POU1F1

Chr 3ADAR

POU class 1 homeobox 1

Also known as: CPHD1, GHF-1, PIT1, POU1F1a, Pit-1

This gene encodes a member of the POU family of transcription factors that regulate mammalian development. The protein regulates expression of several genes involved in pituitary development and hormone expression. Mutations in this genes result in combined pituitary hormone deficiency. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

GeneReviewsOMIMResearchGenerating clinical summary…
LOFmechanismAD/ARLOEUF 0.681 OMIM phenotype
Clinical SummaryPOU1F1
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.32) despite low pLI — interpret in context.
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GeneReview available — POU1F1
Authoritative clinical overview · Recommended first read
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint?
0.68LOEUF
pLI 0.045
Z-score 2.46
OE 0.32 (0.170.68)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?
0.46Z-score
OE missense 0.90 (0.791.03)
149 obs / 165.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.32 (0.170.68)
00.351.4
Missense OE?0.90 (0.791.03)
00.61.4
Synonymous OE?1.09
01.21.6
LoF obs/exp: 5 / 15.4Missense obs/exp: 149 / 165.6Syn Z: -0.53
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitivePOU1F1-related combined pituitary hormone deficiencyLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.7326th %ile
GOF
0.5071th %ile
LOF
0.4825th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Literature Evidence

DNIn this report, we review a case of vertical transmission of a dominant negative POU1F1 mutation in which fetal abnormalities due to the hypothyroxinemic state during gestation may have been exacerbated by a decrease in the mother's levothyroxine dose based on a low TSH in early gestation.1

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

References

  1. 1.PMID 23397938

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

POU1F1 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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