OCRL

Summary

OCRL (OCRL inositol polyphosphate-5-phosphatase, HGNC:8108) is a protein-coding gene on chromosome Xq26.1, encoding Inositol polyphosphate 5-phosphatase OCRL (Q01968). Catalyzes the hydrolysis of the 5-position phosphate of phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) and phosphatidylinositol-3,4,5-bisphosphate (PtdIns(3,4,5)P3), with the greatest catalytic activity towards PtdIns(4,5)P2. It is haploinsufficient (ClinGen: sufficient evidence).

This gene encodes an inositol polyphosphate 5-phosphatase. This protein is involved in regulating membrane trafficking and is located in numerous subcellular locations including the trans-Golgi network, clathrin-coated vesicles and, endosomes and the plasma membrane. This protein may also play a role in primary cilium formation. Mutations in this gene cause oculocerebrorenal syndrome of Lowe and also Dent disease. Alternate splicing results in multiple transcript variants.

Source: NCBI Gene 4952 — RefSeq curated summary.

At a glance

• Gene–disease (curated): oculocerebrorenal syndrome (Definitive, ClinGen) — +1 more curated relationship
• Clinical variants (ClinVar): 1,077 total — 103 pathogenic, 58 likely-pathogenic
• Phenotypes (HPO): 159
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_000276

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8108
Approved symbol	OCRL
Name	OCRL inositol polyphosphate-5-phosphatase
Location	Xq26.1
Locus type	gene with protein product
Status	Approved
Aliases	OCRL1, Dent-2
Ensembl gene	ENSG00000122126
Ensembl biotype	protein_coding
OMIM	300535
Entrez	4952

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 9 protein_coding, 6 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

ENST00000357121, ENST00000371113, ENST00000463271, ENST00000486673, ENST00000646010, ENST00000646914, ENST00000647245, ENST00000689093, ENST00000691455, ENST00000693473, ENST00000851833, ENST00000851834, ENST00000927770, ENST00000927771, ENST00000949289, ENST00000949290, ENST00000949291

RefSeq mRNA: 3 — MANE Select: NM_000276 NM_000276, NM_001318784, NM_001587

CCDS: CCDS35393, CCDS35394

Canonical transcript exons

ENST00000371113 — 24 exons

Exon	Start	End
ENSE00000828179	129589845	129589956
ENSE00000828180	129588886	129589013
ENSE00000828181	129588179	129588263
ENSE00000828182	129587002	129587118
ENSE00000828183	129576317	129576552
ENSE00000828187	129567254	129567363
ENSE00000828188	129565772	129565883
ENSE00000828189	129562599	129562786
ENSE00000828190	129562384	129562500
ENSE00000828191	129561179	129561293
ENSE00000828192	129560550	129560651
ENSE00000828193	129558840	129559001
ENSE00001454375	129584344	129584367
ENSE00001454376	129540744	129540823
ENSE00003463920	129557861	129557950
ENSE00003477861	129575140	129575250
ENSE00003499326	129575897	129576062
ENSE00003607370	129558633	129558753
ENSE00003659695	129569264	129569399
ENSE00003662070	129544958	129545037
ENSE00003677416	129548563	129548601
ENSE00003682369	129557325	129557435
ENSE00003846657	129590146	129592556
ENSE00003848253	129540259	129540478

Expression profiles

Bgee: expression breadth ubiquitous, 225 present calls, max score 92.98.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 17.7381 / max 132.9220, expressed in 1795 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
197525	15.3149	1791
197523	1.2237	867
197526	0.9845	614
197524	0.2026	53
197522	0.0124	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endometrium epithelium	UBERON:0004811	92.98	gold quality
Brodmann (1909) area 10	UBERON:0013541	92.69	gold quality
lower esophagus muscularis layer	UBERON:0035833	92.22	gold quality
lower esophagus	UBERON:0013473	92.16	gold quality
mucosa of stomach	UBERON:0001199	91.93	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	91.84	gold quality
frontal pole	UBERON:0002795	91.74	gold quality
islet of Langerhans	UBERON:0000006	91.20	gold quality
left ovary	UBERON:0002119	90.32	gold quality
right adrenal gland cortex	UBERON:0035827	90.12	gold quality
adenohypophysis	UBERON:0002196	90.01	gold quality
right adrenal gland	UBERON:0001233	89.84	gold quality
left adrenal gland	UBERON:0001234	89.78	gold quality
left adrenal gland cortex	UBERON:0035825	89.69	gold quality
right testis	UBERON:0004534	89.54	gold quality
right ovary	UBERON:0002118	89.49	gold quality
left testis	UBERON:0004533	88.94	gold quality
middle frontal gyrus	UBERON:0002702	88.85	gold quality
left uterine tube	UBERON:0001303	88.83	gold quality
ganglionic eminence	UBERON:0004023	88.81	gold quality
paraflocculus	UBERON:0005351	88.41	gold quality
adrenal gland	UBERON:0002369	88.11	gold quality
pituitary gland	UBERON:0000007	88.08	gold quality
cortical plate	UBERON:0005343	87.59	gold quality
rectum	UBERON:0001052	87.46	gold quality
ventricular zone	UBERON:0003053	87.37	gold quality
adrenal cortex	UBERON:0001235	87.36	gold quality
stromal cell of endometrium	CL:0002255	87.05	gold quality
testis	UBERON:0000473	87.02	gold quality
body of uterus	UBERON:0009853	86.88	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.29

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ZFX

miRNA regulators (miRDB)

143 targeting OCRL, 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-450A-1-3P	100.00	69.33	1837
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-3162-3P	100.00	65.37	363
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-130A-3P	99.90	73.31	1861
HSA-MIR-130B-3P	99.90	73.27	1850
HSA-MIR-301A-3P	99.90	73.15	1839
HSA-MIR-301B-3P	99.90	73.19	1836
HSA-MIR-3666	99.90	73.24	1833
HSA-MIR-4295	99.90	73.11	1838
HSA-MIR-17-5P	99.89	73.83	2665

Functional genomics

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

Literature-anchored findings (GeneRIF, showing 40)

• The deficiency of PIP2 5-phosphatase in Lowe syndrome affects actin polymerization (PMID:12428211)
• OCRL1 interacts with Rac GTPase in the trans-Golgi network. (PMID:12915445)
• suggests that Ocrl1 is active as a PIP2 5-phosphatase in Rac induced membrane ruffles (PMID:15829501)
• OCRL1 is associated with clathrin-coated transport intermediates operating between the trans-Golgi network (TGN) and endosomes (PMID:15917292)
• p.Phe259Ser mutation found in a case of Lowe syndrome (amino acid substitution) (PMID:16420990)
• rabs play a dual role in regulation of OCRL1, firstly targeting it to the Golgi apparatus and endosomes, and secondly, directly stimulating the 5-phosphatase activity of OCRL1 after membrane recruitment. (PMID:16902405)
• One frame shift mutation and two misssense mutations were identified in three male patients with the Dent disease phenotype. (PMID:17384968)
• A role is reported for OCRL in early steps of the endocytic pathway. (PMID:17765681)
• abnormalities in the CLCN5 and OCRL1 genes in Dent’s disease [review] (PMID:18019214)
• Thus, binding to APPL1 helps localize OCRL at specific cellular sites, and disruption of this interaction may play a role in disease. (PMID:18307981)
• There are mutations involving the OCRL1 gene in patients with Lowe syndrome of Indian origin. (PMID:18500547)
• These data point to a novel role for ocrl1 in agonist-induced calcium release (PMID:19172411)
• OCRL1 exists as two functional pools, one participating in clathrin-mediated trafficking events such as endocytosis and another that is much less or not involved in this process (PMID:19211563)
• OCRL1 mutations in Dent 2 patients suggest a mechanism for phenotypic variability. (PMID:19390221)
• A novel clathrin-binding site in OCRL maps to an unusual clathrin-box motif located in a loop of the PH domain, whose mutations reduce recruitment efficiency of OCRL to coated pits. (PMID:19536138)
• Studies showed that three novel CLC-5 mutations were identified, and mutations in OCRL1, CLC-4 and cofilin excluded in causing Dent’s disease. (PMID:19546591)
• Five novel mutations in the OCRL1 gene were identified among 11 patients with the classical Dent’s disease phenotype (PMID:19582483)
• The homologous phosphatase Inpp5b was unable to complement the Ocrl1-dependent cell migration defect. (PMID:19700499)
• OCRL1 does not directly modulate endocytosis or postendocytic membrane traffic, and renal manifestations observed in Lowe syndrome patients are downstream consequences of loss of OCRL1 function. (PMID:19940034)
• This multiplex ligation-dependent probe amplification allows rapid and precise OCRL1 gene quantification. (PMID:20043897)
• Two closely related endocytic proteins, Ses1 and Ses2, which interact with OCRL, were identified. The interaction is mediated by a short amino acid motif similar to that used by the rab-5 effector APPL1. (PMID:20133602)
• evidence for link between OCRL mutations and primary haemostasis disorders in Lowe syndrome; findings suggests that an aberrant RhoA pathway in platelets contributes to CT prolongation and primary haemostasis disorders in Lowe syndrome (PMID:20629659)
• From Lowe syndrome to Dent disease: correlations between mutations of the OCRL1 gene and clinical and biochemical phenotypes (PMID:21031565)
• These data suggest that the mutations observed in OCRL are the result of two de novo events in early embryogenesis of the mother. (PMID:21225285)
• Two novel OCRL1-binding proteins, termed inositol polyphosphate phosphatase interacting protein of 27 kDa (IPIP27)A and B (also known as Ses1 and 2), that also bind the related 5-phosphatase Inpp5b, were identified. (PMID:21233288)
• children with OCRL mutations may present with very mild phenotype (asymptomatic proteinuria with/without mild mental retardation) or severe classic oculocerebrorenal syndrome of Lowe (PMID:21249396)
• OCRL1 mutation is associated with Lowe syndrome. (PMID:21378754)
• The phenylalanine and histidine (F&H) motif binding site on the RhoGAP domain of OCRL was identified. (PMID:21666675)
• the phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P2) 5-phosphatase OCRL, which is mutated in Lowe syndrome patients, is an effector of the Rab35 GTPase in cytokinesis abscission (PMID:21706022)
• Novel nonsense mutation (c.880G>T) in exon 10 and the novel insertion mutation (c.2626dupA) in exon 24 of the OCRL1 gene lead to Lowe syndrome in two Chinese families. (PMID:21854507)
• A role of OCRL1 in junctions of polarized cells may explain the pattern of organs affected in Lowe Syndrome. (PMID:21901156)
• via its 5-phosphatase activity, OCRL controls early endosome function. (PMID:21971085)
• A recurrent OCRL nonsense mutation was found to be the pathogenic mutation in a Chinese family with Lowe syndrome. (PMID:22177125)
• Lowe syndrome displays characteristics of a ciliopathy; findings reveal a novel cellular role for Ocrl1 in cilia assembly – Ocrl1 participates in ciliogenesis by contributing to protein trafficking to this organelle in an Rab8/IPIP27-dependent manner (PMID:22228094)
• Through its phosphatase activity, OCRL restricts Listeria monocytogenes invasion by modulating actin dynamics at bacterial internalization sites. (PMID:22351770)
• All seven Dent-causing OCRL mutations examined exhibited alleviation of the inhibitory effect on TRPV6-mediated Ca(2+) transport. (PMID:22378746)
• a role of OCRL in cilia maintenance and suggest the involvement of ciliary dysfunction in the manifestation of Lowe syndrome. (PMID:22543976)
• This article reviewes biophysical and structural work and discuss possible functional implications of the finding that Rab8 binds with the highest affinity to OCRL1 among the Rab proteins tested.[review] (PMID:22790198)
• The 5-phosphatase OCRL mediates retrograde transport of the mannose 6-phosphate receptor by regulating a Rac1-cofilin signalling module. (PMID:22907655)
• In our study of 187 probands with autism, we have identified a duplication in Xq25 including full gene duplication of OCRL and six flanking genes. (PMID:22965764)

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
danio_rerio	ocrl	ENSDARG00000078106
mus_musculus	Ocrl	ENSMUSG00000001173
rattus_norvegicus	Ocrl	ENSRNOG00000003875
drosophila_melanogaster	CG9784	FBGN0030761
drosophila_melanogaster	CG6805	FBGN0034179
drosophila_melanogaster	Synj	FBGN0034691
drosophila_melanogaster	sp3	FBGN0038890
caenorhabditis_elegans		WBGENE00006763
caenorhabditis_elegans	sac-2	WBGENE00012353

Paralogs (13): SYNJ2 (ENSG00000078269), FIG4 (ENSG00000112367), INPP5K (ENSG00000132376), INPP5E (ENSG00000148384), SYNJ1 (ENSG00000159082), INPPL1 (ENSG00000165458), INPP5D (ENSG00000168918), SH2D1A (ENSG00000183918), INPP5J (ENSG00000185133), SH2D1B (ENSG00000198574), INPP5F (ENSG00000198825), INPP5B (ENSG00000204084), SACM1L (ENSG00000211456)

Protein

Protein identifiers

Inositol polyphosphate 5-phosphatase OCRL — Q01968 (reviewed: Q01968)

Alternative names: Inositol polyphosphate 5-phosphatase OCRL-1, Lowe oculocerebrorenal syndrome protein, Phosphatidylinositol 3,4,5-triphosphate 5-phosphatase

All UniProt accessions (7): A0A2R8YCN4, A0A2R8YF88, A0A2R8YG38, A0A2X0TVZ9, A0A8I5KTM3, A0A8I5KYX7, Q01968

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the hydrolysis of the 5-position phosphate of phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) and phosphatidylinositol-3,4,5-bisphosphate (PtdIns(3,4,5)P3), with the greatest catalytic activity towards PtdIns(4,5)P2. Able also to hydrolyze the 5-phosphate of inositol 1,4,5-trisphosphate and of inositol 1,3,4,5-tetrakisphosphate. Regulates traffic in the endosomal pathway by regulating the specific pool of phosphatidylinositol 4,5-bisphosphate that is associated with endosomes. Involved in primary cilia assembly. Acts as a regulator of phagocytosis, hydrolyzing PtdIns(4,5)P2 to promote phagosome closure, through attenuation of PI3K signaling.

Subunit / interactions. Interacts with APPL1, PHETA1 and PHETA2; APPL1-binding and PHETA1-binding are mutually exclusive. Interacts with clathrin heavy chain. Interacts with several Rab GTPases (in their GTP-bound forms), at least RAB1B, RAB5A, RAB6A, RAB8A, RAB31 and RAB35; these interactions may play a dual role in targeting OCRL to the specific membranes and stimulating the phosphatase activity. Interaction with RAB8A modulates OCRL recruitment to cilia. Interacts with INPP5F.

Subcellular location. Cytoplasmic vesicle. Phagosome membrane. Early endosome membrane. Membrane. Clathrin-coated pit. Cell projection. Cilium. Photoreceptor outer segment. Endosome. Golgi apparatus. trans-Golgi network. Lysosome.

Tissue specificity. Brain, skeletal muscle, heart, kidney, lung, placenta and fibroblasts. Expressed in the retina and the retinal pigment epithelium.

Disease relevance. Lowe oculocerebrorenal syndrome (OCRL) [MIM:309000] X-linked multisystem disorder affecting eyes, nervous system, and kidney. It is characterized by hydrophthalmia, cataract, intellectual disability, vitamin D-resistant rickets, aminoaciduria, and reduced ammonia production by the kidney. Ocular abnormalities include cataract, glaucoma, microphthalmos, and decreased visual acuity. Developmental delay, hypotonia, behavior abnormalities, and areflexia are also present. Renal tubular involvement is characterized by impaired reabsorption of bicarbonate, amino acids, and phosphate. Musculoskeletal abnormalities such as joint hypermobility, dislocated hips, and fractures may develop as consequences of renal tubular acidosis and hypophosphatemia. Cataract is the only significant manifestation in carriers and is detected by slit-lamp examination. The disease is caused by variants affecting the gene represented in this entry. Dent disease 2 (DENT2) [MIM:300555] An X-linked renal disease belonging to the ‘Dent disease complex’, a group of disorders characterized by proximal renal tubular defect, hypercalciuria, nephrocalcinosis, and renal insufficiency. The spectrum of phenotypic features is remarkably similar in the various disorders, except for differences in the severity of bone deformities and renal impairment. Characteristic abnormalities include low-molecular-weight proteinuria and other features of Fanconi syndrome, such as glycosuria, aminoaciduria, and phosphaturia, but typically do not include proximal renal tubular acidosis. Progressive renal failure is common, as are nephrocalcinosis and kidney stones. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The ASH (ASPM-SPD2-Hydin) and RhoGAP (Rho GTPase activating) domains form a single folding module. The ASH domain has an immunoglobulin-like fold, the Rho-GAP domain lacks the catalytic arginine and is catalytically inactive. The ASH-RhoGAP module regulates the majority of the protein-protein interactions currently described. The ASH domain mediates association with membrane-targeting Rab GTPases. The Rho-GAP domain interacts with the endocytic adapter APPL1, which is then displaced by PHETA1 and PHETA2 as endosomes mature.

Similarity. Belongs to the inositol 1,4,5-trisphosphate 5-phosphatase type II family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q01968-1	A	yes
Q01968-2	B

RefSeq proteins (3): NP_000267, NP_001305713, NP_001578 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000198	RhoGAP_dom	Domain
IPR000300	IPPc	Domain
IPR008936	Rho_GTPase_activation_prot	Homologous_superfamily
IPR013783	Ig-like_fold	Homologous_superfamily
IPR031995	OCRL_clath-bd	Domain
IPR036691	Endo/exonu/phosph_ase_sf	Homologous_superfamily
IPR037787	OCRL1_PH	Domain
IPR037793	OCRL1/INPP5B_INPP5c	Domain
IPR046985	IP5	Family
IPR047078	RhoGAP_OCRL1	Domain
IPR048869	OCRL-1_2_ASH	Domain

Pfam: PF00620, PF16726, PF21310, PF22669

Enzyme classification (BRENDA):

• EC 3.1.3.36 — phosphoinositide 5-phosphatase (BRENDA: 28 organisms, 75 substrates, 33 inhibitors, 14 Km, 4 kcat entries)

Substrate kinetics (BRENDA)

7 substrates with measured Km, best-characterized 7. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
PHOSPHATIDYL-MYO-INOSITOL 4,5-BISPHOSPHATE	0.143–0.27	4
1-PHOSPHATIDYL-1D-MYO-INOSITOL 4,5-BISPHOSPHATE	0.0316–0.0738	2
1-PHOSPHATIDYL-1D-MYO-INOSITOL 3,4,5-TRIPHOSPHAT	0.088	1
1D-MYO-INOSITOL 1,4,5-TRISPHOSPHATE	0.421	1
7-METHYL-6-THIOGUANOSINE	0.056	1
INOSITOL 1,3,4,5-TETRAKISPHOSPHATE	0.028	1
INOSITOL 1,4,5-TRISPHOSPHATE	0.123	1

Catalyzed reactions (Rhea), 4 shown:

• 1D-myo-inositol 1,3,4,5-tetrakisphosphate + H2O = 1D-myo-inositol 1,3,4-trisphosphate + phosphate (RHEA:11392)
• 1D-myo-inositol 1,4,5-trisphosphate + H2O = 1D-myo-inositol 1,4-bisphosphate + phosphate (RHEA:19797)
• a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-4,5-bisphosphate) + H2O = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol 4-phosphate) + phosphate (RHEA:22764)
• a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-3,4,5-trisphosphate) + H2O = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-3,4-bisphosphate) + phosphate (RHEA:25528)

UniProt features (127 total): sequence variant 46, strand 36, helix 29, region of interest 3, mutagenesis site 3, domain 2, sequence conflict 2, short sequence motif 2, chain 1, turn 1, site 1, splice variant 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
3QBT	X-RAY DIFFRACTION	2
3QIS	X-RAY DIFFRACTION	2.3
2QV2	X-RAY DIFFRACTION	2.4
4CMN	X-RAY DIFFRACTION	3.13
2KIE	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q01968-F1	82.91	0.60

Functional residue map

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

Catalytic / active sites (1): 757 (arginine finger; crucial for gtp hydrolysis by stabilizing the transition state)

Mutagenesis-validated functional residues (3):

Position	Phenotype
422	does not affect interaction with rab8a.
499	does not affect interaction with rab8a.
668	does not interact with rab8a. does not localize to cilia.

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-1660499	Synthesis of PIPs at the plasma membrane
R-HSA-1660514	Synthesis of PIPs at the Golgi membrane
R-HSA-1855183	Synthesis of IP2, IP, and Ins in the cytosol
R-HSA-1855204	Synthesis of IP3 and IP4 in the cytosol
R-HSA-432722	Golgi Associated Vesicle Biogenesis
R-HSA-8856828	Clathrin-mediated endocytosis
R-HSA-9013409	RHOJ GTPase cycle
R-HSA-9013423	RAC3 GTPase cycle

MSigDB gene sets: 564 (showing top): GOBP_LIPID_MODIFICATION, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_PHOSPHATIDYLINOSITOL_METABOLIC_PROCESS, GOBP_PHOSPHOLIPID_DEPHOSPHORYLATION, GOBP_INOSITOL_PHOSPHATE_METABOLIC_PROCESS, GOBP_POLYOL_METABOLIC_PROCESS, TATTATA_MIR374, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, RIZKI_TUMOR_INVASIVENESS_3D_DN, REACTOME_MEMBRANE_TRAFFICKING, GOMF_GTPASE_BINDING, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_PHOSPHATIDYLINOSITOL_3_PHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_PHOSPHOLIPID_BIOSYNTHETIC_PROCESS

GO Biological Process (13): in utero embryonic development (GO:0001701), lipid metabolic process (GO:0006629), phosphatidylinositol biosynthetic process (GO:0006661), signal transduction (GO:0007165), inositol phosphate metabolic process (GO:0043647), phosphatidylinositol dephosphorylation (GO:0046856), cilium assembly (GO:0060271), membrane organization (GO:0061024), phospholipid metabolic process (GO:0006644), cell projection organization (GO:0030030), phosphatidylinositol-3-phosphate biosynthetic process (GO:0036092), glycerolipid metabolic process (GO:0046486), phosphatidylinositol metabolic process (GO:0046488)

GO Molecular Function (15): phosphatidylinositol-4,5-bisphosphate 5-phosphatase activity (GO:0004439), GTPase activator activity (GO:0005096), small GTPase binding (GO:0031267), phosphatidylinositol-3,4,5-trisphosphate 5-phosphatase activity (GO:0034485), phosphatidylinositol phosphate 4-phosphatase activity (GO:0034596), phosphatidylinositol-3,5-bisphosphate 5-phosphatase activity (GO:0043813), inositol-1,4,5-trisphosphate 5-phosphatase activity (GO:0052658), inositol-1,3,4,5-tetrakisphosphate 5-phosphatase activity (GO:0052659), inositol phosphate phosphatase activity (GO:0052745), inositol-polyphosphate 5-phosphatase activity (GO:0004445), protein binding (GO:0005515), hydrolase activity (GO:0016787), phosphatase activity (GO:0016791), phosphatidylinositol bisphosphate phosphatase activity (GO:0034593), phosphatidylinositol phosphate 5-phosphatase activity (GO:0034595)

GO Cellular Component (24): photoreceptor outer segment (GO:0001750), nucleus (GO:0005634), cytoplasm (GO:0005737), lysosome (GO:0005764), early endosome (GO:0005769), Golgi stack (GO:0005795), Golgi-associated vesicle (GO:0005798), trans-Golgi network (GO:0005802), cytosol (GO:0005829), plasma membrane (GO:0005886), clathrin-coated pit (GO:0005905), cilium (GO:0005929), microtubule cytoskeleton (GO:0015630), membrane (GO:0016020), clathrin-coated vesicle (GO:0030136), phagocytic vesicle membrane (GO:0030670), early endosome membrane (GO:0031901), centriolar satellite (GO:0034451), ciliary basal body (GO:0036064), neuron projection (GO:0043005), endosome (GO:0005768), Golgi apparatus (GO:0005794), cytoplasmic vesicle (GO:0031410), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
PI Metabolism	2
Inositol phosphate metabolism	2
RHO GTPase cycle	2
trans-Golgi Network Vesicle Budding	1
Membrane Trafficking	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
phosphatidylinositol phosphate 5-phosphatase activity	3
phosphatidylinositol phosphate phosphatase activity	3
phosphatidylinositol metabolic process	2
organophosphate metabolic process	2
cellular component organization	2
lipid metabolic process	2
inositol-polyphosphate 5-phosphatase activity	2
Golgi apparatus subcompartment	2
membrane	2
plasma membrane bounded cell projection	2
chordate embryonic development	1
primary metabolic process	1
biosynthetic process	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
polyol metabolic process	1
phospholipid dephosphorylation	1
axoneme assembly	1
intraciliary transport involved in cilium assembly	1
cilium organization	1
protein localization to cilium	1
organelle assembly	1
trans-Golgi to periciliary membrane compartment transport	1
plasma membrane bounded cell projection assembly	1
ciliary transition zone assembly	1
phosphatidylinositol phosphate biosynthetic process	1
phosphorus metabolic process	1
phosphatidylinositol-4,5-bisphosphate phosphatase activity	1
GTPase activity	1
enzyme activator activity	1
GTPase regulator activity	1
GTPase binding	1
phosphatidylinositol trisphosphate phosphatase activity	1
phosphatidylinositol-3-phosphate biosynthetic process	1
phosphatidylinositol-3,5-bisphosphate phosphatase activity	1
inositol tetrakisphosphate phosphatase activity	1

Protein interactions and networks

STRING

1864 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
OCRL	APPL1	Q9UKG1	952
OCRL	RAB35	Q15286	943
OCRL	CLCN5	P51795	937
OCRL	RAB5A	P20339	914
OCRL	RAB8A	P24407	905
OCRL	ARF6	P26438	803
OCRL	GOLGA5	Q8TBA6	766
OCRL	ARHGAP1	Q07960	759
OCRL	RAB6A	P20340	728
OCRL	AMPH	P49418	681
OCRL	ARF1	P10947	680
OCRL	INPP5A	Q14642	670
OCRL	CLTCL1	P53675	666
OCRL	CLINT1	Q14677	656
OCRL	CLTC	Q00610	643

IntAct

165 interactions, top by confidence:

A	B	Type	Score
OCRL	RAB6A	psi-mi:“MI:0407”(direct interaction)	0.870
OCRL	RAB8A	psi-mi:“MI:0407”(direct interaction)	0.870
RAB8A	OCRL	psi-mi:“MI:0407”(direct interaction)	0.870
OCRL	RAB8A	psi-mi:“MI:0915”(physical association)	0.870
RAB6A	OCRL	psi-mi:“MI:0915”(physical association)	0.870
RAB8A	OCRL	psi-mi:“MI:0915”(physical association)	0.870
OCRL	RAB6A	psi-mi:“MI:0915”(physical association)	0.870
RAB8A	OCRL	psi-mi:“MI:0403”(colocalization)	0.870
OCRL	CLTC	psi-mi:“MI:0915”(physical association)	0.800
CLTC	OCRL	psi-mi:“MI:0407”(direct interaction)	0.800
OCRL	RAB5A	psi-mi:“MI:0407”(direct interaction)	0.800
RAB5A	OCRL	psi-mi:“MI:0407”(direct interaction)	0.800
OCRL	RAB5A	psi-mi:“MI:0915”(physical association)	0.800
RAB5A	OCRL	psi-mi:“MI:0915”(physical association)	0.800
CLTC	OCRL	psi-mi:“MI:0915”(physical association)	0.800

BioGRID (240): OCRL (Affinity Capture-RNA), RAB1A (Reconstituted Complex), RAB5A (Reconstituted Complex), RAB6A (Reconstituted Complex), RAB8A (Reconstituted Complex), RAB14 (Reconstituted Complex), RAB6A (Affinity Capture-Western), CLTC (Affinity Capture-Western), OCRL (Affinity Capture-MS), OCRL (Affinity Capture-MS), OCRL (Affinity Capture-MS), OCRL (Affinity Capture-MS), OCRL (Affinity Capture-MS), OCRL (Affinity Capture-MS), OCRL (Affinity Capture-MS)

ESM2 similar proteins: A0A0G2K344, D3ZGS3, F1M386, F1MSG6, F1PBJ0, G5EF51, O00329, O02697, O35242, O35904, O70481, O88763, O94830, P32871, P42336, P42337, P42338, P42339, P42347, P42348, P48736, P50520, P54676, P70600, Q01968, Q14289, Q14BI7, Q16JS8, Q3MHU3, Q3UYK3, Q4KWH5, Q4KWH8, Q5D891, Q5ZI89, Q6AZN6, Q6GQ76, Q6NVF0, Q6PF93, Q7Z392, Q80Y98

Diamond homologs: A0A8I3NFE2, A0FI79, A0JNB0, A1Y2K1, A6QLK6, B2RZ59, B5KFD7, D3ZGS3, D7PF45, F1RDG9, G5ECJ6, O14306, O14796, O15357, O35324, O60880, O88890, O88900, P00519, P00520, P00521, P00522, P03949, P06239, P06241, P09851, P0CE43, P10447, P17713, P20936, P29350, P29351, P32019, P34370, P39688, P42684, P42685, P42686, P50904, P53356

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
RAB5A	“up-regulates activity”	OCRL	binding
OCRL	“down-regulates quantity”	“1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate”	“chemical modification”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 132 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
WNT5A-dependent internalization of FZD4	8	64.1×	2e-11
VLDLR internalisation and degradation	7	52.6×	2e-09
LDL clearance	7	40.1×	1e-08
Trafficking of GluR2-containing AMPA receptors	5	35.4×	7e-06
Nef-mediates down modulation of cell surface receptors by recruiting them to clathrin adapters	5	33.4×	8e-06
The role of Nef in HIV-1 replication and disease pathogenesis	5	33.4×	8e-06
EPH-ephrin mediated repulsion of cells	11	25.4×	5e-11
Plasma lipoprotein clearance	5	25.0×	3e-05

GO biological processes:

GO term	Partners	Fold	FDR
clathrin coat assembly	7	55.4×	8e-09
clathrin-dependent endocytosis	9	46.7×	8e-11
synaptic vesicle endocytosis	7	27.0×	1e-06
receptor internalization	6	17.4×	2e-04
retrograde transport, endosome to Golgi	6	11.0×	2e-03
intracellular protein transport	18	10.4×	8e-11
endocytosis	12	10.2×	5e-07
receptor-mediated endocytosis	5	9.9×	7e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

1077 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	103
Likely pathogenic	58
Uncertain significance	261
Likely benign	349
Benign	50

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1073892	NC_000023.11:g.129565773del	Pathogenic
1074139	NM_000276.4(OCRL):c.723-1G>A	Pathogenic
10856	NM_000276.4(OCRL):c.2470_2581del (p.Val824Leufs*9)	Pathogenic
10857	NM_000276.4(OCRL):c.2530C>T (p.Arg844Ter)	Pathogenic
10858	NM_000276.4(OCRL):c.1499G>A (p.Arg500Gln)	Pathogenic
10859	NM_000276.4(OCRL):c.1572C>G (p.His524Gln)	Pathogenic
10860	NM_000276.4(OCRL):c.1436A>G (p.Tyr479Cys)	Pathogenic
1098718	NM_000276.4(OCRL):c.739del (p.Trp247fs)	Pathogenic
1172588	NM_000276.4(OCRL):c.659_662del (p.Glu220fs)	Pathogenic
1172589	NM_000276.4(OCRL):c.2257-2A>T	Pathogenic
1308675	NM_000276.4(OCRL):c.1925_1926del (p.Ser642fs)	Pathogenic
1308690	NC_000023.11:g.128710337_128710338del	Pathogenic
1340526	GRCh37/hg19 Xq25-26.1(chrX:127435040-128717825)x0	Pathogenic
1344666	NM_000276.4(OCRL):c.1567G>A (p.Asp523Asn)	Pathogenic
1389736	NM_000276.4(OCRL):c.820del (p.Ile274fs)	Pathogenic
1440540	NM_000276.4(OCRL):c.663del (p.Leu222fs)	Pathogenic
1454269	NM_000276.4(OCRL):c.1602+1G>T	Pathogenic
1458671	NM_000276.4(OCRL):c.904G>T (p.Glu302Ter)	Pathogenic
1458962	NC_000023.10:g.(?128674417)(128724247_?)del	Pathogenic
1685996	NM_000276.4(OCRL):c.217_218del (p.Leu73fs)	Pathogenic
1685997	NM_000276.4(OCRL):c.1458G>A (p.Trp486Ter)	Pathogenic
1687290	NM_000276.4(OCRL):c.1987C>T (p.Arg663Ter)	Pathogenic
1804969	NM_000276.4(OCRL):c.1210C>T (p.Gln404Ter)	Pathogenic
194704	NM_000276.4(OCRL):c.1714-1G>A	Pathogenic
195559	NM_000276.4(OCRL):c.2299C>T (p.Gln767Ter)	Pathogenic
2018423	NM_000276.4(OCRL):c.1712del (p.Glu571fs)	Pathogenic
2022661	NM_000276.4(OCRL):c.1492T>C (p.Cys498Arg)	Pathogenic
2027694	NM_000276.4(OCRL):c.1696G>T (p.Glu566Ter)	Pathogenic
2033348	NM_000276.4(OCRL):c.2313_2316del (p.Cys771fs)	Pathogenic
2041949	NM_000276.4(OCRL):c.943C>T (p.Gln315Ter)	Pathogenic

SpliceAI

3487 predictions. Top by Δscore:

Variant	Effect	Δscore
X:129540497:G:GT	donor_gain	1.0000
X:129540504:G:T	donor_gain	1.0000
X:129548561:A:AG	acceptor_gain	1.0000
X:129548562:G:GG	acceptor_gain	1.0000
X:129548601:AG:A	donor_loss	1.0000
X:129548602:G:GG	donor_gain	1.0000
X:129548602:G:T	donor_loss	1.0000
X:129548603:TGAG:T	donor_loss	1.0000
X:129548604:GA:G	donor_loss	1.0000
X:129548605:AGTAT:A	donor_loss	1.0000
X:129550893:G:GA	donor_gain	1.0000
X:129557431:GAAAG:G	donor_gain	1.0000
X:129557433:AAGGT:A	donor_loss	1.0000
X:129557434:AGGTA:A	donor_loss	1.0000
X:129557436:G:A	donor_loss	1.0000
X:129557437:T:G	donor_loss	1.0000
X:129558627:TTTCA:T	acceptor_loss	1.0000
X:129558628:TTCA:T	acceptor_loss	1.0000
X:129558629:TCA:T	acceptor_loss	1.0000
X:129558630:CAG:C	acceptor_loss	1.0000
X:129558631:A:AG	acceptor_gain	1.0000
X:129558631:AG:A	acceptor_gain	1.0000
X:129558631:AGG:A	acceptor_gain	1.0000
X:129558632:G:A	acceptor_loss	1.0000
X:129558632:G:GG	acceptor_gain	1.0000
X:129558632:GG:G	acceptor_gain	1.0000
X:129558632:GGG:G	acceptor_gain	1.0000
X:129558632:GGGC:G	acceptor_gain	1.0000
X:129558749:AAAAT:A	donor_gain	1.0000
X:129558750:AAAT:A	donor_gain	1.0000

AlphaMissense

6026 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:129560566:T:A	W247R	1.000
X:129560566:T:C	W247R	1.000
X:129560569:A:G	N248D	1.000
X:129560571:T:A	N248K	1.000
X:129560571:T:G	N248K	1.000
X:129561187:A:T	E278V	1.000
X:129561243:T:A	W297R	1.000
X:129561243:T:C	W297R	1.000
X:129562605:A:C	K355Q	1.000
X:129562605:A:G	K355E	1.000
X:129562606:A:T	K355I	1.000
X:129562607:A:C	K355N	1.000
X:129562607:A:T	K355N	1.000
X:129562652:C:G	C370W	1.000
X:129562657:T:A	V372D	1.000
X:129562665:C:G	H375D	1.000
X:129562699:G:C	R386T	1.000
X:129562699:G:T	R386M	1.000
X:129562700:G:C	R386S	1.000
X:129562700:G:T	R386S	1.000
X:129565782:T:A	W419R	1.000
X:129565782:T:C	W419R	1.000
X:129565792:A:T	D422V	1.000
X:129565797:A:G	N424D	1.000
X:129565799:T:A	N424K	1.000
X:129565799:T:G	N424K	1.000
X:129565804:G:C	R426T	1.000
X:129567329:A:G	K478E	1.000
X:129567331:G:C	K478N	1.000
X:129567331:G:T	K478N	1.000

dbSNP variants (sampled 300 via entrez): RS1000019519 (X:129547967 T>G), RS1000120514 (X:129575167 C>G,T), RS1000441003 (X:129562592 C>A,G), RS1000507139 (X:129575519 C>G), RS1000518093 (X:129550693 T>C), RS1000570087 (X:129550106 G>A), RS1000575705 (X:129574627 T>A,C), RS1000640756 (X:129542697 A>G), RS1000693117 (X:129542220 T>C), RS1000724536 (X:129560472 T>C), RS1000730072 (X:129541542 A>G), RS1000806402 (X:129554145 A>G), RS1000812913 (X:129543599 G>A), RS1000882456 (X:129569999 G>A), RS1000932738 (X:129569569 G>A)

Disease associations

OMIM: gene MIM:300535 | disease phenotypes: MIM:309000, MIM:300555, MIM:300009, MIM:619320, MIM:143890, MIM:117000, MIM:308350

GenCC curated gene-disease

Disease	Classification	Inheritance
Dent disease type 2	Definitive	X-linked
oculocerebrorenal syndrome	Definitive	X-linked

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
oculocerebrorenal syndrome	Definitive	XL

Mondo (9): oculocerebrorenal syndrome (MONDO:0010645), Dent disease type 2 (MONDO:0010359), intellectual disability (MONDO:0001071), Dent disease (MONDO:0015612), intellectual developmental disorder, autosomal dominant 65 (MONDO:0023657), hypercholesterolemia, familial, 1 (MONDO:0007750), congenital myopathy (MONDO:0019952), epilepsy (MONDO:0005027), genetic developmental and epileptic encephalopathy (MONDO:0100062)

Orphanet (6): Oculocerebrorenal syndrome of Lowe (Orphanet:534), Dent disease (Orphanet:1652), Dent disease type 2 (Orphanet:93623), Homozygous familial hypercholesterolemia (Orphanet:391665), Congenital myopathy (Orphanet:97245), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

159 total (30 of 159 shown, HPO-id order):

HPO	Term
HP:0000023	Inguinal hernia
HP:0000027	Azoospermia
HP:0000028	Cryptorchidism
HP:0000083	Renal insufficiency
HP:0000091	Abnormal renal tubule morphology
HP:0000093	Proteinuria
HP:0000114	Proximal tubulopathy
HP:0000121	Nephrocalcinosis
HP:0000164	Abnormality of the dentition
HP:0000189	Narrow palate
HP:0000194	Open mouth
HP:0000219	Thin upper lip vermilion
HP:0000230	Gingivitis
HP:0000232	Everted lower lip vermilion
HP:0000276	Long face
HP:0000293	Full cheeks
HP:0000303	Mandibular prognathia
HP:0000343	Long philtrum
HP:0000347	Micrognathia
HP:0000358	Posteriorly rotated ears
HP:0000389	Chronic otitis media
HP:0000411	Protruding ear
HP:0000486	Strabismus
HP:0000490	Deeply set eye
HP:0000501	Glaucoma
HP:0000505	Visual impairment
HP:0000518	Cataract
HP:0000519	Developmental cataract
HP:0000557	Buphthalmos
HP:0000559	Corneal scarring

GWAS associations

0 associations (top):

MeSH disease descriptors (5)

Descriptor	Name	Tree numbers
D057973	Dent Disease	C12.050.351.968.419.815.364; C12.200.777.419.815.364; C12.950.419.815.364; C16.320.322.100; C16.320.831.271
D004827	Epilepsy	C10.228.140.490
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D009800	Oculocerebrorenal Syndrome	C10.228.140.163.100.640; C12.050.351.968.419.815.720; C12.200.777.419.815.720; C12.950.419.815.720; C16.131.077.662; C16.320.322.750; C16.320.565.151.600; C16.320.565.189.640; C16.320.709; C16.320.831.750; C18.452.132.100.640; C18.452.648.151.600; C18.452.648.189.640
C564487	Dent Disease 2 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB clinical annotations

2 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs113165732	Other	3	tenofovir	HIV infectious disease
rs757639	Toxicity	3	tenofovir	HIV infectious disease

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs757639	BMPER, OCRL	3	2.00	1	tenofovir
rs113165732	OCRL	3	0.25	1	tenofovir

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — Inositol polyphosphate phosphatases

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Lead	affects splicing, decreases expression	2
pirinixic acid	increases expression, affects binding, increases activity	1
bisphenol A	decreases expression	1
sodium arsenite	increases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
clothianidin	decreases expression	1
Resveratrol	increases expression, affects cotreatment	1
Sunitinib	increases expression	1
Arsenic	affects methylation	1
Vehicle Emissions	decreases expression, increases abundance	1
Benzo(a)pyrene	affects methylation, decreases methylation, increases methylation	1
Ethyl Methanesulfonate	increases expression	1
Ivermectin	decreases expression	1
Methotrexate	increases expression	1
Methyl Methanesulfonate	increases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Urethane	decreases expression	1
Valproic Acid	increases expression	1
Phosphatidylinositol 4,5-Diphosphate	increases hydrolysis, decreases hydrolysis, increases abundance	1
Copper Sulfate	decreases expression	1
Acrylamide	decreases expression	1
Particulate Matter	increases abundance, decreases expression	1

Cellosaurus cell lines

7 cell lines: 4 induced pluripotent stem cell, 2 cancer cell line, 1 finite cell line

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

Cellosaurus	Name	Category	Sex
CVCL_9Q83	GM01676	Finite cell line	Male
CVCL_A4XW	SDUBMSi009-A	Induced pluripotent stem cell	Male
CVCL_A7KS	WMUi031-A	Induced pluripotent stem cell	Male
CVCL_B5SL	CUIMCi004-A	Induced pluripotent stem cell	Male
CVCL_D0DV	CUIMCi004-A-1	Induced pluripotent stem cell	Male
CVCL_TB59	HAP1 OCRL (-) 1	Cancer cell line	Male
CVCL_TB60	HAP1 OCRL (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

239 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
NCT06231459	PHASE4	COMPLETED	Expression of Pro- and Anti-inflammatory Cytokines During Anti-PCSK9 in Familial Hypercholesterolemia
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
NCT00000594	PHASE3	COMPLETED	NHLBI Type II Coronary Intervention Study
NCT00092833	PHASE3	TERMINATED	Investigational Drug in Patients With Hypercholesterolemia or in Patients With Sitosterolemia (0653-026)(COMPLETED)
NCT00134485	PHASE3	COMPLETED	Study To Evaluate The Safety And Efficacy Of Torcetrapib/Atorvastatin In Subjects With Familial Hypercholerolemia
NCT00134511	PHASE3	COMPLETED	Study To Evaluate The Effect Of Torcetrapib/Atorvastatin In Patients With Genetic High Cholesterol Disorder
NCT00136981	PHASE3	COMPLETED	Carotid B-Mode Ultrasound Study to Compare Anti-Atherosclerotic Effect of Torcetrpib/Atorvastatin to Atorvastatin Alone.
NCT00384293	PHASE3	TERMINATED	Carotid IMT (Intima Media Thickening) Study (0524A-041)(TERMINATED)
NCT01524289	PHASE3	COMPLETED	Study to Assess the Tolerability and Efficacy of Anacetrapib (MK-0859) Co-Administered With Statin in Participants With Heterozygous Familial Hypercholesterolemia (MK-0859-020)
NCT07410455	PHASE2	NOT_YET_RECRUITING	An Open-label, Phase 2 Pilot Study on the Efficacy and Safety of Piclidenoson in Patients With Lowe Syndrome
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT00280995	PHASE2	COMPLETED	Dose-escalating Safety Study of ISIS 301012 in Homozygous Familial Hypercholesterolemia Subjects on Lipid Lowering Therapy
NCT00281008	PHASE2	COMPLETED	Study of ISIS 301012 (Mipomersen) in Heterozygous Familial Hypercholesterolemia Subjects on Lipid Lowering Therapy
NCT01375751	PHASE2	COMPLETED	Reduction of Low-Density Lipoprotein Cholesterol (LDL-C) With PCSK9 Inhibition in Heterozygous Familial Hypercholesterolemia Disorder Study
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)
NCT00515307	PHASE1	COMPLETED	Bone Marrow Stem Cells as a Source of Allogenic Hepatocyte Transplantation in Homozygous Familial Hypercholesterolemia
NCT01583647	PHASE1	TERMINATED	A Study of Extended-release (ER) Niacin/Laropiprant in Adolescents With Heterozygous Familial Hypercholesterolemia (MK-0524A-158)
NCT00359515	Not specified	COMPLETED	Genetic Analysis of Oculocerebrorenal Syndrome of Lowe
NCT01314560	Not specified	COMPLETED	Study of the Pathophysiological Mechanisms Involved in Bleeding Events
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
NCT02780297	Not specified	RECRUITING	Prospective Research Rare Kidney Stones (ProRKS)
NCT06065852	Not specified	RECRUITING	National Registry of Rare Kidney Diseases
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