IRF2BP1

protein-coding

interferon regulatory factor 2 binding protein 1

Gene summary

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. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_015649.3

Inheritance

—

ClinVar variants

U:62B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.05

Max pathogenic AF

—

Genomic locus

chr19:45,883,608-45,886,141

External References & Databases

Ensembl (ENSG00000170604)

Transcript & Mutation Effects

hg38 • Region Span ~2.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to IRF2BP1 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 64

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_015649.3. 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						0
missense			62 clinvar	2 clinvar		64
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	62	2	0	64

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 2 of 2 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_015649.3	RefSeq	NP_056464.1	1	MANE Select
ENST00000302165.5	Ensembl	ENSP00000307265.3	1	MANE Select

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

TGF_beta_Receptor

Biological Process

negative regulation of transcription by RNA polymerase II
positive regulation of transcription by RNA polymerase II

Molecular Function

RNA polymerase II regulatory region sequence-specific DNA binding
DNA-binding transcription activator activity, RNA polymerase II-specific
protein binding
transferase activity
metal ion binding

Cellular Component

nucleus
nucleoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000302165
Coding exons: 1
Length: 2511
Individuals with no LoFs: 0
Homozygous LoFs: 0
Heterozygous LoFs: 0
Defined: 0
p: 0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	3.34	198	382	0.519	0.0000265	3621
Missense (PolyPhen)		25	77.476	0.32268		727
Synonymous	0.823	167	181	0.922	0.0000136	1322
Loss of Function	3.75	1	18.3	0.0546	0.00000114	166

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	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0	0.0	absent
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: 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. {ECO:0000269|PubMed:12799427, ECO:0000269|PubMed:18671972}.;

Recessive Scores

pRec: 0.109

Intolerance Scores

LoFtool: 0.0271
RVIS EVS: 0.1
RVIS percentile EVS: 61.49

Essentials

Essential (CRISPR): E
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.908

Gene Damage Prediction

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