NDE1

Summary

NDE1 (nudE neurodevelopment protein 1, HGNC:17619) is a protein-coding gene on chromosome 16p13.11, encoding Nuclear distribution protein nudE homolog 1 (Q9NXR1). Required for centrosome duplication and formation and function of the mitotic spindle. It is a selective cancer dependency (DepMap: 43.0% of cell lines).

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.

Source: NCBI Gene 54820 — RefSeq curated summary.

At a glance

• Gene–disease (curated): microcephaly with lissencephaly and/or hydranencephaly (Definitive, ClinGen) — +4 more curated relationships
• GWAS associations: 5
• Clinical variants (ClinVar): 904 total — 17 pathogenic, 5 likely-pathogenic
• Phenotypes (HPO): 91
• Cancer dependency (DepMap): dependent in 43.0% of screened cell lines
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_017668

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17619
Approved symbol	NDE1
Name	nudE neurodevelopment protein 1
Location	16p13.11
Locus type	gene with protein product
Status	Approved
Aliases	nudE, FLJ20101, NDE
Ensembl gene	ENSG00000072864
Ensembl biotype	protein_coding
OMIM	609449
Entrez	54820

Gene structure

Transcript identifiers

Ensembl transcripts: 36 — 25 protein_coding, 9 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000396354, ENST00000396355, ENST00000570727, ENST00000572503, ENST00000572756, ENST00000572967, ENST00000573203, ENST00000573694, ENST00000574109, ENST00000574163, ENST00000576502, ENST00000577101, ENST00000674538, ENST00000674554, ENST00000674581, ENST00000674588, ENST00000674888, ENST00000674900, ENST00000674995, ENST00000675171, ENST00000675926, ENST00000675951, ENST00000911227, ENST00000911228, ENST00000911229, ENST00000911230, ENST00000911231, ENST00000911232, ENST00000911233, ENST00000911234, ENST00000934469, ENST00000963926, ENST00000963927, ENST00000963928, ENST00000963929, ENST00000963930

RefSeq mRNA: 2 — MANE Select: NM_017668 NM_001143979, NM_017668

CCDS: CCDS10564

Canonical transcript exons

ENST00000396354 — 9 exons

Exon	Start	End
ENSE00000671421	15667286	15667439
ENSE00001106621	15696709	15696860
ENSE00001106632	15691144	15691323
ENSE00001106634	15694165	15694256
ENSE00001524683	15650245	15650294
ENSE00001524685	15724191	15726353
ENSE00001602389	15664736	15664861
ENSE00003612555	15687375	15687511
ENSE00003899077	15677801	15677949

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 99.29.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 24.6915 / max 316.8505, expressed in 1805 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
152909	24.1808	1804
152907	0.2320	71
152906	0.2032	68
152908	0.0754	27

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
colonic epithelium	UBERON:0000397	99.29	gold quality
ventricular zone	UBERON:0003053	97.46	gold quality
corpus callosum	UBERON:0002336	95.70	gold quality
sural nerve	UBERON:0015488	95.10	gold quality
blood	UBERON:0000178	94.18	gold quality
monocyte	CL:0000576	92.95	gold quality
leukocyte	CL:0000738	92.85	gold quality
ganglionic eminence	UBERON:0004023	92.61	gold quality
bone marrow cell	CL:0002092	92.60	gold quality
tonsil	UBERON:0002372	92.45	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	92.02	gold quality
bone marrow	UBERON:0002371	91.86	gold quality
urinary bladder	UBERON:0001255	90.81	gold quality
lower esophagus	UBERON:0013473	90.79	gold quality
lower esophagus muscularis layer	UBERON:0035833	90.79	gold quality
lymph node	UBERON:0000029	90.19	gold quality
muscle layer of sigmoid colon	UBERON:0035805	90.00	gold quality
vermiform appendix	UBERON:0001154	89.72	gold quality
smooth muscle tissue	UBERON:0001135	89.54	gold quality
skin of leg	UBERON:0001511	89.19	gold quality
zone of skin	UBERON:0000014	89.09	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	89.01	gold quality
stromal cell of endometrium	CL:0002255	88.85	gold quality
skin of abdomen	UBERON:0001416	88.71	gold quality
granulocyte	CL:0000094	88.18	gold quality
esophagus	UBERON:0001043	88.15	gold quality
vagina	UBERON:0000996	87.18	gold quality
placenta	UBERON:0001987	86.91	gold quality
myometrium	UBERON:0001296	86.86	gold quality
uterine cervix	UBERON:0000002	86.80	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-7381	yes	365.57
E-ANND-3	yes	3.01

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

75 targeting NDE1, 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-6867-5P	100.00	82.21	3464
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-3185	99.99	68.12	1959
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-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-3663-3P	99.84	70.39	798
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-6794-5P	99.76	66.38	1048
HSA-MIR-2681-5P	99.75	67.64	1655
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-1200	99.71	70.42	1838
HSA-MIR-4716-3P	99.69	66.73	1022
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-6751-5P	99.56	64.99	1145
HSA-MIR-3153	99.55	67.59	2337
HSA-MIR-766-3P	99.47	65.24	1811

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map DepMap (CRISPR cell-line fitness): dependent in 43.0% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 35)

• LIS1 deficiency adversely affects the migration and differentiation of DCX- and Reelin-positive neurons. (PMID:12427674)
• study of the properties of NudE in mitosis; comparative studies suggest that NudE is functionally related to its paralog, Nudel (PMID:12556484)
• Nudel is seen to differentially associate with mitochondrial markers in comparison to DISC1. Disruption of the cytoskeleton results in colocalization of Nudel and mitochondrial markers–the first observation of such a direct relationship. (PMID:15797709)
• findings indicate that Nde1 can form a protein complex with Su48 in the centrosome and plays an important role for successful mitosis (PMID:16682949)
• Two additional loci displayed an evidence of linkage (LOD > 3) and included a locus on 16p13, proximal to the gene encoding NDE1, which has been shown to biologically interact with DISC1. (PMID:17185386)
• required for kinetochore localization of dynein; suppression of Nde1 inhibits metaphase chromosome alignment and activates the spindle checkpoint (PMID:17600710)
• We failed to find the association between the NDE1 gene and schizophrenia in the Japanese population. (PMID:18178387)
• These findings reveal a novel regulatory mechanism of vimentin transport during neurite extension that may have implications in diseases featuring transport/trafficking defects and impaired regeneration. (PMID:18303022)
• NO direct relationship between NDE1 genotype and schizophrenia. (PMID:18469341)
• NDE1, NDEL1 and LIS1, together with their binding partner dynein, associate with DISC1, PDE4B and PDE4D within the cell, and provide evidence that this complex is present at the centrosome. (PMID:18983980)
• NDE1 and NDEL1 act upstream of LIS1 in dynein recruitment, and/or activation, on the membrane. (PMID:20048338)
• The NDE1 gene is disrupted by the inv(16) in 90% of cases with CBFB-MYH11-positive acute myeloid leukemia. (PMID:20072148)
• NDE1 mutations cause a severe microlissencephaly syndrome. Patient’s NDE1 proteins are unstable, cannot bind cytoplasmic dynein, and do not localize properly to the centrosome. (PMID:21529751)
• NDE1 deficiency causes both a severe failure of neurogenesis and a deficiency in cortical lamination (PMID:21529752)
• Mutually exclusive cytoplasmic dynein regulation by NudE-Lis1 and dynactin. (PMID:21911489)
• In three related patients with microhydranencephaly, a homozygous deletion that encompasses NDE1 exon 2 containing the initiation codon was identified. (PMID:22526350)
• analysis of mixed NDE1-NDEL1 complexes demonstrates that NDE1 and NDEL1 can interact directly. (PMID:22843697)
• Description of a severe microcephaly syndrome where an autosomal recessive condition combines an inherited segmental duplication mediated deletion with a mutation in the NDE1 gene within the non-deleted homolog. (PMID:23704059)
• 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)
• study strengthens the evidence for association between rare variants within NDE1 and schizophrenia, and may shed light into the molecular mechanisms underlying this severe psychiatric disorder. (PMID:25332407)
• These data show that cell cycle-dependent mechanisms can control ciliary length through a CDK5-FBW7-NDE1 pathway. (PMID:26206584)
• Interaction between NDE1 and high birth weight was associated with increased susceptibility to schizophrenia. (PMID:26350705)
• Promoter system of NDE1, which produces three distinct transcripts, each encoding for the same full-length NDE1 protein (also known as NudE), was cloned and tested in human cell lines; results highlight and clone the promoter elements required to generate systems in which the NDE1 protein is exogenously expressed under its native promoter, providing a biologically relevant model of 16p13.11 duplication in mental illness (PMID:26975893)
• NDE1/Lissencephaly 1 and dynactin complexes separately mediate two key components of T cell-focused secretion, namely translocation of the MTOC and lytic granules to the IS, respectively. (PMID:27534551)
• the severity of NDE1-associated microcephaly results not from defects in mitosis, but rather the inability of neural progenitors to ever reach this stage (PMID:27553190)
• Results indicate that the NAGK-dynein interaction with the involvements of Lis1 and NudE1 plays an important role in prophase nuclear envelope breakdown (NEB) and metaphase MT-KT attachment during eukaryotic cell division. (PMID:27646688)
• Our results show how evolutionary changes in cis as well as trans acting signals have played a fundamental role in determining NDE1 species specific splicing isoforms supporting the notion that alternative splicing plays a central role in human genome evolution, and possibly human cognitive predominance. (PMID:28266585)
• Variation at the NDE1 locus may alter risk of mental illness, in part through modification of miR-484. NDE1 SNP rs2242549 associates with significant changes in gene expression of DISC1 network. (PMID:29142105)
• These studies identify the LIS1/NDE1 complex as an important FGF signaling regulator and provide insights into the bidirectional regulation of cell signaling and transport machinery for endocytosis. (PMID:29562183)
• Nde1 makes unique contributions to human neurodevelopment through its regulation of both dynein and proteasome function. (PMID:30024347)
• 16p13.11 microduplication in 45 new patients: refined clinical significance and genotype-phenotype correlations. (PMID:30287593)
• CENP-F stabilizes kinetochore-microtubule attachments and limits dynein stripping of corona cargoes. (PMID:32207772)
• [Microlissencephaly due to pathogenic variants of NDE1: from pathology to normal brain development].", trans “Variations pathogenes de NDE1 et microlissencephalie - De la pathologie au developpement cerebral normal. (PMID:33026328)
• Novel lissencephaly-associated NDEL1 variant reveals distinct roles of NDE1 and NDEL1 in nucleokinesis and human cortical malformations. (PMID:38194050)
• Comprehensive analysis indicated that NDE1 is a potential biomarker for pan-cancer and promotes bladder cancer progression. (PMID:38466053)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	nde1	ENSDARG00000103902
mus_musculus	Nde1	ENSMUSG00000022678
rattus_norvegicus	Nde1	ENSRNOG00000058007
drosophila_melanogaster	nudE	FBGN0036059
caenorhabditis_elegans	nud-2	WBGENE00011230

Paralogs (1): NDEL1 (ENSG00000166579)

Protein

Protein identifiers

Nuclear distribution protein nudE homolog 1 — Q9NXR1 (reviewed: Q9NXR1)

All UniProt accessions (14): Q9NXR1, A0A6Q8PEY3, A0A6Q8PG46, A0A6Q8PGV6, A0A6Q8PHH1, I3L2R3, I3L2R9, I3L2S8, I3L2T8, I3L3G9, I3L464, I3L522, I3L533, X5DR54

UniProt curated annotations — full annotation on UniProt →

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 postmitotic 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. Acts 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. Homodimer. Interacts with CNTRL, LIS1, dynein, SLMAP and TCP1. Interacts with CENPF, dynactin, tubulin gamma, PAFAH1B1, PCM1 and PCNT. Interacts with ZNF365. Interacts with GTP-bound RAB9A and RAB9B; the interaction leads to RAB9-dynein motor tethering. Interacts (via C-terminus) with MCRS1 (via C-terminus); phosphorylation of NDE1 inhibits the interaction.

Subcellular location. Cytoplasm. Cytoskeleton. Microtubule organizing center. Centrosome. Chromosome. Centromere. Kinetochore. Spindle. Cleavage furrow. Cytoplasmic vesicle membrane.

Tissue specificity. Expressed in the neuroepithelium throughout the developing brain, including the cerebral cortex and cerebellum.

Post-translational modifications. Phosphorylated in mitosis. Phosphorylated in vitro by CDC2. Phosphorylation at Thr-246 is essential for the G2/M transition.

Disease relevance. Lissencephaly 4 with microcephaly (LIS4) [MIM:614019] A neurodevelopmental disorder characterized by lissencephaly, severe brain atrophy, extreme microcephaly, and profound intellectual disability. The disease is caused by variants affecting the gene represented in this entry. Microhydranencephaly (MHAC) [MIM:605013] A severe neurodevelopmental disorder characterized by microcephaly, severe motor and intellectual disability, spasticity, and brain malformations that include gross dilation of the ventricles with complete absence of the cerebral hemispheres or severe delay in their development. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the nudE family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9NXR1-2	1	yes
Q9NXR1-1	2

RefSeq proteins (2): NP_001137451, NP_060138* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006964	NUDE_dom	Domain
IPR033494	NUDE	Family

Pfam: PF04880

UniProt features (39 total): mutagenesis site 16, modified residue 9, region of interest 5, compositionally biased region 3, chain 1, lipid moiety-binding region 1, splice variant 1, sequence conflict 1, helix 1, coiled-coil region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
7E1T	X-RAY DIFFRACTION	2.45

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NXR1-F1	78.40	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 (10): 211, 215, 228, 231, 239, 243, 246, 282, 309, 274

Mutagenesis-validated functional residues (16):

Position	Phenotype
106	loss of interaction with rab9a. decreased enrichment to rab9a-associated intracellular vesicles.
107	decreased interaction with rab9a.
113	loss of interaction with rab9a.
114	loss of interaction with rab9a. decreased enrichment to rab9a-associated intracellular vesicles.
191	loss of centrosomal localization, reduced znf365-binding and loss of interaction with mcrs1; when associated with e-215;
191	retained on spindle poles during mitosis, no loss of phosphorylation in vivo and increased znf365-binding; when associat
215	loss of centrosomal localization, reduced znf365-binding and loss of interaction with mcrs1; when associated with e-191;
215	retained on spindle poles during mitosis, no loss of phosphorylation in vivo and increased znf365-binding; when associat
228	loss of centrosomal localization, reduced znf365-binding and loss of interaction with mcrs1; when associated with e-191;
228	retained on spindle poles during mitosis, no loss of phosphorylation in vivo and increased znf365-binding; when associat
243	loss of centrosomal localization, reduced znf365-binding and loss of interaction with mcrs1; when associated with e-191;
243	retained on spindle poles during mitosis, no loss of phosphorylation in vivo and increased znf365-binding; when associat
246	loss of centrosomal localization, reduced znf365-binding and loss of interaction with mcrs1; when associated with e-191;
246	retained on spindle poles during mitosis, no loss of phosphorylation in vivo and increased znf365-binding; when associat
282	retained on spindle poles during mitosis, no loss of phosphorylation in vivo and increased znf365-binding; when associat
282	loss of centrosomal localization, reduced znf365-binding and loss of interaction with mcrs1; when associated with e-191;

Function

Pathways and Gene Ontology

Reactome pathways

30 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-2565942	Regulation of PLK1 Activity at G2/M Transition
R-HSA-380259	Loss of Nlp from mitotic centrosomes
R-HSA-380270	Recruitment of mitotic centrosome proteins and complexes
R-HSA-380284	Loss of proteins required for interphase microtubule organization from the centrosome
R-HSA-380320	Recruitment of NuMA to mitotic centrosomes
R-HSA-5620912	Anchoring of the basal body to the plasma membrane
R-HSA-5663220	RHO GTPases Activate Formins
R-HSA-68877	Mitotic Prometaphase
R-HSA-8854518	AURKA Activation by TPX2
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-1852241	Organelle biogenesis and maintenance
R-HSA-194315	Signaling by Rho GTPases
R-HSA-195258	RHO GTPase Effectors
R-HSA-2555396	Mitotic Metaphase and Anaphase
R-HSA-380287	Centrosome maturation
R-HSA-453274	Mitotic G2-G2/M phases
R-HSA-5617833	Cilium Assembly
R-HSA-68882	Mitotic Anaphase
R-HSA-68886	M Phase
R-HSA-69275	G2/M Transition
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: 475 (showing top): GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_UP, GOBP_ESTABLISHMENT_OF_SPINDLE_ORIENTATION, TSENG_IRS1_TARGETS_UP, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_CELL_POLARITY, GOBP_VESICLE_LOCALIZATION, PAL_PRMT5_TARGETS_UP, GOBP_SPINDLE_LOCALIZATION, GOBP_CHROMOSOME_LOCALIZATION, GOCC_KINESIN_COMPLEX, MODULE_493, GOBP_NEUROGENESIS, SCIBETTA_KDM5B_TARGETS_UP, GOBP_ORGANELLE_TRANSPORT_ALONG_MICROTUBULE, GOBP_MICROTUBULE_NUCLEATION, GOCC_MICROTUBULE_ORGANIZING_CENTER

GO Biological Process (18): establishment of mitotic spindle orientation (GO:0000132), neuron migration (GO:0001764), microtubule nucleation (GO:0007020), chromosome segregation (GO:0007059), mitotic centrosome separation (GO:0007100), neuroblast proliferation (GO:0007405), cell migration (GO:0016477), cerebral cortex development (GO:0021987), vesicle transport along microtubule (GO:0047496), chromosome localization (GO:0050000), centrosome duplication (GO:0051298), cell division (GO:0051301), centrosome localization (GO:0051642), nervous system development (GO:0007399), cell differentiation (GO:0030154), forebrain development (GO:0030900), microtubule organizing center organization (GO:0031023), obsolete establishment of chromosome localization (GO:0051303)

GO Molecular Function (4): microtubule binding (GO:0008017), protein domain specific binding (GO:0019904), identical protein binding (GO:0042802), protein binding (GO:0005515)

GO Cellular Component (17): kinetochore (GO:0000776), centrosome (GO:0005813), cytosol (GO:0005829), kinesin complex (GO:0005871), microtubule (GO:0005874), membrane (GO:0016020), cytoplasmic vesicle membrane (GO:0030659), spindle pole centrosome (GO:0031616), cleavage furrow (GO:0032154), synapse (GO:0045202), chromosome, centromeric region (GO:0000775), chromosome (GO:0005694), cytoplasm (GO:0005737), microtubule organizing center (GO:0005815), spindle (GO:0005819), cytoskeleton (GO:0005856), cytoplasmic vesicle (GO:0031410)

Reactome top-level categories

Rollup of top-12 pathways:

Category	Pathways
Mitotic Prometaphase	3
G2/M Transition	2
Centrosome maturation	2
M Phase	2
Amplification of signal from the kinetochores	1
Mitotic Anaphase	1
Loss of proteins required for interphase microtubule organization from the centrosome	1
Assembly of the 9+0 primary cilium	1
RHO GTPase Effectors	1
Mitotic Spindle Checkpoint	1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1
Signaling by Rho GTPases	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular membraneless organelle	4
cellular anatomical structure	4
microtubule cytoskeleton	3
generation of neurons	2
microtubule cytoskeleton organization	2
cell cycle process	2
anatomical structure development	2
protein binding	2
cytoplasm	2
mitotic cell cycle	1
establishment of mitotic spindle localization	1
establishment of spindle orientation	1
cell migration	1
microtubule polymerization	1
centrosome separation	1
mitotic nuclear division	1
mitotic cell cycle process	1
neural precursor cell proliferation	1
cell motility	1
pallium development	1
organelle transport along microtubule	1
vesicle cytoskeletal trafficking	1
organelle localization	1
centrosome cycle	1
cellular process	1
microtubule organizing center localization	1
system development	1
cellular developmental process	1
brain development	1
microtubule-based process	1
cellular component organization	1
tubulin binding	1
binding	1
condensed chromosome, centromeric region	1
supramolecular complex	1
centriole	1
microtubule organizing center	1
microtubule associated complex	1
polymeric cytoskeletal fiber	1
vesicle membrane	1

Protein interactions and networks

STRING

1470 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NDE1	DISC1	Q9NRI5	997
NDE1	OFD1	O75665	976
NDE1	PAFAH1B1	P43034	957
NDE1	DYNLL1	P63167	931
NDE1	TRAK1	Q9UPV9	922
NDE1	NDEL1	Q9GZM8	837
NDE1	PDE4B	Q07343	802
NDE1	CENPF	P49454	802
NDE1	YWHAE	P29360	795
NDE1	NUP133	Q8WUM0	785
NDE1	PAFAH1B2	P68402	773
NDE1	CPAP	Q9HC77	769
NDE1	HDAC6	Q9UBN7	749
NDE1	DCTN1	Q14203	727
NDE1	ZNF365	Q70YC5	723

IntAct

122 interactions, top by confidence:

A	B	Type	Score
NUP54	NUP58	psi-mi:“MI:0914”(association)	0.950
CCDC22	VPS26C	psi-mi:“MI:0914”(association)	0.790
DISC1	NDE1	psi-mi:“MI:0915”(physical association)	0.780
PRPF19	PLRG1	psi-mi:“MI:0914”(association)	0.770
BRK1	HSBP1	psi-mi:“MI:0914”(association)	0.740
DYNLL1	BLTP3B	psi-mi:“MI:0914”(association)	0.730
NDE1	NDEL1	psi-mi:“MI:0915”(physical association)	0.670
NDE1	NDE1	psi-mi:“MI:0407”(direct interaction)	0.650
NDE1	NDE1	psi-mi:“MI:0915”(physical association)	0.650
DYNLL2	BLTP3B	psi-mi:“MI:0914”(association)	0.640
TRIM27	KPNA1	psi-mi:“MI:0914”(association)	0.640
NAP1L5	IQGAP1	psi-mi:“MI:0914”(association)	0.640
NDE1	YWHAE	psi-mi:“MI:0915”(physical association)	0.560
ZNF365	NDE1	psi-mi:“MI:0915”(physical association)	0.540
ZNF365	NDE1	psi-mi:“MI:0403”(colocalization)	0.540
NDE1	ZNF365	psi-mi:“MI:0915”(physical association)	0.540
YWHAZ	BLTP3B	psi-mi:“MI:0914”(association)	0.530
PICK1	ILVBL	psi-mi:“MI:0914”(association)	0.530
AP4E1	AP4M1	psi-mi:“MI:0914”(association)	0.530
DISC1	AP4M1	psi-mi:“MI:0914”(association)	0.530

BioGRID (169): NDE1 (Affinity Capture-RNA), NDE1 (Affinity Capture-RNA), NDE1 (Affinity Capture-MS), NDE1 (Affinity Capture-MS), NDE1 (Affinity Capture-MS), NDE1 (Affinity Capture-MS), NDE1 (Affinity Capture-MS), NDE1 (Affinity Capture-MS), NDE1 (Affinity Capture-MS), NDE1 (Affinity Capture-MS), NDE1 (Affinity Capture-MS), NDE1 (Affinity Capture-MS), NDE1 (Proximity Label-MS), NDE1 (Proximity Label-MS), NDE1 (Affinity Capture-MS)

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

SIGNOR signaling

12 interactions.

A	Effect	B	Mechanism
CDK1	up-regulates	NDE1	phosphorylation
PRKACA	up-regulates	NDE1	phosphorylation
MAPK1	“up-regulates activity”	NDE1	phosphorylation
CyclinB/CDK1	“up-regulates quantity by stabilization”	NDE1	phosphorylation
CDK1	“up-regulates activity”	NDE1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 128 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
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	6	47.4×	2e-07
Activation of BAD and translocation to mitochondria	5	44.8×	2e-06
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	5	39.5×	4e-06
Activation of BH3-only proteins	5	29.2×	2e-05
RHO GTPases activate PKNs	6	22.4×	7e-06
AURKA Activation by TPX2	10	17.9×	7e-08
Intrinsic Pathway for Apoptosis	5	17.2×	2e-04
Loss of Nlp from mitotic centrosomes	9	16.8×	2e-07

GO biological processes:

GO term	Partners	Fold	FDR
protein targeting	7	22.7×	9e-06
intracellular protein localization	11	10.2×	9e-06
microtubule cytoskeleton organization	7	7.5×	5e-03
cilium assembly	9	5.9×	5e-03
intracellular protein transport	9	5.2×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	17
Likely pathogenic	5
Uncertain significance	489
Likely benign	260
Benign	38

Top pathogenic / likely-pathogenic (22)

Variant ID	HGVS	Classification
1384395	NM_002474.3(MYH11):c.4116+1del	Pathogenic
1457720	NC_000016.9:g.(?15802668)(15932109_?)del	Pathogenic
1696425	NM_017668.3(NDE1):c.54G>A (p.Trp18Ter)	Pathogenic
201075	NM_002474.3(MYH11):c.4401C>G (p.Tyr1467Ter)	Pathogenic
224608	NM_017668.3(NDE1):c.-43-3548_83+622del	Pathogenic
2777758	NM_002474.3(MYH11):c.5101_5102del (p.Arg1701fs)	Pathogenic
2809896	NM_002474.3(MYH11):c.4315C>T (p.Gln1439Ter)	Pathogenic
30787	NM_017668.3(NDE1):c.684_685del (p.Pro229fs)	Pathogenic
30789	NM_017668.3(NDE1):c.733dup (p.Leu245fs)	Pathogenic
3663702	NM_002474.3(MYH11):c.4245T>G (p.Tyr1415Ter)	Pathogenic
3724404	NM_002474.3(MYH11):c.4810del (p.Glu1604fs)	Pathogenic
435939	NM_017668.3(NDE1):c.83+1G>T	Pathogenic
574433	NM_002474.3(MYH11):c.5027_5028del (p.Lys1676fs)	Pathogenic
620567	NM_017668.3(NDE1):c.109C>T (p.Arg37Ter)	Pathogenic
625823	GRCh37/hg19 16p13.11(chr16:15758011-15761384)	Pathogenic
832327	NC_000016.10:g.(?15395898)(15884205_?)del	Pathogenic
93623	NM_017668.3(NDE1):c.704-1G>A	Pathogenic
1804129	NM_002474.3(MYH11):c.4578+1del	Likely pathogenic
2858526	NM_002474.3(MYH11):c.3963+1G>T	Likely pathogenic
3764542	NM_017668.3(NDE1):c.734del (p.Leu245fs)	Likely pathogenic
4706769	NM_002474.3(MYH11):c.3963+1G>A	Likely pathogenic
4712052	NM_002474.3(MYH11):c.5613+1G>A	Likely pathogenic

SpliceAI

3800 predictions. Top by Δscore:

Variant	Effect	Δscore
16:15664733:TAGA:T	acceptor_loss	1.0000
16:15664734:A:AG	acceptor_gain	1.0000
16:15664734:AGA:A	acceptor_loss	1.0000
16:15664735:G:GT	acceptor_gain	1.0000
16:15664735:GAC:G	acceptor_gain	1.0000
16:15664735:GACA:G	acceptor_gain	1.0000
16:15664735:GACAC:G	acceptor_gain	1.0000
16:15664778:A:AG	acceptor_gain	1.0000
16:15664778:AAT:A	acceptor_gain	1.0000
16:15664859:GAG:G	donor_gain	1.0000
16:15664860:AGGT:A	donor_loss	1.0000
16:15664862:GTCA:G	donor_loss	1.0000
16:15664863:T:A	donor_loss	1.0000
16:15667281:T:A	acceptor_gain	1.0000
16:15667282:GTA:G	acceptor_loss	1.0000
16:15667284:A:AG	acceptor_gain	1.0000
16:15667284:AG:A	acceptor_gain	1.0000
16:15667285:G:GG	acceptor_gain	1.0000
16:15667285:GG:G	acceptor_gain	1.0000
16:15667285:GGGCA:G	acceptor_gain	1.0000
16:15667436:CAAG:C	donor_loss	1.0000
16:15667438:AGGTG:A	donor_loss	1.0000
16:15667439:GGTG:G	donor_loss	1.0000
16:15667440:G:GC	donor_loss	1.0000
16:15667441:T:G	donor_loss	1.0000
16:15677796:TTCA:T	acceptor_loss	1.0000
16:15677798:CA:C	acceptor_loss	1.0000
16:15677799:A:AG	acceptor_gain	1.0000
16:15677799:A:AT	acceptor_loss	1.0000
16:15677800:G:GT	acceptor_gain	1.0000

AlphaMissense

2182 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:15667309:T:C	L36P	1.000
16:15667363:T:C	L54P	1.000
16:15677913:T:C	L117P	1.000
16:15677934:T:C	L124P	1.000
16:15687421:G:C	A145P	1.000
16:15687443:T:C	L152P	1.000
16:15687455:T:C	L156P	1.000
16:15687494:T:C	L169P	1.000
16:15687505:G:C	A173P	1.000
16:15667317:T:C	F39L	0.999
16:15667318:T:C	F39S	0.999
16:15667319:C:A	F39L	0.999
16:15667319:C:G	F39L	0.999
16:15667344:G:C	A48P	0.999
16:15667393:T:C	L64P	0.999
16:15677862:T:C	L100P	0.999
16:15677917:G:C	E118D	0.999
16:15677917:G:T	E118D	0.999
16:15677919:A:C	Q119P	0.999
16:15677921:G:C	A120P	0.999
16:15677927:G:C	D122H	0.999
16:15677928:A:C	D122A	0.999
16:15677928:A:T	D122V	0.999
16:15677929:C:A	D122E	0.999
16:15677929:C:G	D122E	0.999
16:15677942:G:C	A127P	0.999
16:15677948:C:A	R129S	0.999
16:15677949:G:C	R129P	0.999
16:15687376:G:C	A130P	0.999
16:15687388:T:C	S134P	0.999

dbSNP variants (sampled 300 via entrez): RS1000069000 (16:15661003 G>A), RS1000073725 (16:15713851 T>A), RS1000076353 (16:15680230 C>G,T), RS1000082124 (16:15654992 A>G), RS1000107708 (16:15705572 G>A), RS1000115324 (16:15646079 T>C), RS1000117567 (16:15674362 G>A), RS1000129877 (16:15722775 C>T), RS1000164156 (16:15717858 G>A,T), RS1000167083 (16:15651733 C>G), RS1000201685 (16:15651497 A>G), RS1000224556 (16:15697172 A>G), RS1000237717 (16:15691399 G>A), RS1000272976 (16:15676018 A>T), RS1000359842 (16:15718184 C>T)

Disease associations

OMIM: gene MIM:609449 | disease phenotypes: MIM:132900, MIM:607086, MIM:619351, MIM:619350, MIM:605013, MIM:614019, MIM:194200

GenCC curated gene-disease

Disease	Classification	Inheritance
lissencephaly 4	Definitive	Autosomal recessive
microcephaly with lissencephaly and/or hydranencephaly	Strong	Autosomal recessive
NDE1-related microhydranencephaly	Supportive	Autosomal recessive
microlissencephaly	Supportive	Autosomal recessive
hydranencephaly	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
microcephaly with lissencephaly and/or hydranencephaly	Definitive	AR

Mondo (12): aortic aneurysm, familial thoracic 4 (MONDO:0007568), familial thoracic aortic aneurysm and aortic dissection (MONDO:0019625), megacystis-microcolon-intestinal hypoperistalsis syndrome 2 (MONDO:0025708), visceral myopathy 2 (MONDO:0859157), NDE1-related microhydranencephaly (MONDO:0011504), lissencephaly 4 (MONDO:0013527), intellectual disability (MONDO:0001071), connective tissue disorder (MONDO:0003900), Wolff-Parkinson-White syndrome (MONDO:0008685), microlissencephaly (MONDO:0015204), hydranencephaly (MONDO:0016344), microcephaly with lissencephaly and/or hydranencephaly (MONDO:0700116)

Orphanet (5): Familial thoracic aortic aneurysm and aortic dissection (Orphanet:91387), NDE1-related microhydranencephaly (Orphanet:443162), Microlissencephaly (Orphanet:1083), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658), NON RARE IN EUROPE: Wolff-Parkinson-White syndrome (Orphanet:907)

HPO phenotypes

91 total (30 of 91 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000252	Microcephaly
HP:0000268	Dolichocephaly
HP:0000269	Prominent occiput
HP:0000308	Microretrognathia
HP:0000316	Hypertelorism
HP:0000340	Sloping forehead
HP:0000341	Narrow forehead
HP:0000350	Small forehead
HP:0000369	Low-set ears
HP:0000400	Macrotia
HP:0000426	Prominent nasal bridge
HP:0000431	Wide nasal bridge
HP:0000445	Wide nose
HP:0000479	Abnormal retinal morphology
HP:0000520	Proptosis
HP:0000533	Chorioretinal atrophy
HP:0000601	Hypotelorism
HP:0000609	Optic nerve hypoplasia
HP:0000618	Blindness
HP:0000742	Self-mutilation
HP:0000817	Reduced eye contact
HP:0001181	Adducted thumb
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001254	Lethargy
HP:0001263	Global developmental delay
HP:0001264	Spastic diplegia
HP:0001272	Cerebellar atrophy
HP:0001274	Agenesis of corpus callosum

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST003783_12	Multiple system atrophy (pathologically confirmed)	2.000000e-06
GCST004751_23	Serum uric acid levels in response to allopurinol in gout	5.000000e-06
GCST008595_203	Cognitive ability, years of educational attainment or schizophrenia (pleiotropy)	4.000000e-08
GCST010146_45	Serum immune biomarker levels	1.000000e-08
GCST90002395_188	Mean platelet volume	2.000000e-09

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004761	uric acid measurement
EFO:0004337	intelligence
EFO:0004784	self reported educational attainment
EFO:0004869	YKL40 measurement
EFO:0004872	inflammatory biomarker measurement

MeSH disease descriptors (6)

Descriptor	Name	Tree numbers
D003240	Connective Tissue Diseases	C17.300
D006832	Hydranencephaly	C10.500.450; C16.131.666.450
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D014927	Wolff-Parkinson-White Syndrome	C14.280.067.780.977; C14.280.123.750.977; C16.131.240.400.980
C537784	Aortic aneurysm, familial thoracic 4 (supp.)
C537555	Microhydranencephaly (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, increases expression	4
Aflatoxin B1	increases expression, affects expression, decreases methylation	3
Resveratrol	increases expression, affects cotreatment	2
Cadmium	decreases expression, increases abundance	2
Valproic Acid	decreases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
Cadmium Chloride	decreases expression, increases abundance	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	increases abundance, affects cotreatment, increases expression	1
mono-(2-ethylhexyl)phthalate	increases abundance, increases methylation	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
butyraldehyde	decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
aflatoxin B2	increases methylation	1
methacrylaldehyde	affects cotreatment, increases expression, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
4-phenylbutyric acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	decreases expression, affects cotreatment	1
jinfukang	affects cotreatment, increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Sunitinib	decreases expression	1
Zoledronic Acid	increases expression	1
Acetaminophen	increases expression	1
Acrolein	affects cotreatment, increases expression, increases abundance	1
Air Pollutants	affects cotreatment, increases abundance, increases expression	1
Caffeine	increases phosphorylation	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT01042158	PHASE4	COMPLETED	A Clinical Trial of Ambrisentan and Tadalafil in Pulmonary Arterial Hypertension Associated With Systemic Sclerosis
NCT03688191	PHASE4	UNKNOWN	Study of Sirolimus in CTD-TP in China
NCT04169100	PHASE4	UNKNOWN	Novel Form of Acquired Long QT Syndrome
NCT04197050	PHASE4	UNKNOWN	Effect of Sacubitril/Valsartan on Reduced Right Ventricular Ejection Fraction in Patients With CTD
NCT04928586	PHASE4	UNKNOWN	Immunosuppressant Combined With Pirfenidone in CTD-ILD
NCT05440240	PHASE4	RECRUITING	Percutaneous Needle Fasciotomy +/- Corticosteroid Injection for Dupuytren’s Contracture
NCT05505409	PHASE4	UNKNOWN	Efficacy and Safety of Pirfenidone in CTD-ILD
NCT06499233	PHASE4	RECRUITING	Efficacy and Safety of Prophylactic Treatment for Pneumocystis Jirovecii Pneumonia in Patients With Autoimmune Inflammatory Rheumatic Disease
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT00864201	PHASE3	UNKNOWN	A Study to Evaluate the Use of Bosentan in Patients With Exercise Induced Pulmonary Arterial Hypertension Associated With Connective Tissue Disease
NCT01196091	PHASE3	COMPLETED	A Study of LY2127399 in Participants With Systemic Lupus Erythematosus
NCT01205438	PHASE3	COMPLETED	A Study of LY2127399 in Participants With Systemic Lupus Erythematosus
NCT01488708	PHASE3	TERMINATED	On Open-Label Study in Participants With Systemic Lupus Erythematosus
NCT03626688	PHASE3	COMPLETED	A Study Evaluating the Efficacy and Safety of Ralinepag to Improve Treatment Outcomes in PAH Patients
NCT03683186	PHASE3	ENROLLING_BY_INVITATION	A Study Evaluating the Long-Term Efficacy and Safety of Ralinepag in Subjects With PAH Via an Open-Label Extension
NCT04084678	PHASE3	TERMINATED	A Study of Ralinepag to Evaluate Effects on Exercise Capacity by CPET in Subjects With WHO Group 1 PH
NCT06716606	PHASE3	RECRUITING	A Study to Investigate the Long-term Safety and Efficacy of Belimumab in Adults With Interstitial Lung Disease (ILD) Associated With Systemic Sclerosis (SSc) and Other Connective Tissue Diseases (CTD) (BLISSconneCTD-OLE)
NCT06917690	PHASE3	RECRUITING	A Study to Learn About the Safety and Efficacy of the Drug Oleogel-S10 in Japanese Patients With Epidermolysis Bullosa
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT00004357	PHASE2	COMPLETED	Absorption of Corticosteroids in Children With Juvenile Dermatomyositis
NCT00005675	PHASE2	COMPLETED	Oral Type I Collagen for Relieving Scleroderma
NCT01808196	PHASE2	COMPLETED	Testing Effectiveness of Losartan in Patients With EoE With or Without a CTD
NCT02682511	PHASE2	ACTIVE_NOT_RECRUITING	Oral Ifetroban to Treat Diffuse Cutaneous Systemic Sclerosis (SSc) or SSc-associated Pulmonary Arterial Hypertension
NCT04993885	PHASE2	RECRUITING	Avatrombopag in the Treatment of Adult Immune Thrombocytopenia With Autoantibodies
NCT05516758	PHASE2	TERMINATED	A Study of Peresolimab (LY3462817) in Participants With Moderately-to-Severely Active Rheumatoid Arthritis
NCT05998759	PHASE2	RECRUITING	Telitacicept for the Treatment of Connective Tissue Disease-associated Thrombocytopenia
NCT06104228	PHASE2	RECRUITING	129 Xenon MRI as a Biomarker for Diagnosis and Response to Therapy in Pulmonary Arterial Hypertension (PAH)
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT01093911	PHASE1	COMPLETED	Safety Study of CDP7657 in Healthy Volunteers and Patients With Systemic Lupus Erythematosus (SLE)