CCDC88A

Summary

CCDC88A (coiled-coil and HOOK domain protein 88A, HGNC:25523) is a protein-coding gene on chromosome 2p16.1, encoding Girdin (Q3V6T2). Bifunctional modulator of guanine nucleotide-binding proteins (G proteins).

This gene encodes a member of the Girdin family of coiled-coil domain containing proteins. The encoded protein is an actin-binding protein that is activated by the serine/threonine kinase Akt and plays a role in cytoskeleton remodeling and cell migration. The encoded protein also enhances Akt signaling by mediating phosphoinositide 3-kinase (PI3K)-dependent activation of Akt by growth factor receptor tyrosine kinases and G protein-coupled receptors. Increased expression of this gene and phosphorylation of the encoded protein may play a role in cancer metastasis. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene.

Source: NCBI Gene 55704 — RefSeq curated summary.

At a glance

• Gene–disease (curated): PEHO-like syndrome (Strong, GenCC)
• GWAS associations: 4
• Clinical variants (ClinVar): 1,187 total — 35 pathogenic, 6 likely-pathogenic
• Phenotypes (HPO): 32
• MANE Select transcript: NM_001365480

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25523
Approved symbol	CCDC88A
Name	coiled-coil and HOOK domain protein 88A
Location	2p16.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ10392, APE, GIV, HkRP1, GRDN
Ensembl gene	ENSG00000115355
Ensembl biotype	protein_coding
OMIM	609736
Entrez	55704

Gene structure

Transcript identifiers

Ensembl transcripts: 71 — 32 protein_coding, 23 retained_intron, 11 nonsense_mediated_decay, 5 protein_coding_CDS_not_defined

ENST00000263630, ENST00000336838, ENST00000412148, ENST00000413716, ENST00000426576, ENST00000430086, ENST00000436346, ENST00000444458, ENST00000456975, ENST00000468534, ENST00000471947, ENST00000474059, ENST00000476903, ENST00000642200, ENST00000642266, ENST00000642328, ENST00000642514, ENST00000642563, ENST00000642784, ENST00000642890, ENST00000643103, ENST00000643205, ENST00000643265, ENST00000643375, ENST00000643413, ENST00000643440, ENST00000643634, ENST00000643873, ENST00000644033, ENST00000644127, ENST00000644157, ENST00000644193, ENST00000644332, ENST00000644390, ENST00000644415, ENST00000644456, ENST00000644512, ENST00000644630, ENST00000644662, ENST00000644809, ENST00000644825, ENST00000644890, ENST00000645031, ENST00000645072, ENST00000645168, ENST00000645311, ENST00000645342, ENST00000645450, ENST00000645477, ENST00000645484, ENST00000645485, ENST00000645529, ENST00000645571, ENST00000645860, ENST00000645969, ENST00000646285, ENST00000646324, ENST00000646474, ENST00000646796, ENST00000647098, ENST00000647291, ENST00000647341, ENST00000647383, ENST00000647396, ENST00000647401, ENST00000647517, ENST00000647547, ENST00000935824, ENST00000935825, ENST00000935826, ENST00000935827

RefSeq mRNA: 4 — MANE Select: NM_001365480 NM_001135597, NM_001254943, NM_001365480, NM_018084

CCDS: CCDS33203, CCDS46288, CCDS58710, CCDS92755

Canonical transcript exons

ENST00000436346 — 33 exons

Exon	Start	End
ENSE00000810011	55296258	55296523
ENSE00000962829	55308809	55309023
ENSE00000962830	55301872	55302072
ENSE00000962831	55301206	55301277
ENSE00000962832	55299839	55299919
ENSE00001209869	55295597	55296056
ENSE00001353883	55328294	55328435
ENSE00001381696	55303069	55303152
ENSE00001667210	55317564	55317841
ENSE00001693893	55355579	55355751
ENSE00001703151	55349518	55349599
ENSE00001704231	55374814	55374883
ENSE00001718370	55363950	55364033
ENSE00001720581	55334094	55335164
ENSE00001720587	55291676	55291775
ENSE00001725206	55318843	55319004
ENSE00001731502	55309162	55309254
ENSE00001748939	55343648	55343792
ENSE00001754149	55339464	55339648
ENSE00001758210	55344368	55344514
ENSE00001758410	55317206	55317349
ENSE00001760267	55332566	55332693
ENSE00001767043	55322528	55322692
ENSE00001771895	55346175	55346333
ENSE00001773632	55336681	55336818
ENSE00001796190	55362308	55362448
ENSE00001797126	55372452	55372510
ENSE00001814186	55287842	55291164
ENSE00003492731	55388778	55388886
ENSE00003538538	55315928	55316114
ENSE00003623473	55418816	55418916
ENSE00003673616	55312434	55312579
ENSE00003888693	55419017	55419856

Expression profiles

Bgee: expression breadth ubiquitous, 250 present calls, max score 98.31.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 14.3335 / max 1628.2246, expressed in 1619 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
28468	10.7149	1575
28458	0.8033	208
28465	0.6402	282
28459	0.5564	152
28463	0.4742	186
28466	0.4243	204
28469	0.3793	189
28467	0.3152	140
28455	0.0109	3
28454	0.0096	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
medial globus pallidus	UBERON:0002477	98.31	gold quality
corpus callosum	UBERON:0002336	98.24	gold quality
cortical plate	UBERON:0005343	98.04	gold quality
ventricular zone	UBERON:0003053	98.00	gold quality
globus pallidus	UBERON:0001875	97.98	gold quality
calcaneal tendon	UBERON:0003701	97.36	gold quality
ganglionic eminence	UBERON:0004023	97.36	gold quality
subthalamic nucleus	UBERON:0001906	97.17	gold quality
adrenal tissue	UBERON:0018303	97.13	gold quality
tendon	UBERON:0000043	96.94	gold quality
buccal mucosa cell	CL:0002336	96.89	gold quality
inferior vagus X ganglion	UBERON:0005363	96.85	gold quality
tendon of biceps brachii	UBERON:0008188	96.77	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	96.66	gold quality
lateral globus pallidus	UBERON:0002476	96.29	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	96.26	gold quality
substantia nigra pars reticulata	UBERON:0001966	95.82	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	95.72	gold quality
superior vestibular nucleus	UBERON:0007227	95.66	gold quality
primary visual cortex	UBERON:0002436	95.45	gold quality
spinal cord	UBERON:0002240	95.43	gold quality
substantia nigra pars compacta	UBERON:0001965	95.11	gold quality
monocyte	CL:0000576	94.98	gold quality
left testis	UBERON:0004533	94.88	gold quality
mononuclear cell	CL:0000842	94.71	gold quality
right testis	UBERON:0004534	94.66	gold quality
amygdala	UBERON:0001876	94.55	gold quality
caudate nucleus	UBERON:0001873	94.47	gold quality
testis	UBERON:0000473	94.42	gold quality
pons	UBERON:0000988	94.22	gold quality

Single-cell (SCXA)

Detected in 20 experiment(s), a significant marker in 16.

Experiment	Marker?	Max mean expression
E-MTAB-11121	yes	2588.68
E-GEOD-130148	yes	1993.19
E-HCAD-23	yes	1192.42
E-CURD-122	yes	66.75
E-MTAB-7316	yes	33.35
E-GEOD-134144	yes	27.80
E-ANND-3	yes	27.27
E-MTAB-9221	yes	25.69
E-HCAD-5	yes	22.54
E-HCAD-13	yes	20.84
E-CURD-46	yes	15.77
E-MTAB-9467	yes	12.98
E-CURD-112	yes	12.76
E-CURD-88	yes	11.87
E-MTAB-6701	yes	9.64

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): STAT3

Literature-anchored findings (GeneRIF, showing 40)

• GIV is a novel Galpha-interacting protein associated with COPI transport vesicles that may play a role in Galpha-mediated effects on vesicle trafficking within the Golgi and/or between the ER and the Golgi (PMID:15749703)
• A novel Hook-related protein family and the characterisation of Hook-related protein 1. (PMID:15882442)
• HkRP1 is involved in the process of tubulation of sorting nexin-1 positive membranes from early endosome subdomains (PMID:15882442)
• The Girdin(or Akt-phosphorylation enhancer) is an actin binding protein, and Girdin is essential for the integrity of the actin cytoskeleton and cell migration and provide a direct link between Akt and cell motility. (PMID:16139227)
• the Akt/Girdin signalling pathway is essential in VEGF-mediated postneonatal angiogenesis (PMID:18264090)
• Girdin has an important role in tumor progression with aberrant activation of the Akt signaling pathway (PMID:18316593)
• The Galphai3-GIV switch serves to link direction sensing from different families of chemotactic receptors to formation of the leading edge during cell migration. (PMID:18663145)
• provides the structural and biochemical basis for the prometastatic features of GIV, making the functional disruption of this unique G alpha i-GIV interface a promising target for therapy against cancer metastasis (PMID:19211784)
• A structural determinant that renders G alpha(i) sensitive to activation by GIV/girdin is required to promote cell migration. (PMID:20157114)
• Data show that inclusion or exclusion of GIV’s GEF motif, which activates Galphai, modulates EGFR signaling, generates migration-proliferation dichotomy, and most likely influences cancer progression. (PMID:20462955)
• Studies indicate that girdin plays important roles in cancer progression and angiogenesis. (PMID:20515748)
• It was concluded that GIV-fl is a novel metastasis-related protein and an independent adverse prognosticator that may serve as a useful adjunct to traditional staging strategies in colorectal carcinoma. (PMID:20974669)
• These results provide mechanistic insights into how reversible modulation of Galpha(i3) activity by AGS3 and GIV maintains the delicate equilibrium between promotion and inhibition of autophagy. (PMID:21209316)
• SHP-1 antagonizes the action of receptor and non-receptor-tyrosine kinases on GIV and down-regulates the phospho-GIV-PI3K-Akt axis of signaling. (PMID:21799016)
• Tyrosine phosphorylation of the Galpha-interacting protein GIV promotes activation of phosphoinositide 3-kinase during cell migration. (PMID:21954290)
• High Girdin expression is associated with glioblastoma. (PMID:22020337)
• Girdin protein may be a potential new distant metastasis biomarker of breast cancer (PMID:22116776)
• This functional characterization of GIV’s guanine nucleotide exchange factor motif provides insights into the molecular interactions between nonreceptor GEFs and G proteins and the mechanisms that govern this signal transduction pathway. (PMID:22308453)
• Girdin regulates cell movement in biological contexts that require directional cell movement (PMID:22574214)
• The Girdin protein may be a potential new early liver metastasis biomarker of colorectal cancer. (PMID:22714912)
• These data demonstrate that Girdin is important for efficient cell division (PMID:22755556)
• p-Girdin expression is closely correlated with the malignant progression of breast cancer. (PMID:22780975)
• Our findings define EEA1 endosomes as major sites for proliferative signaling and establish that Galphas and GIV regulate EEA1 but not APPL endosome maturation (PMID:23051738)
• STAT3 activation is directly integrated with the receptor tyrosine kinase-GIV-G protein signaling axis. (PMID:23066027)
• These results demonstrate that girdin and its phosphorylation play an important role in neonatal vascular development and in pathological neovascularization in the retina. (PMID:23195430)
• The levels of Girdin expression correlated inversely with the survival of esophageal squamous cell carcinoma patients. (PMID:23588413)
• Girdin was identified as a new and major regulator of the insulin signal in myoblasts and skeletal muscle. (PMID:23886629)
• The expression of Girdin protein in invasive breast cancer is strongly associated with lymph node metastasis. (PMID:24155038)
• This study identified a novel GWS association (1.17 x 10(-10)) mapped to chromosome 2 at rs1437396, between MTIF2 and CCDC88A, across all of the EA and AA cohorts. (PMID:24166409)
• Up-regulated autophagy was negatively associated with Girdin level. There was a significant correlation between Girdin expression and lymph nodes metastasis in invasive ductal breast carcinoma. (PMID:24326843)
• Findings demonstrate that Dlg5 interacts with and inhibits the activity of Girdin, thereby suppressing the migration of prostate cancer cells. (PMID:24662825)
• Girdin knockdown enhances chemosensitivity of colorectal cancer cells to oxaliplatin via TOP2B down-regulation. (PMID:25009397)
• GIV expression is up-regulated in liver after fibrotic injury and is required for hepatic stellate cells activation.Girdin is a central hub for profibrogenic signalling networks during liver fibrosis. (PMID:25043713)
• This study showed that reduction of Girdin, an actin-binding protein, leads to impaired cell migration, adhesion, and invasion of human glioblastoma cells. (PMID:25060559)
• These results reveal that girdin regulates selective clathrin-mediated endocytosis via a mechanism involving dynamin 2, but not by operating as a cargo-specific adaptor. (PMID:25061227)
• Both SH2 and GEF domains of GIV are required for the formation of a ligand-activated ternary complex between GIV, Galphai3, and EGFR. (PMID:25187647)
• Expression of tumor necrosis factor receptor-assicated factor 4 correlates with expression of Girdin and promotes nuclear translocation of Girdin in breast cancer (PMID:25591657)
• The review discusses how GIV assembles alternative signaling pathways by sensing cues from various classes of surface receptors and relaying them via G protein activation. The dysregulation of this mechanism in disease is discussed. [review] (PMID:25605737)
• The study shows that girdin is phosphorylated on tyrosine 1798 when associated with structures required for migration. (PMID:25707853)
• the positive expression rate of Girdin in hepatocellular carcinoma tissues was 67.5%, higher than that found in adjacent tissues of 16.7% (PMID:25755745)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Ccdc88a	ENSMUSG00000032740
rattus_norvegicus	Ccdc88a	ENSRNOG00000004057
drosophila_melanogaster	Girdin	FBGN0283724
caenorhabditis_elegans		WBGENE00013082

Paralogs (5): CCDC88C (ENSG00000015133), HOOK2 (ENSG00000095066), HOOK1 (ENSG00000134709), CCDC88B (ENSG00000168071), HOOK3 (ENSG00000168172)

Protein

Protein identifiers

Girdin — Q3V6T2 (reviewed: Q3V6T2)

Alternative names: Akt phosphorylation enhancer, Coiled-coil domain-containing protein 88A, G alpha-interacting vesicle-associated protein, Girders of actin filament, Hook-related protein 1

All UniProt accessions (33): Q3V6T2, A0A2R8Y4C6, A0A2R8Y4W8, A0A2R8Y4X4, A0A2R8Y4Z5, A0A2R8Y562, A0A2R8Y5D7, A0A2R8Y5R4, A0A2R8Y6B2, A0A2R8Y7B1, A0A2R8Y7D4, A0A2R8Y7D9, A0A2R8Y7L3, A0A2R8Y802, A0A2R8Y820, A0A2R8Y846, A0A2R8Y885, A0A2R8YCJ0, A0A2R8YCU9, A0A2R8YCW0, A0A2R8YD81, A0A2R8YD99, A0A2R8YDS8, A0A2R8YFK8, A0A2R8YFV1, A0A2R8YG52, A0A2R8YG73, A0A2R8YGU1, A0A2U3TZV9, H0Y470, H0Y7K3, H0Y7U8, H7C2C6

UniProt curated annotations — full annotation on UniProt →

Function. Bifunctional modulator of guanine nucleotide-binding proteins (G proteins). Acts as a non-receptor guanine nucleotide exchange factor which binds to and activates guanine nucleotide-binding protein G(i) alpha subunits. Also acts as a guanine nucleotide dissociation inhibitor for guanine nucleotide-binding protein G(s) subunit alpha GNAS. Essential for cell migration. Interacts in complex with G(i) alpha subunits with the EGFR receptor, retaining EGFR at the cell membrane following ligand stimulation and promoting EGFR signaling which triggers cell migration. Binding to Gi-alpha subunits displaces the beta and gamma subunits from the heterotrimeric G-protein complex which enhances phosphoinositide 3-kinase (PI3K)-dependent phosphorylation and kinase activity of AKT1/PKB. Phosphorylation of AKT1/PKB induces the phosphorylation of downstream effectors GSK3 and FOXO1/FKHR, and regulates DNA replication and cell proliferation. Binds in its tyrosine-phosphorylated form to the phosphatidylinositol 3-kinase (PI3K) regulatory subunit PIK3R1 which enables recruitment of PIK3R1 to the EGFR receptor, enhancing PI3K activity and cell migration. Plays a role as a key modulator of the AKT-mTOR signaling pathway, controlling the tempo of the process of newborn neuron integration during adult neurogenesis, including correct neuron positioning, dendritic development and synapse formation. Inhibition of G(s) subunit alpha GNAS leads to reduced cellular levels of cAMP and suppression of cell proliferation. Essential for the integrity of the actin cytoskeleton. Required for formation of actin stress fibers and lamellipodia. May be involved in membrane sorting in the early endosome. Plays a role in ciliogenesis and cilium morphology and positioning and this may partly be through regulation of the localization of scaffolding protein CROCC/Rootletin.

Subunit / interactions. Homodimer. Interacts (via GBA motif) with guanine nucleotide-binding protein G(i) alpha subunits GNAI1, GNAI2 and GNAI3. Also interacts (via GNA motif) with guanine nucleotide-binding protein G(s) alpha subunit GNAS. Interaction with G(i) alpha subunits occurs before interaction with GNAS and is regulated by phosphorylation; phosphorylation at Ser-1675 enhances binding to G(i) alpha subunits while phosphorylation at Ser-1690 abolishes G(i) alpha subunit binding, promoting binding to GNAS. Interacts (via C-terminal SH2-like region) with growth factor receptors EGFR, INSR and KDR/VEGFR2 (via their autophosphorylated cytoplasmic tails). Forms a complex with EGFR and GNAI3 which leads to enhanced EGFR signaling and triggering of cell migration; ligand stimulation is required for recruitment of GNAI3 to the complex. Interacts (tyrosine-phosphorylated form) with phosphatidylinositol 3-kinase (PI3K) regulatory subunit PIK3R1/p85a (via SH2 domains); the interaction enables recruitment of PIK3R1 to the EGFR receptor, enhancing PI3K activity and cell migration. Interacts with serine/threonine-protein kinase PRKCQ; the interaction leads to phosphorylation of CCDC88A and inhibition of its guanine nucleotide exchange factor activity. Interacts (via C-terminus) with DISC1; the interaction is direct. Interacts with AKT proteins; the interaction is inhibited in the presence of DISC1. Interacts with AKT1/PKB (via C-terminus). The non-phosphorylated form interacts with phosphatidylinositol 4-phosphate [PI(4)P] and weakly with phosphatidylinositol 3-phosphate [PI(3)P]. Interacts with microtubules. Interacts with actin.

Subcellular location. Cell membrane. Cytoplasm. Cytosol. Cytoplasmic vesicle. Cell projection. Lamellipodium. Cytoskeleton. Cilium basal body. Microtubule organizing center. Centrosome. Centriole.

Tissue specificity. Expressed ubiquitously.

Post-translational modifications. Phosphorylation is induced by epidermal growth factor (EGF) in a phosphoinositide 3-kinase (PI3K)-dependent manner. Phosphorylation by AKT1/PKB is necessary for delocalization from the cell membrane and for cell migration. Phosphorylated on tyrosine residues which promotes binding to phosphatidylinositol 3-kinase (PI3K) regulatory subunit PIK3R1/p85a and enhances PI3K activity. Tyrosine-phosphorylated by both receptor and non-receptor tyrosine kinases in vitro. Tyrosine phosphorylation is required for AKT1-dependent phosphorylation of Ser-1417. Phosphorylation at Ser-1690 by PRKCQ disrupts interaction with GNAI3 and inhibits guanine nucleotide exchange factor activity.

Disease relevance. PEHO-like syndrome (PEHOL) [MIM:617507] An autosomal recessive syndrome characterized by microcephaly and moderately severe hypotonia manifesting at birth, seizures that progress into infantile spasms with hypsarrhythmia, brain atrophy with bilateral polymicrogyria and pachygyria, thin corpus callosum, and mild reduction in cerebellar vermis volume. Patients also display optic atrophy, severe cognitive delay, puffiness of the maxillary region of the face, and edema of the dorsum of the hands and feet. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The GBA (G-alpha binding and activating) motif mediates binding to the alpha subunits of guanine nucleotide-binding proteins (G proteins). In the presence of tyrosine-autophosphorylated growth factor receptors, the C-terminus folds into an SH2-like region which promotes the stable recruitment of CCDC88A to the growth factor receptors. The SH2-like region is phosphorylated by the growth factor receptors prior to completion of folding.

Similarity. Belongs to the CCDC88 family.

Isoforms (5)

UniProt ID	Names	Canonical?
Q3V6T2-1	1	yes
Q3V6T2-2	2
Q3V6T2-3	3
Q3V6T2-4	4
Q3V6T2-5	5

RefSeq proteins (4): NP_001129069, NP_001241872, NP_001352409, NP_060554 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001715	CH_dom	Domain
IPR036872	CH_dom_sf	Homologous_superfamily
IPR043936	HOOK_N	Domain

Pfam: PF19047

UniProt features (66 total): mutagenesis site 17, modified residue 15, compositionally biased region 11, region of interest 7, sequence conflict 6, splice variant 3, coiled-coil region 2, chain 1, domain 1, short sequence motif 1, strand 1, helix 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
6MHF	X-RAY DIFFRACTION	2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q3V6T2-F1	67.09	0.10

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 (15): 233, 237, 449, 1020, 1387, 1417, 1421, 1673, 1675, 1690, 1717, 1765, 1799, 1820, 1837

Mutagenesis-validated functional residues (17):

Position	Phenotype
1417	phosphorylation-deficient mutant which disrupts actin organization, cell migration and lamellipodia formation but has no
1417	phosphomimetic mutant which has no effect on tyrosine phosphorylation.
1675	phosphorylation-deficient mutant which disrupts binding to gnai3 and gnas.
1675	phosphomimetic mutant which results in slight increase in binding to gnai3 and gnas. increased inhibition of gnas; when
1684	no effect on guanine nucleotide exchange factor activity.
1686	abolishes interaction with and activation of gnai3 and also abolishes recruitment of gnai3 to egfr. reduced egfr autopho
1689	abolishes interaction with gnai3.
1690	phosphorylation-deficient mutant which retains the ability to bind gnai3.
1690	phosphomimetic mutant which abolishes interaction with gnai3, inhibits guanine nucleotide exchange factor activity, inhi
1723	abolishes binding to phosphorylated egfr.
1725	does not affect binding to phosphorylated egfr.
1746	abolishes binding to phosphorylated egfr.
1750	abolishes binding to phosphorylated egfr.
1765	abolishes phosphorylation and leads to reduced akt phosphorylation, impaired formation of actin stress fibers and impair
1766	increases binding to phosphorylated egfr.
1778	abolishes binding to phosphorylated egfr.
1799	abolishes phosphorylation and leads to reduced akt phosphorylation, impaired formation of actin stress fibers and impair

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-9696264	RND3 GTPase cycle
R-HSA-9696273	RND1 GTPase cycle

MSigDB gene sets: 528 (showing top): GCACCTT_MIR18A_MIR18B, RNGTGGGC_UNKNOWN, GCM_MAP4K4, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_CYTOPLASMIC_MICROTUBULE_ORGANIZATION, GOBP_ACTIN_FILAMENT_BUNDLE_ORGANIZATION, GCM_PTPRD, GOBP_REGULATION_OF_ERBB_SIGNALING_PATHWAY, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GOBP_REGULATION_OF_PHOSPHORYLATION, RORA1_01, TGCACTT_MIR519C_MIR519B_MIR519A, GOBP_PROTEIN_LOCALIZATION_TO_CILIUM, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION

GO Biological Process (20): small GTPase-mediated signal transduction (GO:0007264), nervous system development (GO:0007399), regulation of neuron projection development (GO:0010975), cell migration (GO:0016477), lamellipodium assembly (GO:0030032), cytoskeleton-dependent intracellular transport (GO:0030705), cytoplasmic microtubule organization (GO:0031122), TOR signaling (GO:0031929), activation of protein kinase activity (GO:0032147), regulation of actin cytoskeleton organization (GO:0032956), regulation of cell population proliferation (GO:0042127), positive regulation of cilium assembly (GO:0045724), positive regulation of epidermal growth factor receptor signaling pathway (GO:0045742), positive regulation of stress fiber assembly (GO:0051496), positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051897), membrane organization (GO:0061024), maintenance of protein location in plasma membrane (GO:0072660), positive regulation of protein localization to cilium (GO:1903566), signal transduction (GO:0007165), cell projection organization (GO:0030030)

GO Molecular Function (16): G-protein alpha-subunit binding (GO:0001965), actin binding (GO:0003779), protein kinase C binding (GO:0005080), guanyl-nucleotide exchange factor activity (GO:0005085), GDP-dissociation inhibitor activity (GO:0005092), epidermal growth factor receptor binding (GO:0005154), insulin receptor binding (GO:0005158), microtubule binding (GO:0008017), phosphatidylinositol binding (GO:0035091), SH2 domain binding (GO:0042169), protein homodimerization activity (GO:0042803), vascular endothelial growth factor receptor 2 binding (GO:0043184), protein kinase B binding (GO:0043422), protein serine/threonine kinase activator activity (GO:0043539), dynein light intermediate chain binding (GO:0051959), protein binding (GO:0005515)

GO Cellular Component (15): nucleoplasm (GO:0005654), cytoplasm (GO:0005737), endoplasmic reticulum (GO:0005783), Golgi apparatus (GO:0005794), centrosome (GO:0005813), centriole (GO:0005814), cytosol (GO:0005829), plasma membrane (GO:0005886), membrane (GO:0016020), lamellipodium (GO:0030027), cytoplasmic vesicle (GO:0031410), ciliary basal body (GO:0036064), cytoskeleton (GO:0005856), cell leading edge (GO:0031252), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
RHO GTPase cycle	2

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
cytoplasm	4
microtubule organizing center	3
regulation of cellular process	2
cellular component organization	2
protein binding	2
protein kinase binding	2
GDP binding	2
GTPase regulator activity	2
endomembrane system	2
intracellular membrane-bounded organelle	2
intracellular membraneless organelle	2
intracellular signaling cassette	1
system development	1
neuron projection development	1
regulation of plasma membrane bounded cell projection organization	1
cell motility	1
lamellipodium organization	1
plasma membrane bounded cell projection assembly	1
intracellular transport	1
microtubule cytoskeleton organization	1
supramolecular fiber organization	1
intracellular signal transduction	1
positive regulation of protein kinase activity	1
actin cytoskeleton organization	1
regulation of actin filament-based process	1
regulation of cytoskeleton organization	1
cell population proliferation	1
cilium assembly	1
positive regulation of plasma membrane bounded cell projection assembly	1
regulation of cilium assembly	1
positive regulation of organelle assembly	1
epidermal growth factor receptor signaling pathway	1
regulation of epidermal growth factor receptor signaling pathway	1
positive regulation of ERBB signaling pathway	1
positive regulation of actin filament bundle assembly	1
stress fiber assembly	1
regulation of stress fiber assembly	1
phosphatidylinositol 3-kinase/protein kinase B signal transduction	1
regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	1

Protein interactions and networks

STRING

1046 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CCDC88A	DISC1	Q9NRI5	800
CCDC88A	GNAI3	P08754	652
CCDC88A	AKT1	P31749	643
CCDC88A	EXOC7	Q9UPT5	634
CCDC88A	NDEL1	Q9GZM8	618
CCDC88A	GNA12	Q03113	586
CCDC88A	CDH17	Q12864	555
CCDC88A	COPB1	P53618	535
CCDC88A	GNA13	Q14344	521
CCDC88A	GSK3B	P49841	511
CCDC88A	RABIF	P47224	506
CCDC88A	GNAQ	P50148	487
CCDC88A	DLG5	Q8TDM6	472
CCDC88A	TNS1	Q9HBL0	463
CCDC88A	RHOQ	P17081	457

IntAct

126 interactions, top by confidence:

A	B	Type	Score
PRDM14	CBFA2T2	psi-mi:“MI:0914”(association)	0.860
YWHAQ	WDR62	psi-mi:“MI:0914”(association)	0.830
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
YWHAG	BLTP3B	psi-mi:“MI:2364”(proximity)	0.640
PARD3	PRKCI	psi-mi:“MI:0914”(association)	0.620
YWHAH	PLEKHG3	psi-mi:“MI:0914”(association)	0.610
YWHAB	BLTP3B	psi-mi:“MI:2364”(proximity)	0.610
YWHAH	BLTP3B	psi-mi:“MI:2364”(proximity)	0.570
CBFA2T2	CBFA2T3	psi-mi:“MI:0914”(association)	0.530
YWHAZ	BLTP3B	psi-mi:“MI:0914”(association)	0.530
FKBP6	EEF2K	psi-mi:“MI:0914”(association)	0.530
SKP2	DPYSL4	psi-mi:“MI:0914”(association)	0.530
NUP62	RGPD8	psi-mi:“MI:0914”(association)	0.530
MLF1	NDC80	psi-mi:“MI:0914”(association)	0.530
MAD2L1	PPIP5K2	psi-mi:“MI:0914”(association)	0.530
PIP	TBKBP1	psi-mi:“MI:0914”(association)	0.530
PIH1D1	URI1	psi-mi:“MI:0914”(association)	0.530
NRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.480
YWHAB	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
YWHAQ	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
HTT	CCDC88A	psi-mi:“MI:0915”(physical association)	0.370
Sgo1	OARD1	psi-mi:“MI:0914”(association)	0.350
CCDC88A		psi-mi:“MI:0914”(association)	0.350
		psi-mi:“MI:0914”(association)	0.350
Xpo1	IFT56	psi-mi:“MI:0914”(association)	0.350
EGLN3	FAM168B	psi-mi:“MI:0914”(association)	0.350
NEK4	E2F8	psi-mi:“MI:0914”(association)	0.350
APBB1	SSPOP	psi-mi:“MI:0914”(association)	0.350

BioGRID (299): AKT1 (Affinity Capture-Western), CCDC88A (Affinity Capture-Western), CCDC88A (Reconstituted Complex), CCDC88A (Affinity Capture-MS), GNAI3 (Reconstituted Complex), CCDC88A (Affinity Capture-Western), CCDC88A (Affinity Capture-MS), CCDC88A (Affinity Capture-MS), CCDC88A (Affinity Capture-MS), CCDC88A (Affinity Capture-MS), CCDC88A (Affinity Capture-MS), CCDC88A (Affinity Capture-MS), CCDC88A (Affinity Capture-MS), CCDC88A (Affinity Capture-MS), CCDC88A (Affinity Capture-MS)

ESM2 similar proteins: A0A2R8QCI3, A0JMK8, A3KGV1, A7YH32, A9X1A5, B0KWC9, B6MFW3, B8JK76, G5E861, G9G127, O35550, O35551, P59242, P85120, Q15276, Q3V6T2, Q502I3, Q5BJF6, Q5RG45, Q5SNZ0, Q5TZ80, Q5ZJ27, Q5ZKK5, Q66GS9, Q66KE8, Q6AYX5, Q6DIX6, Q6NRB0, Q6P402, Q6P5D4, Q6PGZ0, Q6VGS5, Q6ZU80, Q7TMK6, Q80UF4, Q80YF0, Q80YT7, Q86SQ7, Q8BIL5, Q8CJ99

Diamond homologs: A0A2R8QCI3, A6NC98, B4KE73, F3Y5P4, O61493, P85120, Q3V6T2, Q4QRL3, Q5SNZ0, Q6VGS5, Q7PWT9, Q86VS8, Q8BUK6, Q9P219, B4N1C2, B0WPU9, B3MNR6, B3NL60, B4G831, B4I5P7, B4JAL5, B4PAF2, B4Q9E6, B6MFW3, Q17AF4, Q24185, Q29N92, Q5TZ80, Q5ZJ27, Q6GQ73, Q7TMK6, Q8BIL5, Q6NRB0, Q96ED9, Q9UJC3

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
AKT	unknown	CCDC88A	phosphorylation
AKT1	unknown	CCDC88A	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 142 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
Activation of BAD and translocation to mitochondria	7	56.1×	4e-09
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	7	49.5×	5e-09
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	7	49.5×	5e-09
Activation of BH3-only proteins	7	36.6×	5e-08
RHO GTPases activate PKNs	7	23.4×	1e-06
Intrinsic Pathway for Apoptosis	7	21.6×	2e-06
RAF activation	6	21.2×	1e-05
Translocation of SLC2A4 (GLUT4) to the plasma membrane	11	17.9×	4e-09

GO biological processes:

GO term	Partners	Fold	FDR
protein targeting	5	14.1×	6e-03
substantia nigra development	5	14.1×	6e-03
intracellular protein localization	12	9.7×	5e-06
positive regulation of neuron projection development	8	8.4×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

1187 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	35
Likely pathogenic	6
Uncertain significance	529
Likely benign	539
Benign	32

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1355384	NM_001365480.1(CCDC88A):c.377dup (p.Leu126fs)	Pathogenic
1365714	NM_001365480.1(CCDC88A):c.1942del (p.Lys647_Ile648insTer)	Pathogenic
1380010	NM_001365480.1(CCDC88A):c.2993_2997del (p.Lys998fs)	Pathogenic
1384224	NM_001365480.1(CCDC88A):c.959_962del (p.Val320fs)	Pathogenic
1434940	NM_001365480.1(CCDC88A):c.1305_1306del (p.Gln435fs)	Pathogenic
1435609	NM_001365480.1(CCDC88A):c.4161_4162dup (p.Pro1388fs)	Pathogenic
1447949	NM_001365480.1(CCDC88A):c.893del (p.Leu298fs)	Pathogenic
1454116	NM_001365480.1(CCDC88A):c.946C>T (p.Arg316Ter)	Pathogenic
1456734	NM_001365480.1(CCDC88A):c.2524C>T (p.Arg842Ter)	Pathogenic
1458823	NM_001365480.1(CCDC88A):c.1911del (p.Glu638fs)	Pathogenic
2017679	NM_001365480.1(CCDC88A):c.739C>T (p.Gln247Ter)	Pathogenic
2032686	NM_001365480.1(CCDC88A):c.3094C>T (p.Arg1032Ter)	Pathogenic
2035420	NM_001365480.1(CCDC88A):c.1517del (p.Lys506fs)	Pathogenic
2035839	NM_001365480.1(CCDC88A):c.1609C>T (p.Gln537Ter)	Pathogenic
2080658	NM_001365480.1(CCDC88A):c.1652_1653del (p.Arg551fs)	Pathogenic
2124976	NM_001365480.1(CCDC88A):c.2131del (p.Glu711fs)	Pathogenic
2169435	NM_001365480.1(CCDC88A):c.2033del (p.Thr678fs)	Pathogenic
2423798	NC_000002.11:g.(?55544322)(55546160_?)del	Pathogenic
253149	NM_001365480.1(CCDC88A):c.2315del (p.Thr771_Leu772insTer)	Pathogenic
2693952	NM_001365480.1(CCDC88A):c.5008_5009del (p.Lys1670fs)	Pathogenic
2818087	NM_001365480.1(CCDC88A):c.925C>T (p.Arg309Ter)	Pathogenic
2819653	NM_001365480.1(CCDC88A):c.286C>T (p.Gln96Ter)	Pathogenic
3001156	NM_001365480.1(CCDC88A):c.4444del (p.Lys1481_Met1482insTer)	Pathogenic
3247479	NC_000002.11:g.(?55615894)(55616042_?)del	Pathogenic
3247481	NC_000002.11:g.(?55544322)(55566804_?)del	Pathogenic
3247482	NC_000002.11:g.(?55526955)(55539735_?)del	Pathogenic
3376503	NM_001365480.1(CCDC88A):c.1292G>A (p.Trp431Ter)	Pathogenic
3376504	NM_001365480.1(CCDC88A):c.1795_1798del (p.Thr599fs)	Pathogenic
3644068	NM_001365480.1(CCDC88A):c.3766C>T (p.Gln1256Ter)	Pathogenic
3647287	NM_001365480.1(CCDC88A):c.724C>T (p.Arg242Ter)	Pathogenic

SpliceAI

5241 predictions. Top by Δscore:

Variant	Effect	Δscore
2:55291675:CCA:C	donor_gain	1.0000
2:55302070:TGG:T	acceptor_gain	1.0000
2:55302073:C:CC	acceptor_gain	1.0000
2:55302078:A:AC	acceptor_gain	1.0000
2:55302078:A:C	acceptor_gain	1.0000
2:55302081:CAAA:C	acceptor_gain	1.0000
2:55308807:A:AC	donor_gain	1.0000
2:55308808:C:CC	donor_gain	1.0000
2:55308808:CTG:C	donor_gain	1.0000
2:55309255:C:CC	acceptor_gain	1.0000
2:55312430:CTAC:C	donor_loss	1.0000
2:55312431:TA:T	donor_loss	1.0000
2:55312432:A:AC	donor_gain	1.0000
2:55312433:C:CT	donor_gain	1.0000
2:55312464:T:TA	donor_gain	1.0000
2:55312473:T:A	donor_gain	1.0000
2:55312576:GCAA:G	acceptor_gain	1.0000
2:55312577:CAA:C	acceptor_gain	1.0000
2:55312577:CAAC:C	acceptor_gain	1.0000
2:55312580:C:CC	acceptor_gain	1.0000
2:55312580:C:CG	acceptor_loss	1.0000
2:55312581:T:A	acceptor_loss	1.0000
2:55315924:TCACC:T	donor_loss	1.0000
2:55315925:CACCT:C	donor_loss	1.0000
2:55315926:ACCTC:A	donor_loss	1.0000
2:55315932:CA:C	donor_gain	1.0000
2:55316110:TCAGC:T	acceptor_gain	1.0000
2:55316111:CAGC:C	acceptor_gain	1.0000
2:55316111:CAGCC:C	acceptor_gain	1.0000
2:55316112:AGC:A	acceptor_gain	1.0000

AlphaMissense

12447 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:55309204:A:C	I1377S	1.000
2:55309204:A:G	I1377T	1.000
2:55309216:A:G	L1373P	1.000
2:55309231:C:G	R1368P	1.000
2:55312533:A:G	L1327P	1.000
2:55312566:A:G	L1316P	1.000
2:55334299:A:G	L841P	1.000
2:55346261:C:G	A319P	1.000
2:55355597:C:G	R261T	1.000
2:55355613:C:G	A256P	1.000
2:55355621:A:G	L253P	1.000
2:55309204:A:T	I1377N	0.999
2:55309206:T:A	K1376N	0.999
2:55309206:T:G	K1376N	0.999
2:55309207:T:A	K1376I	0.999
2:55309208:T:C	K1376E	0.999
2:55309216:A:T	L1373Q	0.999
2:55309224:C:A	K1370N	0.999
2:55309224:C:G	K1370N	0.999
2:55309226:T:C	K1370E	0.999
2:55309232:G:T	R1368S	0.999
2:55309237:A:G	L1366S	0.999
2:55312491:A:G	L1341P	0.999
2:55312539:C:G	R1325P	0.999
2:55312575:A:G	L1313P	0.999
2:55317573:A:G	L1198P	0.999
2:55317594:A:G	L1191P	0.999
2:55317636:A:G	L1177P	0.999
2:55318989:C:G	A1060P	0.999
2:55318994:A:G	L1058P	0.999

dbSNP variants (sampled 300 via entrez): RS1000013818 (2:55389475 A>C), RS1000018770 (2:55308524 C>A), RS1000027740 (2:55296274 T>C,G), RS1000035642 (2:55300090 G>A,C), RS1000059306 (2:55310757 A>G), RS1000071160 (2:55309050 A>G), RS1000101028 (2:55411496 A>G), RS1000110057 (2:55392933 A>G), RS1000112846 (2:55335942 T>C), RS1000153934 (2:55345882 T>G), RS1000172844 (2:55292621 C>G), RS1000174760 (2:55412789 C>G), RS1000193790 (2:55382738 G>T), RS1000212216 (2:55336283 G>A), RS1000258535 (2:55420336 G>C)

Disease associations

OMIM: gene MIM:609736 | disease phenotypes: MIM:617507, MIM:260565

GenCC curated gene-disease

Disease	Classification	Inheritance
PEHO-like syndrome	Strong	Autosomal recessive

Mondo (4): PEHO-like syndrome (MONDO:0020495), autism spectrum disorder (MONDO:0005258), microcephaly (MONDO:0001149), PEHO syndrome (MONDO:0009841)

Orphanet (3): PEHO-like syndrome (Orphanet:99807), PEHO syndrome (Orphanet:2836), NON RARE IN EUROPE: Autism (Orphanet:106)

HPO phenotypes

32 total (30 of 32 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000194	Open mouth
HP:0000253	Progressive microcephaly
HP:0000278	Retrognathia
HP:0000286	Epicanthus
HP:0000293	Full cheeks
HP:0000340	Sloping forehead
HP:0000341	Narrow forehead
HP:0000648	Optic atrophy
HP:0000969	Edema
HP:0001182	Tapered finger
HP:0001252	Hypotonia
HP:0001272	Cerebellar atrophy
HP:0001302	Pachygyria
HP:0001319	Neonatal hypotonia
HP:0001336	Myoclonus
HP:0001339	Lissencephaly
HP:0001344	Absent speech
HP:0001347	Hyperreflexia
HP:0002069	Bilateral tonic-clonic seizure
HP:0002079	Hypoplasia of the corpus callosum
HP:0002119	Ventriculomegaly
HP:0002126	Polymicrogyria
HP:0002133	Status epilepticus
HP:0002187	Profound intellectual disability
HP:0002521	Hypsarrhythmia
HP:0003196	Short nose
HP:0003577	Congenital onset
HP:0007105	Infantile encephalopathy
HP:0011968	Feeding difficulties

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST001263_22	Height	2.000000e-08
GCST010002_365	Refractive error	3.000000e-34
GCST010726_7	Periventricular white matter hyperintensities	7.000000e-06
GCST90000025_744	Appendicular lean mass	2.000000e-11

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0005665	white matter hyperintensity measurement
EFO:0004980	appendicular lean mass

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500
C536317	PEHO syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases abundance, increases expression, affects cotreatment	3
bisphenol A	decreases methylation, increases expression, affects cotreatment, increases methylation	2
trichostatin A	affects cotreatment, decreases expression	2
perfluorooctane sulfonic acid	decreases expression	2
Arsenic	affects cotreatment, decreases expression, increases abundance, increases expression	2
Benzo(a)pyrene	affects methylation, decreases expression	2
Cadmium	increases expression, decreases expression, increases abundance	2
Formaldehyde	increases expression	2
Quercetin	affects phosphorylation, decreases expression	2
Valproic Acid	decreases expression, decreases methylation, increases expression	2
Cadmium Chloride	decreases expression, increases abundance, increases expression	2
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, decreases expression, increases oxidation, increases abundance	1
pirinixic acid	decreases expression, increases activity, affects binding	1
beta-lapachone	decreases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
aflatoxin B2	decreases methylation	1
methacrylaldehyde	affects cotreatment, decreases expression, increases oxidation, increases abundance	1
corosolic acid	increases expression	1
K 7174	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment	1
2,2’,4,4’,5-brominated diphenyl ether	decreases expression	1
torcetrapib	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Temozolomide	decreases expression	1
Sunitinib	decreases expression	1
Fulvestrant	increases methylation, affects cotreatment	1
Leflunomide	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
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
NCT01337700	PHASE4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	PHASE4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02096952	PHASE4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02235467	PHASE4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02940574	PHASE4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	PHASE4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	PHASE4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	PHASE4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	PHASE4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	PHASE4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	PHASE4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	PHASE4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	PHASE4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	PHASE4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665	PHASE4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07054697	PHASE4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	PHASE4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD
NCT07439042	PHASE4	NOT_YET_RECRUITING	Buspirone for Anxiety in Autistic Youth
NCT01302964	PHASE3	COMPLETED	Mirtazapine Treatment of Anxiety in Children and Adolescents With Pervasive Developmental Disorders
NCT01706523	PHASE3	TERMINATED	Open Label Extension Study of STX209 (Arbaclofen) in Autism Spectrum Disorders
NCT01825798	PHASE3	COMPLETED	Treatment of Overweight Induced by Antipsychotic Medication in Young People With Autism Spectrum Disorders (ASD)
NCT01972074	PHASE3	COMPLETED	Behavioral and Neural Response to Memantine in Adolescents With Autism Spectrum Disorder
NCT02985749	PHASE3	COMPLETED	A Study of Oxytocin for the Treatment of Social Impairment in Individuals With High Functioning Autism Spectrum Disorder
NCT03197922	PHASE3	COMPLETED	Treatment of Encopresis in Children With Autism Spectrum Disorders
NCT03504917	PHASE3	TERMINATED	A Study of Balovaptan in Adults With Autism Spectrum Disorder With a 2-Year Open-Label Extension
NCT03553875	PHASE3	TERMINATED	Memantine for the Treatment of Social Deficits in Youth With Disorders of Impaired Social Interactions
NCT03640156	PHASE3	COMPLETED	Modulating Socially Adaptive Mirror System Functioning in Autism by Oxytocin
NCT03715153	PHASE3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children Aged From 2 to Less Than 7 Years Old With Autism Spectrum Disorder.
NCT03715166	PHASE3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children and Adolescents Aged From 7 to Less Than 18 Years Old With Autism Spectrum Disorder
NCT04233502	PHASE3	WITHDRAWN	Efficacy and Safety of Slenyto for Insomnia in Children With ASD
NCT04578756	PHASE3	COMPLETED	Open-Label, Flexible-dose Study to Evaluate the Long-Term Safety and Tolerability of Cariprazine in the Treatment of Pediatric Participants With Schizophrenia, Bipolar I Disorder, or Autism Spectrum Disorder
NCT04623398	PHASE3	COMPLETED	Effect of Lithium in Patients With Autism Spectrum Disorder and Phelan-McDermid Syndrome (SHANK3 Haploinsufficiency)
NCT04725383	PHASE3	TERMINATED	Amitriptyline for Repetitive Behaviors in Autism Spectrum Disorders
NCT05212493	PHASE3	COMPLETED	The Effects of Medical Cannabis in Children With Autistic Spectrum Disorder
NCT05361707	PHASE3	UNKNOWN	Evaluating the Effects of Tasimelteon in Individuals With Autism Spectrum Disorder (ASD) and Sleep Disturbances
NCT05439616	PHASE3	COMPLETED	Study of Cariprazine Oral Capsules or Solution to Assess Adverse Events and Change in Irritability Due to Autism Spectrum Disorder (ASD) in Participants Aged 5-17 Years With ASD
NCT06229210	PHASE3	RECRUITING	Safety and Tolerability Trial of Lumateperone in Pediatric Patients With Schizophrenia, Bipolar Disorder or Autism Spectrum Disorder