pinosylvin	increases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
glycitein	affects cotreatment, increases expression	1
perfluoro-n-nonanoic acid	decreases expression	1
abrine	increases expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Sunitinib	increases expression	1
Zoledronic Acid	decreases expression	1
Acetaminophen	decreases expression	1
Arsenic	affects methylation	1
Benzo(a)pyrene	affects methylation	1
Caffeine	decreases phosphorylation	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Doxorubicin	decreases expression	1
Ivermectin	decreases expression	1
Plant Extracts	decreases expression, affects cotreatment	1
Smoke	decreases expression	1
Thiram	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	decreases expression	1
Urethane	decreases expression	1
Genistein	affects cotreatment, increases expression	1

Clinical trials (associated diseases)

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