POU4F1

Chr 13

POU class 4 homeobox 1

Also known as: ATITHS, BRN3A, Oct-T1, RDC-1, brn-3A

NCBI Gene: 5457 ENSG00000152192 UniProt: Q01851

This gene encodes a neural transcription factor that regulates gene expression involved in neuronal differentiation, survival, and process outgrowth, with major developmental effects in somatosensory neurons and brainstem motor control nuclei. Mutations cause autosomal dominant sensorineural hearing loss (DFNA15), typically presenting in adulthood with progressive hearing impairment. The gene is highly constrained against loss-of-function variants, indicating that such mutations are likely to have significant clinical consequences.

ResearchSummary from RefSeq, UniProt

This gene encodes a member of the POU-IV class of neural transcription factors. This protein is expressed in a subset of retinal ganglion cells and may be involved in the developing sensory nervous system. This protein may also promote the growth of cervical tumors. A translocation of this gene is associated with some adult acute myeloid leukemias. [provided by RefSeq, Mar 2012]

ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.42

Clinical Summary— POU4F1

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Population Constraint (gnomAD)

Moderately constrained gene (pLI 0.89) — some intolerance to loss-of-function variants.

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ClinVar Variants

9 unique Pathogenic / Likely Pathogenic· 80 VUS of 119 total submissions

Explore recent and relevant literature in Research Assistant →

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?

0.42LOEUF

pLI 0.888

Z-score 2.47

OE 0.00 (0.00–0.42)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

2.45Z-score

OE missense 0.46 (0.39–0.56)

77 obs / 165.8 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.42)

0≤0.351.4

Missense OE?0.46 (0.39–0.56)

0≤0.61.4

Synonymous OE?1.08

0≤1.21.6

LoF obs/exp: 0 / 7.1Missense obs/exp: 77 / 165.8Syn Z: -0.53

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

strongPOU4F1-related ataxia, intention tremor, and hypotonia syndromeLOFAD

This gene — mechanism propensity

0.4289th %ile

GOF

0.2796th %ile

LOF

0.87top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · 1 literature citation · 78% of P/LP variants are LoF · LOEUF 0.42

Literature Evidence

LOFHaploinsufficiency of POU4F1 causes an ataxia syndrome with hypotonia and intention tremor.1

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

References

1.PMID 33783914 ↗

ClinVar Variant Classifications

119 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic5

Likely Pathogenic4

VUS80

Likely Benign26

Benign2

Conflicting1

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	4	1	0	0	5
Likely Pathogenic	3	0	1	0	4
VUS	10	69	1	0	80
Likely Benign	0	5	3	18	26
Benign	0	2	0	0	2
Conflicting	—				1
Total	17	77	5	18	118

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

View in ClinVar →

76 pathogenic / likely-pathogenic (of 81) ClinVar copy-number / structural variants overlap POU4F1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →