FEZ1

Chr 11

fasciculation and elongation protein zeta 1

Also known as: UNC-76

This protein functions in axonal outgrowth and guidance, and participates in the transport of mitochondria and other cargos along microtubules. Mutations cause neurodevelopmental disorders with intellectual disability, developmental delay, and seizures, inherited in an autosomal recessive pattern. The gene shows high constraint against loss-of-function variants (LOEUF 0.41), consistent with its essential role in neuronal development.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
5
Pubs (1 yr)
60
P/LP submissions
0%
P/LP missense
0.41
LOEUF
Mechanism
Clinical SummaryFEZ1
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.75) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
60 unique Pathogenic / Likely Pathogenic· 47 VUS of 123 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.41LOEUF
pLI 0.750
Z-score 3.57
OE 0.18 (0.090.41)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.38Z-score
OE missense 0.74 (0.650.84)
163 obs / 220.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.18 (0.090.41)
00.351.4
Missense OE0.74 (0.650.84)
00.61.4
Synonymous OE0.97
01.21.6
LoF obs/exp: 4 / 22.1Missense obs/exp: 163 / 220.6Syn Z: 0.22

ClinVar Variant Classifications

123 submitted variants in ClinVar

Classification Summary

Pathogenic58
Likely Pathogenic2
VUS47
Benign4
58
Pathogenic
2
Likely Pathogenic
47
VUS
4
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
58
0
58
Likely Pathogenic
0
0
2
0
2
VUS
0
43
4
0
47
Likely Benign
0
0
0
0
0
Benign
0
1
2
1
4
Total044661111

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

View in ClinVar →

Protein Context — Lollipop Plot

FEZ1 · 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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