POU4F3 (POU class 4 homeobox 3)

Gene

• Entrez ID: 5459
• Gene name: POU class 4 homeobox 3
• Gene symbol: POU4F3
• Synonyms (NCBI Gene): BRN3C, DFNA15, DFNA42, DFNA52
• Chromosome: 5
• Chromosome location: 5q32
• Summary: This gene encodes a member of the POU-domain family of transcription factors. POU-domain proteins have been observed to play important roles in control of cell identity in several systems. This protein is found in the retina and may play a role in determi

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs121909056	C>T	Pathogenic	Coding sequence variant, missense variant
rs121909057	T>C	Pathogenic	Coding sequence variant, missense variant
rs398123070	G>A	Pathogenic	Coding sequence variant, missense variant
rs398124631	TATCCAGC>-	Pathogenic	Frameshift variant, coding sequence variant
rs759091617	C>A,T	Likely-pathogenic	Missense variant, coding sequence variant
rs766631025	G>-	Likely-pathogenic	Coding sequence variant, frameshift variant
rs1064792854	GCTCGCTGAGCCAA>-	Pathogenic	Coding sequence variant, frameshift variant
rs1554087566	C>T	Likely-pathogenic	Coding sequence variant, stop gained
rs1561590396	C>T	Pathogenic	Coding sequence variant, missense variant
rs1581278366	->TGTG	Likely-pathogenic	Coding sequence variant, frameshift variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT019454	hsa-miR-148b-3p	Microarray	17612493
MIRT029758	hsa-miR-26b-5p	Microarray	19088304

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000785	Component	Chromatin	ISA
GO:0000978	Function	RNA polymerase II cis-regulatory region sequence-specific DNA binding	IBA
GO:0000978	Function	RNA polymerase II cis-regulatory region sequence-specific DNA binding	IDA	15465029
GO:0000981	Function	DNA-binding transcription factor activity, RNA polymerase II-specific	IBA
GO:0000981	Function	DNA-binding transcription factor activity, RNA polymerase II-specific	IEA
GO:0000981	Function	DNA-binding transcription factor activity, RNA polymerase II-specific	ISA
GO:0001228	Function	DNA-binding transcription activator activity, RNA polymerase II-specific	IDA	15465029, 23805044
GO:0003677	Function	DNA binding	IEA
GO:0003700	Function	DNA-binding transcription factor activity	IEA
GO:0003700	Function	DNA-binding transcription factor activity	TAS	9506947
GO:0005515	Function	Protein binding	IPI	32296183
GO:0005634	Component	Nucleus	IDA	28790396
GO:0005634	Component	Nucleus	IEA
GO:0005654	Component	Nucleoplasm	IDA
GO:0005737	Component	Cytoplasm	IDA	28790396
GO:0005737	Component	Cytoplasm	IEA
GO:0006355	Process	Regulation of DNA-templated transcription	IEA
GO:0006357	Process	Regulation of transcription by RNA polymerase II	IBA
GO:0006357	Process	Regulation of transcription by RNA polymerase II	IEA
GO:0007601	Process	Visual perception	TAS	7623109
GO:0007605	Process	Sensory perception of sound	IEA
GO:0007605	Process	Sensory perception of sound	TAS	9506947
GO:0021562	Process	Vestibulocochlear nerve development	IEA
GO:0030154	Process	Cell differentiation	IEA
GO:0031290	Process	Retinal ganglion cell axon guidance	IEA
GO:0042472	Process	Inner ear morphogenesis	IEA
GO:0042491	Process	Inner ear auditory receptor cell differentiation	IEA
GO:0043565	Function	Sequence-specific DNA binding	IEA
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IDA	15465029, 23805044
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IEA
GO:0048675	Process	Axon extension	IEA
GO:0048839	Process	Inner ear development	IEA
GO:0050885	Process	Neuromuscular process controlling balance	IEA
GO:0051402	Process	Neuron apoptotic process	IEA
GO:0060113	Process	Inner ear receptor cell differentiation	IEA
GO:1990837	Function	Sequence-specific double-stranded DNA binding	IDA	28473536

Other IDs

• MIM: 602460
• HGNC: 9220
• e!Ensembl: ENSG00000091010

Protein

• UniProt ID: Q15319
• Protein name: POU domain, class 4, transcription factor 3 (Brain-specific homeobox/POU domain protein 3C) (Brain-3C) (Brn-3C)
• Protein function: Acts as a transcriptional activator (PubMed:18228599). Acts by binding to sequences related to the consensus octamer motif 5'-ATGCAAAT-3' in the regulatory regions of its target genes (PubMed:18228599). Involved in the auditory system developmen
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00157	Pou	182 → 256	Pou domain - N-terminal to homeobox domain	Domain
  PF00046	Homeodomain	275 → 331	Homeodomain	Domain

• Tissue specificity: TISSUE SPECIFICITY: Brain. Seems to be specific to the retina. {ECO:0000269|PubMed:7623109, ECO:0000269|PubMed:9506947}.
• Sequence:

  MMAMNSKQPFGMHPVLQEPKFSSLHSGSEAMRRVCLPAPQLQGNIFGSFDESLLARAEAL
  AAVDIVSHGKNHPFKPDATYHTMSSVPCTSTSSTVPISHPAALTSHPHHAVHQGLEGDLL
  EHISPTLSVSGLGAPEHSVMPAQIHPHHLGAMGHLHQAMGMSHPHTVAPHSAMPACLSDV
  ESDPRELEAFAERFKQRRIKLGVTQADVGAALANLKIPGVGSLSQSTICRFESLTLSHNN
  MIALKPVLQAWLEEAEAAYREKNSKPELFNGSERKRKRTSIAAPEKRSLEAYFAIQPRPS
  SEKIAAIAEKLDLKKNVVRVWFCNQRQKQKRMKYSAVH

• Sequence length: 338

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Autosomal dominant nonsyndromic hearing loss 15	Pathogenic; Likely pathogenic	rs398123070, rs1064792854, rs2126961983, rs2126962041, rs2126960889, rs2126961780, rs2126960899, rs2479690433, rs2479692745, rs398124631, rs121909056, rs121909057, rs2479693124, rs2479693752, rs758938669, rs2479692800, rs2479693967, rs766631025, rs1760430376, rs1760431636, rs1760419273	RCV000082870 RCV000087754 RCV001786490 RCV003229058 RCV001809319 RCV001809322 RCV002250859 RCV003107981 RCV002283862 RCV000007494 RCV000007495 RCV000007496 RCV003229511 RCV003229512 RCV003229513 RCV003881665 RCV004556162 RCV001799512 RCV001250125 RCV001250123 RCV001250126	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Autosomal recessive sensorineural hearing loss	Likely pathogenic; Pathogenic	rs1561590396	RCV000681527	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Hearing impairment	Likely pathogenic	rs1284441535	RCV001375367	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Hearing loss, autosomal recessive	Likely pathogenic; Pathogenic	rs1561590396	RCV001291237	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Rare genetic deafness	Likely pathogenic	rs1581278366	RCV000825604	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
AUTOSOMAL DOMINANT ISOLATED SENSORINEURAL DEAFNESS TYPE DFNA	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
AUTOSOMAL DOMINANT NONSYNDROMIC HEARING LOSS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BELL'S PALSY	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Congenital sensorineural hearing impairment	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CONGENITAL SENSORINEURAL HEARING LOSS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DEAFNESS, AUTOSOMAL DOMINANT 15	—	CTD, Disgenet, HPO CTD, Disgenet, HPO CTD, Disgenet, HPO	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DEAFNESS, AUTOSOMAL RECESSIVE	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MIGRAINE DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Nonsyndromic Hearing Loss, Dominant	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
POU4F3-related disorder	Uncertain significance; Conflicting classifications of pathogenicity; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
RHEUMATOID ARTHRITIS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SCOLIOSIS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SENSORINEURAL HEARING LOSS OF BILATERAL EARS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Alzheimer Disease	Alzheimer disease	Pubtator	24260153	Associate	★☆☆☆☆ Found in Text Mining only
Autosomal dominant non-syndromic sensorineural deafness type DFNA	Non-Syndromic Sensorineural Deafness	Orphanet			★☆☆☆☆ Found in Text Mining only
Carcinoma in situ of uterine cervix	Cervical Intraepithelial Neoplasia	BEFREE	24310984		★☆☆☆☆ Found in Text Mining only
Carcinoma Renal Cell	Renal cell carcinoma	Pubtator	26057869	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma, Ovarian Epithelial	Ovarian Epithelial carcinoma	BEFREE	29185275		★☆☆☆☆ Found in Text Mining only
Congenital sensorineural hearing loss	Congenital Sensorineural Hearing Loss	BEFREE	10320095, 18312703		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Deafness	Deafness	Pubtator	23767834, 25388789, 28790396, 32390314, 34325055	Associate	★☆☆☆☆ Found in Text Mining only
Deafness Autosomal Dominant 15	Deafness	Pubtator	32684921	Associate	★☆☆☆☆ Found in Text Mining only
Deafness, Autosomal Dominant 15	Deafness	UNIPROT_DG	18228599, 18347256, 22938506, 24260153, 25388789, 28545070, 28790396, 9506947		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Deafness, Autosomal Dominant 15	Deafness	BEFREE	24260153		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Deafness, Autosomal Dominant 15	Deafness	GENOMICS_ENGLAND_DG	9506947		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Deafness, Autosomal Dominant 15	Deafness	CLINVAR_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Deafness, Autosomal Dominant 15	Deafness	CTD_human_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Endometrial Carcinoma	Endometrial carcinoma	BEFREE	29185275		★☆☆☆☆ Found in Text Mining only
Endometrial Hyperplasia	Endometrial hyperplasia	Pubtator	26057869	Associate	★☆☆☆☆ Found in Text Mining only
Endometrial Neoplasms	Endometrial neoplasm	Pubtator	29185275	Associate	★☆☆☆☆ Found in Text Mining only
Hearing Loss	Hearing loss	Pubtator	22938506, 24164807, 24556497, 27999687, 28053790, 28545070, 29850532, 32390314, 34250087, 37072551, 37537203	Associate	★☆☆☆☆ Found in Text Mining only
Hearing Loss Sensorineural	Hearing loss	Pubtator	24556497, 34250087, 37072551	Associate	★☆☆☆☆ Found in Text Mining only
Hodgkin Disease	Hodgkin Disease	BEFREE	28545070		★☆☆☆☆ Found in Text Mining only
Low frequency deafness	Low-frequency hearing loss	BEFREE	15490091		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of endometrium	Endometrial Cancer	BEFREE	29185275		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of lung	Lung Cancer	BEFREE	25243889		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of ovary	Ovarian cancer	BEFREE	29185275		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of prostate	Prostate cancer	BEFREE	16276351		★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	27874187		★☆☆☆☆ Found in Text Mining only
Merkel cell carcinoma	Merkel cell carcinoma	BEFREE	12209986		★☆☆☆☆ Found in Text Mining only
Merkel cell carcinoma	Merkel cell carcinoma	LHGDN	12209986		★☆☆☆☆ Found in Text Mining only
Nonsyndromic Deafness	Nonsyndromic Deafness	BEFREE	14585957, 19372648, 24260153, 24275721, 25388789, 29850532		★☆☆☆☆ Found in Text Mining only
Nonsyndromic Deafness	Nonsyndromic Deafness	CLINGEN_DG	15254021, 18228599, 20434433, 23767834, 24260153, 24535414, 24676347, 26697340, 27535032, 27999687, 28545070, 28790396, 29850532, 8637595, 9506947		★☆☆☆☆ Found in Text Mining only
ovarian neoplasm	Ovarian neoplasm	BEFREE	29185275		★☆☆☆☆ Found in Text Mining only
Ovarian Neoplasms	Ovarian neoplasm	Pubtator	29185275	Associate	★☆☆☆☆ Found in Text Mining only
Prostate carcinoma	Prostate cancer	BEFREE	16276351		★☆☆☆☆ Found in Text Mining only
Sensorineural Hearing Loss (disorder)	Hearing Loss	BEFREE	18312703		★☆☆☆☆ Found in Text Mining only
Small cell carcinoma of lung	Lung carcinoma	BEFREE	25243889		★☆☆☆☆ Found in Text Mining only
Vestibular Diseases	Vestibular disease	Pubtator	28545070, 37072551	Associate	★☆☆☆☆ Found in Text Mining only
Wolfram Syndrome	Wolfram Syndrome	BEFREE	15490091		★☆☆☆☆ Found in Text Mining only