FEZF2

Chr 3

FEZ family zinc finger 2

Also known as: FEZ, FEZL, FKSG36, TOF, ZFP312, ZNF312

NCBI Gene: 55079ENSG00000153266UniProt: Q8TBJ5

Predicted to enable several functions, including DNA-binding transcription factor activity, RNA polymerase II-specific; RNA polymerase II cis-regulatory region sequence-specific DNA binding activity; and zinc ion binding activity. Predicted to be involved in regulation of gene expression. Predicted to act upstream of or within several processes, including negative regulation of transcription by RNA polymerase II; nervous system development; and regulation of neuron differentiation. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2025]

0
ClinVar variants
0
Pathogenic / LP
0.99
pLI score· haploinsufficient
0
Active trials
Clinical Summary— FEZF2
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.99). One damaged copy is likely sufficient to cause disease.

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.
0.22LOEUF
pLI 0.989
Z-score 3.40
OE 0.00 (0.00–0.22)
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.
2.07Z-score
OE missense 0.63 (0.55–0.72)
156 obs / 247.9 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

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.0.00 (0.00–0.22)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.63 (0.55–0.72)
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.1.18
0≤1.21.6
LoF obs/exp: 0 / 13.5Missense obs/exp: 156 / 247.9Syn Z: -1.51

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

FEZF2 · protein map & ClinVar variants

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

Gene2Phenotype Curations

FEZF2-related neurodevelopmental disorder

moderate
ADLoss Of FunctionAbsent Gene Product, Altered Gene Product Structure
Dev. Disorders
G2P ↗
missense variantstop gained NMD escapingframeshift variant NMD escapingwhole partial gene deletion

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Identification of epilepsy-associated neuronal subtypes and gene expression underlying epileptogenesis.
Pfisterer U et al.·Nat Commun
2020
Rare predicted deleterious FEZF2 variants are associated with a neurodevelopmental phenotype.
Garber A et al.·Am J Med Genet A
2024
Loss of Fezf2 promotes malignant progression of bladder cancer by regulating the NF-κB signaling pathway.
Chen Z et al.·Lab Invest
2018
Clinical genomics expands the morbid genome of intellectual disability and offers a high diagnostic yield.
Anazi S et al.·Mol Psychiatry
2017
Gene targeting in a HUES line of human embryonic stem cells via electroporation.
Ruby KM et al.·Stem Cells
2009
3p interstitial deletion including PRICKLE2 in identical twins with autistic features.
Okumura A et al.·Pediatr Neurol
2014Case report
Neuronal Cell Sheets of Cortical Motor Neuron Phenotype Derived from Human iPSCs.
Suzuki N et al.·Cell Transplant
2017
Transcription factor programming of human ES cells generates functional neurons expressing both upper and deep layer cortical markers.
Miskinyte G et al.·PLoS One
2018Functional
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.

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External Resources

Links to major genomics databases and tools