NDEL1

Chr 17

nudE neurodevelopment protein 1 like 1

Also known as: EOPA, MITAP1, NDE1L1, NDE2, NUDEL

NCBI Gene: 81565 ENSG00000166579 UniProt: Q9GZM8 OMIM: 607538

The NDEL1 protein regulates microtubule organization and dynein motor activity, and is essential for neuronal migration during brain development and neurite outgrowth. Mutations cause neurodevelopmental disorders with intellectual disability and cortical malformations, inherited in an autosomal recessive pattern. This gene is highly constrained against loss-of-function mutations, indicating its critical role in normal development.

OMIM ResearchSummary from RefSeq, UniProt

Enables identical protein binding activity. Involved in chromosome segregation; positive regulation of GTPase activity; and regulation of intracellular protein transport. Located in kinetochore. Biomarker of schizophrenia. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.30

Clinical Summary— NDEL1

⚡

Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.98). One damaged copy is likely sufficient to cause disease.

📋

ClinVar Variants

30 VUS of 41 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.30LOEUF

pLI 0.984

Z-score 3.88

OE 0.09 (0.04–0.30)

Highly constrained

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

Missense Constraint?

1.66Z-score

OE missense 0.66 (0.57–0.77)

124 obs / 188.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.09 (0.04–0.30)

0≤0.351.4

Missense OE?0.66 (0.57–0.77)

0≤0.61.4

Synonymous OE?0.88

0≤1.21.6

LoF obs/exp: 2 / 21.3Missense obs/exp: 124 / 188.0Syn Z: 0.84

This gene — mechanism propensity

0.5771th %ile

GOF

0.4085th %ile

LOF

0.70top 10%

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

LOFprediction above median · LOEUF 0.30

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

41 submitted variants in ClinVar

ClinVar

Classification Summary

VUS30

VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	30	30
Likely Benign	0	0
Benign	0	0
Total	30	30

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

View in ClinVar →

12 pathogenic / likely-pathogenic (of 17) ClinVar copy-number / structural variants overlap NDEL1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →