FEZF2

Chr 3

FEZ family zinc finger 2

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

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]

OMIMResearchGenerating clinical summary…
LOFmechanismLOEUF 0.22
Clinical SummaryFEZF2
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.
📋
ClinVar Variants
5 unique Pathogenic / Likely Pathogenic· 67 VUS of 77 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint?
0.22LOEUF
pLI 0.989
Z-score 3.40
OE 0.00 (0.000.22)
Highly constrained

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

Missense Constraint?
2.07Z-score
OE missense 0.63 (0.550.72)
156 obs / 247.9 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?
LoF OE?0.00 (0.000.22)
00.351.4
Missense OE?0.63 (0.550.72)
00.61.4
Synonymous OE?1.18
01.21.6
LoF obs/exp: 0 / 13.5Missense obs/exp: 156 / 247.9Syn Z: -1.51
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
moderateFEZF2-related neurodevelopmental disorderLOFAD

This gene — mechanism propensity

DN
0.4090th %ile
GOF
0.3986th %ile
LOF
0.85top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · 80% of P/LP variants are LoF · LOEUF 0.22

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

77 submitted variants in ClinVar

Classification Summary

Pathogenic2
Likely Pathogenic3
VUS67
Likely Benign2
Benign2
Conflicting1
2
Pathogenic
3
Likely Pathogenic
67
VUS
2
Likely Benign
2
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
0
0
0
2
Likely Pathogenic
2
1
0
0
3
VUS
7
59
1
0
67
Likely Benign
0
1
0
1
2
Benign
0
1
1
0
2
Conflicting
1
Total11622177

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

View in ClinVar →

11 pathogenic / likely-pathogenic (of 15) ClinVar copy-number / structural variants overlap FEZF2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

FEZF2 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →