POU3F3

Chr 2

POU class 3 homeobox 3

Also known as: BRN1, OTF8, SNIBFIS, brain-1, oct-8

NCBI Gene: 5455ENSG00000198914UniProt: P20264

This gene encodes a POU-domain containing protein that functions as a transcription factor. The encoded protein recognizes an octamer sequence in the DNA of target genes. This protein may play a role in development of the nervous system. [provided by RefSeq, Apr 2015]

Primary Disease Associations & Inheritance

UniProtSnijders Blok-Fisher syndrome
258
ClinVar variants
67
Pathogenic / LP
0.88
pLI score
0
Active trials
Clinical Summary— POU3F3
🧬
Gene-Disease Validity (ClinGen)
complex neurodevelopmental disorder · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.88) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
67 Pathogenic / Likely Pathogenic· 152 VUS of 258 total submissions
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
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.
0.43LOEUF
pLI 0.883
Z-score 2.45
OE 0.00 (0.00–0.43)
Moderately 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.
3.04Z-score
OE missense 0.36 (0.29–0.44)
63 obs / 176.8 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

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 (0.00–0.43)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.36 (0.29–0.44)
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.1.08
0≤1.21.6
LoF obs/exp: 0 / 7.0Missense obs/exp: 63 / 176.8Syn Z: -0.60

ClinVar Variant Classifications

258 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic27
Likely Pathogenic40
VUS152
Likely Benign35
Benign3
Conflicting1
27
Pathogenic
40
Likely Pathogenic
152
VUS
35
Likely Benign
3
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
8
2
17
0
27
Likely Pathogenic
10
15
15
0
40
VUS
0
135
17
0
152
Likely Benign
0
5
10
20
35
Benign
0
0
2
1
3
Conflicting
—1
Total181576121258

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

View in ClinVar →

Protein Context — Lollipop Plot

POU3F3 · protein map & ClinVar variants

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

Gene2Phenotype Curations

POU3F3-related intellectual disability

definitive
ADUndeterminedUncertain
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
POU3F3-related disorder: Defining the phenotype and expanding the molecular spectrum.
Rossi A et al.·Clin Genet
2023
In vivo CRISPR screening identifies POU3F3 as a novel regulator of ferroptosis resistance in hepatocellular carcinoma via retinoic acid signaling.
Tian Y et al.·Cell Commun Signal
2025
Linc-POU3F3 is overexpressed in hepatocellular carcinoma and regulates cell proliferation, migration and invasion.
Li Y et al.·Biomed Pharmacother
2018
Phosphorylation of POU3F3 Mediated Nuclear Translocation Promotes Proliferation in Non-Small Cell Lung Cancer through Accelerating ATP5PF Transcription and ATP Production.
Zeng QG et al.·Adv Sci (Weinh)
2025
A novel pathogenic variant causing POU3F3-related neurodevelopmental disorder in a child presenting with infantile epileptic spasms syndrome: Expanding the epileptic phenotype.
Terrone G et al.·Seizure
2025Case report
De Novo Variants Disturbing the Transactivation Capacity of POU3F3 Cause a Characteristic Neurodevelopmental Disorder.
Snijders Blok L et al.·Am J Hum Genet
2019
Coexistence of severe developmental delay, epilepsy, and hemangioma in Snijders Blok-Fisher syndrome suggests the presence of a POU3F3-related SNIBFIS endophenotype: A case report.
Torun D et al.·Am J Med Genet A
2021Case report
Effect of Linc-POU3F3 on radiotherapy resistance and cancer stem cell markers of esophageal cancer cells.
Chen Y et al.·Zhong Nan Da Xue Xue Bao Yi Xue Ban
2021
Global methylation profiling for risk prediction of prostate cancer.
Mahapatra S et al.·Clin Cancer Res
2012
Transcriptional characterization of conjunctival melanoma identifies the cellular tumor microenvironment and prognostic gene signatures.
Wolf J et al.·Sci Rep
2020
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