FEZF2

Chr 3

FEZ family zinc finger 2

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

NCBI Gene: 55079 ENSG00000153266 UniProt: Q8TBJ5 OMIM: 607414

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.

OMIM ResearchSummary from RefSeq, UniProt

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]

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.22

Clinical Summary— FEZF2

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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.

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

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?

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?

LoF OE?0.00 (0.00–0.22)

0≤0.351.4

Missense OE?0.63 (0.55–0.72)

0≤0.61.4

Synonymous OE?1.18

0≤1.21.6

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

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.