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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 15 days ago
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POU1F1
POU class 1 homeobox 1
Chromosome 3 Β· 3p11.2
NCBI Gene: 5449Ensembl: ENSG00000064835.12HGNC: HGNC:9210UniProt: P28069
137PubMed Papers
21Diseases
0Drugs
42Pathogenic Variants
FUNCTIONAL ROLE
Transcription Factor
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
DNA-binding transcription factor activitysequence-specific double-stranded DNA bindingpositive regulation of transcription by RNA polymerase IIregulation of DNA-templated transcriptionpituitary hormone deficiency, combined, 1Combined pituitary hormone deficiencies, genetic formscombined pituitary hormone deficiencies, genetic formgenetic disorder
✦AI Summary

POU1F1 is a pituitary-specific transcription factor essential for anterior pituitary development and function 1. It specifies the differentiation and survival of three key anterior pituitary cell types: lactotrophs, somatotrophs, and thyrotrophs 2. POU1F1 functions as a sequence-specific DNA-binding transcription factor that activates growth hormone, prolactin, and thyroid-stimulating hormone genes through binding to consensus sequences and recruitment of RNA polymerase II machinery 3. The gene encodes multiple protein isoforms through alternative splicing, with the alpha and beta isoforms exhibiting distinct transactivation capacities on target promoters 4. Mutations in POU1F1 cause combined pituitary hormone deficiency (CPHD), characterized by deficiencies in growth hormone, prolactin, and thyroid-stimulating hormone, with variable inheritance patterns 5. Pathogenic variants range from missense mutations to intronic variants disrupting pre-mRNA splicing, leading to anterior pituitary hypoplasia and growth failure 4. Notably, POU1F1 interacts genetically with other developmental transcription factors; heterozygous variants in POU1F1 combined with SIX3 mutations cause digenic hypopituitarism with pituitary dysmorphology 6. Additionally, POU1F1 mutations have been associated with precocious or early puberty in some CPHD patients, suggesting roles in gonadotroph regulation 7.

Sources cited
1
POU1F1 is a pituitary transcription factor involved in pituitary development and function
PMID: 28476222
2
POU1F1 specifies lactotroph, somatotroph, and thyrotroph cell lineages in the anterior pituitary
PMID: 31883967
3
POU1F1 activates growth hormone, prolactin, and TSH genes; encodes multiple isoforms with different transactivation capacities
PMID: 16942842
4
POU1F1 mutations disrupt splicing and cause anterior pituitary hypoplasia, growth hormone deficiency, and postnatal growth failure
PMID: 36427334
5
POU1F1 mutations cause combined pituitary hormone deficiency with variable inheritance patterns; the R271W mutation is a dominant negative hotspot
PMID: 18174732
6
Heterozygous POU1F1 variants interact with SIX3 mutations to cause digenic hypopituitarism with pituitary dysmorphology
PMID: 35951005
7
POU1F1 mutations are associated with precocious or early puberty in combined pituitary hormone deficiency; gene regulates gonadotrope function
PMID: 30460459
Disease Associationsβ“˜21
pituitary hormone deficiency, combined, 1Open Targets
0.82Strong
Combined pituitary hormone deficiencies, genetic formsOpen Targets
0.75Strong
combined pituitary hormone deficiencies, genetic formOpen Targets
0.60Moderate
genetic disorderOpen Targets
0.41Moderate
isolated growth hormone deficiency type IIOpen Targets
0.38Weak
congenital hypothyroidismOpen Targets
0.37Weak
hypothyroidism due to deficient transcription factors involved in pituitary development or functionOpen Targets
0.37Weak
prostate carcinomaOpen Targets
0.37Weak
prostate cancerOpen Targets
0.34Weak
intestinal diseaseOpen Targets
0.28Weak
Leber congenital amaurosis 5Open Targets
0.27Weak
type 2 diabetes mellitusOpen Targets
0.22Weak
cataractOpen Targets
0.19Weak
autosominal recessive combined pituitary hormone deficiencyOpen Targets
0.18Weak
response to xenobiotic stimulusOpen Targets
0.17Weak
glomerulonephritisOpen Targets
0.17Weak
poisoningOpen Targets
0.17Weak
neoplasmOpen Targets
0.12Weak
adenomaOpen Targets
0.09Suggestive
breast cancerOpen Targets
0.09Suggestive
Pituitary hormone deficiency, combined, 1UniProt
Pathogenic Variants42
NM_000306.4(POU1F1):c.472G>C (p.Ala158Pro)Pathogenic
Pituitary hormone deficiency, combined, 1|not provided|Combined pituitary hormone deficiencies, genetic form
β˜…β˜…β˜†β˜†2025β†’ Residue 158
NM_000306.4(POU1F1):c.688G>A (p.Glu230Lys)Pathogenic
Pituitary hormone deficiency, combined, 1|not provided|POU1F1-related disorder|Combined pituitary hormone deficiencies, genetic form
β˜…β˜…β˜†β˜†2025β†’ Residue 230
NM_000306.4(POU1F1):c.427C>T (p.Arg143Ter)Pathogenic
Inborn genetic diseases|Combined pituitary hormone deficiencies, genetic form|Pituitary hormone deficiency, combined, 1
β˜…β˜…β˜†β˜†2024β†’ Residue 143
NM_000306.4(POU1F1):c.793C>T (p.Arg265Trp)Pathogenic
not provided|Combined pituitary hormone deficiencies, genetic form
β˜…β˜…β˜†β˜†2024β†’ Residue 265
NM_000306.4(POU1F1):c.515G>A (p.Arg172Gln)Pathogenic
Pituitary hormone deficiency, combined, 1|not provided|Combined pituitary hormone deficiencies, genetic form|POU1F1-related disorder
β˜…β˜…β˜†β˜†2024β†’ Residue 172
NM_000306.4(POU1F1):c.143-83A>GPathogenic
not provided|Pituitary hormone deficiency, combined, 1
β˜…β˜…β˜†β˜†2024
NM_000306.4(POU1F1):c.428G>A (p.Arg143Gln)Pathogenic
Pituitary hormone deficiency, combined, 1|Combined pituitary hormone deficiencies, genetic form
β˜…β˜†β˜†β˜†2025β†’ Residue 143
NM_000306.4(POU1F1):c.731T>C (p.Ile244Thr)Likely pathogenic
Leber congenital amaurosis 5
β˜…β˜†β˜†β˜†2024β†’ Residue 244
NM_000306.4(POU1F1):c.562_565del (p.Ala188fs)Pathogenic
Pituitary hormone deficiency, combined, 1
β˜…β˜†β˜†β˜†2024β†’ Residue 188
NM_000306.4(POU1F1):c.658_661dup (p.Ile221fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 221
NM_000306.4(POU1F1):c.71C>T (p.Pro24Leu)Likely pathogenic
Pituitary hormone deficiency, combined, 1|not provided
β˜…β˜†β˜†β˜†2023β†’ Residue 24
NM_000306.4(POU1F1):c.634_635del (p.Glu212fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2023β†’ Residue 212
NM_000306.4(POU1F1):c.142+2T>CLikely pathogenic
not provided
β˜…β˜†β˜†β˜†2023
NM_000306.4(POU1F1):c.495_496del (p.Phe165fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2023β†’ Residue 165
NM_000306.4(POU1F1):c.7del (p.Cys3fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2023β†’ Residue 3
NM_000306.4(POU1F1):c.143-1G>ALikely pathogenic
not provided
β˜…β˜†β˜†β˜†2023
NM_000306.4(POU1F1):c.787del (p.Cys263fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2023β†’ Residue 263
NM_000306.4(POU1F1):c.142+1G>TLikely pathogenic
not provided
β˜…β˜†β˜†β˜†2023
NM_000306.4(POU1F1):c.96_97delinsTT (p.Glu33Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2023β†’ Residue 33
NM_000306.4(POU1F1):c.440-1G>ALikely pathogenic
not provided
β˜…β˜†β˜†β˜†2023
View on ClinVar β†—
Related Genes
ZBTB7CShared pathway100%TESShared pathway100%CGREF1Shared pathway100%TP53I11Shared pathway100%RARRES1Shared pathway100%THAP12Shared pathway100%
Tissue Expression6 tissues
Brain
100%
Liver
20%
Lung
13%
Ovary
13%
Heart
0%
Bone Marrow
0%
Gene Interaction Network
Click a node to explore
POU1F1ZBTB7CTESCGREF1TP53I11RARRES1THAP12
PROTEIN STRUCTURE
Preparing viewer…
PDB5WC9 Β· 3.15 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.92LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.62 [0.42–0.92]
RankingsWhere POU1F1 stands among ~20K protein-coding genes
  • #3,388of 20,598
    Most Researched137 Β· top quartile
  • #1,485of 5,498
    Most Pathogenic Variants42
  • #8,499of 17,882
    Most Constrained (LOEUF)0.92
Genes detectedPOU1F1
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Pangenomic Classification of Pituitary Neuroendocrine Tumors.
PMID: 31883967
Cancer Cell Β· 2020
1.00
2
Pituitary Hypoplasia.
PMID: 28476222
Endocrinol Metab Clin North Am Β· 2017
0.90
3
Precocious or early puberty in patients with combined pituitary hormone deficiency due to POU1F1 gene mutation: case report and review of possible mechanisms.
PMID: 30460459
Hormones (Athens) Β· 2018
0.80
4
Heterozygous variants in SIX3 and POU1F1 cause pituitary hormone deficiency in mouse and man.
PMID: 35951005
Hum Mol Genet Β· 2023
0.70
5
POU1F1/Pou1f1 c.143-83A > G Variant Disrupts the Branch Site in Pre-mRNA and Leads to Dwarfism.
PMID: 36427334
Endocrinology Β· 2022
0.60