POU4F3

POU class 4 homeobox 3, the group of POU class homeoboxes and pseudogenes

Basic information

Region (hg38): 5:146338839-146341728

Previous symbols: [ "DFNA15", "DFNA52", "DFNA42" ]

Links

ENSG00000091010 ∙ NCBI:5459 ∙ OMIM:602460 ∙ HGNC:9220 ∙ Uniprot:Q15319 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal dominant nonsyndromic hearing loss 15 (Strong), mode of inheritance: AD
• autosomal dominant nonsyndromic hearing loss 15 (Strong), mode of inheritance: AD
• autosomal dominant nonsyndromic hearing loss (Supportive), mode of inheritance: AD
• nonsyndromic genetic hearing loss (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Deafness, autosomal dominant 15	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	Audiologic/Otolaryngologic	9506947; 18228599; 18347256; 19372648; 19462854; 20434433; 22938506

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the POU4F3 gene.

• Autosomal dominant nonsyndromic hearing loss 15 (7 variants)
• not provided (3 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the POU4F3 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	27	5	34
missense	1	7	84	1		93
nonsense	1	3				4
start loss						0
frameshift	7	4				11
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1		1
non coding			2	2	1	5
Total	9	14	88	30	6

Variants in POU4F3

This is a list of pathogenic ClinVar variants found in the POU4F3 region.

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

Position	Type	Phenotype	Significance	ClinVar
5-146338855-G-A			Likely benign (Dec 23, 2018)
5-146339034-C-A		Autosomal dominant nonsyndromic hearing loss 15	Uncertain significance (Jan 13, 2018)
5-146339069-C-A		Autosomal dominant nonsyndromic hearing loss 15	Uncertain significance (Jan 13, 2018)
5-146339136-G-A		Autosomal dominant nonsyndromic hearing loss 15	Conflicting classifications of pathogenicity (Apr 03, 2023)
5-146339138-C-T		Inborn genetic diseases	Uncertain significance (Feb 07, 2023)
5-146339143-G-A			Uncertain significance (Dec 12, 2023)
5-146339147-T-C			Uncertain significance (Mar 02, 2022)
5-146339148-GC-AA			Uncertain significance (Jan 22, 2024)
5-146339148-GC-G		Autosomal dominant nonsyndromic hearing loss 15	Pathogenic (Jul 28, 2022)
5-146339151-C-G			Uncertain significance (Apr 04, 2023)
5-146339164-GA-G		Autosomal dominant nonsyndromic hearing loss 15	Pathogenic (Aug 01, 2020)
5-146339166-A-C		Inborn genetic diseases • POU4F3-related disorder	Uncertain significance (Nov 02, 2022)
5-146339176-TC-T		Autosomal dominant nonsyndromic hearing loss 15	Pathogenic (May 22, 2022)
5-146339178-C-T		POU4F3-related disorder	Likely benign (Sep 11, 2024)
5-146339182-C-T			Likely benign (May 23, 2023)
5-146339183-T-G			Uncertain significance (Dec 23, 2021)
5-146339190-T-A			Likely benign (Mar 01, 2023)
5-146339197-G-A			Uncertain significance (May 02, 2023)
5-146339202-C-T		not specified • Autosomal dominant nonsyndromic hearing loss 15	Benign (Jan 26, 2024)
5-146339208-C-A		not specified	Likely benign (Feb 14, 2019)
5-146339210-G-A			Uncertain significance (Nov 04, 2022)
5-146339212-G-C		Inborn genetic diseases	Uncertain significance (Jan 02, 2024)
5-146339215-T-C		not specified	Uncertain significance (May 23, 2023)
5-146339225-C-A		Autosomal dominant nonsyndromic hearing loss 15	Uncertain significance (Jan 13, 2018)
5-146339230-C-T			Likely pathogenic (Apr 01, 2017)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
POU4F3	protein_coding	protein_coding	ENST00000230732	2	1497

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.920	0.0799	125730	0	2	125732	0.00000795

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.661	208	183	1.14	0.00000939	2210
Missense in Polyphen		40	54.595	0.73266		688
Synonymous	-2.74	105	74.8	1.40	0.00000438	698
Loss of Function	2.63	0	8.08	0.00	3.79e-7	93

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)	0.0000176	0.0000176
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: 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 development, required for terminal differentiation of hair cells in the inner ear (By similarity). {ECO:0000250|UniProtKB:Q63955, ECO:0000269|PubMed:18228599}.

Recessive Scores

• pRec: 0.156

Intolerance Scores

• loftool: 0.111
• rvis_EVS: -0.54
• rvis_percentile_EVS: 20.54

Haploinsufficiency Scores

• pHI: 0.895
• hipred: Y
• hipred_score: 0.755
• ghis: 0.502

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.431

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pou4f3
• Phenotype: cellular phenotype; homeostasis/metabolism phenotype; growth/size/body region phenotype; vision/eye phenotype; hearing/vestibular/ear 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); 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); normal phenotype; reproductive system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Gene ontology

• Biological process: visual perception;sensory perception of sound;vestibulocochlear nerve development;retinal ganglion cell axon guidance;inner ear morphogenesis;inner ear auditory receptor cell differentiation;positive regulation of transcription by RNA polymerase II;axon extension;neuromuscular process controlling balance;neuron apoptotic process
• Cellular component: nucleus;nucleoplasm;cytoplasm
• Molecular function: RNA polymerase II proximal promoter sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription activator activity, RNA polymerase II-specific;DNA-binding transcription factor activity