NDEL1

Summary

NDEL1 (nudE neurodevelopment protein 1 like 1, HGNC:17620) is a protein-coding gene on chromosome 17p13.1, encoding Nuclear distribution protein nudE-like 1 (Q9GZM8). Required for organization of the cellular microtubule array and microtubule anchoring at the centrosome.

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.

Source: NCBI Gene 81565 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 40 total
• MANE Select transcript: NM_030808

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17620
Approved symbol	NDEL1
Name	nudE neurodevelopment protein 1 like 1
Location	17p13.1
Locus type	gene with protein product
Status	Approved
Aliases	NUDEL, MITAP1, NDE1L1, NDE2
Ensembl gene	ENSG00000166579
Ensembl biotype	protein_coding
OMIM	607538
Entrez	81565

Gene structure

Transcript identifiers

Ensembl transcripts: 36 — 28 protein_coding, 4 protein_coding_CDS_not_defined, 3 retained_intron, 1 nonsense_mediated_decay

ENST00000334527, ENST00000380025, ENST00000402554, ENST00000578172, ENST00000579150, ENST00000579880, ENST00000580012, ENST00000580237, ENST00000580738, ENST00000581189, ENST00000581679, ENST00000582277, ENST00000582490, ENST00000582665, ENST00000582812, ENST00000583066, ENST00000583683, ENST00000584866, ENST00000585098, ENST00000852238, ENST00000852239, ENST00000852240, ENST00000852241, ENST00000852242, ENST00000852243, ENST00000852244, ENST00000852245, ENST00000852246, ENST00000852247, ENST00000916783, ENST00000916784, ENST00000916785, ENST00000953597, ENST00000953598, ENST00000953599, ENST00000953600

RefSeq mRNA: 3 — MANE Select: NM_030808 NM_001025579, NM_001330129, NM_030808

CCDS: CCDS11143, CCDS32564, CCDS82070

Canonical transcript exons

ENST00000334527 — 9 exons

Exon	Start	End
ENSE00001104374	8450780	8450953
ENSE00001104376	8460009	8460160
ENSE00001104378	8448550	8448686
ENSE00001104390	8454796	8454887
ENSE00003531352	8446754	8446902
ENSE00003533237	8466930	8468163
ENSE00003555457	8445711	8445864
ENSE00003650796	8444260	8444357
ENSE00003904123	8435884	8436045

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 97.83.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 34.4323 / max 1044.5406, expressed in 1813 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
159498	25.6441	1807
159497	3.7687	1518
159499	1.8411	1007
159493	1.4205	104
159500	0.7678	301
159492	0.6371	76
159496	0.1839	59
159494	0.1322	23
208055	0.0370	13

Top tissues by expression

295 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
adrenal tissue	UBERON:0018303	97.83	gold quality
skin of leg	UBERON:0001511	97.55	gold quality
cervix squamous epithelium	UBERON:0006922	97.53	silver quality
secondary oocyte	CL:0000655	97.49	gold quality
skin of abdomen	UBERON:0001416	97.39	gold quality
blood	UBERON:0000178	97.13	gold quality
zone of skin	UBERON:0000014	97.08	gold quality
oocyte	CL:0000023	97.01	gold quality
right lung	UBERON:0002167	96.92	gold quality
calcaneal tendon	UBERON:0003701	96.82	gold quality
bone marrow cell	CL:0002092	96.61	gold quality
ascending aorta	UBERON:0001496	96.60	gold quality
thoracic aorta	UBERON:0001515	96.57	gold quality
colonic epithelium	UBERON:0000397	96.37	gold quality
aorta	UBERON:0000947	96.13	gold quality
descending thoracic aorta	UBERON:0002345	96.06	gold quality
popliteal artery	UBERON:0002250	95.86	gold quality
tibial artery	UBERON:0007610	95.85	gold quality
sural nerve	UBERON:0015488	95.67	gold quality
endothelial cell	CL:0000115	95.59	gold quality
esophagus mucosa	UBERON:0002469	95.54	gold quality
bone marrow	UBERON:0002371	95.50	gold quality
upper arm skin	UBERON:0004263	95.49	gold quality
right coronary artery	UBERON:0001625	95.42	gold quality
lower esophagus mucosa	UBERON:0035834	95.36	gold quality
left ovary	UBERON:0002119	95.23	gold quality
upper lobe of left lung	UBERON:0008952	95.19	gold quality
left coronary artery	UBERON:0001626	95.04	gold quality
upper lobe of lung	UBERON:0008948	94.88	gold quality
esophagus	UBERON:0001043	94.86	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-6678	no	3.66
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

101 targeting NDEL1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-4283	100.00	66.42	2097
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-4525	99.94	64.38	675
HSA-MIR-5010-5P	99.94	64.11	705
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-22-3P	99.93	68.13	917

Literature-anchored findings (GeneRIF, showing 40)

• disease mutant form of Disrupted-in-Schizophrenia-1 fails to bind NUDEL (PMID:12506198)
• results point to the importance of Nudel-Lis1 interaction for the dynein activity in M phase and to a possible role of Nudel phosphorylation as facilitating such interaction. (PMID:12556484)
• DISC1 inhibits NUDEL-oligopeptidase activity in a competitive fashion. (PMID:15728732)
• NDEL1 is essential for mitotic cell division and neuronal migration not only via regulation of cytoplasmic dynein function but also by modulation of katanin p60 localization and function. (PMID:16203747)
• Aurora-A-mediated phosphorylation of NDEL1 is essential for centrosomal separation and centrosomal maturation and for mitotic entry (PMID:17060449)
• These results suggest a dual role of kinetochore Nudel: it activates dynein-mediated protein transport and, when interacting with both mitosin and dynein, stabilizes kinetochore dynein/dynactin. (PMID:17494871)
• Ndel1-deficient cells enter anaphase in a timely manner but lagging chromosomes then manifest. (PMID:17600710)
• crystallographic study of two fragments of the coiled-coil domain of Ndel1, one of which reveals contiguous high-quality electron density for residues 10-166, the longest such structure reported by X-ray diffraction at high resolution (PMID:17997972)
• Our work uncovers a unique regulatory mechanism of MT organization by PP4c through its targets Cdk1 and NDEL1 via regulation of katanin p60 distribution. (PMID:18347064)
• For DISC1-related sporadic psychiatric disease, impaired cellular control over self-association of DISC1 leads to excessive multimerization and subsequent formation of detergent-resistant aggregates, with loss of ligand binding, exemplified by NDEL1. (PMID:18400883)
• NDEL1 regulates cytoplasmic dynein and involved in the regulation of microtubule organization, and becomes the target of various kinases and phosphatases. (PMID:18421979)
• NDEL1 significantly influences risk for schizophrenia via an interaction with DISC1. (PMID:18469341)
• Data show that LIS1 suppresses the motility of cytoplasmic dynein on microtubules, whereas NDEL1 releases the blocking effect of LIS1 on cytoplasmic dynein. (PMID:18784752)
• NDEL1 protein interacts directly with Cyclic Nucleotide Phosphodiesterases, Type 4 and its isoforms and interaction of NDEL1 protein with phosphodiesterase isoform is uniquely disrupted by elevation of intracellular cyclic AMP levels. (PMID:18845247)
• Nudel regulates microtubule organization in part by facilitating assembly of the lamin B spindle matrix in a dynein-dependent manner. (PMID:19198602)
• These results suggest a novel mechanism for selective reinforcement of nascent adhesions via interplays of Nudel and FAK with paxillin to facilitate cell migration. (PMID:19492042)
• These results indicate an antagonistic effect of alpha1, alpha2 and Ndel1 for Lis1 binding, probably to modulate dynein functions in vivo. (PMID:19622634)
• There was no strong evidence for association with NUDEL in schizophrenia. (PMID:19632097)
• palmitoylated Ndel1 reduced cytoplasmic dynein activity as judged by Golgi distribution, VSVG and short microtubule trafficking, transport of endogenous Ndel1 and LIS1 from neurite tips to the cell body and neuronal migration (PMID:19927128)
• NDE1 and NDEL1 act upstream of LIS1 in dynein recruitment, and/or activation, on the membrane. (PMID:20048338)
• Evidence of statistical epistasis between DISC1, CIT and NDEL1 impacting risk for schizophrenia: biological validation with functional neuroimaging. (PMID:20084519)
• Findings suggest that physiological functions of LIS1 and NDEL1 in neurons have been ascribed for proteins fundamentally required for cell cycle progression and control. (PMID:20168084)
• This data supports a physiological role for the endooligopeptidase activity of Ndel1 and suggests it plays a key role during neurite outgrowth. (PMID:20462516)
• The truncated monomeric form of LIS1 had little effect on dynein motility, but an artificial dimer of truncated LIS1 suppressed dynein motility, which was restored by the N-terminal fragment of NDEL1. (PMID:21036906)
• NDEL1 is essential for a specific late step of neuronal migration: entry into the target lamina. (PMID:21092859)
• Nuclear distribution element-like 1 (Ndel1 or Nudel) was firstly described as a regulator of the cytoskeleton in microtubule and intermediate filament dynamics and microtubule-based transport. (PMID:21948775)
• DISC1 forms octamers via dimers as building blocks. S704C forms higher-order oligomers, without affecting its affinity with NDEL1 (PMID:21998303)
• Studies indicate that binding of dynactin, LIS1 and NudEL regulate cytoplasmic dynein motor activity. (PMID:22373868)
• Cytosolic mfGbeta is recruited to dynein by Nudel and transported to the centrosome for rapid sequestration and degradation. (PMID:22430153)
• Nudel markedly promotes the HSPC300-WAVE2 interaction. (PMID:22453242)
• Short (DISC)1 splice variants show reduced or no binding to nudE nuclear distribution E homolog (NDEL)1 and phosphodiesterase (PDE)4B proteins, but fully interact with FEZ1 and glycogen synthase kinase 3 (GSK3)beta. (PMID:22832604)
• analysis of mixed NDE1-NDEL1 complexes demonstrates that NDE1 and NDEL1 can interact directly. (PMID:22843697)
• The Plasma Ndel1 enzyme activity is reduced in patients with schizophrenia. (PMID:23388542)
• study provided comprehensive documentation of the expression patterns of Nde1 and Ndel1 in cultured cells as well as in mouse and human brains, and also highlighting that dosage effects of these two proteins might contribute to some cases of mental disorder (PMID:24785679)
• This study observed a significantly increased myelin basic protein (MBP) and nuclear distribution protein nudE-like 1 (NDEL1) mRNA levels in FEP patients compared with controls. (PMID:26476704)
• Study showed that Ndel1 enzyme activity is a complex trait influenced by many different genetic variants that may contribute to schizophrenia physiopathology (PMID:26851141)
• results highlight S-Nitrosylation as a key activity-dependent mechanism underlying neonatal brain maturation and suggest that reduction of S-Nitrosylation of NDEL1 acts as a pathological factor mediating neurodevelopmental abnormalities caused by maternal alcohol exposure (PMID:27371763)
• Results demonstrate that Ndel1 interacts with Tara to regulate cell movement revealing a novel role of the Ndel1-Tara complex in actin reorganization during cell movement. (PMID:27546710)
• disrupting DISC1/Ndel1 complex formation prolongs mitotic length and interferes with cell-cycle progression in human cells, and it causes cell-cycle deficits of radial glial cells in the embryonic mouse cortex and human forebrain organoids (PMID:29103808)
• observed a positive correlation between Ndel1 activity and the total YMRS score in BD group (p = 0.030) and a positive correlation between ACE activity and Ham-D score (PMID:30321766)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	ndel1a	ENSDARG00000010953
danio_rerio	ndel1b	ENSDARG00000104225
mus_musculus	Ndel1	ENSMUSG00000018736
rattus_norvegicus	Ndel1	ENSRNOG00000004139
drosophila_melanogaster	nudE	FBGN0036059
caenorhabditis_elegans	nud-2	WBGENE00011230

Paralogs (1): NDE1 (ENSG00000072864)

Protein

Protein identifiers

Nuclear distribution protein nudE-like 1 — Q9GZM8 (reviewed: Q9GZM8)

Alternative names: Mitosin-associated protein 1

All UniProt accessions (11): A6NIZ0, Q9GZM8, J3KRK9, J3KSF2, J3KT16, J3QL31, J3QL85, J3QLD0, J3QRD2, J3QRZ1, J3QSD2

UniProt curated annotations — full annotation on UniProt →

Function. Required for organization of the cellular microtubule array and microtubule anchoring at the centrosome. May regulate microtubule organization at least in part by targeting the microtubule severing protein KATNA1 to the centrosome. Also positively regulates the activity of the minus-end directed microtubule motor protein dynein. May enhance dynein-mediated microtubule sliding by targeting dynein to the microtubule plus ends. Required for several dynein- and microtubule-dependent processes such as the maintenance of Golgi integrity, the centripetal motion of secretory vesicles and the coupling of the nucleus and centrosome. Also required during brain development for the migration of newly formed neurons from the ventricular/subventricular zone toward the cortical plate. Plays a role, together with DISC1, in the regulation of neurite outgrowth. Required for mitosis in some cell types but appears to be dispensible for mitosis in cortical neuronal progenitors, which instead requires NDE1. Facilitates the polymerization of neurofilaments from the individual subunits NEFH and NEFL. Positively regulates lysosome peripheral distribution and ruffled border formation in osteoclasts. Plays a role, together with DISC1, in the regulation of neurite outgrowth. May act as a RAB9A/B effector that tethers RAB9-associated late endosomes to the dynein motor for their retrograde transport to the trans-Golgi network.

Subunit / interactions. Interacts with PLEKHM1 (via N- and C-terminus). Interacts with YWHAE. Interacts directly with NEFL and indirectly with NEFH. Interacts with microtubules. Self-associates. Interacts with DISC1, dynein, dynactin, tubulin gamma, KATNA1, KATNB1, PAFAH1B1, PCM1 and PCNT. Interacts (via C-terminus) with CENPF. Interacts with ZNF365. Interacts with GTP-bound RAB9A; the interaction may lead to RAB9A-dynein motor tethering.

Subcellular location. Cytoplasm. Cytoskeleton. Microtubule organizing center. Centrosome. Chromosome. Centromere. Kinetochore. Spindle.

Tissue specificity. Expressed in brain, heart, kidney, liver, lung, pancreas, placenta and skeletal muscle.

Post-translational modifications. Phosphorylated in mitosis. Can be phosphorylated by CDK1, CDK5 and MAPK1. Phosphorylation by CDK5 promotes interaction with KATNA1 and YWHAE. Palmitoylation at Cys-273 reduces affinity for dynein.

Similarity. Belongs to the nudE family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9GZM8-1	1	yes
Q9GZM8-2	2
Q9GZM8-3	3

RefSeq proteins (3): NP_001020750, NP_001317058, NP_110435* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006964	NUDE_dom	Domain
IPR033494	NUDE	Family

Pfam: PF04880

UniProt features (38 total): mutagenesis site 14, region of interest 10, modified residue 6, splice variant 2, chain 1, coiled-coil region 1, compositionally biased region 1, lipid moiety-binding region 1, sequence conflict 1, helix 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2V66	X-RAY DIFFRACTION	2.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9GZM8-F1	79.05	0.56

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (7): 215, 219, 231, 242, 245, 344, 273

Mutagenesis-validated functional residues (14):

Position	Phenotype
198	abrogates mitotic phosphorylation; when associated with v-219; a-231; a-242 and v-245. abrogates phosphorylation by cdk5
198	enhances interaction with pafah1b1 and impairs centrosomal localization; when associated with e-219; e-231; e-242 and e-
219	abrogates phosphorylation by cdk5; when associated with a-198 and a-231.
219	enhances interaction with pafah1b1 and impairs centrosomal localization; when associated with e-198; e-231; e-242 and e-
219	abrogates mitotic phosphorylation; when associated with a-198; a-231; a-242 and v-245.
231	abrogates mitotic phosphorylation; when associated with a-198; v-219; a-242 and v-245. abrogates phosphorylation by cdk5
231	enhances interaction with pafah1b1 and impairs centrosomal localization; when associated with e-198; e-219; e-242 and e-
242	abrogates mitotic phosphorylation; when associated with a-198; v-219; a-231 and v-245.
242	enhances interaction with pafah1b1 and impairs centrosomal localization; when associated with e-198; e-219; e-231 and e-
245	enhances interaction with pafah1b1 and impairs centrosomal localization; when associated with e-198; e-219; e-231 and e-
245	abrogates mitotic phosphorylation; when associated with a-198; v-219; a-231 and a-242.
266	abolishes interaction with disc1; when associated with a-267.
267	abolishes interaction with disc1; when associated with a-266.
273	abolishes oligopeptidase activity.

Function

Pathways and Gene Ontology

Reactome pathways

18 pathways

ID	Pathway
R-HSA-141444	Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal
R-HSA-2467813	Separation of Sister Chromatids
R-HSA-2500257	Resolution of Sister Chromatid Cohesion
R-HSA-5663220	RHO GTPases Activate Formins
R-HSA-68877	Mitotic Prometaphase
R-HSA-9648025	EML4 and NUDC in mitotic spindle formation
R-HSA-141424	Amplification of signal from the kinetochores
R-HSA-162582	Signal Transduction
R-HSA-1640170	Cell Cycle
R-HSA-194315	Signaling by Rho GTPases
R-HSA-195258	RHO GTPase Effectors
R-HSA-2555396	Mitotic Metaphase and Anaphase
R-HSA-68882	Mitotic Anaphase
R-HSA-68886	M Phase
R-HSA-69278	Cell Cycle, Mitotic
R-HSA-69618	Mitotic Spindle Checkpoint
R-HSA-69620	Cell Cycle Checkpoints
R-HSA-9716542	Signaling by Rho GTPases, Miro GTPases and RHOBTB3

MSigDB gene sets: 404 (showing top): GSE45365_NK_CELL_VS_BCELL_UP, GOBP_ESTABLISHMENT_OF_SPINDLE_ORIENTATION, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_INTERMEDIATE_FILAMENT_BASED_PROCESS, GOBP_AXO_DENDRITIC_TRANSPORT, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_CELL_POLARITY, TGCGCANK_UNKNOWN, GOBP_NEURON_PROJECTION_EXTENSION, GOBP_VESICLE_LOCALIZATION, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, TGCACTT_MIR519C_MIR519B_MIR519A, ENK_UV_RESPONSE_KERATINOCYTE_UP, TTTGTAG_MIR520D, GOBP_SPINDLE_LOCALIZATION

GO Biological Process (25): establishment of mitotic spindle orientation (GO:0000132), inner cell mass cell proliferation (GO:0001833), microtubule nucleation (GO:0007020), chromosome segregation (GO:0007059), mitotic centrosome separation (GO:0007100), retrograde axonal transport (GO:0008090), insulin receptor signaling pathway (GO:0008286), regulation of neuron projection development (GO:0010975), cell migration (GO:0016477), cerebral cortex radially oriented cell migration (GO:0021799), central nervous system neuron axonogenesis (GO:0021955), lysosome localization (GO:0032418), regulation of intracellular protein transport (GO:0033157), positive regulation of GTPase activity (GO:0043547), vesicle transport along microtubule (GO:0047496), centrosome localization (GO:0051642), neurofilament cytoskeleton organization (GO:0060052), radial glia-guided pyramidal neuron migration (GO:0140650), positive regulation of ruffle assembly (GO:1900029), neuron projection extension (GO:1990138), microtubule cytoskeleton organization (GO:0000226), neuron migration (GO:0001764), nervous system development (GO:0007399), cell differentiation (GO:0030154), obsolete establishment of chromosome localization (GO:0051303)

GO Molecular Function (5): microtubule binding (GO:0008017), identical protein binding (GO:0042802), alpha-tubulin binding (GO:0043014), beta-tubulin binding (GO:0048487), protein binding (GO:0005515)

GO Cellular Component (18): kinetochore (GO:0000776), centrosome (GO:0005813), spindle (GO:0005819), cytosol (GO:0005829), kinesin complex (GO:0005871), microtubule (GO:0005874), synaptic vesicle (GO:0008021), cell leading edge (GO:0031252), axon hillock (GO:0043203), neurofilament cytoskeleton (GO:0060053), axon cytoplasm (GO:1904115), chromosome, centromeric region (GO:0000775), chromosome (GO:0005694), cytoplasm (GO:0005737), microtubule organizing center (GO:0005815), cytoskeleton (GO:0005856), microtubule associated complex (GO:0005875), axon (GO:0030424)

Reactome top-level categories

Rollup of top-13 pathways:

Category	Pathways
Mitotic Prometaphase	2
M Phase	2
Cell Cycle	2
Amplification of signal from the kinetochores	1
Mitotic Anaphase	1
RHO GTPase Effectors	1
Mitotic Spindle Checkpoint	1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1
Signaling by Rho GTPases	1
Mitotic Metaphase and Anaphase	1
Cell Cycle, Mitotic	1
Cell Cycle Checkpoints	1
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
intracellular membraneless organelle	4
microtubule cytoskeleton	4
tubulin binding	3
axon	2
mitotic cell cycle	1
establishment of mitotic spindle localization	1
establishment of spindle orientation	1
blastocyst growth	1
cell population proliferation	1
microtubule cytoskeleton organization	1
microtubule polymerization	1
cell cycle process	1
centrosome separation	1
mitotic nuclear division	1
mitotic cell cycle process	1
axonal transport	1
axon cytoplasm	1
cell surface receptor protein tyrosine kinase signaling pathway	1
cellular response to insulin stimulus	1
neuron projection development	1
regulation of plasma membrane bounded cell projection organization	1
cell motility	1
cerebral cortex cell migration	1
axonogenesis	1
central nervous system neuron development	1
vacuolar localization	1
intracellular protein transport	1
regulation of intracellular transport	1
regulation of protein transport	1
GTPase activity	1
regulation of GTPase activity	1
positive regulation of hydrolase activity	1
organelle transport along microtubule	1
vesicle cytoskeletal trafficking	1
microtubule organizing center localization	1
intermediate filament cytoskeleton organization	1
neuron migration	1
ruffle assembly	1
positive regulation of plasma membrane bounded cell projection assembly	1

Protein interactions and networks

STRING

1604 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NDEL1	DISC1	Q9NRI5	998
NDEL1	PAFAH1B1	P43034	988
NDEL1	YWHAE	P29360	937
NDEL1	ARHGAP1	Q07960	859
NDEL1	NDE1	Q9NXR1	837
NDEL1	PDE4B	Q07343	801
NDEL1	PAFAH1B2	P68402	784
NDEL1	CDK5	Q00535	776
NDEL1	DCTN1	Q14203	749
NDEL1	KATNA1	O75449	740
NDEL1	PDE4A	P27815	715
NDEL1	NUDC	Q9Y266	714
NDEL1	AURKA	O14965	675
NDEL1	BICD2	Q8TD16	668
NDEL1	YWHAB	P31946	646

IntAct

384 interactions, top by confidence:

A	B	Type	Score
NDEL1	NDEL1	psi-mi:“MI:0915”(physical association)	0.890
NDEL1	NDEL1	psi-mi:“MI:0407”(direct interaction)	0.890
TRIM27	NDEL1	psi-mi:“MI:0915”(physical association)	0.840
PAFAH1B1	NDEL1	psi-mi:“MI:0915”(physical association)	0.790
NDEL1	PAFAH1B1	psi-mi:“MI:0915”(physical association)	0.790
Pafah1b1	NDEL1	psi-mi:“MI:0407”(direct interaction)	0.780
ZNF544	NDEL1	psi-mi:“MI:0915”(physical association)	0.740
NDEL1	ZNF544	psi-mi:“MI:0915”(physical association)	0.740
USP2	NDEL1	psi-mi:“MI:0915”(physical association)	0.720
XPA	NDEL1	psi-mi:“MI:0915”(physical association)	0.720
ZNF844	NDEL1	psi-mi:“MI:0915”(physical association)	0.720
ZNF599	NDEL1	psi-mi:“MI:0915”(physical association)	0.720
NDEL1	ZNF490	psi-mi:“MI:0915”(physical association)	0.720
TRAF3IP3	NDEL1	psi-mi:“MI:0915”(physical association)	0.720
NDEL1	USP2	psi-mi:“MI:0915”(physical association)	0.720
NDEL1	XPA	psi-mi:“MI:0915”(physical association)	0.720
NDEL1	ZNF844	psi-mi:“MI:0915”(physical association)	0.720
NDEL1	ZNF599	psi-mi:“MI:0915”(physical association)	0.720
ZNF490	NDEL1	psi-mi:“MI:0915”(physical association)	0.720
NDEL1	TRAF3IP3	psi-mi:“MI:0915”(physical association)	0.720

BioGRID (280): NDEL1 (Two-hybrid), NDEL1 (Two-hybrid), NDEL1 (Two-hybrid), NDEL1 (Two-hybrid), NDEL1 (Two-hybrid), NDEL1 (Two-hybrid), NDEL1 (Two-hybrid), NDEL1 (Two-hybrid), NDEL1 (Two-hybrid), NDEL1 (Two-hybrid), NDEL1 (Two-hybrid), NDEL1 (Two-hybrid), NDEL1 (Two-hybrid), NDEL1 (Two-hybrid), NDEL1 (Two-hybrid)

ESM2 similar proteins: A1YB07, A4IGC3, A5PJI6, A8NJZ7, B1PRL5, B8AE37, O08970, O35867, O46480, O94876, P57077, P58500, Q0P4J3, Q0V9C8, Q29EP6, Q2KI75, Q2KJD6, Q3E784, Q3SZV2, Q4R4S6, Q5BKX8, Q5ZMC9, Q66J96, Q66JL0, Q69ZZ6, Q6AYB8, Q6DBR9, Q6DDT0, Q6DFB7, Q6GNW0, Q6IP02, Q6K678, Q6P402, Q6SXP0, Q6TA25, Q78PB6, Q8BHS8, Q8CCX5, Q8N6V9, Q8R2X8

Diamond homologs: O13335, O46480, O74689, Q4I877, Q4R4S6, Q4X1V0, Q5R8T7, Q5ZKH4, Q78PB6, Q9ERR1, Q9GZM8, P0CP38, P0CP39, Q28CJ6, Q5ZMC9, Q66IZ7, Q66J96, Q66JL0, Q6C3S1, Q6DK98, Q6NRJ5, Q7SXI6, Q803Q2, Q9CZA6, Q9ES39, Q9NXR1, Q9VT70, Q4P0N6, O45717

SIGNOR signaling

16 interactions.

A	Effect	B	Mechanism
PPP4C	“down-regulates activity”	NDEL1	dephosphorylation
YWHAE	“up-regulates activity”	NDEL1	binding
DISC1	“up-regulates activity”	NDEL1	binding
CyclinD1/CDK6	“up-regulates activity”	NDEL1	phosphorylation
CDK5	“up-regulates activity”	NDEL1	phosphorylation
CDK5/CDK5R1	“up-regulates activity”	NDEL1	phosphorylation
PAFAH1B1	“up-regulates activity”	NDEL1	binding
NDEL1	“up-regulates activity”	DYNC1H1	binding
AURKA	“down-regulates quantity by destabilization”	NDEL1	phosphorylation
CDK1	“up-regulates activity”	NDEL1	phosphorylation
MAPK1	“up-regulates activity”	NDEL1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 107 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Loss of Nlp from mitotic centrosomes	6	12.5×	7e-04
Loss of proteins required for interphase microtubule organization from the centrosome	6	12.5×	7e-04
AURKA Activation by TPX2	6	12.0×	7e-04
Recruitment of mitotic centrosome proteins and complexes	6	10.7×	1e-03
Regulation of PLK1 Activity at G2/M Transition	6	10.0×	1e-03
Recruitment of NuMA to mitotic centrosomes	6	9.2×	2e-03
Anchoring of the basal body to the plasma membrane	6	8.9×	2e-03
Mitotic G2-G2/M phases	5	8.3×	8e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

40 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	30
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3525 predictions. Top by Δscore:

Variant	Effect	Δscore
17:8444255:CACA:C	acceptor_loss	1.0000
17:8444257:CAGG:C	acceptor_loss	1.0000
17:8444258:A:AG	acceptor_gain	1.0000
17:8444258:A:AT	acceptor_loss	1.0000
17:8444258:AG:A	acceptor_gain	1.0000
17:8444259:G:GC	acceptor_gain	1.0000
17:8444259:GG:G	acceptor_gain	1.0000
17:8444328:G:GT	donor_gain	1.0000
17:8444332:G:GT	donor_gain	1.0000
17:8444343:G:GT	donor_gain	1.0000
17:8444354:AAAG:A	donor_loss	1.0000
17:8444358:GTAAT:G	donor_loss	1.0000
17:8444359:T:G	donor_loss	1.0000
17:8445704:T:TA	acceptor_gain	1.0000
17:8445860:TAAAG:T	donor_loss	1.0000
17:8445861:AAAG:A	donor_loss	1.0000
17:8445862:AAG:A	donor_loss	1.0000
17:8445863:AGGTA:A	donor_loss	1.0000
17:8445864:GGTAA:G	donor_loss	1.0000
17:8445865:G:T	donor_loss	1.0000
17:8445866:T:G	donor_loss	1.0000
17:8446738:ATACT:A	acceptor_gain	1.0000
17:8446740:A:AG	acceptor_gain	1.0000
17:8446740:ACT:A	acceptor_gain	1.0000
17:8446741:C:G	acceptor_gain	1.0000
17:8446742:T:TA	acceptor_gain	1.0000
17:8446752:A:AG	acceptor_gain	1.0000
17:8446753:G:GC	acceptor_gain	1.0000
17:8446753:GGA:G	acceptor_gain	1.0000
17:8446900:AAGG:A	donor_loss	1.0000

AlphaMissense

2222 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:8445734:T:C	L37P	1.000
17:8445742:T:C	F40L	1.000
17:8445743:T:C	F40S	1.000
17:8445744:C:A	F40L	1.000
17:8445744:C:G	F40L	1.000
17:8445796:G:C	A58P	1.000
17:8446866:T:C	L118P	1.000
17:8446870:G:C	E119D	1.000
17:8446870:G:T	E119D	1.000
17:8446872:A:C	Q120P	1.000
17:8446874:G:C	A121P	1.000
17:8446880:G:C	D123H	1.000
17:8446881:A:C	D123A	1.000
17:8446881:A:T	D123V	1.000
17:8446887:T:C	L125P	1.000
17:8446893:G:C	R127P	1.000
17:8446895:G:C	A128P	1.000
17:8446902:G:C	R130T	1.000
17:8446902:G:T	R130M	1.000
17:8448550:G:C	R130S	1.000
17:8448550:G:T	R130S	1.000
17:8448563:T:C	S135P	1.000
17:8448567:T:C	L136P	1.000
17:8448588:T:C	L143P	1.000
17:8448596:G:C	A146P	1.000
17:8448604:A:C	E148D	1.000
17:8448604:A:T	E148D	1.000
17:8448606:G:C	R149P	1.000
17:8448611:G:C	A151P	1.000
17:8448618:T:C	L153S	1.000

dbSNP variants (sampled 300 via entrez): RS1000031279 (17:8446977 C>T), RS1000045214 (17:8438666 C>G,T), RS1000052084 (17:8456825 G>C,T), RS1000144947 (17:8439182 C>T), RS1000188409 (17:8415262 T>G), RS1000211748 (17:8452437 C>T), RS1000286180 (17:8446226 T>G), RS1000306078 (17:8415418 T>C,G), RS1000325772 (17:8466218 G>A), RS1000394339 (17:8417086 T>A), RS1000441722 (17:8453401 A>T), RS1000454531 (17:8435682 A>G), RS1000513528 (17:8432470 C>T), RS1000629947 (17:8458547 A>C,G), RS1000642194 (17:8451232 G>A)

Disease associations

OMIM: gene MIM:607538 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

34 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects cotreatment, decreases methylation, decreases expression	2
Acetaminophen	increases expression	2
Air Pollutants	affects expression, increases abundance, increases expression	2
Tobacco Smoke Pollution	increases expression	2
Cyclosporine	increases expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
GSK-J4	increases expression	1
triphenyl phosphate	affects expression	1
sodium arsenite	increases expression	1
cobaltous chloride	increases expression	1
coumarin	increases phosphorylation	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
CGP 52608	affects binding, increases reaction	1
erucylphospho-N,N,N-trimethylpropylammonium	increases expression	1
PCI 5002	affects cotreatment, increases expression	1
Decitabine	affects expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Arsenic	affects methylation	1
Cadmium	decreases expression, increases abundance	1
Caffeine	affects phosphorylation	1
Cisplatin	affects expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Dimethyl Sulfoxide	increases expression	1
Doxorubicin	decreases expression	1
Ozone	affects expression, increases abundance	1
Potassium Dichromate	increases expression	1
Thiram	increases expression	1
Urethane	increases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.