POU3F2

Chr 6

POU class 3 homeobox 2

Also known as: BRN2, N-Oct3, OCT7, OTF-7, OTF7, POUF3, brn-2, oct-7

NCBI Gene: 5454ENSG00000184486UniProt: P20265

This gene encodes a member of the POU-III class of neural transcription factors. The encoded protein is involved in neuronal differentiation and enhances the activation of corticotropin-releasing hormone regulated genes. Overexpression of this protein is associated with an increase in the proliferation of melanoma cells. [provided by RefSeq, Mar 2012]

87
ClinVar variants
20
Pathogenic / LP
0.92
pLI score· haploinsufficient
0
Active trials
Clinical Summary— POU3F2
⚡
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
20 Pathogenic / Likely Pathogenic· 55 VUS of 87 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.
0.38LOEUF
pLI 0.920
Z-score 3.01
OE 0.08 (0.03–0.38)
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.
2.72Z-score
OE missense 0.49 (0.41–0.57)
108 obs / 222.2 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.0.08 (0.03–0.38)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.49 (0.41–0.57)
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.1.14
0≤1.21.6
LoF obs/exp: 1 / 12.5Missense obs/exp: 108 / 222.2Syn Z: -1.11

ClinVar Variant Classifications

87 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic17
Likely Pathogenic3
VUS55
Likely Benign12
17
Pathogenic
3
Likely Pathogenic
55
VUS
12
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
17
0
17
Likely Pathogenic
0
1
2
0
3
VUS
3
47
5
0
55
Likely Benign
0
2
4
6
12
Benign
0
0
0
0
0
Total35028687

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

View in ClinVar →

Protein Context — Lollipop Plot

POU3F2 · 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
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Reconstructing and reprogramming the tumor-propagating potential of glioblastoma stem-like cells.
Suvà ML et al.·Cell
2014
STAG2 loss rewires oncogenic and developmental programs to promote metastasis in Ewing sarcoma.
Adane B et al.·Cancer Cell
2021
A Novel miR-146a-POU3F2/SMARCA5 Pathway Regulates Stemness and Therapeutic Response in Glioblastoma.
Cui T et al.·Mol Cancer Res
2021
Transcription factor POU3F2 regulates TRIM8 expression contributing to cellular functions implicated in schizophrenia.
Ding C et al.·Mol Psychiatry
2021
Monoallelic intragenic POU3F2 variants lead to neurodevelopmental delay and hyperphagic obesity, confirming the gene's candidacy in 6q16.1 deletions.
Schönauer R et al.·Am J Hum Genet
2023
A De Novo Missense Variant in POU3F2 Identified in a Child with Global Developmental Delay.
Westphal DS et al.·Neuropediatrics
2018Case report
Exclusion of mutations in the PRNP, JPH3, TBP, ATN1, CREBBP, POU3F2 and FTL genes as a cause of disease in Portuguese patients with a Huntington-like phenotype.
Costa MDC et al.·J Hum Genet
2006Cohort
Novel Variants of SOX4 in Patients with Intellectual Disability.
Grosse M et al.·Int J Mol Sci
2023Cohort
The promoting effect of the POU3F2/METTL16/PFKM cascade on glycolysis and tumorigenesis of hepatocellular carcinoma.
Chen M et al.·Ann Hepatol
2025
Small 6q16.1 Deletions Encompassing POU3F2 Cause Susceptibility to Obesity and Variable Developmental Delay with Intellectual Disability.
Kasher PR et al.·Am J Hum Genet
2016
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