FEZF2

Chr 3

FEZ family zinc finger 2

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

FEZF2 encodes a transcription repressor that specifies corticospinal motor neurons and other subcerebral projection neurons, and controls the development of dendritic arborization and spines of large layer V pyramidal neurons. Mutations cause autosomal dominant developmental and epileptic encephalopathy with microcephaly. The gene is highly constrained against loss-of-function variants (pLI 0.99), indicating that haploinsufficiency is likely not tolerated in the general population.

OMIMResearchSummary from RefSeq, UniProt
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.

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 OE0.00 (0.000.22)
00.351.4
Missense OE0.63 (0.550.72)
00.61.4
Synonymous OE1.18
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
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 · 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

0 submitted variants in 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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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