NDE1

Chr 16AR

nudE neurodevelopment protein 1

Also known as: HOM-TES-87, LIS4, MHAC, NDE, NUDE, NUDE1

NCBI Gene: 54820ENSG00000072864UniProt: Q9NXR1

This gene encodes a member of the nuclear distribution E (NudE) family of proteins. The encoded protein is localized at the centrosome and interacts with other centrosome components as part of a multiprotein complex that regulates dynein function. This protein plays an essential role in microtubule organization, mitosis and neuronal migration. Mutations in this gene cause lissencephaly 4, a disorder characterized by lissencephaly, severe brain atrophy, microcephaly, and severe cognitive disability. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2012]

Primary Disease Associations & Inheritance

Lissencephaly 4 (with microcephaly)MIM #614019
AR
MicrohydranencephalyMIM #605013
AR
UniProtLissencephaly 4 with microcephaly
2311
ClinVar variants
15
Pathogenic / LP
0.01
pLI score
0
Active trials
Clinical Summary— NDE1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
15 Pathogenic / Likely Pathogenic· 36 VUS of 2311 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.69LOEUF
pLI 0.007
Z-score 2.56
OE 0.37 (0.21–0.69)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-1.13Z-score
OE missense 1.22 (1.10–1.36)
246 obs / 200.8 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.37 (0.21–0.69)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.22 (1.10–1.36)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.19
0≤1.21.6
LoF obs/exp: 7 / 19.1Missense obs/exp: 246 / 200.8Syn Z: -1.35

ClinVar Variant Classifications

2311 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic5
Likely Pathogenic10
VUS36
Likely Benign44
Benign1
Conflicting4
5
Pathogenic
10
Likely Pathogenic
36
VUS
44
Likely Benign
1
Benign
4
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
5
0
5
Likely Pathogenic
2
0
8
0
10
VUS
1
32
3
0
36
Likely Benign
0
0
10
34
44
Benign
0
0
1
0
1
Conflicting
—4
Total3322734100

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

View in ClinVar →

Protein Context — Lollipop Plot

NDE1 · protein map & ClinVar variants

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

Gene2Phenotype Curations

NDE1-related lissencephaly

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Lissencephaly 4 (with microcephaly)

MIM #614019

Molecular basis of disorder known

Autosomal recessive

Microhydranencephaly

MIM #605013

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
16p13.11 microduplication in 45 new patients: refined clinical significance and genotype-phenotype correlations.
Allach El Khattabi L et al.·J Med Genet
2020Cohort
Novel lissencephaly-associated NDEL1 variant reveals distinct roles of NDE1 and NDEL1 in nucleokinesis and human cortical malformations.
Tsai MH et al.·Acta Neuropathol
2024
Severe congenital microcephaly with 16p13.11 microdeletion combined with NDE1 mutation, a case report and literature review.
Tan L et al.·BMC Med Genet
2017Review
[Microlissencephaly due to pathogenic variants of NDE1: from pathology to normal brain development].
Cabet S et al.·Med Sci (Paris)
2020Review
NDE1-related disorders: A recurrent NDE1 pathogenic variant causing Lissencephaly 4 can also be associated with microhydranencephaly.
Bas H et al.·Am J Med Genet A
2022Case report
Prenatal Diagnosis, Ultrasound Findings, and Follow-Up Evaluation of 16p13.11 Deletion and Duplication Syndromes: Preliminary Assessment of Fetal Genotype-Phenotype.
Luo X et al.·J Clin Lab Anal
2025Natural history
Neuropathology of 16p13.11 deletion in epilepsy.
Liu JY et al.·PLoS One
2012
Using mouse transgenic and human stem cell technologies to model genetic mutations associated with schizophrenia and autism.
St Clair D et al.·Philos Trans R Soc Lond B Biol Sci
2018Review
Phenotypic spectrum of NDE1-related disorders: from microlissencephaly to microhydranencephaly.
Abdel-Hamid MS et al.·Am J Med Genet A
2019Case report
Ohnologs are overrepresented in pathogenic copy number mutations.
McLysaght A et al.·Proc Natl Acad Sci U S A
2014
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools