SHANK3

Summary

SHANK3 (SH3 and multiple ankyrin repeat domains 3, HGNC:14294) is a protein-coding gene on chromosome 22q13.33, encoding SH3 and multiple ankyrin repeat domains protein 3 (Q9BYB0). Major scaffold postsynaptic density protein which interacts with multiple proteins and complexes to orchestrate the dendritic spine and synapse formation, maturation and maintenance. It is haploinsufficient (ClinGen: sufficient evidence).

This gene is a member of the Shank gene family. Shank proteins are multidomain scaffold proteins of the postsynaptic density that connect neurotransmitter receptors, ion channels, and other membrane proteins to the actin cytoskeleton and G-protein-coupled signaling pathways. Shank proteins also play a role in synapse formation and dendritic spine maturation. Mutations in this gene are a cause of autism spectrum disorder (ASD), which is characterized by impairments in social interaction and communication, and restricted behavioral patterns and interests. Mutations in this gene also cause schizophrenia type 15, and are a major causative factor in the neurological symptoms of 22q13.3 deletion syndrome, which is also known as Phelan-McDermid syndrome. Additional isoforms have been described for this gene but they have not yet been experimentally verified.

Source: NCBI Gene 85358 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Phelan-McDermid syndrome (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 13
• Clinical variants (ClinVar): 1,201 total — 136 pathogenic, 63 likely-pathogenic
• Phenotypes (HPO): 81
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_001372044

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14294
Approved symbol	SHANK3
Name	SH3 and multiple ankyrin repeat domains 3
Location	22q13.33
Locus type	gene with protein product
Status	Approved
Aliases	SPANK-2, prosap2, KIAA1650, PSAP2
Ensembl gene	ENSG00000251322
Ensembl biotype	protein_coding
OMIM	606230
Entrez	85358

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 4 protein_coding, 3 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay, 2 retained_intron

ENST00000262795, ENST00000414786, ENST00000659388, ENST00000664402, ENST00000673838, ENST00000673971, ENST00000673995, ENST00000674010, ENST00000674145, ENST00000691768, ENST00000692848

RefSeq mRNA: 1 — MANE Select: NM_001372044 NM_001372044

Canonical transcript exons

ENST00000692848 — 23 exons

Exon	Start	End
ENSE00003784166	50684585	50684651
ENSE00003784958	50676622	50676693
ENSE00003784999	50698690	50698803
ENSE00003785033	50704166	50704248
ENSE00003787315	50703860	50703935
ENSE00003787975	50683340	50683417
ENSE00003788321	50675048	50675251
ENSE00003788381	50704738	50704862
ENSE00003788555	50679312	50679428
ENSE00003788618	50697564	50697715
ENSE00003788781	50694775	50695048
ENSE00003790011	50678769	50678920
ENSE00003790927	50704964	50705096
ENSE00003791507	50678585	50678693
ENSE00003791551	50679019	50679186
ENSE00003896290	50674408	50674579
ENSE00004026339	50730721	50733212
ENSE00004026340	50715669	50715753
ENSE00004026341	50706072	50706152
ENSE00004026342	50711615	50711638
ENSE00004026343	50720184	50722437
ENSE00004026344	50714917	50715047
ENSE00004026345	50674582	50674704

Expression profiles

Bgee: expression breadth ubiquitous, 246 present calls, max score 98.79.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.9324 / max 337.4035, expressed in 1005 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
193045	4.5013	328
193044	2.9571	319
193048	1.4952	565
193046	1.2617	277
193052	0.9088	269
193049	0.6222	328
193047	0.1131	61
193054	0.0587	10
193053	0.0141	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	98.79	gold quality
cerebellar hemisphere	UBERON:0002245	98.43	gold quality
cerebellar cortex	UBERON:0002129	98.42	gold quality
cerebellum	UBERON:0002037	98.37	gold quality
cerebellar vermis	UBERON:0004720	98.32	gold quality
lateral nuclear group of thalamus	UBERON:0002736	97.40	gold quality
spleen	UBERON:0002106	97.28	gold quality
cardiac muscle of right atrium	UBERON:0003379	96.99	gold quality
apex of heart	UBERON:0002098	96.44	gold quality
entorhinal cortex	UBERON:0002728	96.35	gold quality
postcentral gyrus	UBERON:0002581	96.15	gold quality
sural nerve	UBERON:0015488	96.10	gold quality
left ventricle myocardium	UBERON:0006566	96.09	silver quality
right frontal lobe	UBERON:0002810	95.77	gold quality
parietal lobe	UBERON:0001872	95.73	gold quality
subcutaneous adipose tissue	UBERON:0002190	95.44	gold quality
omental fat pad	UBERON:0010414	95.38	gold quality
peritoneum	UBERON:0002358	95.30	gold quality
adipose tissue of abdominal region	UBERON:0007808	95.27	gold quality
right lung	UBERON:0002167	95.19	gold quality
superior frontal gyrus	UBERON:0002661	95.06	gold quality
temporal lobe	UBERON:0001871	94.67	gold quality
Ammon’s horn	UBERON:0001954	94.56	gold quality
upper lobe of left lung	UBERON:0008952	94.19	gold quality
amygdala	UBERON:0001876	93.89	gold quality
anterior cingulate cortex	UBERON:0009835	93.85	gold quality
upper lobe of lung	UBERON:0008948	93.84	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	93.74	gold quality
occipital lobe	UBERON:0002021	93.63	gold quality
primary visual cortex	UBERON:0002436	93.56	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-11268	yes	1093.65
E-GEOD-135922	yes	36.41
E-CURD-119	yes	34.69
E-GEOD-100618	no	47.95
E-ANND-3	no	1.36

Regulation

Is transcription factor: no

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• Haploinsufficiency of the gene SHANK3, which codes for a structural protein of the postsynaptic density, may be a major causative factor in the neurological symptoms of 22q13 deletion syndrome. (PMID:12920066)
• Common breakpoint within SHANK3 responsible for mental retardation and developmental delays. (PMID:16284256)
• Mutation of a single copy of SHANK3 on chromosome 22q13 can result in language and/or social communication disorders. (PMID:17173049)
• Haploinsufficiency of SHANK3 can cause a monogenic form of autism in sufficient frequency to warrant consideration in clinical diagnostic testing. (PMID:17999366)
• Novel de novo SHANK3 mutation in autistic patients is reported. (PMID:18615476)
• Shank3 is one of a number of host synaptic proteins likely to play key roles in bacteria-host interactions. (PMID:19371741)
• SHANK3 deletions may be limited to lower functioning individuals with autism (PMID:19384346)
• Chromosome 22q13.3 deletion syndrome with a de novo interstitial 22q13.3 cryptic deletion disrupting SHANK3 is reported. (PMID:19454329)
• We suggest that SHANK3 might not represent a major susceptibility gene for autism in Chinese Han population (PMID:19566951)
• De novo mutations in the gene encoding the synaptic scaffolding protein SHANK3 in patients ascertained for schizophrenia. (PMID:20385823)
• [review] The presumptive exon containing the variant in the neurodevelopmentally disabled autism case highlighted in this review is not likely to be present in most or all SHANK3 transcripts. (PMID:21062623)
• A translocation between Xq21.33 and 22q13.33 causes an intragenic SHANK3 deletion in a woman with Phelan-McDermid syndrome and hypergonadotropic hypogonadism. (PMID:21271662)
• The SHANK3 gene was analyzed in 128 autistic patients with manifestations similar to those seen in the 22q13.3 deletion syndrome. (PMID:21378602)
• the data of this study provided new insights into the synaptic alterations caused by SHANK3 mutations in humans and provide a robust cellular readout for the development of knowledge-based therapies. (PMID:21606927)
• Deletion size in the SHANK3 gene and adjacent regions determine the severity of phenotypes in Phelan-McDermid syndrome (22q13 deletion syndrome). (PMID:21984749)
• SHANK3 microdeletion is an important genetic component for autism, which may explain 2% typical autism cases. (PMID:22093425)
• These findings suggest that 22q13 deletions may be a more frequent cause for Chinese ID patients than previously thought, and the SHANK3 gene is involved in the neurite development (PMID:22509352)
• n this article we review recent findings in regard to higher brain functions of SHANK3, epigenetic regulation of SHANK3 expression, and SHANK3-related autism spectrum disorder–REVIEW (PMID:22749736)
• SHANK3 variants were detected in patients affected with any autism spectrum disorders subtypes. SNP rs76224556 may have a genotype-phenotype correlation in autism spectrum disorders. (PMID:22892527)
• This study demonistrated that rare variants within the re-sequenced structural domains of ANK3 exon 48 do not contribute to BPD-I. (PMID:22966748)
• This study revealed that alterations in transsynaptic signaling caused by ProSAP2/Shank3 gain or loss of function were also exhibited by neurons expressing ProSAP2/Shank3 carrying the autism-associated mutations R87C, R375C, Q396R, or InsG. (PMID:23100419)
• Mutation or deletion of SHANK3 has been associated with autism. (PMID:23225497)
• Copy number variation in the SHANK3 is associated with variation in fluid intelligence. (PMID:23300510)
• Lack of association between NLGN3, NLGN4, SHANK2 and SHANK3 gene variants and autism spectrum disorder in a Chinese population. (PMID:23468870)
• analysis of SHANK3 mutations associated wtih autism and their effect on ligand binding to the ankyrin repeat region (PMID:23897824)
• We show that Phelan-McDermid syndrome neurons have reduced SHANK3 expression and major defects in excitatory, but not inhibitory, synaptic transmission (PMID:24132240)
• This study is the first to identify specific chromosome 22q13.2q13.32 genomic regions, in addition to the terminal 22q13.33 genomic region encompassing SHANK3, associated with key phenotypes in Phelan-McDermid syndrome. (PMID:24136618)
• findings indicate that SHANK3 overexpression causes a hyperkinetic neuropsychiatric disorder (PMID:24153177)
• The ability to alter the epigenetic modification and expression of SHANK3 by environmental factors suggests that SHANK3 may be a valuable biomarker for dissecting the role of gene and environment interaction in the etiology of ASD. (PMID:24186872)
• This study demonistrated that the uncoupling of ProSAP2/Shank3 nuclear shuttling from synaptic activity may represent a molecular mechanism that contributes to the pathology of SCZ in patients with mutations in ProSAP2/Shank3. (PMID:24382453)
• our results suggested that this commonly genetic variant in SHANK3 gene strikingly decreased the risk of ism spectrum disorder in China. (PMID:24398551)
• because the deletions in our patients do not involve the SHANK3 gene, we posit the existence of a new contiguous gene syndrome proximal to the smallest terminal deletions in the 22q13 region. (PMID:24700646)
• This study identified and confirmed SHANK3 protein changes within the postsynaptic density in schizophrenia (PMID:25048004)
• a mutation in SHANK3 that underscores its relevance in Autism Spectrum Disorder. (PMID:25646853)
• miR-7 binds to 3-prime untranslated regions of SHANK3 mRNA and causes the alteration of neuronal morphology and function, potentially playing a crucial role in the pathophysiological process of schizophrenia (PMID:25882257)
• De novo SHANK3 mutation causes Rett syndrome-like phenotype in a female patient. (PMID:25931020)
• post-transcriptional regulation of SHANK3 expression by three microRNAs (miRNAs), miR-7, miR-34a, and miR-504, is reported. (PMID:26572867)
• these data suggest that SHANK3 mutations predispose to autism, at least partially, by inducing an Ih channelopathy that may be amenable to pharmacological intervention. (PMID:26966193)
• The association of SHANK3 gene polymorphism and autism. (PMID:27271042)
• This study does not provide evidence for a major role of SHANK3 in the pathogenesis of bipolar disorder. (PMID:27512916)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	shank3b	ENSDARG00000063054
danio_rerio	shank3a	ENSDARG00000063332
mus_musculus	Shank3	ENSMUSG00000022623
rattus_norvegicus	Shank3	ENSRNOG00000052296
drosophila_melanogaster	Prosap	FBGN0040752
caenorhabditis_elegans		WBGENE00006444

Paralogs (2): SHANK1 (ENSG00000161681), SHANK2 (ENSG00000162105)

Protein

Protein identifiers

SH3 and multiple ankyrin repeat domains protein 3 — Q9BYB0 (reviewed: Q9BYB0)

Alternative names: Proline-rich synapse-associated protein 2

All UniProt accessions (6): A0A0U1RQS4, A0A590UJL3, A0A590UJY5, A0A669K9V7, A0A669KBA8, A0A8I5KZC4

UniProt curated annotations — full annotation on UniProt →

Function. Major scaffold postsynaptic density protein which interacts with multiple proteins and complexes to orchestrate the dendritic spine and synapse formation, maturation and maintenance. Interconnects receptors of the postsynaptic membrane including NMDA-type and metabotropic glutamate receptors via complexes with GKAP/PSD-95 and HOMER, respectively, and the actin-based cytoskeleton. Plays a role in the structural and functional organization of the dendritic spine and synaptic junction through the interaction with Arp2/3 and WAVE1 complex as well as the promotion of the F-actin clusters. By way of this control of actin dynamics, participates in the regulation of developing neurons growth cone motility and the NMDA receptor-signaling. Also modulates GRIA1 exocytosis and GRM5/MGLUR5 expression and signaling to control the AMPA and metabotropic glutamate receptor-mediated synaptic transmission and plasticity. May be required at an early stage of synapse formation and be inhibited by IGF1 to promote synapse maturation.

Subunit / interactions. May homomultimerize via its SAM domain. Interacts with BAIAP2, DBNL and SLC17A7/VGLUT1. Interacts with DLGAP1/GKAP, GRM1/MGLUR1, GRM5/MGLUR5 and LZTS3 C-termini via its PDZ domain. Interacts with ABI1, HOMER1, HOMER2, HOMER3 and CTTN/cortactin SH3 domain. Is part of a complex with DLG4/PSD-95 and DLGAP1/GKAP. Interacts (via PDZ domain) with the GRIA1 subunit of the AMPA receptor (via PDZ-binding motif). Interacts with WASF1 and CYFIP2; the interactions mediate the association of SHANK3 with the WAVE1 complex. Interacts with ARPC2; the interaction probably mediates the association of SHANK3 with the Arp2/3 complex. Interacts (via ANK repeats) with SHARPIN and SPTAN1. Interacts (via PDZ domain) with ARHGAP44 (probably via PDZ-binding motif); the interaction takes place in dendritic spines and promotes GRIA1 exocytosis. Interacts with CAMK2A. Interacts with DIP2A. Interacts with ADGRL3.

Subcellular location. Cytoplasm. Postsynaptic density. Cell projection. Dendritic spine.

Tissue specificity. Expressed in the cerebral cortex and the cerebellum.

Disease relevance. A chromosomal aberration involving SHANK3 is found in patients with chromosome 22q13.3 deletion syndrome. Translocation t(12;22)(q24.1;q13.3) with APPL2/DIP13B. Defects in SHANK3 are associated with neuropsychiatric disorders such as autism spectrum disorders (ASD), bipolar affective disorders and early dementia onset. ASD are characterized by impairments in reciprocal social interaction and communication as well as restricted and stereotyped patterns of interest and activities. ASD include forms with moderate to severe cognitive impairment and milder forms with higher cognitive ability (Asperger syndrome). Gene duplication is associated with hyperkinetic neuropsychiatric disorders such as hyperactivity, auditory overstimulation, epilepsy and bipolar affective disorders, among others. Phelan-McDermid syndrome (PHMDS) [MIM:606232] A developmental disorder with variable features. Common features include neonatal hypotonia, global developmental delay, normal to accelerated growth, absent to severely delayed speech, autistic behavior, and minor dysmorphic features. The disease is caused by variants affecting the gene represented in this entry. Schizophrenia 15 (SCZD15) [MIM:613950] A complex, multifactorial psychotic disorder or group of disorders characterized by disturbances in the form and content of thought (e.g. delusions, hallucinations), in mood (e.g. inappropriate affect), in sense of self and relationship to the external world (e.g. loss of ego boundaries, withdrawal), and in behavior (e.g bizarre or apparently purposeless behavior). Although it affects emotions, it is distinguished from mood disorders in which such disturbances are primary. Similarly, there may be mild impairment of cognitive function, and it is distinguished from the dementias in which disturbed cognitive function is considered primary. Some patients manifest schizophrenic as well as bipolar disorder symptoms and are often given the diagnosis of schizoaffective disorder. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. In isoform 1, the N-terminal region preceding the ANK repeats interacts with the 6 ANK repeats in an intramolecular manner, thereby restricting access to ligands, such as SHARPIN and SPTAN1.

Miscellaneous. Primarily expressed in neurons. Produced by alternative promoter usage.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9BYB0-1	1, A	yes
Q9BYB0-3	2, B

RefSeq proteins (1): NP_001358973* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001452	SH3_domain	Domain
IPR001478	PDZ	Domain
IPR001660	SAM	Domain
IPR002110	Ankyrin_rpt	Repeat
IPR013761	SAM/pointed_sf	Homologous_superfamily
IPR036028	SH3-like_dom_sf	Homologous_superfamily
IPR036034	PDZ_sf	Homologous_superfamily
IPR036770	Ankyrin_rpt-contain_sf	Homologous_superfamily
IPR041489	PDZ_6	Domain
IPR051569

Pfam: PF00536, PF07653, PF12796, PF17820

UniProt features (120 total): modified residue 31, sequence variant 30, compositionally biased region 17, strand 12, region of interest 11, repeat 6, helix 5, domain 3, chain 1, turn 1, coiled-coil region 1, short sequence motif 1, splice variant 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
7C7I	X-RAY DIFFRACTION	2.28
7C7J	X-RAY DIFFRACTION	2.39
6CPK	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BYB0-F1	53.36	0.20

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 (31): 197, 448, 450, 463, 470, 558, 631, 770, 857, 866, 877, 966, 973, 988, 1006, 1041, 1204, 1208, 1233, 1237 …

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-6794361	Neurexins and neuroligins
R-HSA-8853659	RET signaling

MSigDB gene sets: 393 (showing top): GOBP_DENDRITE_DEVELOPMENT, GOBP_MEMORY, GOBP_POSITIVE_REGULATION_OF_SYNAPTIC_TRANSMISSION_GLUTAMATERGIC, GOBP_ACTIN_FILAMENT_BUNDLE_ORGANIZATION, GOBP_COGNITION, GOBP_BEHAVIOR, GOBP_SYNAPSE_ASSEMBLY, GOBP_REGULATION_OF_NEURONAL_SYNAPTIC_PLASTICITY, GOBP_REGULATION_OF_SYNAPTIC_TRANSMISSION_GLUTAMATERGIC, PEREZ_TP63_TARGETS, GOBP_ADULT_BEHAVIOR, GOBP_ASSOCIATIVE_LEARNING, GOBP_DENDRITIC_SPINE_DEVELOPMENT, GOBP_NEUROGENESIS, GOBP_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT

GO Biological Process (50): MAPK cascade (GO:0000165), synapse assembly (GO:0007416), learning (GO:0007612), memory (GO:0007613), associative learning (GO:0008306), striatal medium spiny neuron differentiation (GO:0021773), adult behavior (GO:0030534), negative regulation of actin filament bundle assembly (GO:0032232), social behavior (GO:0035176), vocal learning (GO:0042297), negative regulation of cell volume (GO:0045794), positive regulation of long-term neuronal synaptic plasticity (GO:0048170), brain morphogenesis (GO:0048854), synapse organization (GO:0050808), neuromuscular process controlling balance (GO:0050885), positive regulation of synapse structural plasticity (GO:0051835), positive regulation of synaptic transmission, glutamatergic (GO:0051968), dendritic spine morphogenesis (GO:0060997), positive regulation of dendritic spine development (GO:0060999), regulation of dendritic spine morphogenesis (GO:0061001), vocalization behavior (GO:0071625), postsynaptic density assembly (GO:0097107), AMPA glutamate receptor clustering (GO:0097113), NMDA glutamate receptor clustering (GO:0097114), guanylate kinase-associated protein clustering (GO:0097117), regulation of long-term synaptic potentiation (GO:1900271), positive regulation of long-term synaptic potentiation (GO:1900273), positive regulation of glutamate receptor signaling pathway (GO:1900451), regulation of long-term synaptic depression (GO:1900452), positive regulation of excitatory postsynaptic potential (GO:2000463), embryonic epithelial tube formation (GO:0001838), learning or memory (GO:0007611), locomotory behavior (GO:0007626), gene expression (GO:0010467), glial cell proliferation (GO:0014009), exploration behavior (GO:0035640), locomotory exploration behavior (GO:0035641), locomotion (GO:0040011), regulation of synaptic plasticity (GO:0048167), modulation of chemical synaptic transmission (GO:0050804)

GO Molecular Function (8): actin binding (GO:0003779), zinc ion binding (GO:0008270), SH3 domain binding (GO:0017124), synaptic receptor adaptor activity (GO:0030160), ionotropic glutamate receptor binding (GO:0035255), scaffold protein binding (GO:0097110), protein binding (GO:0005515), structural constituent of postsynaptic density (GO:0098919)

GO Cellular Component (11): cytosol (GO:0005829), plasma membrane (GO:0005886), postsynaptic density (GO:0014069), neuron projection (GO:0043005), dendritic spine (GO:0043197), neuron spine (GO:0044309), ciliary membrane (GO:0060170), cytoplasm (GO:0005737), cell projection (GO:0042995), synapse (GO:0045202), glutamatergic synapse (GO:0098978)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Protein-protein interactions at synapses	1
Axon guidance	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
learning or memory	2
behavior	2
dendritic spine development	2
intracellular signaling cassette	1
nervous system development	1
cell junction assembly	1
synapse organization	1
learning	1
striatum development	1
forebrain neuron differentiation	1
GABAergic neuron differentiation	1
regulation of actin filament bundle assembly	1
actin filament bundle assembly	1
negative regulation of cytoskeleton organization	1
negative regulation of supramolecular fiber organization	1
biological process involved in intraspecies interaction between organisms	1
auditory behavior	1
imitative learning	1
learned vocalization behavior or vocal learning	1
cell volume homeostasis	1
regulation of long-term neuronal synaptic plasticity	1
positive regulation of neurogenesis	1
brain development	1
animal organ morphogenesis	1
cell junction organization	1
musculoskeletal movement	1
neuromuscular process	1
positive regulation of cellular component organization	1
regulation of synapse structural plasticity	1
synaptic transmission, glutamatergic	1
positive regulation of synaptic transmission	1
regulation of synaptic transmission, glutamatergic	1
neuron projection development	1
neuron projection morphogenesis	1
dendrite morphogenesis	1
dendritic spine organization	1
positive regulation of developmental process	1
regulation of dendritic spine development	1
regulation of neuron projection development	1

Protein interactions and networks

STRING

3090 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SHANK3	DLG4	P78352	993
SHANK3	NLGN4X	Q8N0W4	992
SHANK3	NLGN3	Q9NZ94	987
SHANK3	DLGAP1	P78335	985
SHANK3	NLGN1	Q8N2Q7	955
SHANK3	LZTS3	O60299	953
SHANK3	RABL2B	Q9UNT1	932
SHANK3	NRXN1	Q9ULB1	925
SHANK3	RABL2A	Q9UBK7	923
SHANK3	HCLS1	P14317	900
SHANK3	CTTN	Q14247	895
SHANK3	HOMER1	Q86YM7	886
SHANK3	SYNGAP1	Q96PV0	884
SHANK3	DLGAP3	O95886	881
SHANK3	NLGN2	Q8NFZ4	864

IntAct

235 interactions, top by confidence:

A	B	Type	Score
PRMT2	SHANK3	psi-mi:“MI:0915”(physical association)	0.660
GRB2	SHANK3	psi-mi:“MI:0915”(physical association)	0.570
NCK1	SHANK3	psi-mi:“MI:0915”(physical association)	0.570
SHANK3	GRB2	psi-mi:“MI:0915”(physical association)	0.570
CHCHD3	SHANK3	psi-mi:“MI:0915”(physical association)	0.560
DLGAP1	SHANK3	psi-mi:“MI:0915”(physical association)	0.550
PDHB	SHANK3	psi-mi:“MI:0915”(physical association)	0.550
RPL3	SHANK3	psi-mi:“MI:0915”(physical association)	0.550
CSNK2B	SHANK3	psi-mi:“MI:0915”(physical association)	0.550
PLCG1	SHANK3	psi-mi:“MI:0407”(direct interaction)	0.540
PLCG1	SHANK3	psi-mi:“MI:0915”(physical association)	0.540
ACTN1	SHANK3	psi-mi:“MI:0915”(physical association)	0.510
ARHGEF7	SHANK3	psi-mi:“MI:0915”(physical association)	0.510
FLNA	SHANK3	psi-mi:“MI:0915”(physical association)	0.510
HNRNPC	SHANK3	psi-mi:“MI:0915”(physical association)	0.510
KHDRBS3	SHANK3	psi-mi:“MI:0915”(physical association)	0.510
NELL2	SHANK3	psi-mi:“MI:0915”(physical association)	0.510
PICK1	SHANK3	psi-mi:“MI:0915”(physical association)	0.510
PSMD4	SHANK3	psi-mi:“MI:0915”(physical association)	0.510
SIRT2	SHANK3	psi-mi:“MI:0915”(physical association)	0.510

BioGRID (377): SHANK3 (Affinity Capture-MS), SHANK3 (Affinity Capture-MS), SHANK3 (Biochemical Activity), SHANK3 (Protein-peptide), SHANK3 (Affinity Capture-RNA), SHANK3 (Two-hybrid), ARHGEF7 (Affinity Capture-Western), SHANK3 (Proximity Label-MS), CHCHD3 (Proximity Label-MS), SHANK3 (Affinity Capture-MS), SHANK3 (Affinity Capture-MS), DLGAP1 (Two-hybrid), DLGAP2 (Two-hybrid), DLGAP3 (Two-hybrid), DLGAP4 (Two-hybrid)

ESM2 similar proteins: A0A8P0N4K0, A2AB59, B4F7F3, D3YZU1, D3ZD05, O35681, O75427, O95382, P22455, P22607, P40748, P55144, P70218, Q06418, Q14160, Q1LZH7, Q2PS20, Q32P44, Q495M9, Q4ACU6, Q4H4B6, Q505F5, Q5F488, Q61851, Q63ZY3, Q6P9K8, Q6TLK4, Q6ZUM4, Q7KRY7, Q80T11, Q80U72, Q8BH60, Q8BX02, Q8N1G4, Q8TE68, Q8VC03, Q8VHK1, Q8VHK2, Q8WXD9, Q8WXE0

Diamond homologs: A0A140LI67, A0A8P0N4K0, A4D2P6, A5PKA5, A8MUH7, B7WN72, D3YZU1, G5ECY0, O08774, O14745, O14910, O14924, O15085, O88951, O88952, P31016, P70175, P70441, P78352, Q0P5F3, Q12923, Q13425, Q14160, Q15599, Q15700, Q28619, Q28C55, Q2KIB6, Q32LM6, Q3SZK8, Q3T0X8, Q3UHD6, Q4ACU6, Q4H4B6, Q4KL35, Q4R6G4, Q52KW0, Q5F425, Q5F488, Q5PYH5

SIGNOR signaling

16 interactions.

A	Effect	B	Mechanism
SHANK3	“up-regulates activity”	ACTN1	relocalization
DLGAP1	“up-regulates activity”	SHANK3	relocalization
DLGAP2	“up-regulates activity”	SHANK3	relocalization
DLGAP3	“up-regulates activity”	SHANK3	relocalization
DLGAP4	“up-regulates activity”	SHANK3	relocalization
DLGAP5	“up-regulates activity”	SHANK3	relocalization
SHANK3	“up-regulates quantity”	GRIA1	binding
SHANK3	“up-regulates quantity”	GRIA2	binding
SHANK3	“up-regulates quantity”	GRIA3	binding
SHANK3	“up-regulates quantity”	GRIA4	binding
SHANK3	up-regulates	“Postsynaptic density assembly”
HOMER	“up-regulates activity”	SHANK3	binding
SHANK3	“up-regulates quantity”	AMPA	relocalization
SHANK3	“up-regulates quantity”	NMDA	relocalization
CTTNBP2	“up-regulates activity”	SHANK3	binding
MAPK1	“down-regulates activity”	SHANK3	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 176 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
RHO GTPases Activate WASPs and WAVEs	9	22.1×	6e-08
Parasite infection	8	21.5×	4e-07
Leishmania phagocytosis	8	21.5×	4e-07
Downstream signal transduction	7	20.7×	4e-06
Regulation of signaling by CBL	5	19.2×	2e-04
Nephrin family interactions	5	18.4×	2e-04
FCGR3A-mediated phagocytosis	12	17.4×	2e-09
Fcgamma receptor (FCGR) dependent phagocytosis	8	17.3×	2e-06

GO biological processes:

GO term	Partners	Fold	FDR
dendrite development	7	17.4×	1e-04
focal adhesion assembly	5	16.7×	3e-03
positive regulation of substrate adhesion-dependent cell spreading	7	16.6×	1e-04
ephrin receptor signaling pathway	6	13.1×	3e-03
positive regulation of actin filament polymerization	6	12.6×	3e-03
epidermal growth factor receptor signaling pathway	6	9.4×	6e-03
negative regulation of canonical NF-kappaB signal transduction	7	7.6×	6e-03
endocytosis	9	5.4×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

1201 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	136
Likely pathogenic	63
Uncertain significance	570
Likely benign	248
Benign	79

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1012709	NM_001372044.2(SHANK3):c.3907G>T (p.Glu1303Ter)	Pathogenic
1029037	NM_001372044.2(SHANK3):c.574A>T (p.Lys192Ter)	Pathogenic
1065627	NM_001372044.2(SHANK3):c.5011_5012del (p.Gly1671fs)	Pathogenic
1098333	NM_001372044.2(SHANK3):c.957del (p.Ile320fs)	Pathogenic
1175032	NM_001372044.2(SHANK3):c.4090C>T (p.Gln1364Ter)	Pathogenic
1184123	NM_001372044.2(SHANK3):c.4401_4404del (p.Asp1469fs)	Pathogenic
1189324	NM_001372044.2(SHANK3):c.2087-2_2093del	Pathogenic
1275796	NM_001372044.2(SHANK3):c.3175G>T (p.Glu1059Ter)	Pathogenic
1323593	NM_001372044.2(SHANK3):c.1336C>T (p.Gln446Ter)	Pathogenic
1328816	NM_001372044.2(SHANK3):c.2974C>T (p.Arg992Ter)	Pathogenic
1334393	NM_001372044.2(SHANK3):c.3865dup (p.Ala1289fs)	Pathogenic
1675897	NM_001372044.2(SHANK3):c.3996_4000dup (p.Pro1334fs)	Pathogenic
1675899	NM_001372044.2(SHANK3):c.4647G>A (p.Trp1549Ter)	Pathogenic
1683569	NM_001372044.2(SHANK3):c.3952_3964del (p.Gln1318fs)	Pathogenic
1684578	NM_001372044.2(SHANK3):c.3388del (p.Glu1130fs)	Pathogenic
1700123	NM_001372044.2(SHANK3):c.4835_4839dup (p.Leu1615fs)	Pathogenic
1701444	NM_001372044.2(SHANK3):c.2838C>A (p.Tyr946Ter)	Pathogenic
1708213	NM_001372044.2(SHANK3):c.2871T>A (p.Tyr957Ter)	Pathogenic
1710228	NM_001372044.2(SHANK3):c.3251del (p.Phe1084fs)	Pathogenic
1799563	NM_001372044.2(SHANK3):c.2410_2413del (p.Asp804fs)	Pathogenic
1802552	NM_001372044.2(SHANK3):c.3952dup (p.Gln1318fs)	Pathogenic
1802605	NM_001372044.2(SHANK3):c.3502_3535del (p.Phe1168fs)	Pathogenic
1802610	NM_001372044.2(SHANK3):c.3635dup (p.Asp1212fs)	Pathogenic
1803071	NM_001372044.2(SHANK3):c.4908C>G (p.Tyr1636Ter)	Pathogenic
208759	NM_001372044.2(SHANK3):c.3904dup (p.Ala1302fs)	Pathogenic
2298744	NM_001372044.2(SHANK3):c.1619_1629dup (p.Ser544fs)	Pathogenic
235854	NM_001372044.2(SHANK3):c.3134_3149dup (p.Pro1051fs)	Pathogenic
2430063	NM_001372044.2(SHANK3):c.4907dup (p.Tyr1636Ter)	Pathogenic
2498916	NM_001372044.2(SHANK3):c.756_757del (p.Phe253fs)	Pathogenic
2499587	NM_001372044.2(SHANK3):c.4341del (p.Thr1448fs)	Pathogenic

SpliceAI

4485 predictions. Top by Δscore:

Variant	Effect	Δscore
22:50675247:TGGAG:T	donor_gain	1.0000
22:50675248:GGAG:G	donor_gain	1.0000
22:50675248:GGAGG:G	donor_gain	1.0000
22:50675249:GAG:G	donor_gain	1.0000
22:50675249:GAGG:G	donor_gain	1.0000
22:50675252:G:C	donor_loss	1.0000
22:50675252:G:GG	donor_gain	1.0000
22:50676689:CAAAG:C	donor_loss	1.0000
22:50676690:AAAG:A	donor_loss	1.0000
22:50676692:AGGTA:A	donor_loss	1.0000
22:50676693:GGT:G	donor_loss	1.0000
22:50676695:T:G	donor_loss	1.0000
22:50678583:A:AG	acceptor_gain	1.0000
22:50678584:G:GG	acceptor_gain	1.0000
22:50678690:GGAG:G	donor_gain	1.0000
22:50678691:G:GT	donor_gain	1.0000
22:50678692:AGG:A	donor_loss	1.0000
22:50678694:GTGAG:G	donor_loss	1.0000
22:50678695:T:G	donor_loss	1.0000
22:50678760:T:TA	acceptor_gain	1.0000
22:50678767:A:AG	acceptor_gain	1.0000
22:50678767:A:C	acceptor_loss	1.0000
22:50678767:AGAGT:A	acceptor_gain	1.0000
22:50678768:G:GT	acceptor_gain	1.0000
22:50678768:GA:G	acceptor_gain	1.0000
22:50678768:GAGT:G	acceptor_gain	1.0000
22:50678768:GAGTG:G	acceptor_gain	1.0000
22:50678917:GACG:G	donor_gain	1.0000
22:50678919:CGG:C	donor_loss	1.0000
22:50678921:G:GA	donor_loss	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000020644 (22:50682924 G>T), RS1000054209 (22:50679796 A>C), RS1000100637 (22:50712095 T>C), RS1000155735 (22:50713255 C>T), RS1000156970 (22:50717116 A>G), RS1000183246 (22:50725161 A>G,T), RS1000200679 (22:50673876 G>A), RS1000250108 (22:50688452 G>A), RS1000284996 (22:50688246 G>A,C), RS1000293723 (22:50730450 C>A), RS1000364280 (22:50720781 G>A,C), RS1000421652 (22:50717877 G>A), RS1000465502 (22:50694122 A>G), RS1000469981 (22:50725415 AC>A), RS1000482477 (22:50714519 A>G)

Disease associations

OMIM: gene MIM:606230 | disease phenotypes: MIM:606232, MIM:610805, MIM:613950, MIM:615493, MIM:118220, MIM:209850

GenCC curated gene-disease

Disease	Classification	Inheritance
Phelan-McDermid syndrome	Strong	Autosomal dominant
schizophrenia 15	Limited	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
Phelan-McDermid syndrome	Definitive	AD

Mondo (13): Phelan-McDermid syndrome (MONDO:0011652), intellectual disability (MONDO:0001071), congenital anomaly of kidney and urinary tract (MONDO:0019719), schizophrenia 15 (MONDO:0013498), long QT syndrome (MONDO:0002442), autism spectrum disorder (MONDO:0005258), neurodevelopmental disorder (MONDO:0700092), intellectual disability-hypotonia-spasticity-sleep disorder syndrome (MONDO:0014210), mutism (MONDO:0002905), psychotic disorder (MONDO:0005485), Charcot-Marie-Tooth disease (MONDO:0015626), autism (MONDO:0005260), neurodegenerative disease (MONDO:0005559)

Orphanet (6): Phelan-McDermid syndrome (Orphanet:48652), Renal or urinary tract malformation (Orphanet:93545), ANK3-related intellectual disability-sleep disturbance syndrome (Orphanet:356996), Charcot-Marie-Tooth disease/Hereditary motor and sensory neuropathy (Orphanet:166), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658), NON RARE IN EUROPE: Autism (Orphanet:106)

HPO phenotypes

81 total (30 of 81 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000076	Vesicoureteral reflux
HP:0000077	Abnormality of the kidney
HP:0000098	Tall stature
HP:0000113	Polycystic kidney dysplasia
HP:0000218	High palate
HP:0000252	Microcephaly
HP:0000256	Macrocephaly
HP:0000268	Dolichocephaly
HP:0000272	Malar flattening
HP:0000286	Epicanthus
HP:0000293	Full cheeks
HP:0000307	Pointed chin
HP:0000316	Hypertelorism
HP:0000331	Short chin
HP:0000336	Prominent supraorbital ridges
HP:0000343	Long philtrum
HP:0000347	Micrognathia
HP:0000365	Hearing impairment
HP:0000400	Macrotia
HP:0000411	Protruding ear
HP:0000414	Bulbous nose
HP:0000431	Wide nasal bridge
HP:0000486	Strabismus
HP:0000490	Deeply set eye
HP:0000508	Ptosis
HP:0000527	Long eyelashes
HP:0000574	Thick eyebrow
HP:0000687	Widely spaced teeth
HP:0000689	Dental malocclusion

GWAS associations

13 associations (top):

Study	Trait	p-value
GCST002147_20	Fibrinogen	3.000000e-08
GCST003194_18	Fibrinogen levels	2.000000e-10
GCST004121_19	Fibrinogen levels	4.000000e-08
GCST004122_13	Fibrinogen levels	3.000000e-08
GCST005316_271	Intelligence (MTAG)	4.000000e-09
GCST006151_5	Memory dysfunction in frontotemporal lobe dementia	8.000000e-06
GCST006585_2538	Blood protein levels	7.000000e-33
GCST007044_24	Extremely high intelligence	7.000000e-10
GCST007044_25	Extremely high intelligence	2.000000e-08
GCST008595_235	Cognitive ability, years of educational attainment or schizophrenia (pleiotropy)	3.000000e-09
GCST90002395_628	Mean platelet volume	2.000000e-38
GCST90002402_507	Platelet count	6.000000e-15
GCST90011899_89	Aspartate aminotransferase levels	2.000000e-14

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004337	intelligence
EFO:0001072	memory impairment
EFO:0004784	self reported educational attainment
EFO:0004309	platelet count
EFO:0004736	aspartate aminotransferase measurement

MeSH disease descriptors (9)

Descriptor	Name	Tree numbers
D001321	Autistic Disorder	F03.625.164.113.500
D002607	Charcot-Marie-Tooth Disease	C10.500.300.200; C10.574.500.495.200; C10.668.829.800.300.200; C16.131.666.300.200; C16.320.400.375.200
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D008133	Long QT Syndrome	C14.280.067.565; C14.280.123.625; C16.131.240.400.715; C23.550.073.547
D009155	Mutism	C10.597.606.150.500.800.500; C23.888.592.604.150.500.800.500; F03.625.875
D019636	Neurodegenerative Diseases	C10.574
D065886	Neurodevelopmental Disorders	F03.625
C566906	Cakut (supp.)
C536801	Telomeric 22q13 Monosomy Syndrome (supp.)

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
Valproic Acid	affects cotreatment, decreases expression, affects expression	4
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Aflatoxin B1	decreases expression, increases methylation	2
bisphenol F	affects cotreatment, increases methylation	1
dicrotophos	increases expression	1
chloroacetaldehyde	affects expression	1
bisphenol A	decreases methylation	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment	1
dorsomorphin	affects cotreatment, decreases expression	1
(+)-JQ1 compound	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Temozolomide	increases expression	1
Decitabine	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Vorinostat	decreases expression	1
Cidofovir	affects expression	1
Arsenic	affects methylation	1
Benzo(a)pyrene	affects methylation	1
Clodronic Acid	decreases expression	1
Doxorubicin	decreases expression	1
Estradiol	affects cotreatment, increases expression	1
Methapyrilene	increases methylation	1
Niclosamide	increases expression	1
Oxygen	increases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
1-Methyl-4-phenylpyridinium	increases expression	1
Cyclosporine	decreases expression	1

Cellosaurus cell lines

11 cell lines: 7 embryonic stem cell, 4 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_C1XU	UOHi003-A	Induced pluripotent stem cell	Female
CVCL_C9YY	CEBe033-A-2	Embryonic stem cell	Male
CVCL_C9YZ	CEBe033-A-3	Embryonic stem cell	Male
CVCL_C9Z0	CEBe033-A-4	Embryonic stem cell	Male
CVCL_C9Z1	CEBe033-A-5	Embryonic stem cell	Male
CVCL_C9Z2	CEBe033-A-6	Embryonic stem cell	Male
CVCL_C9Z3	CEBe033-A-7	Embryonic stem cell	Male
CVCL_E4CE	EYQ2-20	Embryonic stem cell	Female
CVCL_E4CG	EP2-15	Induced pluripotent stem cell	Male
CVCL_E4K1	7349-3	Induced pluripotent stem cell	Male

Clinical trials (associated diseases)

284 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
NCT02513940	PHASE4	COMPLETED	Influence of Testosterone Administration on Drug-Induced QT Interval Prolongation and Torsades de Pointes
NCT03834883	PHASE4	COMPLETED	Reducing the Risk of Drug-Induced QT Interval Lengthening in Women
NCT04169100	PHASE4	UNKNOWN	Novel Form of Acquired Long QT Syndrome
NCT04675788	PHASE4	COMPLETED	Novel Approaches for Minimizing Drug-Induced QT Interval Lengthening
NCT00391261	PHASE4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT01028820	PHASE4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01333865	PHASE4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT07281079	PHASE3	RECRUITING	A Study of NNZ-2591 in Pediatric Participants With Phelan-McDermid Syndrome
NCT07593391	PHASE3	RECRUITING	An Open-label Study of NNZ-2591 in Pediatric Participants With Phelan-McDermid Syndrome
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
NCT01525901	PHASE2	COMPLETED	Clinical Trial in 22q13 Deletion Syndrome(Phelan-McDermid Syndrome)
NCT02710084	PHASE2	COMPLETED	Piloting Treatment With Intranasal Oxytocin in Phelan-McDermid Syndrome
NCT03493607	PHASE2	COMPLETED	AMO-01 to Treat Adolescents and Adults With Phelan-McDermid Syndrome (PMS) and Co-morbid Epilepsy
NCT04003207	PHASE2	COMPLETED	Growth Hormone Treatment in Children With Phelan McDermid Syndrome
NCT05025241	PHASE2	COMPLETED	An Open-Label Study of Oral NNZ-2591 in Phelan-McDermid Syndrome (PMS-001)
NCT05187377	PHASE2	COMPLETED	A Controlled Trial of Growth Hormone in Phelan-McDermid Syndrome and Idiopathic Autism
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
NCT01648205	PHASE2	COMPLETED	Long-term Efficacy Study of Sodium Channel Blocker in LQT3 Patients
NCT02412709	PHASE2	UNKNOWN	Long QT Syndrome Screening in Newborns
NCT04581408	PHASE2	COMPLETED	Mutation-specific Therapy for the Long QT Syndrome
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)
NCT04115345	PHASE1	COMPLETED	A Study of a Renal Autologous Cell Therapy (REACT) in Patients With Chronic Kidney Disease (CKD) From Congenital Anomalies of the Kidney and Urinary Tract (CAKUT).
NCT05694169	PHASE1	TERMINATED	A Study of Participants With Chronic Kidney Disease Previously Treated With REACT
NCT00316459	PHASE1	COMPLETED	Study Evaluating the Effects of Multiple Oral Doses of ERB-041 on Cardiac Repolarization in Healthy Subjects
NCT01849003	PHASE1	COMPLETED	Study of the Effect of GS-6615 in Subjects With LQT-3
NCT02365532	PHASE1	COMPLETED	Effect of Oral GS-6615 on Dofetilide-Induced QT Prolongation, Safety, and Tolerability in Healthy Adults
NCT02412098	PHASE1	COMPLETED	Pharmacokinetics of Eleclazine in Adults With Normal and Impaired Hepatic Function
NCT02441829	PHASE1	COMPLETED	Pharmacokinetics of Eleclazine in Adults With Normal and Impaired Renal Function
NCT05759962	PHASE1	COMPLETED	Phase 1 Study of LQT-1213 in Healthy Adults