POU1F1

Chr 3ADAR

POU class 1 homeobox 1

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

NCBI Gene: 5449ENSG00000064835UniProt: P28069

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]

Primary Disease Associations & Inheritance

Pituitary hormone deficiency, combined or isolated, 1MIM #613038
ADAR
0
Active trials
51
Pathogenic / LP
259
ClinVar variants
18
Pubs (1 yr)
0.5
Missense Z
0.68
LOEUF
Clinical Summary— POU1F1
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.32) despite low pLI — interpret in context.
📋
ClinVar Variants
51 Pathogenic / Likely Pathogenic· 62 VUS of 259 total submissions
📖
GeneReview available — POU1F1
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.68LOEUF
pLI 0.045
Z-score 2.46
OE 0.32 (0.17–0.68)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.46Z-score
OE missense 0.90 (0.79–1.03)
149 obs / 165.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.32 (0.17–0.68)
0≤0.351.4
Missense OE0.90 (0.79–1.03)
0≤0.61.4
Synonymous OE1.09
0≤1.21.6
LoF obs/exp: 5 / 15.4Missense obs/exp: 149 / 165.6Syn Z: -0.53
DNLOF
DN
0.7326th %ile
GOF
0.5071th %ile
LOF
0.4825th %ile

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

DNprediction above median · 1 literature citation
LOF29% of P/LP variants are LoF

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

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.PMID:23397938

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

259 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic33
Likely Pathogenic18
VUS62
Likely Benign119
Benign11
Conflicting16
33
Pathogenic
18
Likely Pathogenic
62
VUS
119
Likely Benign
11
Benign
16
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
9
8
14
2
33
Likely Pathogenic
6
7
5
0
18
VUS
0
43
18
1
62
Likely Benign
0
2
57
60
119
Benign
0
2
9
0
11
Conflicting
—16
Total156210363259

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

View in ClinVar →

POU1F1 · protein map & ClinVar variants

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

Gene2Phenotype Curations

POU1F1-related combined pituitary hormone deficiency

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Landmark / reviewRecent case evidence
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Functional Properties of POU1F1 Mutants in the Transcriptional Regulation of the Thyrotropin β Gene Compared with the Prolactin Gene.
Kawauchi Y et al.·Int J Mol Sci
2025Open AccessFunctional
Association of DGAT1 and POU1F1 Gene Polymorphisms With the Milk Traits in the Cross-Bred Hamdani Sheep Bred Under Extensive Management.
Turgut AO et al.·Vet Med Sci
2025Open Access
Short Stature Due to a Novel Compound Heterozygous Mutation of the POU1F1 Gene.
Sasidharan Pillai S et al.·JCEM Case Rep
2025Open Access
Identification of POU1F1 Variants in Vietnamese Patients with Combined Pituitary Hormone Deficiency.
Nguyen HT et al.·Int J Mol Sci
2025Open AccessCohort
Phosphatidylinositol promoted the proliferation and invasion of pituitary adenoma cells by regulating POU1F1 expression.
Xu T et al.·Cancer Metab
2025Open Access
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients