PAX6

paired box 6, the group of PRD class homeoboxes and pseudogenes|Paired boxes

Basic information

Region (hg38): 11:31784779-31817961

Previous symbols: [ "AN1", "AN2" ]

Links

ENSG00000007372 ∙ NCBI:5080 ∙ OMIM:607108 ∙ HGNC:8620 ∙ Uniprot:P26367 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal dominant keratitis (Definitive), mode of inheritance: AD
• coloboma of optic nerve (Definitive), mode of inheritance: AD
• Peters anomaly (Definitive), mode of inheritance: AD
• foveal hypoplasia 1 (Definitive), mode of inheritance: AD
• isolated optic nerve hypoplasia (Definitive), mode of inheritance: AD
• aniridia 1 (Definitive), mode of inheritance: AD
• aniridia-cerebellar ataxia-intellectual disability syndrome (Definitive), mode of inheritance: AD
• diabetes mellitus (Strong), mode of inheritance: AD
• aniridia 1 (Strong), mode of inheritance: AD
• Peters anomaly (Strong), mode of inheritance: AD
• coloboma, ocular, autosomal dominant (Strong), mode of inheritance: AD
• aniridia-cerebellar ataxia-intellectual disability syndrome (Supportive), mode of inheritance: AD
• foveal hypoplasia-presenile cataract syndrome (Supportive), mode of inheritance: AD
• autosomal dominant keratitis (Supportive), mode of inheritance: AD
• Peters anomaly (Supportive), mode of inheritance: AD
• isolated optic nerve hypoplasia (Supportive), mode of inheritance: AD
• isolated aniridia (Supportive), mode of inheritance: AD
• aniridia 1 (Strong), mode of inheritance: AD
• autosomal dominant keratitis (Limited), mode of inheritance: Unknown
• Peters anomaly (Strong), mode of inheritance: AD
• PAX6-related ocular dysgenesis (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Anterior segment dysgenesis 5; Cataract with late-onset corneal dystrophy; Aniridia; Aniridia, cerebellar ataxia, and mental retardation (Gillespie syndrome); Optic nerve hypoplasia; Keratitis; Foveal hypoplasia 1; Microphthalmia/coloboma 12; Morning glory disc anomaly	AD	Ophthalmologic; Pharmacogenomic	Individuals with PAX6 related eye anomalies may be recognizable, but some may also be at high risk of developing glaucoma; Agents that may contribute to glaucoma should be avoided	Neurologic; Ophthalmologic	17948455; 14246186; 868970; 1302030; 8364574; 7951315; 8162071; 7550230; 7668281; 8640214; 9138149; 9482572; 9705283; 9931324; 11553050; 11826019; 12325030; 12721955; 15629294; 16543198; 17148041; 17417613; 17595013; 19876904; 22171686; 24290376
Severe and difficult to treat glaucoma has been reported in many individuals with Anterior segment dysgenesis; Homozygous/compound heterozygous variants may cause severe disease, including neuroanatomic anomalies

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PAX6 gene.

• Aniridia 1;Irido-corneo-trabecular dysgenesis (87 variants)
• Aniridia 1 (71 variants)
• not provided (60 variants)
• Irido-corneo-trabecular dysgenesis;Aniridia 1 (25 variants)
• PAX6-related disorder (4 variants)
• Irido-corneo-trabecular dysgenesis (4 variants)
• Congenital aniridia (3 variants)
• Inborn genetic diseases (2 variants)
• Foveal hypoplasia 1 (1 variants)
• Developmental cataract (1 variants)
• Isolated optic nerve hypoplasia (1 variants)
• 8 conditions (1 variants)
• Coloboma, ocular, autosomal dominant (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PAX6 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		2	4	59	3	68
missense	12	26	94	2		134
nonsense	38	4				42
start loss	4		1			5
frameshift	88	2				90
inframe indel	2		1			3
splice donor/acceptor (+/-2bp)	30	3	3			36
splice region	6	3	19	15	1	44
non coding	6	8	75	66	42	197
Total	180	45	178	127	45

Highest pathogenic variant AF is 0.00000657

Variants in PAX6

This is a list of pathogenic ClinVar variants found in the PAX6 region.

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

Position	Type	Phenotype	Significance	ClinVar
11-31784826-T-C		Anophthalmia-microphthalmia syndrome • Congenital aniridia • Aniridia, Cerebellar Ataxia, And Intellectual Disability • Autosomal dominant keratitis • Foveal hypoplasia 1 • 11p partial monosomy syndrome • carboxymethyl-dextran-A2-gadolinium-DOTA	Benign/Likely benign (Jan 13, 2018)
11-31784928-G-C		Anophthalmia-microphthalmia syndrome • Autosomal dominant keratitis • Foveal hypoplasia 1 • carboxymethyl-dextran-A2-gadolinium-DOTA	Uncertain significance (Jan 13, 2018)
11-31785013-AAT-CATTTCTTTTAATCTGTG		Autosomal dominant keratitis • Aniridia, Cerebellar Ataxia, And Intellectual Disability • Congenital aniridia • Irido-corneo-trabecular dysgenesis • Anophthalmia • 11p partial monosomy syndrome • Foveal hypoplasia 1	Uncertain significance (Jun 14, 2016)
11-31785139-A-C		Foveal hypoplasia 1 • Anophthalmia-microphthalmia syndrome • Autosomal dominant keratitis • carboxymethyl-dextran-A2-gadolinium-DOTA	Uncertain significance (Jan 13, 2018)
11-31785150-G-A		Anophthalmia-microphthalmia syndrome • Foveal hypoplasia 1 • Autosomal dominant keratitis • carboxymethyl-dextran-A2-gadolinium-DOTA	Uncertain significance (Jan 12, 2018)
11-31785238-C-G		Autosomal dominant keratitis • Foveal hypoplasia 1 • Aniridia 1 • 11p partial monosomy syndrome • Anophthalmia-microphthalmia syndrome • carboxymethyl-dextran-A2-gadolinium-DOTA • Aniridia, Cerebellar Ataxia, And Intellectual Disability	Conflicting classifications of pathogenicity (Jan 13, 2018)
11-31785307-T-G		Aniridia 1 • carboxymethyl-dextran-A2-gadolinium-DOTA • Autosomal dominant keratitis • 11p partial monosomy syndrome • Anophthalmia-microphthalmia syndrome • Aniridia, Cerebellar Ataxia, And Intellectual Disability • Foveal hypoplasia 1	Conflicting classifications of pathogenicity (Jan 12, 2018)
11-31785335-A-C		Foveal hypoplasia 1 • Autosomal dominant keratitis • Aniridia, Cerebellar Ataxia, And Intellectual Disability • 11p partial monosomy syndrome • Anophthalmia-microphthalmia syndrome • Congenital aniridia • carboxymethyl-dextran-A2-gadolinium-DOTA	Benign/Likely benign (Jan 12, 2018)
11-31785401-A-G		Foveal hypoplasia 1 • Anophthalmia-microphthalmia syndrome • Aniridia, Cerebellar Ataxia, And Intellectual Disability • Congenital aniridia • 11p partial monosomy syndrome • carboxymethyl-dextran-A2-gadolinium-DOTA • Autosomal dominant keratitis	Uncertain significance (Jan 12, 2018)
11-31785543-CTT-C		Aniridia 1;Irido-corneo-trabecular dysgenesis	Uncertain significance (Oct 17, 2023)
11-31785564-G-C		Autosomal dominant keratitis • Foveal hypoplasia 1 • Congenital aniridia • Aniridia, Cerebellar Ataxia, And Intellectual Disability • carboxymethyl-dextran-A2-gadolinium-DOTA • 11p partial monosomy syndrome • Anophthalmia-microphthalmia syndrome	Benign/Likely benign (Jan 13, 2018)
11-31785565-C-G		Foveal hypoplasia 1 • Autosomal dominant keratitis • Anophthalmia-microphthalmia syndrome • carboxymethyl-dextran-A2-gadolinium-DOTA	Uncertain significance (Jan 12, 2018)
11-31785573-A-G		Aniridia, Cerebellar Ataxia, And Intellectual Disability • Anophthalmia-microphthalmia syndrome • carboxymethyl-dextran-A2-gadolinium-DOTA • 11p partial monosomy syndrome • Congenital aniridia • Foveal hypoplasia 1 • Autosomal dominant keratitis	Uncertain significance (Jan 13, 2018)
11-31785638-C-G		11p partial monosomy syndrome • Foveal hypoplasia 1 • Aniridia 1 • Autosomal dominant keratitis • carboxymethyl-dextran-A2-gadolinium-DOTA • Anophthalmia-microphthalmia syndrome • Aniridia, Cerebellar Ataxia, And Intellectual Disability	Benign (Jan 13, 2018)
11-31785806-G-A		11p partial monosomy syndrome • Aniridia, Cerebellar Ataxia, And Intellectual Disability • Foveal hypoplasia 1 • Congenital aniridia • Autosomal dominant keratitis • carboxymethyl-dextran-A2-gadolinium-DOTA • Anophthalmia-microphthalmia syndrome	Uncertain significance (Jan 13, 2018)
11-31785858-T-G		Foveal hypoplasia 1 • Aniridia, Cerebellar Ataxia, And Intellectual Disability • Congenital aniridia • Autosomal dominant keratitis • Anophthalmia-microphthalmia syndrome • carboxymethyl-dextran-A2-gadolinium-DOTA • 11p partial monosomy syndrome	Uncertain significance (Jan 12, 2018)
11-31785911-C-T		Autosomal dominant keratitis • carboxymethyl-dextran-A2-gadolinium-DOTA • Anophthalmia-microphthalmia syndrome • Foveal hypoplasia 1	Uncertain significance (Jan 13, 2018)
11-31785931-C-A		Congenital aniridia • Anophthalmia-microphthalmia syndrome • Foveal hypoplasia 1 • carboxymethyl-dextran-A2-gadolinium-DOTA • Autosomal dominant keratitis • 11p partial monosomy syndrome • Aniridia, Cerebellar Ataxia, And Intellectual Disability	Uncertain significance (Jan 12, 2018)
11-31785976-C-T		11p partial monosomy syndrome • Autosomal dominant keratitis • Aniridia 1 • Foveal hypoplasia 1 • Aniridia, Cerebellar Ataxia, And Intellectual Disability • carboxymethyl-dextran-A2-gadolinium-DOTA • Anophthalmia-microphthalmia syndrome	Benign (May 13, 2021)
11-31786026-G-A		Congenital aniridia • 11p partial monosomy syndrome • carboxymethyl-dextran-A2-gadolinium-DOTA • Autosomal dominant keratitis • Foveal hypoplasia 1 • Anophthalmia-microphthalmia syndrome • Aniridia, Cerebellar Ataxia, And Intellectual Disability	Uncertain significance (Jan 13, 2018)
11-31786046-G-T		Foveal hypoplasia 1 • Anophthalmia-microphthalmia syndrome • Autosomal dominant keratitis • carboxymethyl-dextran-A2-gadolinium-DOTA	Uncertain significance (Mar 02, 2018)
11-31786049-C-A		carboxymethyl-dextran-A2-gadolinium-DOTA • Congenital aniridia • 11p partial monosomy syndrome • Aniridia, Cerebellar Ataxia, And Intellectual Disability • Autosomal dominant keratitis • Foveal hypoplasia 1 • Anophthalmia-microphthalmia syndrome	Benign/Likely benign (Jan 12, 2018)
11-31786080-T-C			Uncertain significance (Oct 07, 2022)
11-31786188-G-A		Foveal hypoplasia 1 • carboxymethyl-dextran-A2-gadolinium-DOTA • Autosomal dominant keratitis • Anophthalmia-microphthalmia syndrome • Aniridia 1 • Aniridia, Cerebellar Ataxia, And Intellectual Disability • 11p partial monosomy syndrome	Conflicting classifications of pathogenicity (Jan 13, 2018)
11-31786196-CTG-C		Foveal hypoplasia 1 • Autosomal dominant keratitis • Aniridia, Cerebellar Ataxia, And Intellectual Disability • Anophthalmia • Congenital aniridia • Irido-corneo-trabecular dysgenesis • 11p partial monosomy syndrome	Benign (May 14, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PAX6	protein_coding	protein_coding	ENST00000419022	11	33170

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.000251	125741	0	2	125743	0.00000795

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.82	120	244	0.492	0.0000127	2843
Missense in Polyphen		19	88.318	0.21513		1035
Synonymous	-0.850	100	89.8	1.11	0.00000513	855
Loss of Function	4.74	1	28.1	0.0356	0.00000171	269

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	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Transcription factor with important functions in the development of the eye, nose, central nervous system and pancreas. Required for the differentiation of pancreatic islet alpha cells (By similarity). Competes with PAX4 in binding to a common element in the glucagon, insulin and somatostatin promoters. Regulates specification of the ventral neuron subtypes by establishing the correct progenitor domains (By similarity). Isoform 5a appears to function as a molecular switch that specifies target genes. {ECO:0000250}.
• Disease: DISEASE: Aniridia 1 (AN1) [MIM:106210]: A congenital, bilateral, panocular disorder characterized by complete absence of the iris or extreme iris hypoplasia. Aniridia is not just an isolated defect in iris development but it is associated with macular and optic nerve hypoplasia, cataract, corneal changes, nystagmus. Visual acuity is generally low but is unrelated to the degree of iris hypoplasia. Glaucoma is a secondary problem causing additional visual loss over time. {ECO:0000269|PubMed:10234503, ECO:0000269|PubMed:10737978, ECO:0000269|PubMed:11309364, ECO:0000269|PubMed:11553050, ECO:0000269|PubMed:11826019, ECO:0000269|PubMed:12552561, ECO:0000269|PubMed:12634864, ECO:0000269|PubMed:16493447, ECO:0000269|PubMed:17595013, ECO:0000269|PubMed:21850189, ECO:0000269|PubMed:24033328, ECO:0000269|PubMed:8364574, ECO:0000269|PubMed:9147640, ECO:0000269|PubMed:9281415, ECO:0000269|PubMed:9792406, ECO:0000269|PubMed:9856761, ECO:0000269|PubMed:9931324, ECO:0000269|Ref.27, ECO:0000269|Ref.28}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Anterior segment dysgenesis 5 (ASGD5) [MIM:604229]: A form of anterior segment dysgenesis, a group of defects affecting anterior structures of the eye including cornea, iris, lens, trabecular meshwork, and Schlemm canal. Anterior segment dysgeneses result from abnormal migration or differentiation of the neural crest derived mesenchymal cells that give rise to components of the anterior chamber during eye development. Different anterior segment anomalies may exist alone or in combination, including iris hypoplasia, enlarged or reduced corneal diameter, corneal vascularization and opacity, posterior embryotoxon, corectopia, polycoria, abnormal iridocorneal angle, ectopia lentis, and anterior synechiae between the iris and posterior corneal surface. Clinical conditions falling within the phenotypic spectrum of anterior segment dysgeneses include aniridia, Axenfeld anomaly, Reiger anomaly/syndrome, Peters anomaly, and iridogoniodysgenesis. {ECO:0000269|PubMed:10441571, ECO:0000269|PubMed:12721955, ECO:0000269|PubMed:8162071}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Foveal hypoplasia 1 (FVH1) [MIM:136520]: An isolated form of foveal hypoplasia, a developmental defect of the eye defined as the lack of foveal depression with continuity of all neurosensory retinal layers in the presumed foveal area. Clinical features include absence of foveal pit on optical coherence tomography, absence of foveal hyperpigmentation, absence of foveal avascularity, absence of foveal and macular reflexes, decreased visual acuity, and nystagmus. Anterior segment anomalies and cataract are observed in some FVH1 patients. {ECO:0000269|PubMed:8640214, ECO:0000269|PubMed:9931324}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Keratitis hereditary (KERH) [MIM:148190]: An ocular disorder characterized by corneal opacification, recurrent stromal keratitis and vascularization. {ECO:0000269|PubMed:7668281}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Coloboma, ocular, autosomal dominant (COAD) [MIM:120200]: A set of malformations resulting from abnormal morphogenesis of the optic cup and stalk, and the fusion of the fetal fissure (optic fissure). The clinical presentation is variable. Some individuals may present with minimal defects in the anterior iris leaf without other ocular defects. More complex malformations create a combination of iris, uveoretinal and/or optic nerve defects without or with microphthalmia or even anophthalmia. {ECO:0000269|PubMed:12721955}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Coloboma of optic nerve (COLON) [MIM:120430]: An ocular defect that is due to malclosure of the fetal intraocular fissure affecting the optic nerve head. In some affected individuals, it appears as enlargement of the physiologic cup with severely affected eyes showing huge cavities at the site of the disk. {ECO:0000269|PubMed:12721955}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Bilateral optic nerve hypoplasia (BONH) [MIM:165550]: A congenital anomaly in which the optic disk appears abnormally small. It may be an isolated finding or part of a spectrum of anatomic and functional abnormalities that includes partial or complete agenesis of the septum pellucidum, other midline brain defects, cerebral anomalies, pituitary dysfunction, and structural abnormalities of the pituitary. {ECO:0000269|PubMed:12721955}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Aniridia 2 (AN2) [MIM:617141]: A form of aniridia, a congenital, bilateral, panocular disorder characterized by complete absence of the iris or extreme iris hypoplasia. Aniridia is not just an isolated defect in iris development but it is associated with macular and optic nerve hypoplasia, cataract, corneal changes, nystagmus. Visual acuity is generally low but is unrelated to the degree of iris hypoplasia. Glaucoma is a secondary problem causing additional visual loss over time. {ECO:0000269|PubMed:24290376}. Note=The gene represented in this entry is involved in disease pathogenesis. A mutation in a PAX6 long-range cis-regulatory element, known as SIMO, affects PAX6 expression in the developing eye and has pathological consequences. The mutation is located in ELP4 intron 9, 150 kb downstream of PAX6. {ECO:0000269|PubMed:24290376}.
• Pathway: Maturity onset diabetes of the young - Homo sapiens (human);Signaling pathways regulating pluripotency of stem cells - Homo sapiens (human);Cardiac Progenitor Differentiation;Mesodermal Commitment Pathway;Ectoderm Differentiation;CDC42 signaling events (Consensus)

Recessive Scores

• pRec: 0.829

Intolerance Scores

• loftool: 0.0409
• rvis_EVS: -0.36
• rvis_percentile_EVS: 28.63

Haploinsufficiency Scores

• pHI: 0.995
• hipred: Y
• hipred_score: 0.875
• ghis: 0.626

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.654

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pax6
• Phenotype: neoplasm; pigmentation phenotype; normal 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); reproductive system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype; embryo phenotype; skeleton phenotype; immune system phenotype; vision/eye phenotype; craniofacial phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); hearing/vestibular/ear phenotype; digestive/alimentary phenotype; muscle phenotype; endocrine/exocrine gland phenotype; taste/olfaction 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; homeostasis/metabolism phenotype

Zebrafish Information Network

• Gene name: pax6a
• Affected structure: rhombomere
• Phenotype tag: abnormal
• Phenotype quality: condensed

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;establishment of mitotic spindle orientation;blood vessel development;eye development;cell fate determination;neuron migration;negative regulation of protein phosphorylation;positive regulation of neuroblast proliferation;lens development in camera-type eye;type B pancreatic cell differentiation;pancreatic A cell development;transcription by RNA polymerase II;smoothened signaling pathway;axon guidance;central nervous system development;salivary gland morphogenesis;visual perception;response to wounding;regulation of asymmetric cell division;animal organ morphogenesis;dorsal/ventral axis specification;positive regulation of gene expression;oligodendrocyte cell fate specification;cerebral cortex regionalization;forebrain dorsal/ventral pattern formation;commitment of neuronal cell to specific neuron type in forebrain;forebrain-midbrain boundary formation;regulation of transcription from RNA polymerase II promoter involved in spinal cord motor neuron fate specification;regulation of transcription from RNA polymerase II promoter involved in ventral spinal cord interneuron specification;regulation of transcription from RNA polymerase II promoter involved in somatic motor neuron fate commitment;pituitary gland development;habenula development;signal transduction involved in regulation of gene expression;keratinocyte differentiation;regulation of cell migration;positive regulation of epithelial cell differentiation;lacrimal gland development;protein localization to organelle;eye photoreceptor cell development;glucose homeostasis;negative regulation of neuron differentiation;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;regulation of timing of cell differentiation;embryonic camera-type eye morphogenesis;neuron fate commitment;astrocyte differentiation;negative regulation of epithelial cell proliferation;negative regulation of neurogenesis;retina development in camera-type eye;iris morphogenesis;cornea development in camera-type eye;positive regulation of core promoter binding;cellular response to leukemia inhibitory factor;negative regulation of neural precursor cell proliferation
• Cellular component: nuclear chromatin;nucleus;nucleoplasm;cytoplasm;cytosol
• Molecular function: RNA polymerase II proximal promoter sequence-specific DNA binding;RNA polymerase II core promoter sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription repressor activity, RNA polymerase II-specific;DNA-binding transcription activator activity, RNA polymerase II-specific;DNA binding;chromatin binding;DNA-binding transcription factor activity;protein binding;transcription factor binding;protein kinase binding;ubiquitin protein ligase binding;histone acetyltransferase binding;co-SMAD binding;R-SMAD binding;HMG box domain binding