CLDN5

Summary

CLDN5 (claudin 5, HGNC:2047) is a protein-coding gene on chromosome 22q11.21, encoding Claudin-5 (O00501). Plays a major role in tight junction-specific obliteration of the intercellular space.

This gene encodes a member of the claudin family. Claudins are integral membrane proteins and components of tight junction strands. Tight junction strands serve as a physical barrier to prevent solutes and water from passing freely through the paracellular space between epithelial or endothelial cell sheets. Mutations in this gene have been found in patients with velocardiofacial syndrome. Alternative splicing results in multiple transcript variants encoding distinct isoforms.

Source: NCBI Gene 7122 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder (Limited, GenCC)
• Clinical variants (ClinVar): 53 total — 6 pathogenic, 4 likely-pathogenic
• MANE Select transcript: NM_001363066

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2047
Approved symbol	CLDN5
Name	claudin 5
Location	22q11.21
Locus type	gene with protein product
Status	Approved
Aliases	CPETRL1, BEC1
Ensembl gene	ENSG00000184113
Ensembl biotype	protein_coding
OMIM	602101
Entrez	7122

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000403084, ENST00000406028, ENST00000413119, ENST00000618236

RefSeq mRNA: 5 — MANE Select: NM_001363066 NM_001130861, NM_001363066, NM_001363067, NM_001426402, NM_003277

CCDS: CCDS13763, CCDS93118

Canonical transcript exons

ENST00000618236 — 1 exons

Exon	Start	End
ENSE00003714707	19523027	19524410

Expression profiles

Bgee: expression breadth ubiquitous, 268 present calls, max score 99.50.

FANTOM5 (CAGE): breadth broad, TPM avg 12.9081 / max 499.7433, expressed in 470 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
193157	11.9230	467
193158	0.8248	235
193159	0.1603	100

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lung	UBERON:0002167	99.50	gold quality
upper lobe of lung	UBERON:0008948	98.87	gold quality
upper lobe of left lung	UBERON:0008952	98.85	gold quality
pericardium	UBERON:0002407	98.72	gold quality
lower lobe of lung	UBERON:0008949	98.60	gold quality
subcutaneous adipose tissue	UBERON:0002190	98.23	gold quality
omental fat pad	UBERON:0010414	98.06	gold quality
peritoneum	UBERON:0002358	98.02	gold quality
adipose tissue of abdominal region	UBERON:0007808	97.91	gold quality
adipose tissue	UBERON:0001013	97.57	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	97.42	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	97.30	gold quality
inferior olivary complex	UBERON:0002127	97.18	gold quality
spinal cord	UBERON:0002240	96.69	gold quality
olfactory bulb	UBERON:0002264	96.63	silver quality
tibial nerve	UBERON:0001323	96.62	gold quality
connective tissue	UBERON:0002384	96.32	gold quality
apex of heart	UBERON:0002098	96.28	gold quality
putamen	UBERON:0001874	96.26	gold quality
lung	UBERON:0002048	96.06	gold quality
amygdala	UBERON:0001876	95.92	gold quality
body of uterus	UBERON:0009853	95.88	gold quality
substantia nigra	UBERON:0002038	95.49	gold quality
choroid plexus epithelium	UBERON:0003911	95.49	gold quality
midbrain	UBERON:0001891	95.37	gold quality
left lobe of thyroid gland	UBERON:0001120	95.36	gold quality
hypothalamus	UBERON:0001898	94.97	gold quality
caudate nucleus	UBERON:0001873	94.95	gold quality
ventral tegmental area	UBERON:0002691	94.91	gold quality
right frontal lobe	UBERON:0002810	94.82	gold quality

Single-cell (SCXA)

Detected in 40 experiment(s), a significant marker in 38.

Experiment	Marker?	Max mean expression
E-MTAB-6308	yes	8833.70
E-CURD-88	yes	6639.29
E-MTAB-6653	yes	6289.55
E-MTAB-10662	yes	6239.02
E-MTAB-6911	yes	5286.13
E-HCAD-25	yes	4891.04
E-CURD-126	yes	4805.89
E-HCAD-15	yes	4511.08
E-HCAD-1	yes	4067.20
E-HCAD-11	yes	4059.88
E-GEOD-134144	yes	3561.76
E-MTAB-10287	yes	3543.79
E-GEOD-124263	yes	3261.73
E-MTAB-8410	yes	2708.99
E-MTAB-8381	yes	2428.73

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

3 targets.

Target	Regulation
CLDN1	Activation
CLDN15	Activation
CLDN2	Repression

Upstream regulators (CollecTRI, top): CDH5, E2F1, ERG, ETV5, FOXO1, NFKB, NR3C1, RAMP2, RELA, RUNX1, SOX18

miRNA regulators (miRDB)

11 targeting CLDN5, 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-6715A-3P	99.83	68.05	1473
HSA-MIR-3714	99.71	70.74	2671
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-4763-3P	99.10	67.83	2649
HSA-MIR-661	99.09	65.94	2062
HSA-MIR-6715B-3P	98.80	68.07	1204
HSA-MIR-3135B	98.61	65.33	1470
HSA-MIR-4722-5P	98.46	66.34	1611
HSA-MIR-1287-5P	96.80	65.30	743
HSA-MIR-7108-3P	94.37	64.79	183
HSA-MIR-6869-3P	83.17	65.88	30

Literature-anchored findings (GeneRIF, showing 40)

• Claudin 5 is transiently expressed during the development of the retinal pigment epithelium. (PMID:11944085)
• The Blood-Brain Barrier against small molecules (<800 D), but not larger molecules, was selectively affected in Claudin-5 deficient mice. (PMID:12743111)
• Airway tight junctions are regulated by claudin interactions that confer the selectivity of the junction. (PMID:12909588)
• Showed that residues located C-terminal to the last transmembrane domain of claudin 5 are required for the proper targeting to apical TJ.s. (PMID:15260435)
• CLDN5 protein may predispose to schizophrenia (PMID:15363474)
• CLDN5 may be involved in forming a permeability barrier in the gut and, together with DQB, confer a susceptibility to schizophrenia. (PMID:15617864)
• CLDN5 may be associated with schizophrenia in Chinese of Han descent (PMID:15820333)
• CLDN5 may be classified as a tight junction protein capable of “sealing” a tight junction. (PMID:16158492)
• gamma linolenic acid, iodine, and selenium alone, or in combination are able to strengthen the function of tight junctions in human endothelial cells, by way of regulating the distribution of Claudin-5, Occludin, and ZO-1 (PMID:16514648)
• overexpression of claudin-5 leads to formation of elaborate networks of junction strands, which are absent in untransduced endothelial cells (PMID:16959372)
• Claudin tight junction proteins in endoscopy biopsy samples showed Barrett’s metaplasia contains more claudin-2 and claudin-3 than found in normal esophageal mucosa, but markedly lower claudins 1 and 5, indicating very different tight junction barriers. (PMID:17103306)
• Squamous cell carcinomas were positive for CLDN-1 and negative for CLDN-5, whereas adenocarcinomas were positive for CLDN-5 and negative for CLDN-1. (PMID:17585317)
• data for the first time explain how two claudins hold onto each other and constrict the paracellular space. The intermolecular interface includes aromatic (F147, Y148, Y158) and hydrophilic (Q156, E159) residues (PMID:17761522)
• Data show that claudin-5 was only detected in human umbilical vein endothelial cells derived from healthy newborns with a strong family history of myocardial infarction. (PMID:17765294)
• an obligatory role for SOX-18 in the regulation of claudin-5 gene expression in an endothelial-specific and cell density-dependent manner is established (PMID:18065521)
• claudin-5 may participate in novel mechanisms in the pathway to end-stage heart failure. (PMID:18513742)
• endothelial VE-cadherin at AJs upregulates the gene encoding the TJ adhesive protein claudin-5 (PMID:18604199)
• For the first time this study proves the presence of Claudin-1, Claudin-3 and Claudin-5 in ECV304 (obtained from ECACC) cell layers and the inducibility of their expression by glioma-conditioned media. (PMID:18817843)
• Endothelial claudin 5 expression levels is associated with increased permeability. (PMID:19168871)
• Expression pattern of claudins 5 and 7 distinguishes solid-pseudopapillary from pancreatoblastoma, acinar cell and endocrine tumors of the pancreas. (PMID:19194274)
• claudin-4, in addition to 1 and 5, might be a useful differential diagnostic marker of lung cancer in Korean people. (PMID:19231096)
• Structure and function of extracellular claudin domains (PMID:19538285)
• Increased claudin-5 expression is associated with aggressive behavior in serous ovarian adenocarcinoma. (PMID:20044634)
• The results of this study showed weak association of the CLDN5 locus with schizophrenia in Chinese. (PMID:20452046)
• Claudin-1, -3, -4, -5, and -7 are expressed in developing human lung from week 12 to week 40 with distinct locations and in divergent quantities. (PMID:20478039)
• This study sought to determine the cell signaling mechanism controlling endothelial CLDN5 expression during acute lung injury. (PMID:20525806)
• tyrosine phosphorylation of claudin-5 is involved in the increased paracellular permeability of central nervous system-derived vascular endothelium induced by TGF-beta1. (PMID:21168935)
• Interendothelial claudin-5 expression depends on cerebral endothelial cell-matrix adhesion by beta(1)-integrins. (PMID:21772312)
• Data suggest that the degradation of tight junction proteins ZO-1, claudin-5 and occludin by MMP-2 and -9 secreted by leukemic cells constitutes an important mechanism in the BBB breakdown which contributes to the invasion of leukemic cells to the CNS. (PMID:21857898)
• Claudin-5 is a promising new marker for angiosarcomas and hemangioendotheliomas. (PMID:21959309)
• GDNF increased the expression of claudin-5 and the transendothelial electrical resistance (TEER) of BMECs and PnMECs, whereas BDNF did not have this effect (PMID:22002662)
• this study portrays a new and interesting role for Claudin-5 in cell motility involving the N-WASP and ROCK signalling cascade (PMID:22038628)
• ERG plays a pivotal role in regulating endothelial cell barrier function and that this effect is mediated in part through its regulation of CLDN5 gene expression. (PMID:22235125)
• Galphai2 as a novel claudin-5 partner required for TJ integrity in brain endothelial cells. (PMID:22333621)
• study demonstrated that claudin 5 is a protein with a short half-life that can undergo polyubiquitinationmainly on lysine 199, which apparently leads to its subsequent degradation (PMID:22389112)
• Study portrays a role for Claudin-5 in cell motility involving the N-WASP signalling cascade indicating a possible role for Claudin-5 in the metastasis of human breast cancer. (PMID:22559840)
• CLDN5 gene DNA meyhylation suggesting the pathogenesis of idiopathic pulmonary fibrosis. (PMID:22700861)
• Letter: confirm the endothelial cell origin of cutaneous angiosarcoma and demonstrate that both endoglin and claudin-5 show promise as markers for cutaneous angiosarcoma. (PMID:23000880)
• Over-expression of claudin-5 was sufficient to prevent replication-deficient virus-induced permeability (PMID:23115643)
• Claudin-5 expression and junctional organization controls intercellular barriers of human dermal microvascular but not human umbilical vein endothelial cells. (PMID:23288152)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	cldn5b	ENSDARG00000014059
danio_rerio	cldn5a	ENSDARG00000043716
mus_musculus	Cldn5	ENSMUSG00000041378
rattus_norvegicus	Cldn5	ENSRNOG00000077978

Paralogs (22): CLDN11 (ENSG00000013297), CLDN18 (ENSG00000066405), CLDN15 (ENSG00000106404), CLDN16 (ENSG00000113946), CLDN10 (ENSG00000134873), CLDN17 (ENSG00000156282), CLDN8 (ENSG00000156284), CLDN14 (ENSG00000159261), CLDN1 (ENSG00000163347), CLDN19 (ENSG00000164007), CLDN3 (ENSG00000165215), CLDN2 (ENSG00000165376), CLDN20 (ENSG00000171217), CLDN22 (ENSG00000177300), CLDN7 (ENSG00000181885), CLDN6 (ENSG00000184697), CLDN24 (ENSG00000185758), CLDN4 (ENSG00000189143), CLDN9 (ENSG00000213937), CLDN25 (ENSG00000228607), CLDN34 (ENSG00000234469), CLDN23 (ENSG00000253958)

Protein

Protein identifiers

Claudin-5 — O00501 (reviewed: O00501)

Alternative names: Transmembrane protein deleted in VCFS

All UniProt accessions (2): D3DX19, O00501

UniProt curated annotations — full annotation on UniProt →

Function. Plays a major role in tight junction-specific obliteration of the intercellular space.

Subunit / interactions. Directly interacts with TJP1/ZO-1, TJP2/ZO-2 and TJP3/ZO-3. Interacts with MPDZ.

Subcellular location. Cell junction. Tight junction. Cell membrane.

Similarity. Belongs to the claudin family.

RefSeq proteins (5): NP_001124333, NP_001349995, NP_001349996, NP_001413331, NP_003268 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003551	Claudin5	Family
IPR004031	PMP22/EMP/MP20/Claudin	Family
IPR006187	Claudin	Family
IPR017974	Claudin_CS	Conserved_site

Pfam: PF00822

UniProt features (11 total): topological domain 5, transmembrane region 4, chain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O00501-F1	83.42	0.51

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-420029	Tight junction interactions
R-HSA-8935964	RUNX1 regulates expression of components of tight junctions

MSigDB gene sets: 278 (showing top): GOBP_ENDOTHELIAL_CELL_DEVELOPMENT, CREL_01, MODULE_52, GOBP_RESPONSE_TO_ETHANOL, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_BODY_MORPHOGENESIS, WALLACE_PROSTATE_CANCER_RACE_UP, GOBP_COGNITION, GOBP_BEHAVIOR, GOBP_CIRCULATORY_SYSTEM_PROCESS, YAO_HOXA10_TARGETS_VIA_PROGESTERONE_UP, GOBP_EPITHELIAL_CELL_DEVELOPMENT, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, GOBP_APICAL_JUNCTION_ASSEMBLY, GOBP_REGULATION_OF_ENDOTHELIAL_CELL_DIFFERENTIATION

GO Biological Process (22): outflow tract morphogenesis (GO:0003151), cell-cell junction assembly (GO:0007043), cell adhesion (GO:0007155), transforming growth factor beta receptor signaling pathway (GO:0007179), learning (GO:0007612), positive regulation of cell population proliferation (GO:0008284), positive regulation of gene expression (GO:0010628), negative regulation of gene expression (GO:0010629), calcium-independent cell-cell adhesion (GO:0016338), negative regulation of angiogenesis (GO:0016525), negative regulation of cell migration (GO:0030336), maintenance of blood-brain barrier (GO:0035633), myelination (GO:0042552), negative regulation of vascular permeability (GO:0043116), response to ethanol (GO:0045471), roof of mouth development (GO:0060021), face morphogenesis (GO:0060325), bicellular tight junction assembly (GO:0070830), tight junction assembly (GO:0120192), positive regulation of establishment of endothelial barrier (GO:1903142), positive regulation of bicellular tight junction assembly (GO:1903348), establishment of blood-retinal barrier (GO:1990963)

GO Molecular Function (3): structural molecule activity (GO:0005198), identical protein binding (GO:0042802), protein binding (GO:0005515)

GO Cellular Component (12): plasma membrane (GO:0005886), cell-cell junction (GO:0005911), bicellular tight junction (GO:0005923), membrane (GO:0016020), apicolateral plasma membrane (GO:0016327), lateral plasma membrane (GO:0016328), cell junction (GO:0030054), paranode region of axon (GO:0033270), Schmidt-Lanterman incisure (GO:0043220), tight junction (GO:0070160), cortical actin cytoskeleton (GO:0030864), anchoring junction (GO:0070161)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Cell-cell junction organization	1
Transcriptional regulation by RUNX1	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
anatomical structure morphogenesis	2
gene expression	2
regulation of gene expression	2
heart morphogenesis	1
cell junction assembly	1
cell-cell junction organization	1
cellular process	1
cellular response to transforming growth factor beta stimulus	1
transforming growth factor beta receptor superfamily signaling pathway	1
learning or memory	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
positive regulation of macromolecule biosynthetic process	1
negative regulation of macromolecule biosynthetic process	1
cell-cell adhesion	1
angiogenesis	1
regulation of angiogenesis	1
negative regulation of blood vessel morphogenesis	1
cell migration	1
regulation of cell migration	1
negative regulation of cell motility	1
tissue homeostasis	1
axon ensheathment	1
regulation of vascular permeability	1
response to alcohol	1
anatomical structure development	1
head morphogenesis	1
face development	1
apical junction assembly	1
tight junction assembly	1
cell-cell junction assembly	1
tight junction organization	1
establishment of endothelial barrier	1
positive regulation of endothelial cell development	1
regulation of establishment of endothelial barrier	1
molecular_function	1
protein binding	1
binding	1

Protein interactions and networks

STRING

2492 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CLDN5	OCLN	Q16625	999
CLDN5	TJP1	Q07157	999
CLDN5	TJP2	Q9UDY2	990
CLDN5	CDH5	P33151	989
CLDN5	F11R	Q9Y624	956
CLDN5	CLDN12	P56749	918
CLDN5	ANGPTL4	Q9BY76	907
CLDN5	CDH17	Q12864	885
CLDN5	TJP3	O95049	846
CLDN5	CLDN3	O15551	844
CLDN5	GJA1	P17302	819
CLDN5	PECAM1	P16284	800
CLDN5	MARVELD2	Q8N4S9	775
CLDN5	ESAM	Q96AP7	754
CLDN5	MMP9	P14780	746

IntAct

112 interactions, top by confidence:

A	B	Type	Score
VAMP5	CLDN5	psi-mi:“MI:0915”(physical association)	0.560
PMP22	CLDN5	psi-mi:“MI:0915”(physical association)	0.560
ERG28	CLDN5	psi-mi:“MI:0915”(physical association)	0.560
SFTPC	CLDN5	psi-mi:“MI:0915”(physical association)	0.560
TMEM182	CLDN5	psi-mi:“MI:0915”(physical association)	0.560
TF	CLDN5	psi-mi:“MI:0915”(physical association)	0.560
CLDN5	EFNA5	psi-mi:“MI:0915”(physical association)	0.560
	CLDN5	psi-mi:“MI:0915”(physical association)	0.560
CLDN5	BTNL8	psi-mi:“MI:0915”(physical association)	0.560
CLDN5	TMEM140	psi-mi:“MI:0915”(physical association)	0.560
CLDN5	SLC35B4	psi-mi:“MI:0915”(physical association)	0.560
CLDN5	RPRM	psi-mi:“MI:0915”(physical association)	0.560
CLDN5	VAMP5	psi-mi:“MI:0915”(physical association)	0.560
CLRN2	CLDN5	psi-mi:“MI:0915”(physical association)	0.560
CLDN5	SGCG	psi-mi:“MI:0915”(physical association)	0.560
CLDN5	PMP22	psi-mi:“MI:0915”(physical association)	0.560
CLDN5	ERG28	psi-mi:“MI:0915”(physical association)	0.560
CLDN5	ERMP1	psi-mi:“MI:0915”(physical association)	0.560
CLDN5	TSPAN2	psi-mi:“MI:0915”(physical association)	0.560
CLDN5	CXCL9	psi-mi:“MI:0915”(physical association)	0.560
CLDN5	CORIN	psi-mi:“MI:0915”(physical association)	0.560
CLDN5	SFTPC	psi-mi:“MI:0915”(physical association)	0.560
CLDN5	TMEM128	psi-mi:“MI:0915”(physical association)	0.560
CLDN5	GYPA	psi-mi:“MI:0915”(physical association)	0.560
CLDN5	CYB561A3	psi-mi:“MI:0915”(physical association)	0.560
CLDN5	EHHADH	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (41): CLDN5 (Affinity Capture-Western), CLDN3 (Affinity Capture-Western), CLDN5 (Two-hybrid), CLDN5 (Two-hybrid), CLDN5 (Two-hybrid), CLDN5 (Two-hybrid), CLDN5 (Two-hybrid), CLDN5 (Two-hybrid), CLDN5 (Two-hybrid), CLDN5 (Two-hybrid), CLDN5 (Two-hybrid), CLDN5 (Two-hybrid), CLDN5 (Two-hybrid), CLDN5 (Two-hybrid), CLDN5 (Two-hybrid)

ESM2 similar proteins: A0A8C0N7E5, C3VMW3, D3ZQJ0, O00501, O14493, O15551, O19005, O35054, O35912, O54942, O88551, O95471, O95484, O95832, P56745, P56746, P56747, P56748, P56750, P78369, Q2HJ22, Q2KIY2, Q3B7N4, Q5E9L0, Q5QT56, Q5R8E5, Q63400, Q6BBL6, Q6DHB5, Q6DHP1, Q6L708, Q765N9, Q8BXA6, Q8N6F1, Q95KM5, Q9D1D1, Q9ET38, Q9JKD6, Q9QYW5, Q9YH90

Diamond homologs: A0A8C0N7E5, A6NM45, C3VMW3, C9JDP6, D3ZQJ0, O00501, O14493, O15551, O19005, O35054, O54942, O75508, O88551, O88552, O95471, O95484, O95500, O95832, P56745, P56746, P56747, P56748, P56750, P56856, P56857, P56880, P57739, P78369, Q0VCN0, Q2HJ22, Q2KIY2, Q3B7N4, Q3MHK4, Q4R3L1, Q5E9L0, Q5I0E5, Q5QT56, Q5R8E5, Q60771, Q63400

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
ERG	“up-regulates quantity by expression”	CLDN5	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	6
Likely pathogenic	4
Uncertain significance	34
Likely benign	7
Benign	2

Top pathogenic / likely-pathogenic (10)

Variant ID	HGVS	Classification
2628323	NM_001363066.2(CLDN5):c.178G>A (p.Gly60Arg)	Pathogenic
3340659	NM_001363066.2(CLDN5):c.121G>A (p.Val41Met)	Pathogenic
3770191	NM_001363066.2(CLDN5):c.176C>T (p.Thr59Ile)	Pathogenic
816201	GRCh37/hg19 22q11.21(chr22:18970561-21040836)x3	Pathogenic
997047	GRCh37/hg19 22q11.21(chr22:18628019-20311763)	Pathogenic
997809	Single allele	Pathogenic
2572405	NM_001363066.2(CLDN5):c.187C>A (p.Gln63Lys)	Likely pathogenic
3067178	NM_001363066.2(CLDN5):c.175_177dup (p.Thr59_Gly60insThr)	Likely pathogenic
393549	GRCh37/hg19 22q11.21(chr22:18915347-21463730)x1	Likely pathogenic
4537854	NM_001363066.2(CLDN5):c.174C>G (p.Ser58Arg)	Likely pathogenic

SpliceAI

176 predictions. Top by Δscore:

Variant	Effect	Δscore
22:19523661:TC:T	donor_gain	0.6700
22:19523607:A:AC	donor_gain	0.6500
22:19523613:T:TA	donor_gain	0.6300
22:19523661:T:TA	donor_gain	0.6200
22:19523544:AT:A	donor_gain	0.6100
22:19523535:C:A	donor_gain	0.5700
22:19523479:T:A	donor_gain	0.5500
22:19523496:CCGCG:C	donor_gain	0.5500
22:19523497:CGCGC:C	donor_gain	0.5500
22:19523592:AGCGC:A	donor_gain	0.5500
22:19523596:C:CA	donor_gain	0.5500
22:19523659:CT:C	donor_gain	0.5500
22:19523660:TT:T	donor_gain	0.5500
22:19523871:C:CT	acceptor_gain	0.5500
22:19523372:T:TA	donor_gain	0.5400
22:19523501:C:CT	donor_gain	0.5400
22:19523502:T:TT	donor_gain	0.5400
22:19523787:T:TA	donor_gain	0.5300
22:19523534:C:CA	donor_gain	0.5200
22:19523607:AGTT:A	donor_gain	0.5200
22:19523724:CGCCT:C	donor_loss	0.5200
22:19523725:GCCTA:G	donor_loss	0.5200
22:19523726:CCTA:C	donor_loss	0.5200
22:19523727:CTA:C	donor_loss	0.5200
22:19523728:TACC:T	donor_loss	0.5200
22:19523729:A:C	donor_loss	0.5200
22:19523731:C:G	donor_loss	0.5100
22:19523352:C:CT	acceptor_gain	0.4900
22:19523608:G:C	donor_gain	0.4900
22:19523729:A:AC	donor_gain	0.4900

AlphaMissense

1371 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:19523815:A:C	F147L	0.998
22:19523815:A:T	F147L	0.998
22:19523817:A:G	F147L	0.998
22:19524111:C:G	G49R	0.997
22:19524111:C:T	G49R	0.997
22:19524166:C:A	W30C	0.997
22:19524166:C:G	W30C	0.997
22:19524065:C:G	C64S	0.996
22:19524066:A:T	C64S	0.996
22:19524103:C:A	W51C	0.996
22:19524103:C:G	W51C	0.996
22:19524105:A:G	W51R	0.996
22:19524105:A:T	W51R	0.996
22:19523775:C:A	G161C	0.994
22:19523775:C:G	G161R	0.994
22:19523816:A:C	F147C	0.994
22:19524095:C:T	C54Y	0.994
22:19524110:C:T	G49E	0.994
22:19524111:C:A	G49W	0.994
22:19524168:A:G	W30R	0.994
22:19524168:A:T	W30R	0.994
22:19523754:A:G	W168R	0.993
22:19523754:A:T	W168R	0.993
22:19524066:A:G	C64R	0.993
22:19524095:C:G	C54S	0.993
22:19524096:A:T	C54S	0.993
22:19524151:G:C	F35L	0.993
22:19524151:G:T	F35L	0.993
22:19524153:A:G	F35L	0.993
22:19523774:C:A	G161V	0.992

dbSNP variants (sampled 300 via entrez): RS1001152998 (22:19523146 C>G), RS1001730761 (22:19526481 T>C), RS1001851757 (22:19523168 G>A,C), RS1002526343 (22:19523309 G>A), RS1002674658 (22:19524749 C>T), RS1003136632 (22:19524957 C>T), RS1003246157 (22:19524348 C>G,T), RS1003843461 (22:19525560 C>T), RS1004906615 (22:19526305 C>G), RS1004957401 (22:19526511 T>A), RS1005133070 (22:19527211 G>T), RS1005638063 (22:19524230 A>G), RS1006030052 (22:19522800 C>T), RS1008024423 (22:19525190 G>A,C), RS1008493089 (22:19524956 C>T)

Disease associations

OMIM: gene MIM:602101 | disease phenotypes: MIM:192350

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder	Limited	Autosomal dominant

Mondo (5): syndromic disease (MONDO:0002254), neurodevelopmental disorder (MONDO:0700092), VACTERL/vater association (MONDO:0008642), intellectual disability (MONDO:0001071), epilepsy (MONDO:0005027)

Orphanet (2): VACTERL/VATER association (Orphanet:887), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D004827	Epilepsy	C10.228.140.490
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D065886	Neurodevelopmental Disorders	F03.625
D013577	Syndrome	C23.550.288.500

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one	decreases reaction, increases expression, decreases expression	3
sodium bisulfide	decreases expression, decreases reaction, increases abundance	2
deguelin	decreases expression, increases expression	2
Acetylcysteine	affects localization, decreases expression, decreases reaction	2
Benzo(a)pyrene	affects methylation, increases expression	2
Dexamethasone	decreases expression, decreases reaction, increases abundance	2
Nickel	decreases reaction, affects expression, decreases expression	2
Progesterone	affects cotreatment, increases expression	2
Tobacco Smoke Pollution	decreases expression, increases expression	2
Particulate Matter	decreases expression, increases abundance, decreases reaction, affects reaction	2
N-(1,2,3,5,6,7-hexahydro-S-indacen-4-ylcarbamoyl)-4-(2-hydroxy-2-propanyl)-2-furansulfonamide	decreases expression, decreases reaction	1
linsidomine	decreases expression	1
oxybenzone	decreases expression	1
9,10-phenanthrenequinone	affects localization, decreases expression, decreases reaction, increases reaction	1
triphenyl phosphate	affects expression	1
sanguinarine	decreases expression	1
palmidrol	decreases expression	1
bisphenol A	affects cotreatment, increases methylation	1
lead acetate	decreases expression, decreases reaction	1
trichostatin A	affects expression, decreases reaction	1
tobacco tar	decreases expression	1
diallyl disulfide	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression	1
loxoprofen	increases expression	1
diallyl trisulfide	decreases expression	1
cordycepin	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
benzyloxycarbonylleucyl-leucyl-leucine aldehyde	decreases expression, decreases reaction, affects localization	1
1,3-dihydroxy-4,4,5,5-tetramethyl-2-(4-carboxyphenyl)tetrahydroimidazole	decreases expression, decreases reaction	1
CGP 52608	affects binding, increases reaction	1

Cellosaurus cell lines

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

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

Cellosaurus	Name	Category	Sex
CVCL_C3VB	HT-1080/hCLDN-5	Cancer cell line	Male
CVCL_D3PP	CHO/CLDN5	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
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
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
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
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00027456	PHASE2	COMPLETED	Leptin to Treat Severe Insulin Resistance - Pilot Study
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
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
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)
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders