POU3F4 (POU class 3 homeobox 4)

Gene

• Entrez ID: 5456
• Gene name: POU class 3 homeobox 4
• Gene symbol: POU3F4
• Synonyms (NCBI Gene): BRAIN-4, BRN-4, BRN4, DFN3, DFNX2, OCT-9, OTF-9, OTF9
• Chromosome: X
• Chromosome location: Xq21.1
• Summary: This gene encodes a member of the POU-III class of neural transcription factors. This family member plays a role in inner ear development. The protein is thought to be involved in the mediation of epigenetic signals which induce striatal neuron-precursor

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs104894920	A>T	Pathogenic	Coding sequence variant, stop gained
rs104894921	T>G	Pathogenic	Coding sequence variant, missense variant
rs104894922	A>G	Pathogenic	Coding sequence variant, missense variant
rs104894923	A>T	Pathogenic	Coding sequence variant, missense variant
rs104894924	C>G,T	Pathogenic, uncertain-significance	Coding sequence variant, missense variant
rs111033345	C>T	Pathogenic	Coding sequence variant, stop gained
rs267606974	A>-	Pathogenic	Frameshift variant, coding sequence variant
rs387906502	C>T	Pathogenic	Missense variant, coding sequence variant
rs397516335	T>C	Likely-pathogenic	Missense variant, coding sequence variant
rs397516336	AT>-	Pathogenic	Frameshift variant, coding sequence variant
rs398122516	->T	Pathogenic	Frameshift variant, coding sequence variant
rs398122517	A>-	Pathogenic	Frameshift variant, coding sequence variant
rs727503377	ACTG>-	Likely-pathogenic	3 prime UTR variant, frameshift variant, terminator codon variant, stop lost
rs727505246	G>A	Likely-pathogenic	Missense variant, coding sequence variant
rs730882189	AGTG>-	Pathogenic	Frameshift variant, coding sequence variant
rs780027419	C>G,T	Pathogenic	Coding sequence variant, missense variant, synonymous variant
rs866754647	G>A	Likely-pathogenic	Missense variant, coding sequence variant
rs876657719	CAAA>-	Pathogenic	Frameshift variant, coding sequence variant
rs1060499806	G>T	Uncertain-significance, pathogenic	Missense variant, coding sequence variant
rs1555984570	G>-	Pathogenic	Frameshift variant, coding sequence variant
rs1569280385	G>A	Pathogenic	Coding sequence variant, stop gained

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: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:0003677	Function	DNA binding	IEA
GO:0003700	Function	DNA-binding transcription factor activity	IEA
GO:0003700	Function	DNA-binding transcription factor activity	TAS	7839145
GO:0005515	Function	Protein binding	IPI	9105675
GO:0005634	Component	Nucleus	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:0007420	Process	Brain development	IEA
GO:0007605	Process	Sensory perception of sound	TAS	7839145
GO:0090103	Process	Cochlea morphogenesis	ISS
GO:1990837	Function	Sequence-specific double-stranded DNA binding	IDA	28473536
GO:2001054	Process	Negative regulation of mesenchymal cell apoptotic process	ISS

Other IDs

• MIM: 300039
• HGNC: 9217
• e!Ensembl: ENSG00000196767

Protein

• UniProt ID: P49335
• Protein name: POU domain, class 3, transcription factor 4 (Brain-specific homeobox/POU domain protein 4) (Brain-4) (Brn-4) (Octamer-binding protein 9) (Oct-9) (Octamer-binding transcription factor 9) (OTF-9)
• Protein function: Probable transcription factor which exert its primary action widely during early neural development and in a very limited set of neurons in the mature brain.
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00157	Pou	189 → 260	Pou domain - N-terminal to homeobox domain	Domain
  PF00046	Homeodomain	279 → 335	Homeodomain	Domain

• Tissue specificity: TISSUE SPECIFICITY: Brain specific.
• Sequence:

  MATAASNPYSILSSTSLVHADSAGMQQGSPFRNPQKLLQSDYLQGVPSNGHPLGHHWVTS
  LSDGGPWSSTLATSPLDQQDVKPGREDLQLGAIIHHRSPHVAHHSPHTNHPNAWGASPAP
  NPSITSSGQPLNVYSQPGFTVSGMLEHGGLTPPPAAASAQSLHPVLREPPDHGELGSHHC
  QDHSDEETPTSDELEQFAKQFKQRRIKLGFTQADVGLALGTLYGNVFSQTTICRFEGLQL
  SFKNMCKLKPLLNKWLEEADSSTGSPTSIDKIAAQGRKRKKRTSIEVSVKGVLETHFLKC
  PKPAAQEISSLADSLQLEKEVVRVWFCNRRQKEKRMTPPGDQQPHEVYSHTVKTDTSCHD
  L

• Sequence length: 361

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 recessive sensorineural hearing loss	Pathogenic	rs1569280235	RCV000681550	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Ear malformation	Likely pathogenic	rs1602641906	RCV001814383	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Nonsyndromic genetic hearing loss	Likely pathogenic	rs397516335	RCV004799758	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Rare genetic deafness	Likely pathogenic; Pathogenic	rs727505246, rs727503377, rs876657719, rs111033343, rs111033345, rs397516335, rs397516336	RCV000156766 RCV000151671 RCV000215388 RCV000036254 RCV000036255 RCV000036258 RCV000036260	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
X-linked mixed hearing loss with perilymphatic gusher	Pathogenic; Likely pathogenic	rs2147996200, rs2147996672, rs1199790524, rs926775037, rs267606974, rs2147996471, rs727505246, rs2520216844, rs2520216752, rs876657719, rs878853242, rs2520215844, rs2520216767, rs2520216564, rs1555984570, rs104894920, rs104894921, rs104894922, rs730882189, rs387906502, rs104894923, rs104894924, rs2520215518, rs2520215450, rs753206337, rs398122516, rs398122517, rs397516335, rs397516336, rs1569280138, rs1569280385, rs1454033665	RCV001823209 RCV001823269 RCV001823227 RCV002051729 RCV000144387 RCV002248470 RCV001786336 RCV002444375 RCV002444376 RCV001374673 RCV000225042 RCV003155596 RCV003445223 RCV003445224 RCV003445225 RCV000012443 RCV000012444 RCV000012445 RCV000012446 RCV000012447 RCV000012448 RCV000012449 RCV000012450 RCV003314065 RCV003333904 RCV003333905 RCV004585129 RCV000034343 RCV000034344 RCV003445093 RCV001004804 RCV000678987 RCV000735984 RCV000770854	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
AYAZI SYNDROME	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BIPOLAR DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CHOROIDEREMIA-DEAFNESS-OBESITY SYNDROME	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CHROMOSOME XQ21 DELETION SYNDROME	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CONGENITAL EAR ANOMALY NOS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DEAFNESS, NONSYNDROMIC SENSORINEURAL, MITOCHONDRIAL	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DEAFNESS, X-LINKED 2	—	HPO	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ependymoma	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MENTAL OR BEHAVIOURAL DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
POU3F4-related disorder	Conflicting classifications of pathogenicity; Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PROGRESSIVE HEARING LOSS STAPES FIXATION	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SCHIZOPHRENIA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SCOLIOSIS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
X-LINKED ISOLATED SENSORINEURAL HEARING LOSS TYPE DFN	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
X-linked nonsyndromic hearing loss	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
XQ21 MICRODELETION SYNDROME	—	Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Adrenoleukodystrophy	Adrenoleukodystrophy	Pubtator	32952548	Associate	★☆☆☆☆ Found in Text Mining only
Bone Diseases	Bone disease	Pubtator	16365218, 27941975	Associate	★☆☆☆☆ Found in Text Mining only
Cardiomyopathy Dilated	Dilated cardiomyopathy	Pubtator	16365218	Associate	★☆☆☆☆ Found in Text Mining only
Choroideremia	Choroideremia	BEFREE	10644430, 11035551, 2491012		★☆☆☆☆ Found in Text Mining only
Choroideremia	Choroideremia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Cochlear Diseases	Cochlear diseases	Pubtator	33860785	Associate	★☆☆☆☆ Found in Text Mining only
Conductive hearing loss	Hearing Loss	BEFREE	23400403		★☆☆☆☆ Found in Text Mining only
Conductive hearing loss	Hearing Loss	HPO_DG			★☆☆☆☆ Found in Text Mining only
Contiguous gene syndrome	Contiguous gene syndrome	BEFREE	10644430		★☆☆☆☆ Found in Text Mining only
Deafness	Deafness	Pubtator	1609803, 16365218, 22389666, 25792666, 25928534, 27941975, 32048449, 33976695, 35062939, 7825582	Associate	★☆☆☆☆ Found in Text Mining only
Deafness Autosomal Recessive 3	Deafness	Pubtator	25928534, 34133399, 9298820	Associate	★☆☆☆☆ Found in Text Mining only
DEAFNESS, X-LINKED 1 (disorder)	Deafness	BEFREE	22201925		★☆☆☆☆ Found in Text Mining only
Developmental Disabilities	Developmental disability	Pubtator	25792666	Associate	★☆☆☆☆ Found in Text Mining only
Global developmental delay	Developmental Delay	HPO_DG			★☆☆☆☆ Found in Text Mining only
Growth Disorders	Growth disorder	Pubtator	26323392	Associate	★☆☆☆☆ Found in Text Mining only
Hearing Loss	Hearing loss	Pubtator	21633365, 24096866, 25792666, 27941975, 28051029, 30176854, 32952548, 33638616, 35189936, 35982127, 36743950, 39272213	Associate	★☆☆☆☆ Found in Text Mining only
Hearing Loss	Hearing loss	Pubtator	7839145	Stimulate	★☆☆☆☆ Found in Text Mining only
Hearing Loss Sensorineural	Hearing loss	Pubtator	29986705	Associate	★☆☆☆☆ Found in Text Mining only
Hearing Loss, Mixed Conductive-Sensorineural	Hearing Loss	BEFREE	24687041, 2491012, 27779564, 2904400, 31786483, 7839145, 9109724, 9778298		★☆☆☆☆ Found in Text Mining only
Hypertensive disease	Hypertension	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hypothalamic hamartomas	Hypothalamic Hamartomas	BEFREE	31440883		★☆☆☆☆ Found in Text Mining only
Intellectual Disability	Mental retardation	BEFREE	10644430, 26323392		★☆☆☆☆ Found in Text Mining only
Isolated somatotropin deficiency	Isolated Somatotropin Deficiency	HPO_DG			★☆☆☆☆ Found in Text Mining only
Leber Congenital Amaurosis	Leber congenital amaurosis	Pubtator	21633365	Associate	★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of lung	Lung Cancer	BEFREE	25243889		★☆☆☆☆ Found in Text Mining only
Medulloblastoma	Medulloblastoma	Pubtator	18664619	Associate	★☆☆☆☆ Found in Text Mining only
Mental Retardation	Mental retardation	BEFREE	10644430		★☆☆☆☆ Found in Text Mining only
Mental Retardation, X-Linked	Mental retardation	BEFREE	1511979		★☆☆☆☆ Found in Text Mining only
Mental Retardation, X-Linked 1	Mental Retardation, X-Linked	BEFREE	10644430		★☆☆☆☆ Found in Text Mining only
Mild Mental Retardation	Mental retardation	HPO_DG			★☆☆☆☆ Found in Text Mining only
Mitochondrial non-syndromic sensorineural deafness	Mitochondrial Non-Syndromic Sensorineural Deafness	Orphanet			★☆☆☆☆ Found in Text Mining only
Neurodegenerative Disorders	Neurodegenerative Disorders	BEFREE	31518606		★☆☆☆☆ Found in Text Mining only
Nonsyndromic Deafness	Nonsyndromic Deafness	CLINGEN_DG	10407036, 10587581, 23606368, 25259580, 25299585, 27941975, 7581392, 7839145		★☆☆☆☆ Found in Text Mining only
Nonsyndromic Deafness	Nonsyndromic Deafness	BEFREE	21193157, 23076972, 23606368, 30874365		★☆☆☆☆ Found in Text Mining only
Nystagmus	Nystagmus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Obesity	Obesity	HPO_DG			★☆☆☆☆ Found in Text Mining only
Optic Atrophy	Optic Atrophy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Progressive hearing loss stapes fixation	Hearing loss with stapes fixation	Pubtator	1609803, 16365218, 21633365, 24096866, 2491012, 25130324, 25928534, 26323392, 30176854, 30289920, 33860785, 35189936, 36743950, 7825582, 7839145, 7891371	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Progressive hearing loss stapes fixation	Deafness	BEFREE	19671658, 20668882, 24096866, 8589693, 9778298		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Progressive hearing loss stapes fixation	Deafness	CLINVAR_DG	23606368		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Progressive hearing loss stapes fixation	Deafness	UNIPROT_DG	7581392, 7839145, 9298820, 9778298		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Progressive hearing loss stapes fixation	Deafness	GENOMICS_ENGLAND_DG	9298820		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Progressive hearing loss stapes fixation	Deafness	CTD_human_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Renal Artery Stenosis	Renal Artery Stenosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Reticular pigmentary degeneration	Reticular pigmentary degeneration	HPO_DG			★☆☆☆☆ Found in Text Mining only
Secondary hypothyroidism	Hypothyroidism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Sensorineural Hearing Loss (disorder)	Hearing Loss	BEFREE	29986705		★☆☆☆☆ Found in Text Mining only
Sensorineural hearing loss, bilateral	Sensorineural hearing loss	HPO_DG			★☆☆☆☆ Found in Text Mining only
Small cell carcinoma of lung	Lung carcinoma	BEFREE	25243889		★☆☆☆☆ Found in Text Mining only
Somatotropin deficiency	Somatotropin Deficiency	HPO_DG			★☆☆☆☆ Found in Text Mining only
Strabismus	Strabismus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Uranostaphyloschisis	Uranostaphyloschisis	BEFREE	26323392		★☆☆☆☆ Found in Text Mining only
Vestibular Diseases	Vestibular disease	Pubtator	16365218	Associate	★☆☆☆☆ Found in Text Mining only
Xq21 microdeletion syndrome	Xp21 Deletion Syndrome	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations