POU5F1

Chr 6

POU class 5 homeobox 1

Also known as: OCT3, OCT4, OCT4Borf1, OTF-3, OTF3, OTF4, Oct-3, Oct-4

NCBI Gene: 5460ENSG00000204531UniProt: Q01860

This gene encodes a transcription factor containing a POU homeodomain that plays a key role in embryonic development and stem cell pluripotency. Aberrant expression of this gene in adult tissues is associated with tumorigenesis. This gene can participate in a translocation with the Ewing's sarcoma gene on chromosome 21, which also leads to tumor formation. Alternative splicing, as well as usage of alternative AUG and non-AUG translation initiation codons, results in multiple isoforms. One of the AUG start codons is polymorphic in human populations. Related pseudogenes have been identified on chromosomes 1, 3, 8, 10, and 12. [provided by RefSeq, Oct 2013]

33
ClinVar variants
7
Pathogenic / LP
0.95
pLI score· haploinsufficient
3
Active trials
Clinical Summary— POU5F1
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.95). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
7 Pathogenic / Likely Pathogenic· 20 VUS of 33 total submissions
💊
Clinical Trials
3 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.34LOEUF
pLI 0.954
Z-score 3.55
OE 0.11 (0.04–0.34)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.76Z-score
OE missense 0.66 (0.57–0.76)
136 obs / 207.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.11 (0.04–0.34)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.66 (0.57–0.76)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.79
0≤1.21.6
LoF obs/exp: 2 / 18.5Missense obs/exp: 136 / 207.2Syn Z: 1.59

ClinVar Variant Classifications

33 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic4
Likely Pathogenic3
VUS20
Likely Benign6
4
Pathogenic
3
Likely Pathogenic
20
VUS
6
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
4
0
4
Likely Pathogenic
0
0
3
0
3
VUS
0
17
3
0
20
Likely Benign
0
6
0
0
6
Benign
0
0
0
0
0
Total02310033

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

View in ClinVar →

Protein Context — Lollipop Plot

POU5F1 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Endothelial β-catenin upregulation and Y142 phosphorylation drive diabetic angiogenesis via upregulating KDR/HDAC9.
Chen Z et al.·Cell Commun Signal
2024
Epigenetic Regulation of Driver Genes in Testicular Tumorigenesis.
von Eyben FE et al.·Int J Mol Sci
2023Review
FBF1 maintains stem cell-like properties in breast cancer via PI3K/AKT/SOX2 axis.
Guo C et al.·Stem Cell Res Ther
2025
Myoepithelial tumors of soft tissue and bone in children and young adults: A clinicopathologic study of 40 cases occurring in patients ≤ 21 Years of age.
Logan SJ et al.·Hum Pathol
2024Cohort
Metastases and treatment-resistant lineages in patient-derived cancer cells of colorectal cancer.
Fujino S et al.·Commun Biol
2023
Role of OCT4 in cancer stem-like cells and chemotherapy resistance.
Mohiuddin IS et al.·Biochim Biophys Acta Mol Basis Dis
2020Review
Epigenetic and risk factors of testicular germ cell tumors: a brief review.
Landero-Huerta DA et al.·Front Biosci (Landmark Ed)
2017Review
Nuclear receptor TLX functions to promote cancer stemness and EMT in prostate cancer via its direct transactivation of CD44 and stem cell-regulatory transcription factors.
Chow ST et al.·Br J Cancer
2024
Primary renal sarcoma with SS18::POU5F1 gene fusion.
Argani P et al.·Genes Chromosomes Cancer
2022Case report
LGR4 maintains HGSOC cell epithelial phenotype and stem-like traits.
Wang Z et al.·Gynecol Oncol
2020
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Open Angle Glaucoma (OAG)NAION( Non-arteritic Anterior Ischemic Optic Neuropathy)

Evaluating ER-100 for Safety in People With Glaucoma or Non-Arteritic Anterior Ischemic Optic Neuropathy (Optic Nerve Conditions)

RECRUITING
NCT07290244Phase PHASE1Life Biosciences Inc.Started 2026-03-02
ER-100 epigenetic therapy
Infertility, MaleGene AbnormalitySterility, Male

Spermatogonial Differentiation Via Testicular Organoid

RECRUITING
NCT06841861Phase PHASE1, PHASE2CellARTs Inc.Started 2024-03-28
Stem cellGenetic ScreeningGenetic Reprogramming
Fistula Repair

Endoscopic Injection of Autologous, Activated and Emulsified Fat in Chronic Fistulas of the Gastrointestinal Tract and Pelvic Organs

RECRUITING
NCT06930079Fondazione Policlinico Universitario Agostino Gemelli IRCCSStarted 2025-03-20

External Resources

Links to major genomics databases and tools