POU4F3

Chr 5AD

POU class 4 homeobox 3

Also known as: BRN3C, DFNA15, DFNA42, DFNA52

NCBI Gene: 5459ENSG00000091010UniProt: Q15319

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 determining or maintaining the identities of a small subset of visual system neurons. Defects in this gene are the cause of non-syndromic sensorineural deafness autosomal dominant type 15. [provided by RefSeq, Mar 2009]

Primary Disease Associations & Inheritance

Deafness, autosomal dominant 15/52MIM #602459
AD
276
ClinVar variants
47
Pathogenic / LP
0.92
pLI score· haploinsufficient
0
Active trials
Clinical Summary— POU4F3
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.92). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
47 Pathogenic / Likely Pathogenic· 81 VUS of 276 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.37LOEUF
pLI 0.920
Z-score 2.63
OE 0.00 (0.00–0.37)
Highly constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.66Z-score
OE missense 1.14 (1.01–1.28)
208 obs / 182.8 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.00 (0.00–0.37)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.14 (1.01–1.28)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.40
0≤1.21.6
LoF obs/exp: 0 / 8.1Missense obs/exp: 208 / 182.8Syn Z: -2.74

ClinVar Variant Classifications

276 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic25
Likely Pathogenic22
VUS81
Likely Benign29
Benign7
Conflicting12
25
Pathogenic
22
Likely Pathogenic
81
VUS
29
Likely Benign
7
Benign
12
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
6
6
13
0
25
Likely Pathogenic
7
8
7
0
22
VUS
0
73
6
2
81
Likely Benign
0
0
4
25
29
Benign
0
0
0
7
7
Conflicting
—12
Total13873034176

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

POU4F3 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Deafness, autosomal dominant 15/52

MIM #602459

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Genetic etiology of non-syndromic hearing loss in Europe.
Del Castillo I et al.·Hum Genet
2022Review
Optimized in vivo base editing restores auditory function in a DFNA15 mouse model.
Wang M et al.·Nat Commun
2025Functional
A Missense POU4F3 Variant Associated with Autosomal Dominant Midfrequency Hearing Loss Alters Subnuclear Localization and Transcriptional Capabilities.
Bai D et al.·Biomed Res Int
2021
POU4F3 Is a Sensitive and Specific Marker of Merkel Cell Carcinoma.
Karpinski P et al.·Mod Pathol
2025
Identification of two novel mutations in POU4F3 gene associated with autosomal dominant hearing loss in Chinese families.
Bai X et al.·J Cell Mol Med
2020
Functional Correlation of Two Novel Nonsense POU4F3 Mutations Causing Late-Onset Progressive Nonsyndromic Hearing Loss in DFNA15 Families.
Zhang T et al.·Mol Genet Genomic Med
2025Functional
Genomics and hearing impairment.
Keats BJ et al.·Genome Res
1999Review
Highly variable hearing loss due to POU4F3 (c.37del) is revealed by longitudinal, frequency specific analyses.
Singh S et al.·Eur J Hum Genet
2023Natural history
TFE2 and GATA3 enhance induction of POU4F3 and myosin VIIa positive cells in nonsensory cochlear epithelium by ATOH1.
Masuda M et al.·Dev Biol
2012
Genetics of dizziness: cerebellar and vestibular disorders.
Requena T et al.·Curr Opin Neurol
2014Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools