IRF2BPL

interferon regulatory factor 2 binding protein like

Basic information

Region (hg38): 14:77024543-77028708

Previous symbols: [ "C14orf4" ]

Links

ENSG00000119669 ∙ NCBI:64207 ∙ OMIM:611720 ∙ HGNC:14282 ∙ Uniprot:Q9H1B7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures (Moderate), mode of inheritance: AD
• neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures (Strong), mode of inheritance: AD
• neurodegenerative disease (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic	30057031

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the IRF2BPL gene.

• not provided (11 variants)
• Neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures (10 variants)
• Inborn genetic diseases (2 variants)
• Autism spectrum disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the IRF2BPL gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				52	6	58
missense		4	136	16		156
nonsense	5	13	1			19
start loss						0
frameshift	17	17	3	1		38
inframe indel			15	17	10	42
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			1			1
Total	22	34	156	86	16

Variants in IRF2BPL

This is a list of pathogenic ClinVar variants found in the IRF2BPL region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
14-77025406-G-A		IRF2BPL-related disorder	Uncertain significance (Aug 04, 2023)
14-77025413-TCTC-T			Uncertain significance (Nov 22, 2022)
14-77025439-G-A		Inborn genetic diseases	Uncertain significance (Jun 01, 2023)
14-77025448-G-A			Uncertain significance (Dec 18, 2019)
14-77025484-T-C			Uncertain significance (Mar 10, 2020)
14-77025494-C-G		IRF2BPL-related disorder • Inborn genetic diseases	Uncertain significance (Aug 09, 2021)
14-77025505-T-C		Inborn genetic diseases	Uncertain significance (Feb 05, 2024)
14-77025531-G-T			Likely benign (Feb 01, 2024)
14-77025555-ACT-A			Likely pathogenic (Aug 01, 2019)
14-77025571-G-C			Uncertain significance (Feb 09, 2024)
14-77025573-G-A			Likely benign (Sep 01, 2023)
14-77025587-G-T			Uncertain significance (Feb 22, 2024)
14-77025589-C-A		Rare genetic intellectual disability	Uncertain significance (-)
14-77025590-T-A		IRF2BPL-related disorder	Likely benign (Jul 01, 2024)
14-77025593-G-A		Neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures • IRF2BPL-related disorder	Uncertain significance (Sep 17, 2023)
14-77025596-C-A			Uncertain significance (Dec 18, 2023)
14-77025632-GT-G		Neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures	Pathogenic (Nov 29, 2022)
14-77025640-CA-C		Inborn genetic diseases	Likely pathogenic (Nov 14, 2017)
14-77025654-GA-G			Pathogenic (Dec 01, 2020)
14-77025655-AG-A		Neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures	Likely pathogenic (Aug 25, 2022)
14-77025655-A-AGG		Neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures	Likely pathogenic (Sep 27, 2022)
14-77025657-G-GAC		Neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures	Pathogenic (Jul 02, 2020)
14-77025670-G-C			Uncertain significance (Nov 27, 2023)
14-77025670-GC-G		IRF2BPL-related disorder	Pathogenic/Likely pathogenic (May 20, 2022)
14-77025672-C-G			Uncertain significance (Jan 24, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
IRF2BPL	protein_coding	protein_coding	ENST00000238647	1	4147

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.836	0.164	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.734	377	419	0.899	0.0000220	4934
Missense in Polyphen		29	34.784	0.83372		362
Synonymous	-9.69	372	198	1.88	0.0000116	1728
Loss of Function	3.42	3	19.1	0.157	8.70e-7	216

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May contribute to the control of female reproductive function (By similarity). May play a role in gene transcription by transactivating GNRH1 promoter and repressing PENK promoter. {ECO:0000250}.

Recessive Scores

• pRec: 0.112

Haploinsufficiency Scores

• pHI: 0.696
• hipred: Y
• hipred_score: 0.762
• ghis: 0.504

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.114

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Irf2bpl

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;positive regulation of transcription by RNA polymerase II;development of secondary female sexual characteristics
• Cellular component: extracellular space;nucleus;nucleoplasm
• Molecular function: RNA polymerase II regulatory region sequence-specific DNA binding;DNA-binding transcription activator activity, RNA polymerase II-specific;molecular_function;metal ion binding