CDK5RAP2

Summary

CDK5RAP2 (CDK5 regulatory subunit associated protein 2, HGNC:18672) is a protein-coding gene on chromosome 9q33.2, encoding CDK5 regulatory subunit-associated protein 2 (Q96SN8). Potential regulator of CDK5 activity via its interaction with CDK5R1.

This gene encodes a regulator of CDK5 (cyclin-dependent kinase 5) activity. The protein encoded by this gene is localized to the centrosome and Golgi complex, interacts with CDK5R1 and pericentrin (PCNT), plays a role in centriole engagement and microtubule nucleation, and has been linked to primary microcephaly and Alzheimer’s disease. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 55755 — RefSeq curated summary.

At a glance

• Gene–disease (curated): autosomal recessive primary microcephaly (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 6
• Clinical variants (ClinVar): 1,107 total — 51 pathogenic, 28 likely-pathogenic
• Phenotypes (HPO): 29
• MANE Select transcript: NM_018249

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18672
Approved symbol	CDK5RAP2
Name	CDK5 regulatory subunit associated protein 2
Location	9q33.2
Locus type	gene with protein product
Status	Approved
Aliases	C48, FLJ10867, CEP215
Ensembl gene	ENSG00000136861
Ensembl biotype	protein_coding
OMIM	608201
Entrez	55755

Gene structure

Transcript identifiers

Ensembl transcripts: 48 — 14 protein_coding, 12 protein_coding_CDS_not_defined, 11 nonsense_mediated_decay, 11 retained_intron

ENST00000349780, ENST00000360190, ENST00000360822, ENST00000416449, ENST00000425647, ENST00000433194, ENST00000468989, ENST00000472883, ENST00000473282, ENST00000474262, ENST00000479584, ENST00000480112, ENST00000480467, ENST00000481266, ENST00000482047, ENST00000483412, ENST00000484546, ENST00000491334, ENST00000495406, ENST00000684780, ENST00000685866, ENST00000686376, ENST00000686842, ENST00000687024, ENST00000687279, ENST00000687311, ENST00000687633, ENST00000688512, ENST00000688923, ENST00000689012, ENST00000689688, ENST00000690474, ENST00000690646, ENST00000690814, ENST00000691504, ENST00000691551, ENST00000692155, ENST00000692746, ENST00000693137, ENST00000693386, ENST00000693433, ENST00000693702, ENST00000693714, ENST00000693728, ENST00000862947, ENST00000862948, ENST00000862949, ENST00000963700

RefSeq mRNA: 6 — MANE Select: NM_018249 NM_001011649, NM_001272039, NM_001410992, NM_001410993, NM_001410994, NM_018249

CCDS: CCDS43871, CCDS6823, CCDS75888, CCDS94468, CCDS94469, CCDS94470

Canonical transcript exons

ENST00000349780 — 38 exons

Exon	Start	End
ENSE00001016473	120550792	120550902
ENSE00001016474	120545714	120545790
ENSE00001089289	120568321	120568388
ENSE00001089290	120571974	120572041
ENSE00001226044	120460572	120460667
ENSE00001377554	120539041	120539164
ENSE00001832713	120388875	120389292
ENSE00003468172	120536372	120536526
ENSE00003484754	120402806	120403071
ENSE00003505175	120409127	120409316
ENSE00003507006	120470111	120470220
ENSE00003520479	120400742	120400885
ENSE00003529666	120415040	120415159
ENSE00003530188	120411358	120411474
ENSE00003538584	120471748	120471878
ENSE00003539770	120477350	120477450
ENSE00003540133	120529978	120530140
ENSE00003540496	120437295	120437527
ENSE00003546744	120408347	120408468
ENSE00003556025	120404036	120404113
ENSE00003571161	120407012	120407248
ENSE00003576763	120524986	120525078
ENSE00003580609	120467860	120467997
ENSE00003584525	120491307	120491477
ENSE00003596472	120453456	120453873
ENSE00003641813	120528744	120528797
ENSE00003643860	120527806	120527925
ENSE00003647581	120458450	120458622
ENSE00003654637	120447895	120448126
ENSE00003669943	120422693	120422741
ENSE00003672406	120518427	120518645
ENSE00003674549	120394512	120394638
ENSE00003676188	120389741	120389787
ENSE00003683541	120439399	120439972
ENSE00003684307	120487294	120487437
ENSE00003689143	120443620	120443742
ENSE00003691375	120419788	120419960
ENSE00003844797	120579920	120580167

Expression profiles

Bgee: expression breadth ubiquitous, 272 present calls, max score 98.08.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 18.0863 / max 662.9361, expressed in 1798 samples.

FANTOM5 promoters (16 alternative TSS)

Promoter ID	TPM avg	Samples expressed
102293	14.6928	1779
102277	1.2532	392
102291	0.3934	177
102279	0.3172	98
102292	0.2857	135
102281	0.2075	49
102282	0.1853	71
102276	0.1839	81
102280	0.1477	54
102275	0.1389	69

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	98.08	gold quality
ventricular zone	UBERON:0003053	96.14	gold quality
right coronary artery	UBERON:0001625	95.26	gold quality
ganglionic eminence	UBERON:0004023	94.40	gold quality
hindlimb stylopod muscle	UBERON:0004252	94.11	gold quality
gastrocnemius	UBERON:0001388	94.09	gold quality
muscle of leg	UBERON:0001383	93.83	gold quality
tendon of biceps brachii	UBERON:0008188	93.69	gold quality
minor salivary gland	UBERON:0001830	93.64	gold quality
ascending aorta	UBERON:0001496	93.63	gold quality
thoracic aorta	UBERON:0001515	93.58	gold quality
colonic epithelium	UBERON:0000397	93.56	gold quality
apex of heart	UBERON:0002098	93.30	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	93.09	gold quality
tendon	UBERON:0000043	93.06	gold quality
calcaneal tendon	UBERON:0003701	92.83	gold quality
corpus callosum	UBERON:0002336	92.53	gold quality
muscle organ	UBERON:0001630	92.52	gold quality
aorta	UBERON:0000947	92.47	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	92.41	gold quality
coronary artery	UBERON:0001621	92.36	gold quality
descending thoracic aorta	UBERON:0002345	92.33	gold quality
left coronary artery	UBERON:0001626	92.29	gold quality
right hemisphere of cerebellum	UBERON:0014890	92.28	gold quality
tibia	UBERON:0000979	92.16	gold quality
saliva-secreting gland	UBERON:0001044	92.12	gold quality
parietal pleura	UBERON:0002400	92.05	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	92.05	gold quality
mouth mucosa	UBERON:0003729	91.95	gold quality
cerebellar hemisphere	UBERON:0002245	91.89	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.20
E-MTAB-6058	no	98.09

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

2 targets.

Target	Regulation
BUB1B	Activation
MAD2L1	Activation

Upstream regulators (CollecTRI, top): YY1

miRNA regulators (miRDB)

21 targeting CDK5RAP2, 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-3646	100.00	73.56	5283
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-203A-3P	99.49	70.56	2806
HSA-MIR-5584-5P	99.49	68.22	2814
HSA-MIR-7515	99.31	68.22	1795
HSA-MIR-3614-5P	99.30	65.25	837
HSA-MIR-3064-5P	99.26	66.13	1497
HSA-MIR-3085-3P	99.26	66.16	1490
HSA-MIR-6504-5P	99.26	65.95	1487
HSA-MIR-670-3P	99.03	68.88	2404
HSA-MIR-210-5P	98.57	64.37	832
HSA-MIR-6864-5P	98.38	66.59	1079
HSA-MIR-3179	98.22	65.90	1445
HSA-MIR-15B-3P	97.85	66.68	974

Literature-anchored findings (GeneRIF, showing 40)

• Mutations in CDK5RAP2 gene is associated with autosomal recessive primary microcephaly (PMID:15793586)
• pattern of molecular evolution seen in CDK5RAP2 appears to parallel, at least approximately, that seen in two other previously identified primary microcephaly genes, microcephalin and ASPM (PMID:16631324)
• Centrosome malfunction due to the CDK5RAP2 mutations may underlie autosomal recessive primary microcephaly. (PMID:17959831)
• Cep215 associates with centrosomes throughout the cell cycle and does not appear to interact with Cep68, rootletin or C-Nap1; data suggest Cep215 functionally interacts with pericentrin (PMID:18042621)
• CDK5RAP2 is required for spindle checkpoint function. (PMID:19282672)
• Results show that CDK5RAP2 targets growing microtubule tips in association with EB1 to regulate microtubule dynamics. (PMID:19553473)
• CEP 215 regulates a dynein-dependent transport of the pericentriolar matrix proteins during the centrosome maturation. (PMID:20139723)
• CDK5RAP2 may represent a novel mechanism for centrosomal and Golgi localization. (PMID:20466722)
• We conclude that the common variations we measured in the 4 microcephaly genes, ASPM, MCPH1, CDK5RAP2, and CENPJ, do not affect the risk of Alzheimer disease (PMID:21297427)
• A report of an novel alternatively spliced variant form of hCDK5RAP2, hCDK5RAP2 variant 1 (hCDK5RAP2-V1) which lacks the 237 nucleotide residues of hCDK5RAP2 exon 32. (PMID:21346412)
• The deletion of the C-terminal structural maintenance of chromosome (SMC) domain and the p35-binding domain in both patient pedigrees 1 and 2 CDK5RAP2 is sufficient for the development of MCPH3-associated primary microcephaly. (PMID:21512315)
• Human expression pattern of CDK5RAP2 is similar to that seen in mice and is in concordance with pathology suggested by neuroimaging studies in humans and mouse (PMID:22806269)
• Sequencing of the coding exons and exon/intron splice junctions of the CDK5RAP2 gene identified homozygosity for the novel nonsense mutation, c.4441C > T (p.Arg1481*), in both affected sons (PMID:23587236)
• results reveal a key role of the dynein-dynactin complex in the dynamic recruitment of CDK5RAP2 to centrosomes (PMID:23874654)
• The CEP215-pericentrin interaction is required for centrosome maturation and subsequent bipolar spindle formation during mitosis. (PMID:24466316)
• DPP4, CDK5RAP2, and CCR6 are risk loci for rheumatoid arthritis in Han Chinese and congruence with risk variants in Europeans. (PMID:24782177)
• Cep68 degradation allows Cep215 removal from peripheral pericentriolar material (PCM) preventing centriole separation following disengagement, PCNT cleavage mediates Cep215 removal from core of the PCM to inhibit centriole disengagement and duplication (PMID:25503564)
• LRRK1 regulates mitotic spindle orientation downstream of PLK1 through CDK5RAP2-dependent centrosome maturation. (PMID:26192437)
• Three siblings with isolated agenesis of corpus callosum carry compound heterozygous variants, p.[Gly94Arg];[Asn1232Ser], in CDK5RAP2 gene. (PMID:26197979)
• These results show that Cep169 targets microtubule tips and regulates stability of microtubules with CDK5RAP2. (PMID:26485573)
• mouse expresses only one form of CDK5RAP2 that is equivalent to the human and rat alternatively spliced variant forms (PMID:26550838)
• stabilization of the centrosome-spindle pole interface by the CEP215-HSET complex could promote survival of cancer cells containing supernumerary centrosomes. (PMID:26987684)
• CDK5RAP2 may play a role in primary microcephaly and interacts with components of the Hippo signaling pathway (PMID:28004182)
• Using homozygosity mapping complemented with whole-exome, gene panel or Sanger sequencing, we identified 12 novel mutations in 3 known MCPH-associated genes - 9 in ASPM, 2 in MCPH1 and 1 in CDK5RAP2. The 2 MCPH1 mutations were homozygous microdeletions of 164,250 and 577,594 bp, respectively, for which we were able to map the exact breakpoints (PMID:28004384)
• results suggest that EB1 cooperates with CDK5RAP2 and perhaps other SXIP-containing +TIPs in tracking growing microtubule tips. (PMID:28320860)
• A frameshift mutation in CDK5RAP2 gene is associated with primary microcephaly with speech impairment and sparse eyebrows in a consanguineous Pakistani family. (PMID:28778786)
• ASPM protein is a spindle pole-focusing factor that functions redundantly with CDK5RAP2. (PMID:28883092)
• Data suggest that CDK5RAP2 and CEP170 both interact with microtubule nucleation-promoting region of AKAP350A; CEP68 interacts with distal C-terminal region of AKAP350A; AKAP350A spans the bridge between centrioles. (CDK5RAP2 = CDK5 regulatory subunit associated protein 2; CEP170 = centrosomal protein 170kDa; AKAP350A = A kinase (PRKA) anchor protein (yotiao) 9; CEP68 = centrosomal protein 68kDa) (PMID:29054927)
• new clinical manifestation of CDK5RAP2 microcephaly and congenital cataracts in a consanguineous Saudi family (PMID:29271474)
• The rs10984186 risk and rs4837766 protective polymorphic variants of theCDK5RAP2gene might act as potent genetic modifiers for AD risk and/or conversion by modulating the expres-sion of this gene. (PMID:29360470)
• CDK5RAP2 primary microcephaly is associated with hypothalamic, retinal and cochlear developmental defects. (PMID:32015000)
• Cep215 is essential for morphological differentiation of astrocytes. (PMID:33046744)
• Centriole-independent mitotic spindle assembly relies on the PCNT-CDK5RAP2 pericentriolar matrix. (PMID:33170211)
• Centromeric chromatin integrity is compromised by loss of Cdk5rap2, a transcriptional activator of CENP-A. (PMID:33725591)
• Triple deletion of TP53, PCNT, and CEP215 promotes centriole amplification in the M phase. (PMID:34233584)
• Further insights into the spectrum phenotype of TRAPPC9 and CDK5RAP2 genes, segregating independently in a large Tunisian family with intellectual disability and microcephaly. (PMID:34737153)
• CDK5RAP2 loss-of-function causes premature cell senescence via the GSK3beta/beta-catenin-WIP1 pathway. (PMID:34930892)
• CDK5RAP2 is a Wnt target gene and promotes stemness and progression of oral squamous cell carcinoma. (PMID:36774351)
• A novel missense variant in CDK5RAP2 associated with non-obstructive azoospermia. (PMID:38008501)
• MORC2 regulates RBM39-mediated CDK5RAP2 alternative splicing to promote EMT and metastasis in colon cancer. (PMID:39048555)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	cdk5rap2	ENSDARG00000024219
mus_musculus	Cdk5rap2	ENSMUSG00000039298
rattus_norvegicus	Cdk5rap2	ENSRNOG00000005788

Paralogs (1): PDE4DIP (ENSG00000178104)

Protein

Protein identifiers

CDK5 regulatory subunit-associated protein 2 — Q96SN8 (reviewed: Q96SN8)

Alternative names: CDK5 activator-binding protein C48, Centrosome-associated protein 215

All UniProt accessions (19): A0A0A0MRG9, A0A8I5KPG9, A0A8I5KRU7, Q96SN8, A0A8I5KSG3, A0A8I5KTP5, A0A8I5KWN7, A0A8I5KX24, A0A8I5KXB5, A0A8I5KXG0, A0A8I5KYJ8, A0A8I5KYS3, A0A8I5QJG6, A0A8I5QKL1, B1AMJ5, F8WBJ0, F8WCI3, F8WF55, Q5JTU8

UniProt curated annotations — full annotation on UniProt →

Function. Potential regulator of CDK5 activity via its interaction with CDK5R1. Negative regulator of centriole disengagement (licensing) which maintains centriole engagement and cohesion. Involved in regulation of mitotic spindle orientation. Plays a role in the spindle checkpoint activation by acting as a transcriptional regulator of both BUBR1 and MAD2 promoter. Together with EB1/MAPRE1, may promote microtubule polymerization, bundle formation, growth and dynamics at the plus ends. Regulates centrosomal maturation by recruitment of the gamma-tubulin ring complex (gTuRC) onto centrosomes. In complex with PDE4DIP isoform 13/MMG8/SMYLE, MAPRE1 and AKAP9, contributes to microtubules nucleation and extension from the centrosome to the cell periphery. Required for the recruitment of AKAP9 to centrosomes. Plays a role in neurogenesis.

Subunit / interactions. Homodimer. Interacts with CDK5R1 (p35 form). CDK5RAP1, CDK5RAP2 and CDK5RAP3 show competitive binding to CDK5R1. May form a complex with CDK5R1 and CDK5. Interacts with pericentrin/PCNT; the interaction is leading to centrosomal and Golgi localization of CDK5RAP2 and PCNT. Interacts with AKAP9; the interaction targets CDK5RAP2 and AKAP9 to Golgi apparatus. Interacts with MAPRE1; the interaction is direct and targets CDK5RAP2 and EB1/MAPRE1 to microtubule plus ends. Interacts with TUBG1; the interaction is leading to the centrosomal localization of CDK5RAP2 and TUBG1. Interacts with TUBGCP3. Interacts with CALM1. Interacts with CDC20. Interacts with CEP68; degradation of CEP68 in early mitosis leads to removal of CDK5RAP2 from the centrosome which promotes centriole disengagement and subsequent centriole separation. Interacts with NCKAP5L. Forms a pericentrosomal complex with AKAP9, MAPRE1 and PDE4DIP isoform 13/MMG8/SMYLE; within this complex, MAPRE1 binding to CDK5RAP2 may be mediated by PDE4DIP. Interacts with LGALS3BP; this interaction may connect the pericentrosomal complex to the gamma-tubulin ring complex (gTuRC) to promote microtubule assembly and acetylation. Interacts with CCDC66. Associates (via CM1 motif) with TUBGCP2 of the gTuRC; the interaction plays a role in gTuRC activation.

Subcellular location. Cytoplasm. Cytoskeleton. Microtubule organizing center. Centrosome. Golgi apparatus.

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

Post-translational modifications. Phosphorylated in vitro by CDK5.

Disease relevance. Microcephaly 3, primary, autosomal recessive (MCPH3) [MIM:604804] A disease defined as a head circumference more than 3 standard deviations below the age-related mean. Brain weight is markedly reduced and the cerebral cortex is disproportionately small. Despite this marked reduction in size, the gyral pattern is relatively well preserved, with no major abnormality in cortical architecture. Affected individuals have mild to moderate intellectual disability. Primary microcephaly is further defined by the absence of other syndromic features or significant neurological deficits due to degenerative brain disorder. The disease is caused by variants affecting the gene represented in this entry.

Isoforms (4)

UniProt ID	Names	Canonical?
Q96SN8-1	1	yes
Q96SN8-2	2
Q96SN8-3	3
Q96SN8-4	4

RefSeq proteins (6): NP_001011649, NP_001258968, NP_001397921, NP_001397922, NP_001397923, NP_060719* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR012943	Cnn_1N	Domain
IPR042791	CDK5RAP2	Family
IPR056273	CDK5RAP2_MYOME_CC	Domain

Pfam: PF07989, PF23246

UniProt features (47 total): region of interest 12, sequence conflict 9, modified residue 7, compositionally biased region 6, sequence variant 6, splice variant 3, mutagenesis site 3, chain 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
8RX1	ELECTRON MICROSCOPY	3.57
9G40	ELECTRON MICROSCOPY	4.3
6X0V	ELECTRON MICROSCOPY	4.5
9H9P	ELECTRON MICROSCOPY	4.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96SN8-F1	60.11	0.03

Functional residue map

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

Post-translational modifications (7): 547, 1001, 1238, 1490, 1663, 1666, 1893

Mutagenesis-validated functional residues (3):

Position	Phenotype
938–939	loss of interaction with mapre1.
1865	no effect on centrosomal attachment, golgi localization and loss of interaction with calm1; when associated with a-1869.
1869	no effect on centrosomal attachment, golgi localization and loss of interaction to calm1; when associated with a-1865.

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-2565942	Regulation of PLK1 Activity at G2/M Transition
R-HSA-380259	Loss of Nlp from mitotic centrosomes
R-HSA-380270	Recruitment of mitotic centrosome proteins and complexes
R-HSA-380284	Loss of proteins required for interphase microtubule organization from the centrosome
R-HSA-380320	Recruitment of NuMA to mitotic centrosomes
R-HSA-5620912	Anchoring of the basal body to the plasma membrane
R-HSA-8854518	AURKA Activation by TPX2

MSigDB gene sets: 308 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_DN, GOBP_CHROMOSOME_ORGANIZATION, GOBP_ESTABLISHMENT_OF_SPINDLE_ORIENTATION, GOBP_REGULATION_OF_CELL_CYCLE_CHECKPOINT, GOBP_REGULATION_OF_PROTEIN_POLYMERIZATION, GOBP_NEGATIVE_REGULATION_OF_NEURON_DIFFERENTIATION, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_CELL_POLARITY, GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, GOBP_REGULATION_OF_NUCLEAR_DIVISION, GOBP_SPINDLE_LOCALIZATION, GOBP_CELL_CYCLE_PHASE_TRANSITION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_CHROMOSOME_SEPARATION, GOBP_NEUROGENESIS, GOBP_POSITIVE_REGULATION_OF_ORGANELLE_ORGANIZATION

GO Biological Process (15): establishment of mitotic spindle orientation (GO:0000132), microtubule cytoskeleton organization (GO:0000226), microtubule bundle formation (GO:0001578), chromosome segregation (GO:0007059), centrosome cycle (GO:0007098), centriole replication (GO:0007099), brain development (GO:0007420), neurogenesis (GO:0022008), microtubule organizing center organization (GO:0031023), positive regulation of microtubule polymerization (GO:0031116), regulation of neuron differentiation (GO:0045664), negative regulation of neuron differentiation (GO:0045665), positive regulation of DNA-templated transcription (GO:0045893), negative regulation of centriole replication (GO:0046600), regulation of mitotic cell cycle spindle assembly checkpoint (GO:0090266)

GO Molecular Function (8): transcription cis-regulatory region binding (GO:0000976), calmodulin binding (GO:0005516), microtubule binding (GO:0008017), tubulin binding (GO:0015631), protein kinase binding (GO:0019901), gamma-tubulin binding (GO:0043015), protein-containing complex binding (GO:0044877), protein binding (GO:0005515)

GO Cellular Component (19): pericentriolar material (GO:0000242), spindle pole (GO:0000922), cytoplasm (GO:0005737), Golgi apparatus (GO:0005794), centrosome (GO:0005813), cytosol (GO:0005829), cytoskeleton (GO:0005856), microtubule (GO:0005874), cell junction (GO:0030054), microtubule plus-end (GO:0035371), ciliary basal body (GO:0036064), perinuclear region of cytoplasm (GO:0048471), extracellular exosome (GO:0070062), sperm midpiece (GO:0097225), sperm principal piece (GO:0097228), mitotic spindle pole (GO:0097431), gamma-tubulin ring complex (GO:0000931), microtubule organizing center (GO:0005815), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
G2/M Transition	2
Centrosome maturation	2
Loss of proteins required for interphase microtubule organization from the centrosome	1
Mitotic Prometaphase	1
Assembly of the 9+0 primary cilium	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	10
cell cycle process	3
cytoplasm	3
microtubule-based process	2
microtubule cytoskeleton organization	2
neuron differentiation	2
tubulin binding	2
binding	2
microtubule organizing center	2
microtubule cytoskeleton	2
sperm flagellum	2
mitotic cell cycle	1
establishment of mitotic spindle localization	1
establishment of spindle orientation	1
cytoskeleton organization	1
microtubule organizing center organization	1
centrosome duplication	1
centriole assembly	1
central nervous system development	1
animal organ development	1
head development	1
nervous system development	1
cell differentiation	1
cellular component organization	1
positive regulation of microtubule polymerization or depolymerization	1
regulation of microtubule polymerization	1
positive regulation of protein polymerization	1
microtubule polymerization	1
positive regulation of supramolecular fiber organization	1
regulation of cell differentiation	1
negative regulation of cell differentiation	1
regulation of neuron differentiation	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
centriole replication	1
negative regulation of centrosome duplication	1
regulation of centriole replication	1
negative regulation of organelle assembly	1
regulation of mitotic nuclear division	1

Protein interactions and networks

STRING

872 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CDK5RAP2	CEP152	O94986	969
CDK5RAP2	CPAP	Q9HC77	948
CDK5RAP2	MCPH1	Q8NEM0	942
CDK5RAP2	PCNT	O95613	942
CDK5RAP2	STIL	Q15468	932
CDK5RAP2	ASPM	Q8IZT6	932
CDK5RAP2	KIFC1	Q9BW19	851
CDK5RAP2	CEP192	Q8TEP8	847
CDK5RAP2	WDR62	O43379	846
CDK5RAP2	CDK5R1	Q15078	808
CDK5RAP2	CROCC	Q5TZA2	789
CDK5RAP2	TUBGCP4	Q9UGJ1	785
CDK5RAP2	CEP63	Q96MT8	785
CDK5RAP2	CEP135	Q66GS9	768
CDK5RAP2	LRRC45	Q96CN5	766

IntAct

139 interactions, top by confidence:

A	B	Type	Score
PRPS1	PRPSAP2	psi-mi:“MI:0914”(association)	0.840
PRKACB	PRKAR1A	psi-mi:“MI:0914”(association)	0.790
DYNLL1	BLTP3B	psi-mi:“MI:0914”(association)	0.730
PRKACA	VAPB	psi-mi:“MI:0914”(association)	0.730
CEP68	CDK5RAP2	psi-mi:“MI:0914”(association)	0.680
CEP68	CDK5RAP2	psi-mi:“MI:0915”(physical association)	0.680
FAM9C	NDC80	psi-mi:“MI:0914”(association)	0.670
DYNLL2	BLTP3B	psi-mi:“MI:0914”(association)	0.640
LPXN	PCNT	psi-mi:“MI:0914”(association)	0.640
RALBP1	JUN	psi-mi:“MI:0914”(association)	0.640
rep	TBKBP1	psi-mi:“MI:0914”(association)	0.530
MLF1	NDC80	psi-mi:“MI:0914”(association)	0.530
ZAR1L	BCL2L11	psi-mi:“MI:0914”(association)	0.530
FAM81B	PCNT	psi-mi:“MI:0914”(association)	0.530
FGL2	PCNT	psi-mi:“MI:0914”(association)	0.530
PRKAR2B	AMY1A	psi-mi:“MI:0914”(association)	0.530
BORCS6	HSBP1	psi-mi:“MI:0914”(association)	0.530
PRKACB	VAPB	psi-mi:“MI:0914”(association)	0.530
CEP68	PCNT	psi-mi:“MI:0914”(association)	0.500
CDK5RAP2	CEP72	psi-mi:“MI:0915”(physical association)	0.500

BioGRID (276): CDK5RAP2 (Affinity Capture-MS), CDK5RAP2 (Affinity Capture-MS), CDK5RAP2 (Affinity Capture-MS), CDK5RAP2 (Affinity Capture-MS), CDK5RAP2 (Affinity Capture-MS), CDK5RAP2 (Affinity Capture-MS), CDK5RAP2 (Affinity Capture-MS), CDK5RAP2 (Affinity Capture-MS), CDK5RAP2 (Affinity Capture-MS), CDK5RAP2 (Affinity Capture-Western), CDK5RAP2 (Synthetic Growth Defect), CDK5RAP2 (Synthetic Growth Defect), CDK5RAP2 (Proximity Label-MS), CDK5RAP2 (Proximity Label-MS), CDK5RAP2 (Proximity Label-MS)

ESM2 similar proteins: A0A0A6YYL3, A0JP26, A2A2Z9, A2RUR9, A6NC57, A6NI47, A6QR20, A8MYB1, A9JSR5, A9ZSY0, B2RU33, B7ZQJ9, F1M5M3, H3BUK9, O15050, P51954, P98182, Q19UN5, Q4UJ75, Q501X2, Q5CZ79, Q5DW34, Q5SQ80, Q5TYW2, Q5VUR7, Q66HB6, Q6NSI1, Q6S545, Q6S5H5, Q6S8J7, Q71S21, Q7TPV2, Q7TSC3, Q7ZT11, Q80X59, Q811D2, Q86Y13, Q86YR6, Q8IVF6, Q8IYA2

Diamond homologs: P54623, Q19UN5, Q80YT7, Q8K389, Q96SN8, Q9JLH5, Q9WUJ3, Q32LC2, Q5VU43, Q9BE52, A0A087WUL8, B4DH59, P0C2Y1, P0DPF3, Q3BBV0, Q3BBV2, Q5TAG4, Q5TI25, Q5VWK0, Q6P3W6, Q86T75, Q86XG9, Q8N660, Q96M43, Q9H094

SIGNOR signaling

13 interactions.

A	Effect	B	Mechanism
PCNT	“up-regulates activity”	CDK5RAP2	binding
CDK5RAP2	“up-regulates activity”	TUBG1	binding
CDK5RAP2	“down-regulates activity”	CDC20	binding
CDK5RAP2	“up-regulates quantity by expression”	BUB1B	“transcriptional regulation”
CDK5RAP2	“up-regulates quantity by expression”	MAD2L1	“transcriptional regulation”
CDK5RAP2	“up-regulates quantity by stabilization”	APP	phosphorylation
SPAG5	“up-regulates activity”	CDK5RAP2	relocalization
CEP72	“up-regulates activity”	CDK5RAP2	relocalization
CDK5RAP2	“up-regulates activity”	CEP152	relocalization
CDK5RAP2	“up-regulates activity”	CEP63	relocalization
CDK5RAP2	“up-regulates activity”	WDR62	relocalization
LRRK1	“up-regulates activity”	CDK5RAP2	phosphorylation
CEP68	“up-regulates activity”	CDK5RAP2	relocalization

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 157 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
PKA activation	6	41.8×	1e-07
PKA-mediated phosphorylation of CREB	6	37.6×	3e-07
PKA activation in glucagon signalling	5	36.9×	3e-06
DARPP-32 events	6	31.4×	7e-07
Centrosome maturation	10	27.9×	1e-10
Response of endothelial cells to shear stress	8	26.4×	2e-08
Anti-inflammatory response favouring Leishmania parasite infection	6	26.0×	2e-06
Leishmania parasite growth and survival	6	26.0×	2e-06

GO biological processes:

GO term	Partners	Fold	FDR
centriole replication	6	33.3×	2e-05
vascular endothelial cell response to laminar fluid shear stress	5	27.8×	5e-04
renal water homeostasis	5	19.3×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

1107 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	51
Likely pathogenic	28
Uncertain significance	456
Likely benign	349
Benign	82

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1029683	NM_018249.6(CDK5RAP2):c.1279C>T (p.Arg427Ter)	Pathogenic
1177460	NM_018249.6(CDK5RAP2):c.564_565dup (p.Lys189fs)	Pathogenic
127196	NM_018249.6(CDK5RAP2):c.524_528del (p.Gln175fs)	Pathogenic
1322052	NM_018249.6(CDK5RAP2):c.3545_3546del (p.His1182fs)	Pathogenic
1322053	NM_018249.6(CDK5RAP2):c.355G>T (p.Glu119Ter)	Pathogenic
158146	NM_018249.6(CDK5RAP2):c.4005-1G>A	Pathogenic
158157	NM_018249.6(CDK5RAP2):c.5227C>T (p.Gln1743Ter)	Pathogenic
1802606	NM_018249.6(CDK5RAP2):c.558_559del (p.Glu186fs)	Pathogenic
1995483	NM_018249.6(CDK5RAP2):c.4977T>G (p.Tyr1659Ter)	Pathogenic
209966	NM_018249.6(CDK5RAP2):c.3097del (p.Val1033fs)	Pathogenic
209967	NM_018249.6(CDK5RAP2):c.4604+1G>C	Pathogenic
210631	NM_018249.6(CDK5RAP2):c.1018del (p.Glu340fs)	Pathogenic
2188880	NM_018249.6(CDK5RAP2):c.1668_1674del (p.Leu557fs)	Pathogenic
2488	NM_018249.6(CDK5RAP2):c.246T>A (p.Tyr82Ter)	Pathogenic
2489	NM_018249.6(CDK5RAP2):c.4005-15A>G	Pathogenic
2628755	NM_018249.6(CDK5RAP2):c.448C>T (p.Arg150Ter)	Pathogenic
2673189	NM_018249.6(CDK5RAP2):c.4420C>T (p.Gln1474Ter)	Pathogenic
2687848	NM_018249.6(CDK5RAP2):c.140T>N (p.Val47Xaa)	Pathogenic
2714845	NM_018249.6(CDK5RAP2):c.2914C>T (p.Gln972Ter)	Pathogenic
2731926	NM_018249.6(CDK5RAP2):c.4566del (p.Ile1523fs)	Pathogenic
2751227	NM_018249.6(CDK5RAP2):c.923_924insCT (p.Thr308_Glu309insTer)	Pathogenic
2838897	NM_018249.6(CDK5RAP2):c.727G>T (p.Glu243Ter)	Pathogenic
3006817	NM_018249.6(CDK5RAP2):c.2457_2466del (p.Asp820fs)	Pathogenic
3014614	NM_018249.6(CDK5RAP2):c.3901C>T (p.Gln1301Ter)	Pathogenic
3063572	NM_018249.6(CDK5RAP2):c.217_220del (p.Glu73fs)	Pathogenic
3064144	NM_018249.6(CDK5RAP2):c.3851T>A (p.Leu1284Ter)	Pathogenic
3233369	NM_018249.6(CDK5RAP2):c.1865C>G (p.Ser622Ter)	Pathogenic
3245363	NC_000009.11:g.(?123334232)(123334339_?)del	Pathogenic
3336691	NM_018249.6(CDK5RAP2):c.4421del (p.Gln1474fs)	Pathogenic
3336693	NM_018249.6(CDK5RAP2):c.3460C>T (p.Gln1154Ter)	Pathogenic

SpliceAI

7037 predictions. Top by Δscore:

Variant	Effect	Δscore
9:120389788:C:CC	acceptor_gain	1.0000
9:120394506:A:AC	donor_gain	1.0000
9:120394507:C:CC	donor_gain	1.0000
9:120394507:CT:C	donor_gain	1.0000
9:120394507:CTCA:C	donor_gain	1.0000
9:120394508:TCA:T	donor_loss	1.0000
9:120394509:CACAT:C	donor_loss	1.0000
9:120394510:A:AC	donor_gain	1.0000
9:120394511:C:CC	donor_gain	1.0000
9:120394511:CA:C	donor_gain	1.0000
9:120394511:CATTG:C	donor_gain	1.0000
9:120394532:T:A	donor_gain	1.0000
9:120394548:G:C	donor_gain	1.0000
9:120394634:CCAAT:C	acceptor_gain	1.0000
9:120394635:CAAT:C	acceptor_gain	1.0000
9:120394635:CAATC:C	acceptor_gain	1.0000
9:120394636:AATC:A	acceptor_loss	1.0000
9:120394637:AT:A	acceptor_gain	1.0000
9:120394637:ATCT:A	acceptor_loss	1.0000
9:120394638:TCTA:T	acceptor_loss	1.0000
9:120394639:C:CC	acceptor_gain	1.0000
9:120394639:C:CG	acceptor_loss	1.0000
9:120394640:T:C	acceptor_loss	1.0000
9:120400737:CCTA:C	donor_loss	1.0000
9:120400739:TA:T	donor_loss	1.0000
9:120400740:A:C	donor_loss	1.0000
9:120400741:CCTG:C	donor_gain	1.0000
9:120400789:T:A	donor_gain	1.0000
9:120400881:GGACC:G	acceptor_gain	1.0000
9:120400884:CC:C	acceptor_gain	1.0000

AlphaMissense

12518 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:120550868:A:G	L77P	0.998
9:120550862:A:G	L79P	0.997
9:120545780:A:G	L106P	0.996
9:120550859:C:G	R80P	0.995
9:120550873:A:C	F75L	0.991
9:120550873:A:T	F75L	0.991
9:120550875:A:G	F75L	0.991
9:120467987:A:G	L660P	0.988
9:120550849:G:C	F83L	0.987
9:120550849:G:T	F83L	0.987
9:120550851:A:G	F83L	0.987
9:120545759:A:G	L113P	0.986
9:120550864:C:A	K78N	0.986
9:120550864:C:G	K78N	0.986
9:120545747:A:G	L117P	0.985
9:120389766:A:G	L1867P	0.982
9:120389787:A:G	L1860S	0.982
9:120550847:A:G	L84P	0.982
9:120550862:A:T	L79H	0.982
9:120550866:T:C	K78E	0.982
9:120550889:A:G	L70S	0.982
9:120415081:A:G	L1419P	0.980
9:120415103:A:G	S1412P	0.980
9:120550876:G:C	N74K	0.978
9:120550876:G:T	N74K	0.978
9:120550885:C:A	K71N	0.978
9:120550885:C:G	K71N	0.978
9:120568327:A:C	F63L	0.978
9:120568327:A:T	F63L	0.978
9:120568329:A:G	F63L	0.978

dbSNP variants (sampled 300 via entrez): RS1000018691 (9:120451592 C>A), RS1000041942 (9:120491884 C>T), RS1000047246 (9:120466713 T>A), RS1000047798 (9:120402642 T>A,C), RS1000072843 (9:120563997 C>G,T), RS1000073942 (9:120408985 C>T), RS1000094181 (9:120448338 G>A), RS1000096066 (9:120542331 C>G), RS1000101546 (9:120455053 T>C,G), RS1000108224 (9:120474689 A>C), RS1000119098 (9:120578660 G>A,C), RS1000125375 (9:120444546 T>C), RS1000155903 (9:120544594 C>T), RS1000156330 (9:120521785 A>G), RS1000157279 (9:120427366 A>C)

Disease associations

OMIM: gene MIM:608201 | disease phenotypes: MIM:604804

GenCC curated gene-disease

Disease	Classification	Inheritance
microcephaly 3, primary, autosomal recessive	Strong	Autosomal recessive
autosomal recessive primary microcephaly	Supportive	Autosomal recessive
corpus callosum, agenesis of	Limited	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
autosomal recessive primary microcephaly	Definitive	AR

Mondo (6): microcephaly 3, primary, autosomal recessive (MONDO:0011488), intellectual disability (MONDO:0001071), coloboma (MONDO:0001476), microcephaly (MONDO:0001149), corpus callosum, agenesis of (MONDO:0009022), autosomal recessive primary microcephaly (MONDO:0016660)

Orphanet (3): Autosomal recessive primary microcephaly (Orphanet:2512), OBSOLETE: Ocular coloboma (Orphanet:194), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

29 total (29 of 29 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000076	Vesicoureteral reflux
HP:0000122	Unilateral renal agenesis
HP:0000219	Thin upper lip vermilion
HP:0000252	Microcephaly
HP:0000340	Sloping forehead
HP:0000407	Sensorineural hearing impairment
HP:0000410	Mixed hearing impairment
HP:0000448	Prominent nose
HP:0000520	Proptosis
HP:0000582	Upslanted palpebral fissure
HP:0000687	Widely spaced teeth
HP:0001263	Global developmental delay
HP:0001274	Agenesis of corpus callosum
HP:0001302	Pachygyria
HP:0001338	Partial agenesis of the corpus callosum
HP:0001347	Hyperreflexia
HP:0001510	Growth delay
HP:0002119	Ventriculomegaly
HP:0002282	Gray matter heterotopia
HP:0002342	Moderate intellectual disability
HP:0002472	Small cerebral cortex
HP:0003103	Abnormal cortical bone morphology
HP:0003577	Congenital onset
HP:0004322	Short stature
HP:0007333	Hypoplasia of the frontal lobes
HP:0009879	Simplified gyral pattern
HP:0010864	Severe intellectual disability
HP:0011451	Primary microcephaly

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST000635_5	Response to statin therapy	1.000000e-06
GCST002433_5	Rheumatoid arthritis	1.000000e-16
GCST002433_8	Rheumatoid arthritis	1.000000e-12
GCST003831_30	Asthma	3.000000e-06
GCST003992_32	Photic sneeze reflex	8.000000e-34
GCST008163_36	Height	5.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007887	autosomal dominant compelling helio-ophthalmic outburst syndrome

MeSH disease descriptors (6)

Descriptor	Name	Tree numbers
D061085	Agenesis of Corpus Callosum	C10.500.034; C16.131.666.034; C23.300.008
D003103	Coloboma	C11.250.110; C11.270.147; C16.131.384.282
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
C579935	Autosomal Recessive Primary Microcephaly (supp.)
C565746	Microcephaly, Primary Autosomal Recessive, 3 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases expression	4
Resveratrol	affects cotreatment, increases expression	3
Tetrachlorodibenzodioxin	increases expression	3
bisphenol A	decreases expression, increases methylation	2
Acetaminophen	decreases expression, increases expression	2
Valproic Acid	decreases expression	2
Cyclosporine	decreases expression, increases expression	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
beta-lapachone	decreases expression	1
arsenite	affects binding, decreases reaction	1
sodium arsenite	increases expression	1
cobaltous chloride	increases expression	1
9,10-dihydro-9,10-dihydroxybenzo(a)pyrene	increases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
cupric chloride	increases expression	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
beta-methylcholine	affects expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	increases expression	1
bisphenol S	decreases methylation	1
(+)-JQ1 compound	decreases expression	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Air Pollutants	increases oxidation, affects cotreatment, increases abundance	1
Caffeine	increases phosphorylation	1

Clinical trials (associated diseases)

211 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
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
NCT01678105	PHASE2	COMPLETED	A Phase II Study of Dovitinib in Recurrent and/or Metastatic Adenoid Cystic Carcinoma of the Salivary Glands
NCT06066333	PHASE2	RECRUITING	Study of Radiotherapy and Pembrolizumab in People With Adrenocortical Carcinoma
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
NCT01898715	PHASE1	COMPLETED	Phase 1 Study of ATR-101 in Subjects With Advanced Adrenocortical Carcinoma
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)
NCT01262235	PHASE1/PHASE2	COMPLETED	A Dose Finding Study of TKM-080301 Infusion in Neuroendocrine Tumors (NET) and Adrenocortical Carcinoma (ACC) Patients
NCT00170326	Not specified	COMPLETED	Progressive Ventricular Dysfunction Prevention in Pacemaker Patients
NCT01117792	Not specified	COMPLETED	Subcutaneous Implantable Defibrillator (S-ICD) System - CE Clinical Investigation
NCT02267161	Not specified	COMPLETED	Infants With Agenesis of the Corpus Callosum
NCT02826824	Not specified	UNKNOWN	BECOME CHILDREN OF HOLDERS Corpus Callosum Agenesis Screened IN PERIOD Antenatal
NCT05843110	Not specified	UNKNOWN	Decision-making Process of Couples Confronted With Prenatal Diagnosis of an Isolated CCA
NCT06262152	Not specified	UNKNOWN	Sleep Profile of Patients With Septo-optic Dysplasia
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
NCT01652963	Not specified	UNKNOWN	Picture-based Computerised Assessment and Training of Cognitive Behaviour Therapy Skills
NCT01695395	Not specified	COMPLETED	Mental Health Care Provision for Adults With Intellectual Disability and a Mental Disorder
NCT01867554	Not specified	COMPLETED	Research and Characterization of New Genes Involved in Intellectual Disability
NCT01915381	Not specified	COMPLETED	Improving Adherence Healthy Lifestyle With a Smartphone Application Based on Adults With Intellectual Disabilities
NCT01988623	Not specified	COMPLETED	Pivotal Response Treatment for Individuals With Intellectual Disabilities
NCT02099773	Not specified	COMPLETED	Support Staff-client Interactions With Augmentative and Alternative Communication
NCT02136849	Not specified	COMPLETED	Inter-regional Project of the Great Western Exploration Approach for Exome Molecular Causes Severe Intellectual Disability Isolated or Syndromic
NCT02225041	Not specified	COMPLETED	Sedation Strategy and Cognitive Outcome After Critical Illness in Early Childhood
NCT02414438	Not specified	COMPLETED	Establishing the Clinical Utility of First StepDx PLUS and NextStepDx PLUS Study
NCT02451761	Not specified	COMPLETED	Apparently Balanced Chromosomal Translocation/ Next-generation Sequencing/ Intellectual Disability
NCT02461420	Not specified	ACTIVE_NOT_RECRUITING	Mapping the Genotype, Phenotype, and Natural History of Phelan-McDermid Syndrome