NDE1

nudE neurodevelopment protein 1, the group of MicroRNA protein coding host genes

Basic information

Region (hg38): 16:15643266-15734691

Links

ENSG00000072864 ∙ NCBI:54820 ∙ OMIM:609449 ∙ HGNC:17619 ∙ Uniprot:Q9NXR1 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• lissencephaly 4 (Definitive), mode of inheritance: AR
• lissencephaly 4 (Moderate), mode of inheritance: AR
• lissencephaly 4 (Strong), mode of inheritance: AR
• hydranencephaly (Supportive), mode of inheritance: AR
• microlissencephaly (Supportive), mode of inheritance: AR
• NDE1-related microhydranencephaly (Supportive), mode of inheritance: AR
• lissencephaly 4 (Strong), mode of inheritance: AR
• NDE1-related microhydranencephaly (Limited), mode of inheritance: Unknown
• lissencephaly 4 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Lissencephaly 4; Microhydranencephaly	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic	10762554; 21529751; 21529752; 22526350

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NDE1 gene.

• Familial thoracic aortic aneurysm and aortic dissection (872 variants)
• Aortic aneurysm, familial thoracic 4 (794 variants)
• not provided (494 variants)
• not specified (188 variants)
• Lissencephaly 4 (134 variants)
• Lissencephaly, Recessive (88 variants)
• Inborn genetic diseases (37 variants)
• Aortic aneurysm, familial thoracic 4;Visceral myopathy 2;Megacystis-microcolon-intestinal hypoperistalsis syndrome 2 (36 variants)
• Connective tissue disorder (26 variants)
• Cardiovascular phenotype (25 variants)
• Visceral myopathy 2;Megacystis-microcolon-intestinal hypoperistalsis syndrome 2;Aortic aneurysm, familial thoracic 4 (20 variants)
• MYH11-related condition (11 variants)
• Visceral myopathy 2 (7 variants)
• Familial aortopathy (7 variants)
• Megacystis-microcolon-intestinal hypoperistalsis syndrome 2 (6 variants)
• Visceral myopathy 2;Aortic aneurysm, familial thoracic 4;Megacystis-microcolon-intestinal hypoperistalsis syndrome 2 (4 variants)
• Isolated thoracic aortic aneurysm (4 variants)
• Congenital aneurysm of ascending aorta (3 variants)
• Lissencephaly 4;NDE1-related microhydranencephaly (2 variants)
• Intellectual disability (2 variants)
• Stroke disorder (2 variants)
• NDE1-related microhydranencephaly (2 variants)
• Megacystis-microcolon-intestinal hypoperistalsis syndrome 2;Aortic aneurysm, familial thoracic 4;Visceral myopathy 2 (2 variants)
• Aortic aneurysm, familial thoracic 6 (2 variants)
• NDE1-related microhydranencephaly;Lissencephaly 4 (2 variants)
• Megacystis-microcolon-intestinal hypoperistalsis syndrome 2;Visceral myopathy 2;Aortic aneurysm, familial thoracic 4 (2 variants)
• Pulmonic stenosis (1 variants)
• Chronic intestinal pseudoobstruction (1 variants)
• Aortic aneurysm (1 variants)
• Megacystis-microcolon-intestinal hypoperistalsis syndrome 2;Familial thoracic aortic aneurysm and aortic dissection (1 variants)
• Aortic aneurysm, familial thoracic 4;Visceral myopathy 2 (1 variants)
• Aortic dilatation (1 variants)
• Abnormality of connective tissue (1 variants)
• Mitral regurgitation;Abnormal left ventricle morphology;Tricuspid regurgitation;Myopia;Aortic root aneurysm (1 variants)
• Small cervical vertebral bodies (1 variants)
• Bicuspid aortic valve (1 variants)
• Wolff-Parkinson-White pattern (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NDE1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			4	30	1	35
missense		1	63	2		66
nonsense	2		2			4
start loss						0
frameshift	1		1			2
inframe indel			1			1
splice donor/acceptor (+/-2bp)	2			1		3
splice region			8	3	1	12
non coding	8	16	692	502	63	1281
Total	13	17	763	535	64

Highest pathogenic variant AF is 0.0000329

Variants in NDE1

This is a list of pathogenic ClinVar variants found in the NDE1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
16-15643268-G-A		Lissencephaly 4	Uncertain significance (Feb 02, 2018)
16-15643281-C-T		Lissencephaly 4	Uncertain significance (Jan 12, 2018)
16-15643299-C-T		Lissencephaly 4	Uncertain significance (Jan 12, 2018)
16-15643320-G-A		Lissencephaly 4	Likely benign (Jan 13, 2018)
16-15643328-C-T		Lissencephaly 4	Uncertain significance (Jan 13, 2018)
16-15643346-C-CG		Lissencephaly, Recessive	Uncertain significance (Jun 14, 2016)
16-15643398-C-T		Lissencephaly 4	Uncertain significance (Jan 12, 2018)
16-15643406-C-T		Lissencephaly 4	Likely benign (Jan 12, 2018)
16-15643418-G-A		Lissencephaly 4	Benign (Jan 12, 2018)
16-15643529-C-T		Lissencephaly 4	Benign (Jan 13, 2018)
16-15643548-A-G		Lissencephaly 4	Benign (Jan 12, 2018)
16-15643555-AC-A		Lissencephaly, Recessive	Likely benign (Jun 14, 2016)
16-15643558-C-A		Lissencephaly 4	Likely benign (Jan 13, 2018)
16-15643570-C-CT		Lissencephaly, Recessive	Uncertain significance (Jun 14, 2016)
16-15643581-T-G		Lissencephaly 4	Uncertain significance (Jan 12, 2018)
16-15643614-C-T		Lissencephaly 4	Uncertain significance (Jan 12, 2018)
16-15643695-A-C		Lissencephaly 4	Uncertain significance (Jan 12, 2018)
16-15643740-A-G		Lissencephaly 4	Likely benign (Jan 13, 2018)
16-15643753-T-A		Lissencephaly 4	Uncertain significance (Jan 12, 2018)
16-15643791-A-G		Lissencephaly 4	Likely benign (Jan 13, 2018)
16-15643829-CAAGA-C		Lissencephaly, Recessive	Uncertain significance (Jun 14, 2016)
16-15643847-A-C		Lissencephaly 4	Uncertain significance (Jan 13, 2018)
16-15643861-A-G		Lissencephaly 4	Benign (Jan 13, 2018)
16-15643907-G-T		Lissencephaly 4	Uncertain significance (Jan 13, 2018)
16-15649332-TTGTC-T		Lissencephaly, Recessive	Conflicting classifications of pathogenicity (May 24, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NDE1	protein_coding	protein_coding	ENST00000396355	8	83087

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00669	0.990	125713	0	34	125747	0.000135

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-1.13	246	201	1.22	0.0000140	2175
Missense in Polyphen		45	48.219	0.93324		591
Synonymous	-1.35	99	83.3	1.19	0.00000603	652
Loss of Function	2.56	7	19.1	0.367	0.00000120	210

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000177	0.000177
Ashkenazi Jewish	0.0000994	0.0000992
East Asian	0.000109	0.000109
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000150	0.000149
Middle Eastern	0.000109	0.000109
South Asian	0.000196	0.000196
Other	0.000327	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Required for centrosome duplication and formation and function of the mitotic spindle. Essential for the development of the cerebral cortex. May regulate the production of neurons by controlling the orientation of the mitotic spindle during division of cortical neuronal progenitors of the proliferative ventricular zone of the brain. Orientation of the division plane perpendicular to the layers of the cortex gives rise to two proliferative neuronal progenitors whereas parallel orientation of the division plane yields one proliferative neuronal progenitor and a post- mitotic neuron. A premature shift towards a neuronal fate within the progenitor population may result in an overall reduction in the final number of neurons and an increase in the number of neurons in the deeper layers of the cortex. {ECO:0000269|PubMed:17600710, ECO:0000269|PubMed:21529752}.
• Disease: DISEASE: Lissencephaly 4 (LIS4) [MIM:614019]: A neurodevelopmental disorder characterized by lissencephaly, severe brain atrophy, extreme microcephaly, and profound mental retardation. {ECO:0000269|PubMed:21529751, ECO:0000269|PubMed:21529752}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Microhydranencephaly (MHAC) [MIM:605013]: A severe neurodevelopmental disorder characterized by microcephaly, severe motor and mental retardation, spasticity, and brain malformations that include gross dilation of the ventricles with complete absence of the cerebral hemispheres or severe delay in their development. {ECO:0000269|PubMed:22526350}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Signal Transduction;Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal;Amplification of signal from the kinetochores;Mitotic Spindle Checkpoint;Cell Cycle Checkpoints;RHO GTPases Activate Formins;RHO GTPase Effectors;Signaling by Rho GTPases;Regulation of PLK1 Activity at G2/M Transition;Recruitment of mitotic centrosome proteins and complexes;Loss of Nlp from mitotic centrosomes;Loss of proteins required for interphase microtubule organization from the centrosome;Centrosome maturation;AURKA Activation by TPX2;G2/M Transition;Mitotic G2-G2/M phases;Recruitment of NuMA to mitotic centrosomes;Mitotic Prometaphase;Separation of Sister Chromatids;Mitotic Anaphase;Mitotic Metaphase and Anaphase;M Phase;Cell Cycle;Resolution of Sister Chromatid Cohesion;Cell Cycle, Mitotic;Anchoring of the basal body to the plasma membrane;Cilium Assembly;Organelle biogenesis and maintenance (Consensus)

Recessive Scores

• pRec: 0.169

Intolerance Scores

• loftool: 0.135
• rvis_EVS: -0.82
• rvis_percentile_EVS: 11.77

Haploinsufficiency Scores

• pHI: 0.470
• hipred: Y
• hipred_score: 0.666
• ghis: 0.648

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.824

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Nde1
• Phenotype: cellular phenotype; embryo phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan)

Zebrafish Information Network

• Gene name: nde1
• Affected structure: head
• Phenotype tag: abnormal
• Phenotype quality: decreased size

Gene ontology

• Biological process: G2/M transition of mitotic cell cycle;establishment of mitotic spindle orientation;neuron migration;microtubule nucleation;chromosome segregation;mitotic centrosome separation;neuroblast proliferation;regulation of G2/M transition of mitotic cell cycle;cell migration;cerebral cortex development;vesicle transport along microtubule;centrosome duplication;cell division;establishment of chromosome localization;centrosome localization;ciliary basal body-plasma membrane docking;regulation of microtubule motor activity
• Cellular component: kinetochore;condensed chromosome kinetochore;centrosome;cytosol;kinesin complex;microtubule;membrane;spindle pole centrosome;cleavage furrow;synapse
• Molecular function: protein binding;microtubule binding;protein domain specific binding;identical protein binding