POU6F2

Chr 7ADSomatic

POU class 6 homeobox 2

NCBI Gene: 11281ENSG00000106536UniProt: P78424

Probable transcription factor likely to be involved in early steps in the differentiation of amacrine and ganglion cells. Recognizes and binds to the DNA sequence 5'-ATGCAAAT-3'. Isoform 1 does not bind DNA

Primary Disease Associations & Inheritance

{Wilms tumor susceptibility-5}MIM #601583
ADSomatic
UniProtHereditary susceptibility to Wilms tumor 5
92
ClinVar variants
4
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— POU6F2
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.34) despite low pLI — interpret in context.
📋
ClinVar Variants
4 Pathogenic / Likely Pathogenic· 81 VUS of 92 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
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.
0.56LOEUF
pLI 0.002
Z-score 3.52
OE 0.34 (0.21–0.56)
Moderately constrained

More LoF-intolerant than ~75% 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.
0.46Z-score
OE missense 0.93 (0.86–1.02)
361 obs / 386.2 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.0.34 (0.21–0.56)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.93 (0.86–1.02)
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.1.02
0≤1.21.6
LoF obs/exp: 11 / 32.7Missense obs/exp: 361 / 386.2Syn Z: -0.22

ClinVar Variant Classifications

92 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic2
Likely Pathogenic2
VUS81
Likely Benign3
Benign3
Conflicting1
2
Pathogenic
2
Likely Pathogenic
81
VUS
3
Likely Benign
3
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
2
0
2
Likely Pathogenic
0
0
2
0
2
VUS
2
76
3
0
81
Likely Benign
0
2
0
1
3
Benign
0
0
2
1
3
Conflicting
—1
Total2789292

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

View in ClinVar →

Protein Context — Lollipop Plot

POU6F2 · 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

{Wilms tumor susceptibility-5}

MIM #601583

Molecular basis of disorder known

Autosomal dominantSomatic mutation
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
The m(6)A modification mediated-lncRNA POU6F2-AS1 reprograms fatty acid metabolism and facilitates the growth of colorectal cancer via upregulation of FASN.
Jiang T et al.·Mol Cancer
2024
Long non-coding RNA POU6F2-AS2 promotes cell proliferation and drug resistance in colon cancer by regulating miR-377/BRD4.
Xu G et al.·J Cell Mol Med
2020
LncRNA POU6F2-AS2 contributes to malignant phenotypes and paclitaxel resistance by promoting SKP2 expression in stomach adenocarcinoma.
Jin Y et al.·J Chemother
2023
lncRNA POU6F2-AS1 Regulated by KIAA1429 Contributes to Colorectal Cancer Progression in an m(6)A Modification Manner.
Lu D et al.·Mol Biotechnol
2025
Genomic locus modulating corneal thickness in the mouse identifies POU6F2 as a potential risk of developing glaucoma.
King R et al.·PLoS Genet
2018Functional
Transcriptome analyses of human corneal endothelial cell lines derived from patients with Fuchs endothelial corneal dystrophy.
Ashraf S et al.·Sci Rep
2025Cohort
Therapeutic response to pazopanib: case report and literature review on molecular abnormalities of aggressive prolactinomas.
Medina EJ et al.·Front Endocrinol (Lausanne)
2023Review
Clinical description and epigenetic profiling of a new Danish OCD case-control cohort.
Staunstrup NH et al.·J Psychiatr Res
2026Cohort
Identification and prediction of novel non-coding and coding RNA-associated competing endogenous RNA networks in colorectal cancer.
Liang Y et al.·World J Gastroenterol
2018
Wilms tumor in monozygous twins: clinical, pathological, cytogenetic and molecular case report.
Perotti D et al.·J Pediatr Hematol Oncol
2005Case report
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

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools