IRF6

interferon regulatory factor 6, the group of Interferon regulatory factors

Basic information

Region (hg38): 1:209785617-209806175

Previous symbols: [ "VWS", "LPS" ]

Links

ENSG00000117595 ∙ NCBI:3664 ∙ OMIM:607199 ∙ HGNC:6121 ∙ Uniprot:O14896 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• van der Woude syndrome 1 (Definitive), mode of inheritance: AD
• autosomal dominant popliteal pterygium syndrome (Definitive), mode of inheritance: AD
• van der Woude syndrome (Supportive), mode of inheritance: AD
• autosomal dominant popliteal pterygium syndrome (Supportive), mode of inheritance: AD
• tooth agenesis (Supportive), mode of inheritance: AD
• autosomal dominant popliteal pterygium syndrome (Strong), mode of inheritance: AD
• van der Woude syndrome 1 (Strong), mode of inheritance: AD
• orofacial cleft 6, susceptibility to (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Popliteal pterygium syndrome; van der Woude syndrome 1; Orofacial cleft 6	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	Craniofacial; Dermatologic; Genitourinary; Musculoskeletal	13158329; 6573981; 2164325; 7628117; 10593995; 12219090; 14757865; 15317890; 16096995; 15558496; 17539900; 18247422; 18478600; 18836445; 20803643; 20799332; 21045959; 21082654; 21468557; 21739575; 21995291; 22488974; 24442519
Variants may additionally act as susceptibility factors (rather than being involved in Mendelian-inherited dominant disease)

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the IRF6 gene.

• not provided (17 variants)
• Popliteal pterygium syndrome;Van der Woude syndrome;Orofacial cleft 6, susceptibility to (14 variants)
• Orofacial cleft 6, susceptibility to;Van der Woude syndrome;Popliteal pterygium syndrome (10 variants)
• Van der Woude syndrome 1 (9 variants)
• Orofacial cleft 6, susceptibility to;Popliteal pterygium syndrome;Van der Woude syndrome (7 variants)
• Popliteal pterygium syndrome;Orofacial cleft 6, susceptibility to;Van der Woude syndrome (3 variants)
• Van der Woude syndrome (2 variants)
• Van der Woude syndrome;Orofacial cleft 6, susceptibility to;Popliteal pterygium syndrome (2 variants)
• IRF6-related disorder (2 variants)
• Popliteal pterygium syndrome (2 variants)
• Autosomal dominant popliteal pterygium syndrome (2 variants)
• Van der Woude syndrome;Popliteal pterygium syndrome;Orofacial cleft 6, susceptibility to (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the IRF6 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			3	12	5	20
missense	14	22	68	1	2	107
nonsense	20	3				23
start loss	1					1
frameshift	14	1	2			17
inframe indel			1			1
splice donor/acceptor (+/-2bp)	3	1	1			5
splice region			4	4	3	11
non coding			35	8	48	91
Total	52	27	110	21	55

Variants in IRF6

This is a list of pathogenic ClinVar variants found in the IRF6 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-209785625-C-T		Van der Woude syndrome 1 • Orofacial cleft 6, susceptibility to	Uncertain significance (Jan 12, 2018)
1-209785762-T-G		Orofacial cleft 6, susceptibility to • Van der Woude syndrome 1	Uncertain significance (Jan 12, 2018)
1-209785823-C-T		Orofacial cleft 6, susceptibility to • Van der Woude syndrome 1	Benign (Jan 13, 2018)
1-209785948-C-T		Orofacial cleft 6, susceptibility to • Van der Woude syndrome 1	Benign (Jan 13, 2018)
1-209786006-C-T		Orofacial cleft 6, susceptibility to • Van der Woude syndrome 1	Likely benign (Apr 27, 2017)
1-209786025-C-CT		Van der Woude syndrome 1 • Popliteal pterygium syndrome • Cleft Lip +/- Cleft Palate, Autosomal Dominant	Likely benign (Jun 14, 2016)
1-209786076-G-A		Van der Woude syndrome 1 • Orofacial cleft 6, susceptibility to	Uncertain significance (Jan 12, 2018)
1-209786152-G-A		Van der Woude syndrome 1 • Orofacial cleft 6, susceptibility to	Uncertain significance (Jan 13, 2018)
1-209786269-G-T		Orofacial cleft 6, susceptibility to • Van der Woude syndrome 1	Benign (Jan 13, 2018)
1-209786298-A-G		Orofacial cleft 6, susceptibility to • Van der Woude syndrome 1	Benign (Jan 13, 2018)
1-209786356-C-T		Van der Woude syndrome 1 • Orofacial cleft 6, susceptibility to	Uncertain significance (Jan 12, 2018)
1-209786414-A-G		Orofacial cleft 6, susceptibility to • Van der Woude syndrome 1	Uncertain significance (Jan 13, 2018)
1-209786418-T-C		Orofacial cleft 6, susceptibility to • Van der Woude syndrome 1	Uncertain significance (Jan 12, 2018)
1-209786421-A-G		Van der Woude syndrome 1 • Orofacial cleft 6, susceptibility to	Uncertain significance (Jan 15, 2018)
1-209786527-G-A		Van der Woude syndrome 1 • Orofacial cleft 6, susceptibility to	Benign (Jan 12, 2018)
1-209786550-C-G		Van der Woude syndrome 1 • Orofacial cleft 6, susceptibility to	Uncertain significance (Jan 12, 2018)
1-209786576-C-T		Van der Woude syndrome 1 • Orofacial cleft 6, susceptibility to	Uncertain significance (Jan 13, 2018)
1-209786649-T-C		Orofacial cleft 6, susceptibility to • Van der Woude syndrome 1	Benign (Jan 13, 2018)
1-209786653-C-T		Van der Woude syndrome 1 • Orofacial cleft 6, susceptibility to	Uncertain significance (Jan 12, 2018)
1-209786708-A-G		Orofacial cleft 6, susceptibility to • Van der Woude syndrome 1	Uncertain significance (Jan 13, 2018)
1-209786720-C-G		Orofacial cleft 6, susceptibility to • Van der Woude syndrome 1	Uncertain significance (Jan 12, 2018)
1-209786720-C-T		Orofacial cleft 6, susceptibility to • Van der Woude syndrome 1	Uncertain significance (Jan 13, 2018)
1-209786741-TA-T		Cleft Lip +/- Cleft Palate, Autosomal Dominant • Van der Woude syndrome 1	Benign (Jun 14, 2016)
1-209786835-G-A		Orofacial cleft 6, susceptibility to • Van der Woude syndrome 1	Uncertain significance (Jan 12, 2018)
1-209786909-G-A		Van der Woude syndrome 1 • Orofacial cleft 6, susceptibility to	Benign (Jan 13, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
IRF6	protein_coding	protein_coding	ENST00000367021	7	20430

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.000390	125713	0	1	125714	0.00000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.74	138	263	0.524	0.0000143	3098
Missense in Polyphen		23	112.37	0.20468		1304
Synonymous	1.70	79	101	0.785	0.00000542	883
Loss of Function	4.40	0	22.5	0.00	0.00000116	238

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)	0.00000879	0.00000879
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Probable DNA-binding transcriptional activator. Key determinant of the keratinocyte proliferation-differentiation switch involved in appropriate epidermal development (By similarity). Plays a role in regulating mammary epithelial cell proliferation (By similarity). May regulate WDR65 transcription (By similarity). {ECO:0000250}.
• Disease: DISEASE: Van der Woude syndrome 1 (VWS1) [MIM:119300]: An autosomal dominant developmental disorder characterized by lower lip pits, cleft lip and/or cleft palate. {ECO:0000269|PubMed:12219090, ECO:0000269|PubMed:12920575, ECO:0000269|PubMed:14618417, ECO:0000269|PubMed:14640121, ECO:0000269|PubMed:15300989, ECO:0000269|PubMed:17122170, ECO:0000269|PubMed:18478600, ECO:0000269|PubMed:19036739}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Popliteal pterygium syndrome (PPS) [MIM:119500]: An autosomal dominant disorder characterized by oro-facial, skin and genital anomalies. Expressivity is variable. Clinical features include cleft lip/palate, lower lip cysts, syngnathia, congenital ankyloblepharon filiforme in some cases, bifid scrotum, hypoplastic scrotum, hypoplastic uterus, talipes equinovarus. {ECO:0000269|PubMed:12219090, ECO:0000269|PubMed:14640121, ECO:0000269|PubMed:19036739, ECO:0000269|PubMed:20803643}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Non-syndromic orofacial cleft 6 (OFC6) [MIM:608864]: A birth defect consisting of cleft lips with or without cleft palate. Cleft lips are associated with cleft palate in two-third of cases. A cleft lip can occur on one or both sides and range in severity from a simple notch in the upper lip to a complete opening in the lip extending into the floor of the nostril and involving the upper gum. {ECO:0000269|PubMed:15317890, ECO:0000269|PubMed:21082654}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.
• Pathway: Apoptosis;Primary Focal Segmental Glomerulosclerosis FSGS;Apoptotic Signaling Pathway;Hypothetical Craniofacial Development Pathway;the information processing pathway at the ifn beta enhancer;Cytokine Signaling in Immune system;Immune System;Interferon gamma signaling;Interferon alpha/beta signaling;Interferon Signaling (Consensus)

Recessive Scores

• pRec: 0.413

Intolerance Scores

• loftool: 0.0332
• rvis_EVS: -0.18
• rvis_percentile_EVS: 39.95

Haploinsufficiency Scores

• pHI: 0.814
• hipred: Y
• hipred_score: 0.825
• ghis: 0.574

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.978

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Irf6
• Phenotype: mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); embryo phenotype; skeleton phenotype; limbs/digits/tail phenotype; hearing/vestibular/ear phenotype; digestive/alimentary phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; cellular phenotype; craniofacial phenotype

Gene ontology

• Biological process: cell cycle arrest;negative regulation of cell population proliferation;keratinocyte differentiation;keratinocyte proliferation;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;cell development;interferon-gamma-mediated signaling pathway;type I interferon signaling pathway;mammary gland epithelial cell differentiation
• Cellular component: nucleus;cytoplasm;cytosol;cell junction;extracellular exosome
• Molecular function: DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription activator activity, RNA polymerase II-specific;DNA binding;DNA-binding transcription factor activity;protein binding;sequence-specific DNA binding;transcription regulatory region DNA binding