POU3F3

Chr 2AD

POU class 3 homeobox 3

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

NCBI Gene: 5455 ENSG00000198914 UniProt: P20264 OMIM: 602480

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.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Snijders Blok-Fisher syndromeMIM #618604

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · complex neurodevelopmental disorder · AD · ClinGen 2024

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.43

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

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?

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?

LoF OE?0.00 (0.00–0.43)

0≤0.351.4

Missense OE?0.36 (0.29–0.44)

0≤0.61.4

Synonymous OE?1.08

0≤1.21.6

LoF obs/exp: 0 / 7.0Missense obs/exp: 63 / 176.8Syn Z: -0.60

Background carrier burden — how many people carry a rare variant somewhere in POU3F3?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 200

646 rare PASS variants

Rare truncating (LoF)

1 in 2,200

70 rare PASS variants

Rare synonymous (reference)

1 in 100

457 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for POU3F3. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 250	1 in 3,100
South Asian	~43k	1 in 100	1 in 490
Remaining (unassigned)	~30k	1 in 210	1 in 3,000
European (Finnish)	~27k	1 in 120	1 in 260
Admixed American	~22k	1 in 70	1 in 1,100
African / African American	~21k	1 in 160	≈ 1 in 4,800
East Asian	~20k	1 in 110	1 in 710
Ashkenazi Jewish	~13k	1 in 330	1 in 720
Middle Eastern	~2,884	1 in 120	≈ 1 in 1,300

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 0 of 1 coding exons well covered in gnomAD exomes; exon 1 marginal. Genomes: 0 of 1 (exon 1 below).? see exons ↓