VLDLR

Summary

VLDLR (very low density lipoprotein receptor, HGNC:12698) is a protein-coding gene on chromosome 9p24.2, encoding Very low-density lipoprotein receptor (P98155). Multifunctional cell surface receptor that binds VLDL and transports it into cells by endocytosis and therefore plays an important role in energy metabolism.

The low density lipoprotein receptor (LDLR) gene family consists of cell surface proteins involved in receptor-mediated endocytosis of specific ligands. This gene encodes a lipoprotein receptor that is a member of the LDLR family and plays important roles in VLDL-triglyceride metabolism and the reelin signaling pathway. Mutations in this gene cause VLDLR-associated cerebellar hypoplasia. Alternative splicing generates multiple transcript variants encoding distinct isoforms for this gene.

Source: NCBI Gene 7436 — RefSeq curated summary.

At a glance

• Gene–disease (curated): cerebellar ataxia, intellectual disability, and dysequilibrium syndrome 1 (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 33
• Clinical variants (ClinVar): 811 total — 36 pathogenic, 27 likely-pathogenic
• Phenotypes (HPO): 40
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity unscored
• MANE Select transcript: NM_003383

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12698
Approved symbol	VLDLR
Name	very low density lipoprotein receptor
Location	9p24.2
Locus type	gene with protein product
Status	Approved
Aliases	CARMQ1, CHRMQ1, VLDLRCH
Ensembl gene	ENSG00000147852
Ensembl biotype	protein_coding
OMIM	192977
Entrez	7436

Gene structure

Transcript identifiers

Ensembl transcripts: 38 — 16 retained_intron, 14 protein_coding, 8 nonsense_mediated_decay

ENST00000382096, ENST00000382099, ENST00000382100, ENST00000478776, ENST00000679488, ENST00000679718, ENST00000679750, ENST00000679780, ENST00000679851, ENST00000680021, ENST00000680043, ENST00000680150, ENST00000680219, ENST00000680243, ENST00000680296, ENST00000680332, ENST00000680440, ENST00000680745, ENST00000680746, ENST00000680751, ENST00000680891, ENST00000680975, ENST00000681087, ENST00000681306, ENST00000681486, ENST00000681518, ENST00000681618, ENST00000681644, ENST00000681770, ENST00000681806, ENST00000681876, ENST00000681942, ENST00000916501, ENST00000916502, ENST00000947327, ENST00000947328, ENST00000947329, ENST00000947330

RefSeq mRNA: 4 — MANE Select: NM_003383 NM_001018056, NM_001322225, NM_001322226, NM_003383

CCDS: CCDS34979, CCDS6446, CCDS94376, CCDS94377

Canonical transcript exons

ENST00000382100 — 19 exons

Exon	Start	End
ENSE00000982061	2639859	2639981
ENSE00000982062	2641377	2641499
ENSE00001257347	2635453	2635572
ENSE00001626953	2645574	2645745
ENSE00001638697	2648208	2648347
ENSE00001655382	2643837	2643959
ENSE00001673529	2651874	2651954
ENSE00001687844	2648669	2648810
ENSE00001696031	2650370	2650516
ENSE00001700967	2644734	2644853
ENSE00001715686	2652780	2652949
ENSE00001735963	2643628	2643750
ENSE00001738995	2646334	2646552
ENSE00001740203	2651415	2651498
ENSE00001798149	2647474	2647592
ENSE00001803937	2644957	2645082
ENSE00001931208	2621787	2622271
ENSE00002174845	2643160	2643531
ENSE00003709721	2653833	2660056

Expression profiles

Bgee: expression breadth ubiquitous, 273 present calls, max score 96.76.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.5637 / max 332.8752, expressed in 1437 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
95866	5.5507	1276
95864	2.4900	923
95869	1.8512	823
95867	1.3406	645
95865	0.2282	97
95868	0.1031	39

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
heart right ventricle	UBERON:0002080	96.76	gold quality
left ovary	UBERON:0002119	96.48	gold quality
right ovary	UBERON:0002118	95.66	gold quality
left ventricle myocardium	UBERON:0006566	93.99	gold quality
islet of Langerhans	UBERON:0000006	93.87	gold quality
ovary	UBERON:0000992	93.75	gold quality
myocardium	UBERON:0002349	93.54	gold quality
cardiac muscle of right atrium	UBERON:0003379	93.11	gold quality
heart left ventricle	UBERON:0002084	93.05	gold quality
cardiac ventricle	UBERON:0002082	93.03	gold quality
right atrium auricular region	UBERON:0006631	92.66	gold quality
cardiac atrium	UBERON:0002081	92.64	gold quality
gingival epithelium	UBERON:0001949	92.59	gold quality
biceps brachii	UBERON:0001507	92.38	gold quality
cortical plate	UBERON:0005343	92.20	gold quality
body of pancreas	UBERON:0001150	92.13	gold quality
heart	UBERON:0000948	91.75	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	91.71	gold quality
pancreas	UBERON:0001264	91.64	gold quality
germinal epithelium of ovary	UBERON:0001304	91.64	gold quality
gingiva	UBERON:0001828	90.98	gold quality
apex of heart	UBERON:0002098	90.67	gold quality
esophagus squamous epithelium	UBERON:0006920	90.43	gold quality
choroid plexus epithelium	UBERON:0003911	89.74	gold quality
hindlimb stylopod muscle	UBERON:0004252	89.71	gold quality
secondary oocyte	CL:0000655	89.53	gold quality
gastrocnemius	UBERON:0001388	88.61	gold quality
epithelium of esophagus	UBERON:0001976	88.60	gold quality
pigmented layer of retina	UBERON:0001782	88.55	gold quality
tibial artery	UBERON:0007610	88.33	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-10137	yes	169.10
E-ANND-3	yes	6.66
E-MTAB-5061	yes	5.64
E-MTAB-2983	no	2451.99

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CEBPA, CEBPB, CEBPG, ESR1, FOXC1, GLI1, HIC1, HIF1A, NFYA, NR3C1, PPARA, PPARG, SP1

miRNA regulators (miRDB)

194 targeting VLDLR, 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-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-3912-5P	99.95	66.11	925
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity Not yet evaluated (unscored). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• binds to two adjacent copies of human rhinovirus VP1 proteins (PMID:12857919)
• like the LDL receptor, LRP prefers lipid-bound forms of apoE, but in contrast to the LDL receptor, both LRP and the VLDL receptor recognize all apoE isoforms (PMID:15863833)
• The effects of apoE on receptor proteolysis were mediated by the ligand binding domain of the receptor. We suggest that signaling promoted by these receptors depends in part on these regulated proteolytic events. (PMID:15950758)
• These artificial receptors protected HeLa cells against infection with human rhinovirus serotype 2 (HRV2) to a degree that strongly increased with the number of repeats present. (PMID:15950998)
• Results suggest that VLDLR CGG repeat polymorphism was associated with bone mineral density (BMD) in men, with two (CGG)(n > or= 8) alleles being related to increased BMD. (PMID:15953542)
• Homozygous deletion of the very low density lipoprotein receptor gene causes autosomal recessive cerebellar hypoplasia with cerebral gyral simplification. (PMID:16080122)
• These data suggest that LRP6, VEGF, and VLDLR may play a role in the risk of developing (age-related macular degeneration)AMD. (PMID:16384981)
• Transfected ecombinant human VLDLR bound mouse Pafah1b3 or Pafah1b2 but not with Lis1. (PMID:17330141)
• fluorescence correlation spectroscopy was used to determine the equilibrium binding constants and the mode of attachment of recombinant concatemers of ligand binding module 3 of the human VLDLR to Human rhinovirus HRV2 (PMID:17472347)
• VLDLR functions as a negative regulator of CNV, and this function is mediated through the wnt pathway. (PMID:17890782)
• Our findings suggest that peripheral VLDLR mRNA levels may serve as a reliable peripheral biological marker of schizophrenia, and that the reelin-VLDLR/ApoER2 signaling pathway plays a role in the pathophysiology of schizophrenia. (PMID:17936586)
• TSP1 and TSP2, together with the VLDLR, initiate a nonapoptotic pathway for maintenance of the normal adult vascular endothelium in a quiescent state. (PMID:18032585)
• the activity of PCSK9 and its binding affinity on VLDLR and ApoER2 does not depend on the presence of LDLR. (PMID:18039658)
• A nonsense mutation in patients with dysequilibrium syndrome affects the very low-density lipoprotein receptor (VLDLR) exclusively, confirming the central role of the VLDLR in the etiology of this condition. (PMID:18043714)
• one tagSNP (SNP 1226; rs1454626) located in the 5’ flanking region of VLDLR was associated with CAAD, BMI, and LDL-associated apoB. (PMID:18056683)
• the binding sites for VLDLR (very low density lipoprotein receptor) and LRP (low-density lipoprotein receptor-related protein) within Factor VIII overlap and the A2 site becomes exposed upon physiological activation of Factor VIII. (PMID:18277139)
• mutations in VLDLR impair cerebrocerebellar function, conferring in these families a dramatic influence on gait, and that hereditary disorders associated with quadrupedal gait in humans are genetically heterogeneous (PMID:18326629)
• Associated with cerebellar ataxia, which can lead to quadrupedal locomotion. (PMID:18364738)
• Interaction of the A2 domain of F8 with VLDLR follows the general mode, requires dissociation of factor VIII from von Willebrand factor, and is activation sensitive. (PMID:18685438)
• VLDL or beta-VLDL-induced VLDLR expression via PKC/ERK cascades and the effect was linked to the transcriptional activation of VLDLR gene promoter. (PMID:19224153)
• These results suggest that a VLDLR variant lacking the third complement-type repeat is generated by neuron-specific alternative splicing. Such differential splicing may result in different lipid uptake in neurons and astrocytes. (PMID:19393635)
• These results indicated that extracellular ligands can change the expression of type II VLDLR to affect cell proliferation and migration. (PMID:20624392)
• VLDLR II may have a role in lymph node and distant metastasis in gastric and breast cancer patients, and has a potential link with beta-catenin signaling pathway (PMID:21047397)
• Insulin could down-regulate expression of type I VLDLR and up-regulate the expression of type II VLDLR in SGC7901 cells. (PMID:21063833)
• In later stages of cerebral cortical development, ApoER2 is expressed earlier than VLDLR in migrating neurons. (PMID:21601501)
• RIG-I signaling results in the inhibitions of infections of rhinoviruses 1B through the miR-23b-mediated down-regulation of its receptor VLDLR (PMID:21642441)
• activation of VLDLR and apoER2 by reelin and apoE induces ABCA1 expression and cholesterol efflux via a Dab1-PI3K-PKCzeta-Sp1 signaling cascade. (PMID:22170052)
• In the expression study, only ARG1 (4.5-fold) and VLDLR (4-fold) expressions were significantly upregulated in the overweight group compared with the normal-weight group. (PMID:22189190)
• Copy number variation of VLDLR is associated with age-related macular degeneration. (PMID:22355348)
• Variation in genes encoding proteins at the gateway of Reelin signaling: ligands RELN and APOE, their common receptors APOER2 and VLDLR, and adaptor DAB1, was examined. (PMID:22419519)
• In this report, we present 3 patients from 2 different families displaying very low density lipoprotein receptor-associated pontocerebellar hypoplasia, cortical dysplasia, mental retardation, and bipedal gait. (PMID:22532556)
• Results show variation in VLDLR is implicated in disordered gambling (PMID:22780124)
• VLDLR encodes very low-dentisy lipoprotein receptor. (PMID:22876580)
• A homozygous missense mutation (c.2117 G > T, p.C706F) is identified in the VLDLR gene in both families on a shared affected haplotype block. (PMID:22973972)
• The pathological increase of HIF-1alpha in clear-cell renal cell carcinoma cells upregulates VLDL-R, which mediates increased uptake and accumulation of lipids. (PMID:23185271)
• an unusual constellation of VLDLR mutations in Cerebellar ataxia, mental retardation and dysequilibrium syndrome 1 is reported (PMID:23670308)
• Stx5 might play a role in modulating VLDL-R physiology by participating in an abrasively described or completely novel Golgi-bypass pathway. (PMID:23701949)
• These results conclude that in the hypoxic hearts of mice and men, the VLDLr gene is regulated by a direct binding of Hif-1alpha to the VLDLr promoter (PMID:23811271)
• study identified a novel homozygous VLDLR c.2248C>T mutation (p.Q750X) and distinctive MRI findings in 2 siblings with ataxia; also marked vitamin E deficiency was detected in the proband (PMID:23813796)
• ectopic expression of HIC1 in U2OS and MDA-MB-231 cell lines decreases expression of the ApoER2 and VLDLR genes, encoding two canonical tyrosine kinase receptors for Reelin. (PMID:24076391)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	vldlr	ENSDARG00000006257
mus_musculus	Vldlr	ENSMUSG00000024924
rattus_norvegicus	Vldlr	ENSRNOG00000027491
drosophila_melanogaster	arr	FBGN0000119

Paralogs (14): LRP6 (ENSG00000070018), LRP2 (ENSG00000081479), NID2 (ENSG00000087303), NID1 (ENSG00000116962), LRP1 (ENSG00000123384), LDLR (ENSG00000130164), LRP3 (ENSG00000130881), LRP4 (ENSG00000134569), EGF (ENSG00000138798), LRP12 (ENSG00000147650), LRP8 (ENSG00000157193), LRP5 (ENSG00000162337), LRP1B (ENSG00000168702), LRP10 (ENSG00000197324)

Protein

Protein identifiers

Very low-density lipoprotein receptor — P98155 (reviewed: P98155)

All UniProt accessions (15): P98155, A0A7P0T897, A0A7P0T8C1, A0A7P0T8F7, A0A7P0T8N6, A0A7P0T8N9, A0A7P0T9P7, A0A7P0TA42, A0A7P0TAL1, A0A7P0TB10, A0A7P0TBI2, A0A7P0Z477, A0A804CHQ2, Q5VVF5, Q5VVF8

UniProt curated annotations — full annotation on UniProt →

Function. Multifunctional cell surface receptor that binds VLDL and transports it into cells by endocytosis and therefore plays an important role in energy metabolism. Also binds to a wide range of other molecules including Reelin/RELN or apolipoprotein E/APOE-containing ligands as well as clusterin/CLU. In the off-state of the pathway, forms homooligomers or heterooligomers with LRP8. Upon binding to ligands, homooligomers are rearranged to higher order receptor clusters that transmit the extracellular RELN signal to intracellular signaling processes by binding to DAB1. This interaction results in phosphorylation of DAB1 leading to the ultimate cell responses required for the correct positioning of newly generated neurons. Later, mediates a stop signal for migrating neurons, preventing them from entering the marginal zone. (Microbial infection) Acts as a receptor for Semliki Forest virus.

Subunit / interactions. Homooligomer. Binds to the extracellular matrix protein Reelin/RELN. Interacts with LRP8. Interacts with LDLRAP1. Interacts with SNX17. Interacts with DAB1. Interacts with PCSK9. Interacts with PAFAH1B3 and PAFAH1B2, the catalytic complex of (PAF-AH (I)) heterotetrameric enzyme; these interactions may modulate the Reelin pathway. Interacts with STX5; this interaction mediates VLDLR translocation from the endoplasmic reticulum to the plasma membrane. Interacts with CLU. (Microbial infection) Interacts with protein VP1 of the minor-group human rhinoviruses (HRVs) through the second and third LDL-receptor class A domains. (Microbial infection) Interacts (via class A repeats) with Semliki Forest virus spike glycoprotein E1 (via DIII); this interaction mediates viral entry into host cell. (Microbial infection) Interacts (via class A repeats) with Eastern equine encephalitis virus spike glycoprotein E2 (via E2-A); this interaction mediates viral entry into host cell.

Subcellular location. Cell membrane. Membrane. Clathrin-coated pit.

Tissue specificity. Abundant in heart and skeletal muscle; also ovary and kidney; not in liver.

Post-translational modifications. Ubiquitinated at Lys-839 by MYLIP leading to degradation. Glycosylated.

Disease relevance. Cerebellar ataxia, impaired intellectual development, and dysequilibrium syndrome 1 (CAMRQ1) [MIM:224050] An autosomal recessive, congenital, non-progressive cerebellar ataxia associated with disturbed equilibrium, delayed ambulation, intellectual disability, cerebellar hypoplasia and mild cerebral gyral simplification. Additional features include short stature, strabismus, pes planus and, rarely, seizures. The disease is caused by variants affecting the gene represented in this entry.

Isoforms (2)

UniProt ID	Names	Canonical?
P98155-1	Long	yes
P98155-2	Short

RefSeq proteins (4): NP_001018066, NP_001309154, NP_001309155, NP_003374* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000033	LDLR_classB_rpt	Repeat
IPR000152	EGF-type_Asp/Asn_hydroxyl_site	PTM
IPR000742	EGF	Domain
IPR001881	EGF-like_Ca-bd_dom	Domain
IPR002172	LDrepeatLR_classA_rpt	Repeat
IPR011042	6-blade_b-propeller_TolB-like	Homologous_superfamily
IPR018097	EGF_Ca-bd_CS	Conserved_site
IPR023415	LDLR_class-A_CS	Conserved_site
IPR036055	LDL_receptor-like_sf	Homologous_superfamily
IPR049883	NOTCH1_EGF-like	Domain
IPR051221	LDLR-related	Family

Pfam: PF00057, PF00058, PF07645, PF14670

UniProt features (112 total): disulfide bond 33, strand 14, mutagenesis site 13, domain 11, helix 7, sequence variant 7, repeat 6, sequence conflict 5, turn 3, glycosylation site 3, topological domain 2, region of interest 2, signal peptide 1, chain 1, short sequence motif 1, transmembrane region 1, cross-link 1, splice variant 1

Structure

Experimental structures (PDB)

27 structures.

PDB	Method	Resolution (Å)
9DQZ	ELECTRON MICROSCOPY	2.9
8IHP	ELECTRON MICROSCOPY	3
9UIO	ELECTRON MICROSCOPY	3.03
9EAU	ELECTRON MICROSCOPY	3.06
8UFC	ELECTRON MICROSCOPY	3.09
9WSL	ELECTRON MICROSCOPY	3.27
8XI4	ELECTRON MICROSCOPY	3.4
8XI5	ELECTRON MICROSCOPY	3.4
8YW1	ELECTRON MICROSCOPY	3.44
8YVZ	ELECTRON MICROSCOPY	3.45
3DPR	X-RAY DIFFRACTION	3.5
8X0K	ELECTRON MICROSCOPY	3.5
8X0L	ELECTRON MICROSCOPY	3.5
8X0M	ELECTRON MICROSCOPY	3.5
8YW0	ELECTRON MICROSCOPY	3.55
8UA4	ELECTRON MICROSCOPY	3.58
1V9U	X-RAY DIFFRACTION	3.6
9L99	ELECTRON MICROSCOPY	3.6
8UA8	ELECTRON MICROSCOPY	3.7
8YW2	ELECTRON MICROSCOPY	3.7
8UFB	ELECTRON MICROSCOPY	3.89
9L9A	ELECTRON MICROSCOPY	3.9
9E9Z	ELECTRON MICROSCOPY	3.95
9E9Y	ELECTRON MICROSCOPY	3.96
8YS4	ELECTRON MICROSCOPY	4.8
8YS2	ELECTRON MICROSCOPY	5.2
6BYV	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P98155-F1	76.12	0.26

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 (1): 839

Disulfide bonds (33): 33–45, 40–58, 52–67, 72–84, 79–97, 91–108, 113–127, 120–140, 134–149, 154–166, 161–179, 173–188, 193–205, 200–218, 212–229, 239–251, 246–264, 258–273, 278–290, 285–303 …

Glycosylation sites (3): 151, 765, 781

Mutagenesis-validated functional residues (13):

Position	Phenotype
89	complete loss of entry of semliki virus into the cell.
92	complete loss of entry of semliki virus into the cell.
94	complete loss of entry of semliki virus into the cell.
96	complete loss of entry of semliki virus into the cell.
117	complete loss of interaction with semliki virus spike glycoprotein e1.
129	complete loss of interaction with semliki virus spike glycoprotein e1.
132	complete loss of interaction with semliki virus spike glycoprotein e1.
135	complete loss of interaction with semliki virus spike glycoprotein e1.
137	complete loss of interaction with semliki virus spike glycoprotein e1.
139	complete loss of interaction with semliki virus spike glycoprotein e1.
825	insensitive to mylip-triggered degradation; when associated with r-828 and r-839.
828	insensitive to mylip-triggered degradation; when associated with r-825 and r-839.
839	insensitive to mylip-triggered degradation. insensitive to mylip-triggered degradation; when associated with r-825 and r

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-8866376	Reelin signalling pathway
R-HSA-8866427	VLDLR internalisation and degradation
R-HSA-8964046	VLDL clearance

MSigDB gene sets: 377 (showing top): GOBP_SPINAL_CORD_DEVELOPMENT, GOBP_DENDRITE_DEVELOPMENT, GOBP_MEMORY, RNGTGGGC_UNKNOWN, VERHAAK_AML_WITH_NPM1_MUTATED_DN, GOBP_COGNITION, GOBP_BEHAVIOR, DACOSTA_UV_RESPONSE_VIA_ERCC3_XPCS_DN, GOBP_SYNAPSE_ASSEMBLY, GOCC_VACUOLAR_MEMBRANE, NKX25_02, TGCACTT_MIR519C_MIR519B_MIR519A, GOZGIT_ESR1_TARGETS_DN, AAGCCAT_MIR135A_MIR135B, GOBP_NEUROGENESIS

GO Biological Process (16): lipid transport (GO:0006869), receptor-mediated endocytosis (GO:0006898), signal transduction (GO:0007165), nervous system development (GO:0007399), memory (GO:0007613), cholesterol metabolic process (GO:0008203), ventral spinal cord development (GO:0021517), glycoprotein transport (GO:0034436), very-low-density lipoprotein particle clearance (GO:0034447), reelin-mediated signaling pathway (GO:0038026), dendrite morphogenesis (GO:0048813), regulation of synapse assembly (GO:0051963), positive regulation of dendrite development (GO:1900006), lipid metabolic process (GO:0006629), endocytosis (GO:0006897), steroid metabolic process (GO:0008202)

GO Molecular Function (9): low-density lipoprotein particle receptor activity (GO:0005041), calcium ion binding (GO:0005509), very-low-density lipoprotein particle receptor activity (GO:0030229), apolipoprotein binding (GO:0034185), very-low-density lipoprotein particle binding (GO:0034189), cargo receptor activity (GO:0038024), reelin receptor activity (GO:0038025), calcium-dependent protein binding (GO:0048306), protein binding (GO:0005515)

GO Cellular Component (10): lysosomal membrane (GO:0005765), plasma membrane (GO:0005886), clathrin-coated pit (GO:0005905), membrane (GO:0016020), very-low-density lipoprotein particle (GO:0034361), signaling receptor complex (GO:0043235), glutamatergic synapse (GO:0098978), obsolete extracellular space (GO:0005615), endomembrane system (GO:0012505), synapse (GO:0045202)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Plasma lipoprotein clearance	2
Axon guidance	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein binding	3
dendrite development	2
vesicle-mediated transport	2
lipoprotein particle receptor activity	2
membrane	2
cellular anatomical structure	2
transport	1
lipid localization	1
endocytosis	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
system development	1
learning or memory	1
sterol metabolic process	1
secondary alcohol metabolic process	1
spinal cord development	1
anatomical structure development	1
protein transport	1
carbohydrate derivative transport	1
plasma lipoprotein particle clearance	1
cell surface receptor signaling pathway	1
cell morphogenesis involved in neuron differentiation	1
neuron projection morphogenesis	1
synapse assembly	1
regulation of synapse organization	1
regulation of cell junction assembly	1
positive regulation of neuron projection development	1
regulation of dendrite development	1
positive regulation of developmental process	1
primary metabolic process	1
vesicle budding from membrane	1
membrane invagination	1
import into cell	1
lipid metabolic process	1
low-density lipoprotein particle binding	1
metal ion binding	1
very-low-density lipoprotein particle binding	1

Protein interactions and networks

STRING

1719 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
VLDLR	APOE	P02649	997
VLDLR	RELN	P78509	984
VLDLR	LRP8	Q14114	940
VLDLR	THBS1	P07996	907
VLDLR	SERPINE1	P05121	885
VLDLR	CA8	P35219	864
VLDLR	CLU	P10909	864
VLDLR	YWHAQ	P27348	788
VLDLR	CETP	P11597	777
VLDLR	LPL	P06858	750
VLDLR	PCSK9	Q8NBP7	749
VLDLR	INHBE	P58166	739
VLDLR	APOB	P04114	724
VLDLR	DAB1	O75553	724
VLDLR	APBB1	O00213	688

IntAct

35 interactions, top by confidence:

A	B	Type	Score
Reln	VLDLR	psi-mi:“MI:0915”(physical association)	0.780
Reln	VLDLR	psi-mi:“MI:0407”(direct interaction)	0.780
VLDLR	Reln	psi-mi:“MI:0915”(physical association)	0.780
VLDLR	LRPAP1	psi-mi:“MI:0915”(physical association)	0.770
LRPAP1	VLDLR	psi-mi:“MI:0407”(direct interaction)	0.770
LRRC4C	DVL2	psi-mi:“MI:0914”(association)	0.530
LRPAP1	LRP4	psi-mi:“MI:0914”(association)	0.530
ZNF408	LRP4	psi-mi:“MI:0914”(association)	0.530
SYT1	PGK2	psi-mi:“MI:0914”(association)	0.530
SYT1	SYT5	psi-mi:“MI:0914”(association)	0.530
APOE	VLDLR	psi-mi:“MI:0407”(direct interaction)	0.440
VLDLR	Lrpap1	psi-mi:“MI:0915”(physical association)	0.400
Lrpap1	VLDLR	psi-mi:“MI:0915”(physical association)	0.400
CTBP1	TAF15	psi-mi:“MI:0914”(association)	0.350
SYT2	ARHGAP10	psi-mi:“MI:0914”(association)	0.350
ANKRD36B	CCDC66	psi-mi:“MI:0914”(association)	0.350
ST14	LIPT2	psi-mi:“MI:0914”(association)	0.350
IGFL3	CBX4	psi-mi:“MI:0914”(association)	0.350
HPN	TOR1A	psi-mi:“MI:0914”(association)	0.350
NDST2	CLGN	psi-mi:“MI:0914”(association)	0.350
SYT1	AP3B1	psi-mi:“MI:0914”(association)	0.350
SYT11	PJA2	psi-mi:“MI:0914”(association)	0.350
SYT2	SMAP	psi-mi:“MI:0914”(association)	0.350

BioGRID (63): VLDLR (Reconstituted Complex), Clu (Far Western), VLDLR (Affinity Capture-MS), VLDLR (Affinity Capture-MS), VLDLR (Affinity Capture-MS), VLDLR (Affinity Capture-MS), SEL1L (Affinity Capture-Western), CANX (Affinity Capture-Western), VLDLR (Reconstituted Complex), VLDLR (Reconstituted Complex), VLDLR (Affinity Capture-RNA), VLDLR (Affinity Capture-Western), VLDLR (Affinity Capture-Western), ZSCAN12 (Two-hybrid), RELN (Reconstituted Complex)

ESM2 similar proteins: A0A6I8RMG7, A2A863, A2VCU8, A7E2Z9, P01130, P01131, P04412, P0CY46, P16144, P18563, P18564, P24043, P35555, P35950, P35952, P35953, P98133, P98155, P98156, P98165, P98166, Q1RPR6, Q28832, Q2KIT5, Q3UZV7, Q4G063, Q4V7M2, Q5XH36, Q60438, Q61220, Q61554, Q62918, Q64632, Q6AYF4, Q6DDW2, Q6UXH1, Q7SXF6, Q7ZXL5, Q863C4, Q8CFM6

Diamond homologs: A2AR95, A2ARV4, A4IHY6, C0HL13, E9Q6D8, G3V928, O75074, O75197, O75581, O88204, O88307, O88572, P0DSP1, P13671, P35953, P56677, P61134, P61135, P86091, P98153, P98154, P98155, P98156, P98157, P98158, P98160, P98163, P98164, P98165, P98166, P98167, Q04833, Q06561, Q07954, Q0IIH7, Q14114, Q28832, Q29RU4, Q5HZW5, Q5R662

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
APOE	up-regulates	VLDLR	binding
RELN	up-regulates	VLDLR	binding
TFPI	up-regulates	VLDLR	binding
HIC1	“down-regulates quantity by repression”	VLDLR	“transcriptional regulation”
MYLIP	“down-regulates quantity by destabilization”	VLDLR	ubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 35 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
Cargo recognition for clathrin-mediated endocytosis	5	23.8×	2e-04
Vesicle-mediated transport	5	7.9×	8e-03

GO biological processes:

GO term	Partners	Fold	FDR
vesicle-mediated transport	5	16.6×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	36
Likely pathogenic	27
Uncertain significance	213
Likely benign	425
Benign	44

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1180758	NM_003383.5(VLDLR):c.2466G>A (p.Trp822Ter)	Pathogenic
12201	NM_003383.5(VLDLR):c.769C>T (p.Arg257Ter)	Pathogenic
12202	NM_003383.5(VLDLR):c.2339del (p.Ile780fs)	Pathogenic
1223471	NM_003383.5(VLDLR):c.835C>T (p.Arg279Ter)	Pathogenic
21381	NM_003383.5(VLDLR):c.1342C>T (p.Arg448Ter)	Pathogenic
2577844	NM_003383.5(VLDLR):c.901C>T (p.Arg301Ter)	Pathogenic
2577846	NM_003383.5(VLDLR):c.149G>A (p.Trp50Ter)	Pathogenic
2577847	NM_003383.5(VLDLR):c.1961A>G (p.Glu654Gly)	Pathogenic
2577848	NM_003383.5(VLDLR):c.1724G>A (p.Trp575Ter)	Pathogenic
265344	NM_003383.5(VLDLR):c.1586G>A (p.Trp529Ter)	Pathogenic
2698407	NM_003383.5(VLDLR):c.379dup (p.Cys127fs)	Pathogenic
2706526	NM_003383.5(VLDLR):c.1240A>T (p.Lys414Ter)	Pathogenic
2708334	NM_003383.5(VLDLR):c.1983del (p.Asp661fs)	Pathogenic
2750364	NM_003383.5(VLDLR):c.1252_1253del (p.Lys418fs)	Pathogenic
2753414	NM_003383.5(VLDLR):c.120C>A (p.Cys40Ter)	Pathogenic
2766171	NM_003383.5(VLDLR):c.139dup (p.Thr47fs)	Pathogenic
2787504	NM_003383.5(VLDLR):c.2270_2279del (p.Thr757fs)	Pathogenic
2826269	NM_003383.5(VLDLR):c.2239C>T (p.Arg747Ter)	Pathogenic
2827540	NM_003383.5(VLDLR):c.2278G>T (p.Glu760Ter)	Pathogenic
2832321	NM_003383.5(VLDLR):c.2274C>A (p.Tyr758Ter)	Pathogenic
2837856	NM_003383.5(VLDLR):c.291C>A (p.Cys97Ter)	Pathogenic
2838121	NM_003383.5(VLDLR):c.2220C>A (p.Tyr740Ter)	Pathogenic
2842085	NM_003383.5(VLDLR):c.1707del (p.Phe569fs)	Pathogenic
2855138	NM_003383.5(VLDLR):c.565del (p.Ala189fs)	Pathogenic
2860356	NM_003383.5(VLDLR):c.1716del (p.Trp572fs)	Pathogenic
2908853	NM_003383.5(VLDLR):c.1134C>A (p.Tyr378Ter)	Pathogenic
2978710	NM_003383.5(VLDLR):c.826C>T (p.Arg276Ter)	Pathogenic
2999329	NM_003383.5(VLDLR):c.2170C>T (p.Gln724Ter)	Pathogenic
3245313	NC_000009.11:g.(?2622190)(2653868_?)del	Pathogenic
3245314	NC_000009.11:g.(?2622190)(2650536_?)del	Pathogenic

SpliceAI

2685 predictions. Top by Δscore:

Variant	Effect	Δscore
9:2622272:G:GG	donor_gain	1.0000
9:2635446:A:AG	acceptor_gain	1.0000
9:2635449:CTA:C	acceptor_loss	1.0000
9:2635450:TA:T	acceptor_loss	1.0000
9:2635451:A:AG	acceptor_gain	1.0000
9:2635451:AG:A	acceptor_gain	1.0000
9:2635451:AGG:A	acceptor_gain	1.0000
9:2635452:G:GT	acceptor_gain	1.0000
9:2635452:GG:G	acceptor_gain	1.0000
9:2635452:GGG:G	acceptor_gain	1.0000
9:2635452:GGGA:G	acceptor_gain	1.0000
9:2635568:CTGTG:C	donor_gain	1.0000
9:2635570:GTG:G	donor_gain	1.0000
9:2635571:TG:T	donor_gain	1.0000
9:2635571:TGGTA:T	donor_loss	1.0000
9:2635572:GG:G	donor_gain	1.0000
9:2635573:G:GA	donor_loss	1.0000
9:2635573:G:GG	donor_gain	1.0000
9:2635574:T:A	donor_loss	1.0000
9:2639977:GTGCC:G	donor_gain	1.0000
9:2643527:CTGTC:C	donor_gain	1.0000
9:2643529:GTC:G	donor_gain	1.0000
9:2643530:TC:T	donor_gain	1.0000
9:2643530:TCGTA:T	donor_loss	1.0000
9:2643532:G:A	donor_loss	1.0000
9:2643532:G:GG	donor_gain	1.0000
9:2643533:TAA:T	donor_loss	1.0000
9:2643536:G:GG	donor_gain	1.0000
9:2643622:TTGTA:T	acceptor_loss	1.0000
9:2643623:T:TA	acceptor_gain	1.0000

AlphaMissense

5842 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:2639945:T:A	C97S	0.999
9:2639946:G:C	C97S	0.999
9:2635542:T:A	C58S	0.998
9:2635543:G:C	C58S	0.998
9:2641451:T:A	C134S	0.998
9:2641452:G:C	C134S	0.998
9:2641469:T:A	C140S	0.998
9:2641470:G:C	C140S	0.998
9:2643246:T:A	C179S	0.998
9:2643247:G:C	C179S	0.998
9:2643248:C:G	C179W	0.998
9:2643501:T:A	C264S	0.998
9:2643502:G:C	C264S	0.998
9:2644778:T:A	C371S	0.998
9:2644779:G:C	C371S	0.998
9:2635483:T:G	F38C	0.997
9:2635488:T:A	C40S	0.997
9:2635489:G:C	C40S	0.997
9:2635543:G:A	C58Y	0.997
9:2635544:T:G	C58W	0.997
9:2639891:T:A	C79S	0.997
9:2639892:G:C	C79S	0.997
9:2639927:T:A	C91S	0.997
9:2639928:G:C	C91S	0.997
9:2639946:G:A	C97Y	0.997
9:2639947:C:G	C97W	0.997
9:2641430:T:A	C127S	0.997
9:2641431:G:C	C127S	0.997
9:2643192:T:A	C161S	0.997
9:2643193:G:C	C161S	0.997

dbSNP variants (sampled 300 via entrez): RS1000086057 (9:2628156 C>G), RS1000123214 (9:2621859 T>C,G), RS1000126333 (9:2633360 A>G), RS1000143461 (9:2655111 C>T), RS1000325029 (9:2626075 G>T), RS1000339448 (9:2637848 C>G), RS1000353280 (9:2637915 C>T), RS1000428625 (9:2630882 G>A), RS1000434716 (9:2655247 C>A), RS1000436587 (9:2628400 C>T), RS1000469318 (9:2624988 C>A), RS1000530290 (9:2658668 T>C), RS1000549825 (9:2646484 C>A,G,T), RS1000591976 (9:2626294 G>C), RS1000616579 (9:2647659 G>A,C)

Disease associations

OMIM: gene MIM:192977 | disease phenotypes: MIM:224050

GenCC curated gene-disease

Disease	Classification	Inheritance
cerebellar ataxia, intellectual disability, and dysequilibrium syndrome 1	Definitive	Autosomal recessive
cerebellar ataxia, intellectual disability, and dysequilibrium	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
cerebellar ataxia, intellectual disability, and dysequilibrium syndrome 1	Definitive	AR

Mondo (6): cerebellar ataxia, intellectual disability, and dysequilibrium syndrome 1 (MONDO:0024542), congenital nervous system disorder (MONDO:0002320), intellectual disability (MONDO:0001071), cerebellar ataxia, intellectual disability, and dysequilibrium (MONDO:0009133), primary amenorrhea (MONDO:1060208), microcephaly (MONDO:0001149)

Orphanet (2): Dysequilibrium syndrome (Orphanet:1766), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

40 total (30 of 40 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000478	Abnormality of the eye
HP:0000486	Strabismus
HP:0000504	Abnormality of vision
HP:0000518	Cataract
HP:0000640	Gaze-evoked nystagmus
HP:0000750	Delayed speech and language development
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001260	Dysarthria
HP:0001263	Global developmental delay
HP:0001272	Cerebellar atrophy
HP:0001288	Gait disturbance
HP:0001290	Generalized hypotonia
HP:0001302	Pachygyria
HP:0001310	Dysmetria
HP:0001321	Cerebellar hypoplasia
HP:0001347	Hyperreflexia
HP:0001763	Pes planus
HP:0002066	Gait ataxia
HP:0002075	Dysdiadochokinesis
HP:0002078	Truncal ataxia
HP:0002080	Intention tremor
HP:0002136	Broad-based gait
HP:0002365	Hypoplasia of the brainstem
HP:0002395	Lower limb hyperreflexia
HP:0002465	Poor speech
HP:0003202	Skeletal muscle atrophy

GWAS associations

33 associations (top):

Study	Trait	p-value
GCST001155_3	Vascular endothelial growth factor levels	1.000000e-39
GCST001280_4	Alzheimer’s disease (age of onset)	4.000000e-06
GCST001601_2	Gambling	3.000000e-06
GCST001601_5	Gambling	5.000000e-06
GCST002221_73	Cholesterol, total	7.000000e-10
GCST002222_3	LDL cholesterol	2.000000e-09
GCST003403_6	Vascular endothelial growth factor levels	4.000000e-14
GCST003403_7	Vascular endothelial growth factor levels	9.000000e-99
GCST003670_6	Systolic blood pressure	9.000000e-09
GCST004233_20	LDL cholesterol levels	5.000000e-10
GCST004422_31	Vascular endothelial growth factor levels	3.000000e-15
GCST004604_130	Hematocrit	1.000000e-10
GCST004615_59	Hemoglobin concentration	2.000000e-11
GCST006612_14	LDL cholesterol	1.000000e-11
GCST006614_18	Total cholesterol levels	1.000000e-14
GCST008198_3	Vascular endothelial growth factor levels	2.000000e-13
GCST008969_1	White coat effect (clinic diastolic blood pressure minus ambulatory diastolic blood pressure)	2.000000e-06
GCST009243_4	Cytokine levels	7.000000e-14
GCST009244_11	Cytokine network levels (multivariate analysis)	4.000000e-13
GCST010083_336	Hemoglobin levels	7.000000e-22
GCST010204_169	Low density lipoprotein cholesterol levels	2.000000e-14
GCST010243_238	Apolipoprotein B levels	5.000000e-10
GCST010245_61	LDL cholesterol levels	3.000000e-11
GCST90000584_11	Inflammatory biomarkers (multivariate analysis)	2.000000e-17
GCST90002383_506	Hematocrit	7.000000e-25
GCST90002384_253	Hemoglobin	8.000000e-26
GCST90002389_342	Lymphocyte percentage of white cells	5.000000e-11
GCST90002393_368	Monocyte count	1.000000e-17
GCST90002398_247	Neutrophil count	4.000000e-19
GCST90002400_457	Plateletcrit	2.000000e-17

EFO canonical traits (23, from GWAS)

EFO ID	Trait name
EFO:0004847	age at onset
EFO:0004699	gambling behaviour
EFO:0004574	total cholesterol measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0006335	systolic blood pressure
EFO:0004348	hematocrit
EFO:0004509	hemoglobin measurement
EFO:0006945	diastolic blood pressure change measurement
EFO:0004750	interleukin 10 measurement
EFO:0004753	interleukin 12 measurement
EFO:0004810	interleukin-6 measurement
EFO:0008165	interferon gamma measurement
EFO:0008174	interleukin 17 measurement
EFO:0008184	interleukin 4 measurement
EFO:0008293	stromal cell-derived factor 1 alpha measurement
EFO:0004615	apolipoprotein B measurement
EFO:0004872	inflammatory biomarker measurement
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0005091	monocyte count
EFO:0004833	neutrophil count
EFO:0007985	platelet crit
EFO:0004309	platelet count
EFO:0004305	erythrocyte count

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
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
C535731	Dysequilibrium syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Cyclosporine	affects expression, decreases expression, increases expression	6
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	4
Valproic Acid	decreases expression, increases expression	4
cobaltous chloride	increases expression	3
Arsenic Trioxide	increases expression	3
Benzo(a)pyrene	decreases expression	3
Tretinoin	decreases expression, increases expression	3
mono-(2-ethylhexyl)phthalate	increases expression	2
perfluorooctanoic acid	decreases expression, increases expression	2
perfluorooctane sulfonic acid	decreases expression, increases expression	2
Air Pollutants	increases abundance, increases expression, decreases expression	2
Estradiol	affects cotreatment, increases expression, decreases expression	2
Oxygen	increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tetrachlorodibenzodioxin	decreases expression, decreases reaction, affects cotreatment, increases expression	2
Particulate Matter	increases abundance, increases expression, decreases expression	2
aristolochic acid I	decreases expression	1
tungsten carbide	affects binding, increases expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
pirinixic acid	increases activity, increases expression, affects binding	1
bisphenol A	increases expression	1
2,5,2’,5’-tetrachlorobiphenyl	increases expression	1
2-methyl-4-isothiazolin-3-one	decreases expression	1
terbufos	increases methylation	1
trichostatin A	decreases expression	1
arsenite	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
cypermethrin	increases expression	1
tetrabromobisphenol A	increases expression	1

Cellosaurus cell lines

3 cell lines: 2 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D1UX	Abcam U-87MG VLDLR KO	Cancer cell line	Male
CVCL_D4BT	HEK293E_Ecto short VLDLR-C-tag	Transformed cell line	Female
CVCL_E0SY	Ubigene HeLa VLDLR KO	Cancer cell line	Female

Clinical trials (associated diseases)

198 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
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
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)
NCT06366230	PHASE1/PHASE2	RECRUITING	Adding Urea to the Final Dialysis Fluid
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
NCT02461459	Not specified	ACTIVE_NOT_RECRUITING	Autism Spectrum Disorder (ASD) and Intellectual Disability (ID) Determinants in Tuberous Sclerosis Complex (TSC)
NCT02486081	Not specified	COMPLETED	Development and Application-Smart Football for Movement Evaluation and Training in the Special Education Population
NCT02504502	Not specified	COMPLETED	Enhancing Genomic Laboratory Reports to Enhance Communication and Empower Patients
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