POU3F3

Chr 2AD

POU class 3 homeobox 3

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

This transcription factor recognizes octamer DNA sequences and plays a role in neuronal development, acting synergistically with SOX11 and SOX4. Mutations cause Snijders Blok-Fisher syndrome with autosomal dominant inheritance. The gene is highly constrained against loss-of-function variants (pLI 0.88, LOEUF 0.43), reflecting its critical role in nervous system development.

OMIMResearchSummary from RefSeq, OMIM, UniProt
MultiplemechanismADLOEUF 0.431 OMIM phenotype
Clinical SummaryPOU3F3
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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.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.43LOEUF
pLI 0.883
Z-score 2.45
OE 0.00 (0.000.43)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
3.04Z-score
OE missense 0.36 (0.290.44)
63 obs / 176.8 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.00 (0.000.43)
00.351.4
Missense OE0.36 (0.290.44)
00.61.4
Synonymous OE1.08
01.21.6
LoF obs/exp: 0 / 7.0Missense obs/exp: 63 / 176.8Syn Z: -0.60
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitivePOU3F3-related intellectual disabilityOTHERAD
DN
0.3396th %ile
GOF
0.3193th %ile
LOF
0.90top 5%

This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to loss-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

LOFprediction above median · 1 literature citation · LOEUF 0.43
GOF1 literature citation

Literature Evidence

GOFGain-of-function assays showed that the overexpression of lncRNA POU3F3 maintained cell survival with DTIC treatment, while the knockdown of lncRNA POU3F3 restored cell sensitivity to DTIC.PMID:33816296
LOFIn this paper, we discuss the possible role of POU3F3 haploinsufficiency in relation to the boy's phenotype.PMID:24550763

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants 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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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