NIPBL

Summary

NIPBL (NIPBL cohesin loading factor, HGNC:28862) is a protein-coding gene on chromosome 5p13.2, encoding Nipped-B-like protein (Q6KC79). Plays an important role in the loading of the cohesin complex on to DNA. It is a selective cancer dependency (DepMap: 26.7% of cell lines) and haploinsufficient (ClinGen: sufficient evidence).

This gene encodes the homolog of the Drosophila melanogaster Nipped-B gene product and fungal Scc2-type sister chromatid cohesion proteins. The Drosophila protein facilitates enhancer-promoter communication of remote enhancers and plays a role in developmental regulation. It is also homologous to a family of chromosomal adherins with broad roles in sister chromatid cohesion, chromosome condensation, and DNA repair. The human protein has a bipartite nuclear targeting sequence and a putative HEAT repeat. Condensins, cohesins and other complexes with chromosome-related functions also contain HEAT repeats. Mutations in this gene result in Cornelia de Lange syndrome, a disorder characterized by dysmorphic facial features, growth delay, limb reduction defects, and cognitive disability. Two transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 25836 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Cornelia de Lange syndrome (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 10
• Clinical variants (ClinVar): 2,395 total — 422 pathogenic, 161 likely-pathogenic
• Phenotypes (HPO): 173
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 2 cancer types
• Cancer dependency (DepMap): dependent in 26.7% of screened cell lines
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity little evidence
• MANE Select transcript: NM_133433

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28862
Approved symbol	NIPBL
Name	NIPBL cohesin loading factor
Location	5p13.2
Locus type	gene with protein product
Status	Approved
Aliases	IDN3, DKFZp434L1319, FLJ11203, FLJ12597, FLJ13354, FLJ13648, Scc2
Ensembl gene	ENSG00000164190
Ensembl biotype	protein_coding
OMIM	608667
Entrez	25836

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 4 protein_coding, 4 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000282516, ENST00000448238, ENST00000503274, ENST00000504430, ENST00000505998, ENST00000509429, ENST00000513819, ENST00000514335, ENST00000652901

RefSeq mRNA: 2 — MANE Select: NM_133433 NM_015384, NM_133433

CCDS: CCDS3920, CCDS47198

Canonical transcript exons

ENST00000282516 — 47 exons

Exon	Start	End
ENSE00001082267	37027359	37027412
ENSE00001082268	37002662	37002765
ENSE00001082270	37024585	37024719
ENSE00001082271	37022051	37022149
ENSE00001082272	37019311	37019400
ENSE00001082273	37003261	37003347
ENSE00001082274	37000817	37000888
ENSE00001082275	37000373	37000570
ENSE00001082276	37044347	37044487
ENSE00001082277	37026229	37026327
ENSE00001082278	37046109	37046199
ENSE00001082281	37048502	37048675
ENSE00001082282	37008008	37008088
ENSE00001082283	37036379	37036487
ENSE00001082284	37049111	37049301
ENSE00001082285	37038602	37038738
ENSE00001082286	37051779	37051886
ENSE00001082287	37010087	37010225
ENSE00001082288	37006357	37006588
ENSE00001082291	37020775	37020877
ENSE00001082293	37016038	37016170
ENSE00001082294	37000989	37001078
ENSE00001082295	37008623	37008723
ENSE00001082296	37044636	37044729
ENSE00001082297	37022244	37022390
ENSE00001082300	37007323	37007474
ENSE00001082301	37045443	37045597
ENSE00001082302	37017019	37017162
ENSE00001082303	37020459	37020673
ENSE00001082304	37014683	37014765
ENSE00001490176	37064527	37066413
ENSE00001490221	36953618	36953760
ENSE00001490222	36876769	36877178
ENSE00003471473	36961484	36961583
ENSE00003471553	37060844	37061018
ENSE00003492746	36962123	36962274
ENSE00003497667	36975776	36976402
ENSE00003505393	37058891	37059165
ENSE00003512380	37052366	37052566
ENSE00003521288	36955472	36955637
ENSE00003535903	36971945	36972041
ENSE00003564116	36995622	36995804
ENSE00003576989	36970876	36971036
ENSE00003609335	37057186	37057332
ENSE00003615642	36958104	36958231
ENSE00003627626	36984676	36986301
ENSE00003666458	37063790	37063978

Expression profiles

Bgee: expression breadth ubiquitous, 288 present calls, max score 94.88.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 27.9522 / max 440.0178, expressed in 1809 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
56160	13.1068	1755
56158	11.5593	1714
56159	1.0401	639
56168	0.6232	227
56166	0.5609	226
56163	0.4176	199
56164	0.3581	170
56162	0.2188	98
56161	0.0673	16

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	94.88	gold quality
calcaneal tendon	UBERON:0003701	94.82	gold quality
colonic epithelium	UBERON:0000397	94.47	gold quality
ventricular zone	UBERON:0003053	94.37	gold quality
cervix squamous epithelium	UBERON:0006922	94.17	gold quality
ganglionic eminence	UBERON:0004023	93.99	gold quality
tendon	UBERON:0000043	93.79	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	92.23	gold quality
pancreatic ductal cell	CL:0002079	92.07	gold quality
cortical plate	UBERON:0005343	91.97	gold quality
esophagus squamous epithelium	UBERON:0006920	91.92	gold quality
medial globus pallidus	UBERON:0002477	91.68	gold quality
sural nerve	UBERON:0015488	91.53	gold quality
tendon of biceps brachii	UBERON:0008188	91.46	gold quality
visceral pleura	UBERON:0002401	91.40	gold quality
squamous epithelium	UBERON:0006914	91.37	gold quality
tonsil	UBERON:0002372	91.27	gold quality
embryo	UBERON:0000922	90.83	gold quality
monocyte	CL:0000576	90.74	gold quality
leukocyte	CL:0000738	90.71	gold quality
mononuclear cell	CL:0000842	90.68	gold quality
pleura	UBERON:0000977	90.64	gold quality
bone marrow cell	CL:0002092	90.43	gold quality
endothelial cell	CL:0000115	90.41	gold quality
parietal pleura	UBERON:0002400	90.38	gold quality
bone marrow	UBERON:0002371	90.24	gold quality
adrenal tissue	UBERON:0018303	90.24	gold quality
blood	UBERON:0000178	90.22	gold quality
pylorus	UBERON:0001166	90.10	gold quality
Brodmann (1909) area 23	UBERON:0013554	90.09	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.23

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
FOXP3

miRNA regulators (miRDB)

174 targeting NIPBL, 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-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4713-3P	100.00	65.92	505
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 1 (little evidence). ClinGen Gene Dosage Map DepMap (CRISPR cell-line fitness): dependent in 26.7% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• identified mutations in one gene, NIPBL, in four sporadic and two familial cases of Cornelia de Lange syndrome (PMID:15146186)
• results show that NIPBL mutations are present in only 35% of Cornelia de Lange syndrome cases, strongly suggesting the genetic heterogeneity of this syndrome (PMID:15591270)
• Mutations in NIPBL, the human homologue of the Drosophila Nipped-B gene, were found to cause De Lange syndrome. (PMID:16236812)
• So far, two genes (NIPBL and SMC1L1) have been identified causing Cornelia de Lange syndrome (CdLS) or CdLS-like phenotypes. (PMID:17106445)
• Large NIPBL deletion in a patient with Cornelia de Lange Syndrome. (PMID:17264868)
• NIPBL mutations in Cornelia de Lange syndrome: truncating, splice-site, missense, in-frame deletion & regulatory; truncating mutations most frequent in patients with high clinical score; most splice-site & all missense mutations in low-medium score group (PMID:17661813)
• identified as one of five genes containing 11 somatic mutations in a panel that included 132 colorectal cancers, then demonstrated that down-regulation of such homologs resulted in chromosomal instability and chromatid cohesion defects in human cells (PMID:18299561)
• This study identified duplications Cornelia de Lange syndrome (CdLS) on chromosomes 5 or X using genome wide array comparative genomic hybridisation (aCGH). The duplicated regions contain either the NIPBL or the SMC1A genes. (PMID:19052029)
• Transcription in severely affected Cornelia de Lange Syndrome probands has identified a unique profile of dysregulated gene expression that correlates with phenotypic severity. (PMID:19468298)
• NIPBL mutation is associated with Cornelia de Lange syndrome. (PMID:20124326)
• The identification of 14 additional mutations of the cohesin complex genes NIPBL and SMC1A in a cohort of 30 unrelated patients with Cornelia de Lange syndrome, is reported. (PMID:20358602)
• In patient with Cornelia de Lange syndrome, a large deletion encompassing exons 35 to 47 of the NIPBL gene was identified. (PMID:20727427)
• Development of NIPBL locus-specific database using LOVD: from novel mutations to further genotype-phenotype correlations in Cornelia de Lange Syndrome. (PMID:20824775)
• this study reveals that human NIPBL is a novel protein recruited to DSB sites, and the recruitment is controlled by MDC1, RNF168 and HP1gamma. (PMID:21784059)
• Specific novel mutations at the N-terminus of the MAU2-interacting domain of NIBPL result in markedly reduced MAU2 binding. (PMID:21934712)
• Our findings suggest a potential clinical utility to testing for copy number variations involving NIPBL when clinically diagnosed CdLS cases are mutation-negative by DNA-sequencing studies. (PMID:22241092)
• Large deletions/duplications in the NIPBL gene are detected in Cornelia de Lange patients. (PMID:22353942)
• The mutational analysis in Chinese patients with Cornelia de Lange syndrome revealed splice-site mutations in NIPBL in 2 out of 4 patients. (PMID:22857006)
• NIPBL, SMC1A, and SMC3 mutation-positive patients were equally likely to have congenital heart diseases in Cornelia de lange syndrome. (PMID:22965847)
• In the present study, conducted on a group of 64 unrelated Polish Cornelia de Lange syndrome patients, 25 various NIPBL sequence variants, including 22 novel point mutations, were detected. (PMID:23254390)
• Somatic mosaicism for an NIPBL mutation is frequent (10/44; 23%) clinically in reliably diagnosed Cornelia de Lange syndrome individuals. (PMID:23505322)
• Results show that NIPBL has a function in modulating chromatin architecture that is not dependent on SMC3/cohesin or CTCF in classical Cornelia de Lange syndrome. (PMID:23760082)
• These data suggest that NBPBL is frequently inactived in gastric and colorectal neoplasms with microsatellite instability. (PMID:23912250)
• Canonical WNT pathway and CCND1 downregulation was observed in NIPBL-mutated patient-specific fibroblasts. (PMID:24136230)
• In B cells from Cornelia de Lange Syndrome, found strong correlation between heterozygous loss-of-function mutations in cohesin loading protein NIPBL and a shift toward microhomology-based end joining during IG class switch recombination. (PMID:24145515)
• Letter/Case Report: novel NIPBL mutation giving rise to Cornelia de Lange syndrome and intrauterine fetal death. (PMID:24189319)
• There was an increased frequncy of NIPBL mutations in a cohort of prenatal ultrasound detected phenotypes of Cornelia de Lange syndrome. (PMID:24218399)
• defects of NIPBL might lead to cohesin-loading defects and thereby alter gene expression and second, NIPBL deficiency might affect genes directly via its role at the respective promoters. (PMID:24550742)
• Nine mutations affecting splice-sites in the NIPBL gene and four new splicing isoforms DeltaE10, DeltaE12, DeltaE33,34, and B’ was identified in twelve CdLS patients. (PMID:24918291)
• A new Sanger sequencing reveals new hidden mutations in NIPBL gene not detected with conventional approach. (PMID:25196272)
• analysis of the mutation spectrum of NIPBL in in Chinese patients with Cornelia de Lange syndrome (PMID:25447906)
• NIPBL expression conferred poor prognosis and resistance to chemotherapy in non-small cell lung cancer (PMID:25963978)
• Scc2 normally promotes a gene expression program that supports translational fidelity. . translational dysfunction may contribute to the human disorder Cornelia de Lange syndrome, which is caused by mutations in NIPBL, the human ortholog of SCC2. (PMID:26176819)
• NIPBL gene mutation is associated with Thrombocytopenia in Cornelia de Lange syndrome. (PMID:26437745)
• 37 novel nipped-B-like protein (NIPBL) mutations were identified in Cornelia de Lange syndrome patients, including 34 in leukocytes and 3 in buccal cells only. (PMID:26701315)
• This study provides insight into the molecular pathology of Cornelia de Lange syndrome by establishing a relationship between NIPBL and HDAC8 mutations and PKR activation. (PMID:26725122)
• Subsequent quantitative PCR analysis demonstrated a 30% decrease of the total NIPBL mRNA levels associated with the frameshift transcript (PMID:26925417)
• Nipbl seems to have also additional roles, for instance as transcription factor.This chapter summarizes our current knowledge on kollerin function and the recent studies on the genomic localization of Scc2, highlighting and critically discussing controversial data. (PMID:27797076)
• NIPBL has evolved a sophisticated response to damaged DNA that is influenced by the form of damage, suggesting a highly dynamic role for NIPBL in maintaining genomic stability. (PMID:28167679)
• Pathological variant specific of the isoform A of NIPBL was identified in two patients with Cornelia de Lange Syndrome. (PMID:28241484)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	nipblb	ENSDARG00000061052
danio_rerio	nipbla	ENSDARG00000098272
mus_musculus	Nipbl	ENSMUSG00000022141
rattus_norvegicus	Nipbl	ENSRNOG00000056907
drosophila_melanogaster	Nipped-B	FBGN0026401
caenorhabditis_elegans		WBGENE00004166

Protein

Protein identifiers

Nipped-B-like protein — Q6KC79 (reviewed: Q6KC79)

Alternative names: Delangin, SCC2 homolog

All UniProt accessions (3): A0A590UJS4, Q6KC79, H0Y8M3

UniProt curated annotations — full annotation on UniProt →

Function. Plays an important role in the loading of the cohesin complex on to DNA. Forms a heterodimeric complex (also known as cohesin loading complex) with MAU2/SCC4 which mediates the loading of the cohesin complex onto chromatin. Plays a role in cohesin loading at sites of DNA damage. Its recruitment to double-strand breaks (DSBs) sites occurs in a CBX3-, RNF8- and RNF168-dependent manner whereas its recruitment to UV irradiation-induced DNA damage sites occurs in a ATM-, ATR-, RNF8- and RNF168-dependent manner. Along with ZNF609, promotes cortical neuron migration during brain development by regulating the transcription of crucial genes in this process. Preferentially binds promoters containing paused RNA polymerase II. Up-regulates the expression of SEMA3A, NRP1, PLXND1 and GABBR2 genes, among others.

Subunit / interactions. Heterodimerizes with MAU2/SCC4 to form the cohesin loading complex. The NIPBL-MAU2 heterodimer interacts with the cohesin complex composed of SMC1A/B and SMC3 heterodimer, RAD21 and STAG1/SA1. NIPBL directly contacts all members of the complex, RAD21, SMC1A/B, SMC3 and STAG1. Interacts directly (via PxVxL motif) with CBX5. Interacts with ZNF609 (via N-terminus). Interacts with the multiprotein complex Integrator. Interacts (via PxVxL motif) with CBX3. Interacts with BRD4. Interacts with PRR12; the interaction is relevant for nuclear localization of the cohesin complex.

Subcellular location. Nucleus. Chromosome.

Tissue specificity. Widely expressed. Highly expressed in heart, skeletal muscle, fetal and adult liver, fetal and adult kidney. Expressed at intermediates level in thymus, placenta, peripheral leukocyte and small intestine. Weakly or not expressed in brain, colon, spleen and lung.

Disease relevance. Cornelia de Lange syndrome 1 (CDLS1) [MIM:122470] A form of Cornelia de Lange syndrome, a clinically heterogeneous developmental disorder associated with malformations affecting multiple systems. Characterized by facial dysmorphisms, abnormal hands and feet, growth delay, cognitive retardation, hirsutism, gastroesophageal dysfunction and cardiac, ophthalmologic and genitourinary anomalies. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. Contains one Pro-Xaa-Val-Xaa-Leu (PxVxL) motif, which is required for interaction with chromoshadow domains. This motif requires additional residues -7, -6, +4 and +5 of the central Val which contact the chromoshadow domain. The C-terminal region containing HEAT repeats and Pro-Xaa-Val-Xaa-Leu (PxVxL) motif are involved in the recruitment of NIPBL to sites of DNA damage.

Similarity. Belongs to the SCC2/Nipped-B family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q6KC79-1	1, A, IDN3-A	yes
Q6KC79-2	2, B, IDN3-B
Q6KC79-3	3

RefSeq proteins (2): NP_056199, NP_597677* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011989	ARM-like	Homologous_superfamily
IPR016024	ARM-type_fold	Homologous_superfamily
IPR024986	Nipped-B_C	Domain
IPR026003	Cohesin_HEAT	Repeat
IPR033031	Scc2/Nipped-B	Family

Pfam: PF12765, PF12830

UniProt features (125 total): sequence variant 48, modified residue 36, compositionally biased region 15, region of interest 7, repeat 5, sequence conflict 5, mutagenesis site 4, splice variant 3, chain 1, short sequence motif 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
6WGE	ELECTRON MICROSCOPY	3.9
6WG3	ELECTRON MICROSCOPY	5.3
7W1M	ELECTRON MICROSCOPY	6.5

Predicted structure (AlphaFold)

No AlphaFold model available for Q6KC79 — AlphaFold DB does not currently provide models for proteins above ~3000 aa.

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 (36): 2667, 2672, 150, 162, 243, 256, 274, 280, 284, 301, 306, 318, 350, 713, 746, 912, 1082, 1089, 1090, 1096 …

Mutagenesis-validated functional residues (4):

Position	Phenotype
1003	abolishes interaction with cbx3; when associated with a-1005.
1003	abolishes interaction with cbx5; when associated with e-1005.
1005	abolishes interaction with cbx3; when associated with a-1003.
1005	abolishes interaction with cbx5; when associated with e-1003.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-2470946	Cohesin Loading onto Chromatin

MSigDB gene sets: 832 (showing top): AHRARNT_01, E2F_Q4, GOBP_CHROMOSOME_ORGANIZATION, E2F_Q4_01, RRAGTTGT_UNKNOWN, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_HEPATICOBILIARY_SYSTEM_DEVELOPMENT, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_RESPONSE_TO_IONIZING_RADIATION, MULLIGHAN_NPM1_SIGNATURE_3_UP, GOBP_BODY_MORPHOGENESIS, FREAC2_01, GOBP_COGNITION, GOBP_METANEPHROS_DEVELOPMENT, PAX4_01

GO Biological Process (44): mitotic sister chromatid segregation (GO:0000070), negative regulation of transcription by RNA polymerase II (GO:0000122), metanephros development (GO:0001656), heart morphogenesis (GO:0003007), outflow tract morphogenesis (GO:0003151), chromatin remodeling (GO:0006338), DNA damage response (GO:0006974), mitotic sister chromatid cohesion (GO:0007064), brain development (GO:0007420), sensory perception of sound (GO:0007605), intracellular protein localization (GO:0008104), establishment of mitotic sister chromatid cohesion (GO:0034087), maintenance of mitotic sister chromatid cohesion (GO:0034088), somatic stem cell population maintenance (GO:0035019), embryonic forelimb morphogenesis (GO:0035115), forelimb morphogenesis (GO:0035136), external genitalia morphogenesis (GO:0035261), positive regulation of multicellular organism growth (GO:0040018), ear morphogenesis (GO:0042471), regulation of hair cycle (GO:0042634), fat cell differentiation (GO:0045444), positive regulation of ossification (GO:0045778), positive regulation of transcription by RNA polymerase II (GO:0045944), regulation of embryonic development (GO:0045995), embryonic digestive tract morphogenesis (GO:0048557), digestive tract development (GO:0048565), developmental growth (GO:0048589), eye morphogenesis (GO:0048592), regulation of developmental growth (GO:0048638), embryonic viscerocranium morphogenesis (GO:0048703), cognition (GO:0050890), face morphogenesis (GO:0060325), gallbladder development (GO:0061010), uterus morphogenesis (GO:0061038), establishment of protein localization to chromatin (GO:0071169), cellular response to X-ray (GO:0071481), chromatin looping (GO:0140588), replication-born double-strand break repair via sister chromatid exchange (GO:1990414), positive regulation of neuron migration (GO:2001224), regulation of transcription by RNA polymerase II (GO:0006357)

GO Molecular Function (8): chromatin binding (GO:0003682), transcription corepressor activity (GO:0003714), mediator complex binding (GO:0036033), histone deacetylase binding (GO:0042826), cohesin loader activity (GO:0061775), chromo shadow domain binding (GO:0070087), promoter-specific chromatin binding (GO:1990841), protein binding (GO:0005515)

GO Cellular Component (9): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytosol (GO:0005829), integrator complex (GO:0032039), SMC loading complex (GO:0032116), extracellular exosome (GO:0070062), Scc2-Scc4 cohesin loading complex (GO:0090694), chromosome (GO:0005694)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Mitotic Telophase/Cytokinesis	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
mitotic cell cycle process	2
negative regulation of DNA-templated transcription	2
mitotic sister chromatid cohesion	2
binding	2
nuclear protein-containing complex	2
sister chromatid segregation	1
mitotic nuclear division	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
kidney development	1
heart development	1
animal organ morphogenesis	1
heart morphogenesis	1
anatomical structure morphogenesis	1
chromatin organization	1
cellular response to stress	1
sister chromatid cohesion	1
central nervous system development	1
animal organ development	1
head development	1
sensory perception of mechanical stimulus	1
macromolecule localization	1
mitotic cell cycle	1
establishment of sister chromatid cohesion	1
maintenance of sister chromatid cohesion	1
stem cell population maintenance	1
embryonic limb morphogenesis	1
forelimb morphogenesis	1
limb morphogenesis	1
genitalia morphogenesis	1
multicellular organism growth	1
regulation of multicellular organism growth	1
positive regulation of developmental growth	1
positive regulation of multicellular organismal process	1
ear development	1
embryonic organ morphogenesis	1
sensory organ morphogenesis	1
hair cycle	1
regulation of multicellular organismal process	1

Protein interactions and networks

STRING

2911 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NIPBL	MAU2	Q9Y6X3	998
NIPBL	SMC1A	Q14683	998
NIPBL	SMC3	Q9UQE7	998
NIPBL	WAPL	Q7Z5K2	995
NIPBL	PDS5A	Q29RF7	991
NIPBL	CDCA5	Q96FF9	970
NIPBL	RAD21	O60216	961
NIPBL	PDS5B	Q9NTI5	951
NIPBL	BRD4	O60885	897
NIPBL	ESCO2	Q56NI9	879
NIPBL	ESPL1	Q14674	868
NIPBL	HDAC8	Q9BY41	862
NIPBL	CTCF	P49711	852
NIPBL	STAG2	Q8N3U4	846
NIPBL	STAG1	Q8WVM7	840

IntAct

109 interactions, top by confidence:

A	B	Type	Score
COPRS	PRMT5	psi-mi:“MI:0914”(association)	0.770
MAU2	NIPBL	psi-mi:“MI:0915”(physical association)	0.720
NIPBL	MAU2	psi-mi:“MI:0915”(physical association)	0.720
KPNA1	TCERG1	psi-mi:“MI:0914”(association)	0.640
MAU2	CBX5	psi-mi:“MI:0914”(association)	0.530
KSR2	POLR3A	psi-mi:“MI:0914”(association)	0.530
SMC1A	PDS5B	psi-mi:“MI:0914”(association)	0.530
	RAD21	psi-mi:“MI:0915”(physical association)	0.490
NIPBL	RAD21	psi-mi:“MI:0915”(physical association)	0.490
NIPBL	CBX5	psi-mi:“MI:0915”(physical association)	0.480
AR	NIPBL	psi-mi:“MI:0915”(physical association)	0.470
EN1	NFIB	psi-mi:“MI:2364”(proximity)	0.470
MAP1LC3C	NIPBL	psi-mi:“MI:0407”(direct interaction)	0.440
CDK6	NIPBL	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
Rpl35	RPS6	psi-mi:“MI:0914”(association)	0.350
Cbx1		psi-mi:“MI:0914”(association)	0.350
TFG	NCOA4	psi-mi:“MI:0914”(association)	0.350
RPL10	RPS6	psi-mi:“MI:0914”(association)	0.350
SUCO	RPL10	psi-mi:“MI:0914”(association)	0.350
LDHD	METTL8	psi-mi:“MI:0914”(association)	0.350
MKI67	ARHGAP10	psi-mi:“MI:0914”(association)	0.350

BioGRID (258): NIPBL (Affinity Capture-MS), NIPBL (Affinity Capture-MS), NIPBL (Affinity Capture-MS), NIPBL (Affinity Capture-MS), NIPBL (Affinity Capture-MS), MAU2 (Co-fractionation), NIPBL (Proximity Label-MS), NIPBL (Affinity Capture-MS), NIPBL (Affinity Capture-MS), NIPBL (Affinity Capture-MS), NIPBL (Affinity Capture-MS), NIPBL (Affinity Capture-MS), NIPBL (Affinity Capture-MS), NIPBL (Affinity Capture-MS), NIPBL (Proximity Label-MS)

ESM2 similar proteins: A2AJK6, A2ICN5, A2VDZ3, F1LYL9, O18896, O94900, P0CB49, P34545, P46936, P46937, P48436, P49750, P55197, P61753, P61754, Q02078, Q03414, Q04887, Q06A37, Q08D57, Q2MJT0, Q3L8U1, Q3TLH4, Q571K4, Q5F3P8, Q5REW7, Q60929, Q66J90, Q66JW3, Q6F2E7, Q6KC79, Q6KCD5, Q6YXY2, Q7YRJ7, Q7ZXH3, Q8BXJ2, Q8BYH8, Q8CHI8, Q8N5C8, Q96EV2

Diamond homologs: F1QBY1, F5HSE3, Q6KC79, Q6KCD5, Q7PLI2, Q95XZ5

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
NIPBL	“up-regulates activity”	“Cohesin complex”	binding
CBX3	“up-regulates activity”	NIPBL	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 131 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
Processing of Capped Intron-Containing Pre-mRNA	7	6.1×	9e-03
mRNA Splicing - Major Pathway	10	5.8×	9e-04
Metabolism of RNA	10	4.4×	7e-03

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of miRNA transcription	5	12.1×	7e-03
chromatin remodeling	9	5.5×	5e-03

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 2 cancer types — LGGNOS, NSCLC.

Clinical variants and AI predictions

ClinVar

2395 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	422
Likely pathogenic	161
Uncertain significance	912
Likely benign	544
Benign	104

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1000617	NM_133433.4(NIPBL):c.7199G>C (p.Arg2400Pro)	Pathogenic
1066128	NM_133433.4(NIPBL):c.5808+2T>C	Pathogenic
1070037	NM_133433.4(NIPBL):c.7854del (p.Tyr2618_Leu2619insTer)	Pathogenic
1071194	NM_133433.4(NIPBL):c.5269del (p.Val1757fs)	Pathogenic
1072674	NM_133433.4(NIPBL):c.4675_4750dup (p.Leu1584delinsGlnThrThrValTer)	Pathogenic
1074354	NM_133433.4(NIPBL):c.4643+1G>A	Pathogenic
1075044	NM_133433.4(NIPBL):c.2837dup (p.Leu946fs)	Pathogenic
1075076	NC_000005.9:g.(?36953799)(37064994_?)del	Pathogenic
1075092	NM_133433.4(NIPBL):c.7013del (p.Ala2338fs)	Pathogenic
1075290	NM_133433.4(NIPBL):c.1942del (p.Thr648fs)	Pathogenic
1076020	NM_133433.4(NIPBL):c.4335T>G (p.Tyr1445Ter)	Pathogenic
1076024	NM_133433.4(NIPBL):c.8326del (p.Ile2776fs)	Pathogenic
1076298	NM_133433.4(NIPBL):c.2207del (p.Pro736fs)	Pathogenic
1183995	NM_133433.4(NIPBL):c.8374_8375del (p.Leu2792fs)	Pathogenic
1319757	NM_133433.4(NIPBL):c.4643+1_4643+10del	Pathogenic
1320125	NM_133433.4(NIPBL):c.10dup (p.Asp4fs)	Pathogenic
1328515	NM_133433.4(NIPBL):c.7948dup (p.Ile2650fs)	Pathogenic
1338267	NM_133433.4(NIPBL):c.5822_5834del (p.Arg1941fs)	Pathogenic
1338435	NM_133433.4(NIPBL):c.3709C>T (p.Gln1237Ter)	Pathogenic
1351385	NM_133433.4(NIPBL):c.3178del (p.Glu1060fs)	Pathogenic
1359106	NM_133433.4(NIPBL):c.6359T>G (p.Leu2120Ter)	Pathogenic
1366117	NM_133433.4(NIPBL):c.4455_4456dup (p.Tyr1486fs)	Pathogenic
1379181	NM_133433.4(NIPBL):c.1786_1790del (p.Asn595_His596insTer)	Pathogenic
1382932	NM_133433.4(NIPBL):c.3040del (p.Gln1014fs)	Pathogenic
1383143	NM_133433.4(NIPBL):c.3100A>T (p.Lys1034Ter)	Pathogenic
1390979	NM_133433.4(NIPBL):c.4502_4503dup (p.Val1502fs)	Pathogenic
1395044	NM_133433.4(NIPBL):c.373C>T (p.Gln125Ter)	Pathogenic
1399376	NM_133433.4(NIPBL):c.6080_6083dup (p.Gln2028fs)	Pathogenic
1406195	NM_133433.4(NIPBL):c.5725dup (p.Thr1909fs)	Pathogenic
1420453	NM_133433.4(NIPBL):c.3040C>T (p.Gln1014Ter)	Pathogenic

SpliceAI

6717 predictions. Top by Δscore:

Variant	Effect	Δscore
5:36943183:G:GG	donor_gain	1.0000
5:36953616:A:AG	acceptor_gain	1.0000
5:36953617:G:GA	acceptor_gain	1.0000
5:36953617:GT:G	acceptor_gain	1.0000
5:36953757:GACC:G	donor_gain	1.0000
5:36953761:G:GG	donor_gain	1.0000
5:36955466:A:AG	acceptor_gain	1.0000
5:36955467:A:G	acceptor_gain	1.0000
5:36955469:TA:T	acceptor_loss	1.0000
5:36955470:A:AG	acceptor_gain	1.0000
5:36955470:AGTC:A	acceptor_loss	1.0000
5:36955471:G:GA	acceptor_gain	1.0000
5:36955471:GT:G	acceptor_gain	1.0000
5:36955471:GTC:G	acceptor_gain	1.0000
5:36955471:GTCC:G	acceptor_gain	1.0000
5:36955471:GTCCT:G	acceptor_gain	1.0000
5:36955635:CAT:C	donor_gain	1.0000
5:36958218:A:G	donor_gain	1.0000
5:36958229:GTG:G	donor_gain	1.0000
5:36958375:A:G	donor_gain	1.0000
5:36961477:T:TA	acceptor_gain	1.0000
5:36961480:A:AG	acceptor_gain	1.0000
5:36961480:ATAG:A	acceptor_gain	1.0000
5:36961481:T:G	acceptor_gain	1.0000
5:36961482:A:AC	acceptor_loss	1.0000
5:36961482:A:AG	acceptor_gain	1.0000
5:36961482:AG:A	acceptor_gain	1.0000
5:36961483:G:GG	acceptor_gain	1.0000
5:36961483:G:GT	acceptor_loss	1.0000
5:36961483:GG:G	acceptor_gain	1.0000

AlphaMissense

18586 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:36953719:T:A	V8D	1.000
5:36953722:C:A	P9H	1.000
5:36953725:T:A	I10N	1.000
5:36953725:T:C	I10T	1.000
5:36953725:T:G	I10S	1.000
5:36953734:T:A	L13H	1.000
5:36953734:T:C	L13P	1.000
5:36953739:G:A	G15R	1.000
5:36953739:G:C	G15R	1.000
5:36953739:G:T	G15W	1.000
5:36953740:G:A	G15E	1.000
5:36953752:T:A	L19H	1.000
5:36953752:T:C	L19P	1.000
5:36955472:T:C	L22P	1.000
5:36955475:T:C	L23P	1.000
5:36955484:T:C	L26P	1.000
5:36955490:T:A	L28H	1.000
5:36955601:T:C	L65P	1.000
5:36955613:T:C	L69P	1.000
5:36958109:T:C	L79S	1.000
5:36976343:G:C	R479P	1.000
5:36984694:G:C	R505T	1.000
5:36984695:A:C	R505S	1.000
5:36984695:A:T	R505S	1.000
5:37006429:G:C	A1310P	1.000
5:37007457:G:C	D1408H	1.000
5:37007457:G:T	D1408Y	1.000
5:37007458:A:C	D1408A	1.000
5:37007458:A:G	D1408G	1.000
5:37007458:A:T	D1408V	1.000

dbSNP variants (sampled 300 via entrez): RS1000029013 (5:36892055 A>G), RS1000039307 (5:36916808 T>C), RS1000054623 (5:37052273 A>G,T), RS1000072870 (5:36961184 C>G,T), RS1000078099 (5:37050798 T>C), RS1000083577 (5:37052670 A>G,T), RS1000091026 (5:36922503 G>A), RS1000101315 (5:36992016 T>A,C), RS1000120365 (5:37005232 G>A,T), RS1000134553 (5:36960896 G>A), RS1000140503 (5:36904039 C>T), RS1000146508 (5:37026516 G>A,T), RS1000169451 (5:36875976 G>A,C), RS1000177955 (5:36934575 T>A), RS1000203829 (5:36879181 G>T)

Disease associations

OMIM: gene MIM:608667 | disease phenotypes: MIM:122470, MIM:119530, MIM:617391, MIM:142340, MIM:219050, MIM:187500, MIM:256100

GenCC curated gene-disease

Disease	Classification	Inheritance
Cornelia de Lange syndrome 1	Definitive	Autosomal dominant
Cornelia de Lange syndrome	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
Cornelia de Lange syndrome	Definitive	AD

Mondo (19): Cornelia de Lange syndrome 1 (MONDO:0007387), intellectual disability (MONDO:0001071), orofacial cleft 1 (MONDO:0007335), breast ductal adenocarcinoma (MONDO:0005590), neurodevelopmental disorder (MONDO:0700092), developmental and epileptic encephalopathy, 54 (MONDO:0033363), brachydactyly (MONDO:0021004), fetal growth restriction (MONDO:0005030), congenital diaphragmatic hernia (MONDO:0005711), cryptorchidism (MONDO:0009047), pulmonary hypoplasia (MONDO:0800133), coloboma (MONDO:0001476), hypertrophic cardiomyopathy (MONDO:0005045), Cornelia de Lange syndrome (MONDO:0016033), microcephaly (MONDO:0001149)

Orphanet (8): Cornelia de Lange syndrome (Orphanet:199), Congenital diaphragmatic hernia (Orphanet:2140), OBSOLETE: Ocular coloboma (Orphanet:194), Rare hypertrophic cardiomyopathy (Orphanet:217569), Cleft palate (Orphanet:2014), Tetralogy of Fallot (Orphanet:3303), Nephronophthisis (Orphanet:655), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

173 total (30 of 173 shown, HPO-id order):

HPO	Term
HP:0000003	Multicystic kidney dysplasia
HP:0000006	Autosomal dominant inheritance
HP:0000023	Inguinal hernia
HP:0000028	Cryptorchidism
HP:0000047	Hypospadias
HP:0000050	Hypoplastic male external genitalia
HP:0000059	Hypoplastic labia majora
HP:0000076	Vesicoureteral reflux
HP:0000083	Renal insufficiency
HP:0000085	Horseshoe kidney
HP:0000086	Ectopic kidney
HP:0000089	Renal hypoplasia
HP:0000093	Proteinuria
HP:0000107	Renal cyst
HP:0000126	Hydronephrosis
HP:0000130	Abnormality of the uterus
HP:0000175	Cleft palate
HP:0000204	Cleft upper lip
HP:0000218	High palate
HP:0000219	Thin upper lip vermilion
HP:0000233	Thin vermilion border
HP:0000248	Brachycephaly
HP:0000252	Microcephaly
HP:0000294	Low anterior hairline
HP:0000319	Smooth philtrum
HP:0000341	Narrow forehead
HP:0000343	Long philtrum
HP:0000347	Micrognathia
HP:0000358	Posteriorly rotated ears
HP:0000365	Hearing impairment

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST001762_656	Obesity-related traits	7.000000e-06
GCST002647_146	Height	4.000000e-16
GCST008152_53	Weight	1.000000e-06
GCST008163_326	Height	8.000000e-09
GCST008163_70	Height	6.000000e-06
GCST008839_146	Height	2.000000e-14
GCST010143_4	Meat-related diet	5.000000e-08
GCST010725_6	Malaria	9.000000e-07
GCST010725_66	Malaria	1.000000e-06
GCST010725_85	Malaria	5.000000e-06

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0003940	physical activity
EFO:0004338	body weight
EFO:0008111	diet measurement

MeSH disease descriptors (14)

Descriptor	Name	Tree numbers
D059327	Brachydactyly	C05.660.585.262; C16.131.621.585.262
D018270	Carcinoma, Ductal, Breast	C04.557.470.200.025.232.500; C04.557.470.615.132.500; C04.588.180.390; C17.800.090.500.390
D002312	Cardiomyopathy, Hypertrophic	C14.280.238.100; C14.280.484.048.750.070.160
D002972	Cleft Palate	C05.500.460.185; C05.660.207.540.460.185; C07.320.440.185; C07.465.525.185; C07.650.500.460.185; C07.650.525.185; C16.131.621.207.540.460.185; C16.131.850.500.460.185; C16.131.850.525.185
D003103	Coloboma	C11.250.110; C11.270.147; C16.131.384.282
D003456	Cryptorchidism	C12.100.500.829.258; C12.200.294.829.258; C12.200.706.258; C12.800.258; C16.131.939.258; C19.391.829.258
D005317	Fetal Growth Retardation	C12.050.703.277.370; C16.300.390; C23.550.393.450
D065630	Hernias, Diaphragmatic, Congenital	C16.131.433; C23.300.707.960.500.116
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500
D065886	Neurodevelopmental Disorders	F03.625
D013771	Tetralogy of Fallot	C14.240.400.849; C14.280.400.849; C16.131.240.400.849
D014718	Vesico-Ureteral Reflux	C12.050.351.968.829.920; C12.200.777.829.920; C12.950.829.920
C566121	Orofacial Cleft 1 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression	4
trichostatin A	affects cotreatment, decreases expression	3
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
geldanamycin	increases expression	1
2,4,6-tribromophenol	increases expression	1
decabromobiphenyl ether	increases expression	1
4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone	increases response to substance, increases expression, decreases expression, increases reaction	1
afimoxifene	affects response to substance	1
sodium arsenite	decreases expression	1
tetrabromobisphenol A	increases expression	1
tobacco tar	decreases expression	1
coumarin	decreases phosphorylation	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic 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
abrine	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
jinfukang	affects cotreatment, decreases expression	1
Vorinostat	decreases expression	1
Caffeine	affects phosphorylation	1
Cisplatin	affects cotreatment, decreases expression	1
Clorgyline	increases expression	1
Enzyme Inhibitors	increases O-linked glycosylation, decreases activity	1
Quercetin	affects phosphorylation	1
Ribonucleotides	affects binding	1
Rotenone	increases expression	1
Selenium	decreases expression	1
Thimerosal	decreases expression	1

Cellosaurus cell lines

2 cell lines: 1 induced pluripotent stem cell, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_C1LL	KMUGMCi002-A	Induced pluripotent stem cell	Female
CVCL_E127	GM20000	Transformed cell line	Male

Clinical trials (associated diseases)

305 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
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
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
NCT03414970	PHASE3	ACTIVE_NOT_RECRUITING	Hypofractionated Radiation Therapy After Mastectomy in Preventing Recurrence in Patients With Stage IIa-IIIa Breast Cancer
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT04381897	PHASE2	NOT_YET_RECRUITING	Use of N-Acetylcysteine in the Treatment of Repetitive and Self-Injurious Behaviors in Cornelia de Lange Syndrome
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
NCT00461344	PHASE2	TERMINATED	Docetaxel + Doxorubicin as Neoadjuvant Chemotherapy in Patients With Breast Cancer
NCT07499999	PHASE2	NOT_YET_RECRUITING	Randomized Double-Blind Phase II Trial of Baby Exemestane Versus Baby Tamoxifen in Post-Menopausal Women at High Risk for Breast Cancer
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
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)
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT06789783	PHASE2/PHASE3	RECRUITING	Cornelia De Lange Syndrome: Assessing Positive Effects of Lithium Treatment
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
NCT03113877	Not specified	TERMINATED	Evaluation of Autonomic Function in Individuals With Cornelia de Lange Syndrome (CdLS)
NCT04463316	Not specified	RECRUITING	GROWing Up With Rare GENEtic Syndromes
NCT05829668	Not specified	RECRUITING	Behavioral Assessment and Treatment of Problem Behavior in Children With Cornelia de Lange Syndrome
NCT03479476	PHASE2/PHASE3	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome
NCT02616796	PHASE1/PHASE2	COMPLETED	Effects of Social Gaze Training on Brain and Behavior in Fragile X Syndrome
NCT06860672	EARLY_PHASE1	RECRUITING	Clinical Trial of the Dual Vector Base Editor for the Treatment of the CHD3-R1025W Mutation
NCT00597948	Not specified	COMPLETED	Healthy Lifestyles for People With Intellectual Disabilities
NCT01087320	Not specified	RECRUITING	Genome Medical Sequencing for Gene Discovery