CLDN4

Summary

CLDN4 (claudin 4, HGNC:2046) is a protein-coding gene on chromosome 7q11.23, encoding Claudin-4 (O14493). Can associate with other claudins to regulate tight junction structural and functional strand dynamics.

The protein encoded by this intronless gene belongs to the claudin family. Claudins are integral membrane proteins that are components of the epithelial cell tight junctions, which regulate movement of solutes and ions through the paracellular space. This protein is a high-affinity receptor for Clostridium perfringens enterotoxin (CPE) and may play a role in internal organ development and function during pre- and postnatal life. This gene is deleted in Williams-Beuren syndrome, a neurodevelopmental disorder affecting multiple systems.

Source: NCBI Gene 1364 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 30 total — 1 pathogenic
• GTEx eGene: eQTL in 32 tissues, sQTL in 0 (q < 0.05)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.44 (unconstrained)
• MANE Select transcript: NM_001305

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2046
Approved symbol	CLDN4
Name	claudin 4
Location	7q11.23
Locus type	gene with protein product
Status	Approved
Aliases	CPE-R, WBSCR8, hCPE-R
Ensembl gene	ENSG00000189143
Ensembl biotype	protein_coding
OMIM	602909
Entrez	1364

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 3 protein_coding, 2 protein_coding_CDS_not_defined

MANE Select: ENST00000340958

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 2: 2, TSL 4: 2

ENST00000340958, ENST00000431918, ENST00000435050, ENST00000466411, ENST00000476494

RefSeq mRNA: 1 — MANE Select: NM_001305 NM_001305

CCDS: CCDS5560

Canonical transcript exons

ENST00000340958 — 1 exons

Exon	Start	End
ENSE00001371777	73830996	73832690

Expression profiles

Bgee: expression breadth ubiquitous, 209 present calls, max score 99.36.

FANTOM5 (CAGE): breadth broad, TPM avg 50.2292 / max 1043.2680, expressed in 663 samples.

Highest expression (Bgee): mucosa of transverse colon, uterine tube, endometrium epithelium, olfactory segment of nasal mucosa, lower esophagus mucosa.

Genetic regulation across tissues (GTEx eQTL / sQTL)

CLDN4 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 32 tissues and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 32 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Adipose Subcutaneous	eqtl	2.3e-38	-0.49	7:73824000:C:T
Brain Cerebellar Hemisphere	eqtl	1.2e-26	-0.77	7:73827962:T:TTAGTCACTTCTG
Brain Cerebellum	eqtl	1.9e-19	-0.76	7:73821936:G:A
Brain Nucleus accumbens basal ganglia	eqtl	1.6e-16	-0.74	7:73827962:T:TTAGTCACTTCTG
Brain Caudate basal ganglia	eqtl	2.6e-16	-0.66	7:73832131:A:G
Thyroid	eqtl	5.1e-12	-0.17	7:73856561:C:T
Nerve Tibial	eqtl	3.4e-11	-0.38	7:73824842:T:C
Adipose Visceral Omentum	eqtl	8.2e-11	-0.43	7:73832874:G:A
Brain Putamen basal ganglia	eqtl	8.3e-11	-0.73	7:73832131:A:G
Brain Hippocampus	eqtl	4.6e-10	-0.49	7:73846917:G:A
Pituitary	eqtl	1.8e-08	-0.32	7:73846340:C:T
Brain Frontal Cortex BA9	eqtl	1.8e-08	-0.53	7:73827962:T:TTAGTCACTTCTG
Brain Cortex	eqtl	5.4e-08	-0.47	7:73829456:T:G
Pancreas	eqtl	1.3e-06	-0.26	7:73847487:T:C
Esophagus Muscularis	eqtl	2.0e-06	-0.25	7:73829456:T:G
Cells Cultured fibroblasts	eqtl	2.4e-06	-0.24	7:73828809:T:C
Brain Anterior cingulate cortex BA24	eqtl	3.9e-05	-0.48	7:73808747:C:T
Adrenal Gland	eqtl	5.2e-05	-0.46	7:73832131:A:G
Heart Left Ventricle	eqtl	1.7e-04	-0.39	7:73812477:C:T
Brain Hypothalamus	eqtl	2.0e-04	-0.38	7:73858574:G:C

FANTOM5 promoters

4 alternative TSS:

Promoter ID	TPM avg	Samples expressed
79028	49.9824	658
79027	0.1018	59
79026	0.0740	34
79023	0.0710	12

Top tissues by expression

showing 100 of 287 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
mucosa of transverse colon	UBERON:0004991	99.36	gold quality
right uterine tube	UBERON:0001302	98.28	gold quality
endometrium epithelium	UBERON:0004811	98.19	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	98.19	gold quality
lower esophagus mucosa	UBERON:0035834	97.62	gold quality
skin of abdomen	UBERON:0001416	97.58	gold quality
skin of leg	UBERON:0001511	97.38	gold quality
minor salivary gland	UBERON:0001830	97.34	gold quality
rectum	UBERON:0001052	97.27	gold quality
left lobe of thyroid gland	UBERON:0001120	96.95	gold quality
esophagus mucosa	UBERON:0002469	96.92	gold quality
mucosa of sigmoid colon	UBERON:0004993	96.75	gold quality
right lobe of thyroid gland	UBERON:0001119	96.53	gold quality
body of pancreas	UBERON:0001150	96.35	gold quality
saliva-secreting gland	UBERON:0001044	96.17	gold quality
colonic mucosa	UBERON:0000317	96.11	gold quality
thyroid gland	UBERON:0002046	96.11	gold quality
metanephros cortex	UBERON:0010533	95.87	gold quality
mouth mucosa	UBERON:0003729	95.85	gold quality
nasal cavity epithelium	UBERON:0005384	95.18	gold quality
islet of Langerhans	UBERON:0000006	94.86	gold quality
zone of skin	UBERON:0000014	94.63	gold quality
gall bladder	UBERON:0002110	94.43	gold quality
pancreas	UBERON:0001264	94.31	gold quality
mucosa of urinary bladder	UBERON:0001259	94.04	gold quality
cervix epithelium	UBERON:0004801	93.56	gold quality
upper lobe of left lung	UBERON:0008952	93.36	gold quality
cervix squamous epithelium	UBERON:0006922	92.92	silver quality
upper lobe of lung	UBERON:0008948	92.81	gold quality
transverse colon	UBERON:0001157	92.46	gold quality
amniotic fluid	UBERON:0000173	92.38	gold quality
right lung	UBERON:0002167	92.13	gold quality
parotid gland	UBERON:0001831	92.02	gold quality
tongue squamous epithelium	UBERON:0006919	91.95	silver quality
duodenum	UBERON:0002114	91.44	gold quality
small intestine Peyer’s patch	UBERON:0003454	91.40	gold quality
mammary duct	UBERON:0001765	91.22	gold quality
epithelium of mammary gland	UBERON:0003244	90.91	gold quality
oral cavity	UBERON:0000167	89.88	gold quality
small intestine	UBERON:0002108	89.78	gold quality
epithelium of bronchus	UBERON:0002031	89.66	gold quality
epithelium of nasopharynx	UBERON:0001951	89.53	silver quality
bronchus	UBERON:0002185	89.25	gold quality
upper arm skin	UBERON:0004263	89.04	silver quality
mucosa of paranasal sinus	UBERON:0005030	88.93	silver quality
prostate gland	UBERON:0002367	88.84	gold quality
adult mammalian kidney	UBERON:0000082	88.52	gold quality
oviduct epithelium	UBERON:0004804	88.20	gold quality
bronchial epithelial cell	CL:0002328	88.16	gold quality
fallopian tube	UBERON:0003889	87.82	gold quality
palpebral conjunctiva	UBERON:0001812	87.75	gold quality
lung	UBERON:0002048	87.28	gold quality
squamous epithelium	UBERON:0006914	87.17	silver quality
tonsil	UBERON:0002372	87.03	gold quality
urinary bladder	UBERON:0001255	86.93	gold quality
epithelium of esophagus	UBERON:0001976	86.90	gold quality
lower lobe of lung	UBERON:0008949	86.83	silver quality
vermiform appendix	UBERON:0001154	86.69	gold quality
vagina	UBERON:0000996	86.55	gold quality
nasal cavity mucosa	UBERON:0001826	86.55	gold quality
seminal vesicle	UBERON:0000998	86.54	gold quality
gingiva	UBERON:0001828	86.29	gold quality
jejunal mucosa	UBERON:0000399	85.94	gold quality
placenta	UBERON:0001987	85.73	gold quality
intestine	UBERON:0000160	85.64	gold quality
esophagus squamous epithelium	UBERON:0006920	85.45	gold quality
gingival epithelium	UBERON:0001949	85.21	silver quality
colonic epithelium	UBERON:0000397	85.17	gold quality
ileal mucosa	UBERON:0000331	84.69	gold quality
kidney	UBERON:0002113	84.57	gold quality
large intestine	UBERON:0000059	84.33	gold quality
colon	UBERON:0001155	84.02	gold quality
periodontal ligament	UBERON:0008266	83.17	silver quality
buccal mucosa cell	CL:0002336	83.00	silver quality
caecum	UBERON:0001153	82.51	gold quality
mammary gland	UBERON:0001911	82.49	gold quality
thoracic mammary gland	UBERON:0005200	82.31	gold quality
cortex of kidney	UBERON:0001225	81.48	gold quality
pharyngeal mucosa	UBERON:0000355	81.13	gold quality
uterine cervix	UBERON:0000002	80.56	gold quality
endometrium	UBERON:0001295	80.29	gold quality
trachea	UBERON:0003126	80.24	gold quality
left uterine tube	UBERON:0001303	80.15	gold quality
esophagus	UBERON:0001043	79.77	gold quality
corpus epididymis	UBERON:0004359	79.29	gold quality
adenohypophysis	UBERON:0002196	78.76	gold quality
pituitary gland	UBERON:0000007	78.55	gold quality
metanephros	UBERON:0000081	78.41	gold quality
caput epididymis	UBERON:0004358	77.81	gold quality
decidua	UBERON:0002450	77.68	silver quality
mammalian vulva	UBERON:0000997	77.41	silver quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	76.94	silver quality
nephron tubule	UBERON:0001231	76.70	silver quality
jejunum	UBERON:0002115	74.77	gold quality
body of stomach	UBERON:0001161	74.68	gold quality
endocervix	UBERON:0000458	74.28	gold quality
oocyte	CL:0000023	73.05	gold quality
female reproductive system	UBERON:0000474	73.05	gold quality
upper leg skin	UBERON:0004262	72.99	gold quality
sigmoid colon	UBERON:0001159	72.98	gold quality

Single-cell (SCXA)

Detected in 28 experiment(s), a significant marker in 26.

Experiment	Marker?	Max mean expression
E-GEOD-81547	yes	10858.75
E-MTAB-9841	yes	8529.45
E-MTAB-8221	yes	4379.17
E-GEOD-114530	yes	3994.78
E-GEOD-124472	yes	3907.15
E-MTAB-10287	yes	3711.28
E-MTAB-10885	yes	3248.31
E-CURD-114	yes	2150.08
E-HCAD-10	yes	2002.85
E-MTAB-6701	yes	1483.62
E-GEOD-130473	yes	1430.23
E-HCAD-23	yes	940.72
E-MTAB-10662	yes	806.94
E-MTAB-8530	yes	697.74
E-MTAB-8142	yes	541.87

HPA expression

RNA tissue specificity: Tissue enhanced

53 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Urinary bladder	tissue	282.7	high
Colon	tissue	215.5	high
Small intestine	tissue	179.5	high
Salivary gland	tissue	159.9	medium
Duodenum	tissue	119.3	high
Esophagus	tissue	116.8	medium
Rectum	tissue	115.9	high
Vagina	tissue	107.3	low
Prostate	tissue	76.2	medium
Fallopian tube	tissue	71.3	medium
Thyroid gland	tissue	69.4	medium
Pancreas	tissue	62.4	high
Lung	tissue	49.7	low
Parathyroid gland	tissue	48.7	low
Gallbladder	tissue	45.9	medium
Breast	tissue	42.5	medium
Seminal vesicle	tissue	36.9	medium
Skin 1	tissue	35.8	high
Tonsil	tissue	35.2	medium
Placenta	tissue	34.1	high
Kidney	tissue	29.8	high
Endometrium 1	tissue	25.1	medium
Epididymis	tissue	23.1	medium
Appendix	tissue	21.7	high
Cervix	tissue	20.6	low
Pituitary gland	tissue	13.6
Choroid plexus	tissue	11.2
Stomach 1	tissue	10.7	not detected
Thymus	tissue	10.0
Smooth muscle	tissue	6.9	not detected
Liver	tissue	4.5	not detected
Adipose tissue	tissue	2.5	not detected
Postcentral gyrus	tissue	1.1
Locus coeruleus	tissue	1.0
Lymph node	tissue	0.9	not detected
Nucleus accumbens	tissue	0.8
Hippocampus	tissue	0.8	low
Spleen	tissue	0.6	not detected
Skeletal muscle	tissue	0.3	not detected
Superior colliculi	tissue	0.3
Spinal cord	tissue	0.3
Testis	tissue	0.2	not detected
Heart muscle	tissue	0.2	not detected
Retina	tissue	0.2
Tongue	tissue	0.2
Bone marrow	tissue	0.2	not detected
Ovary	tissue	0.1	not detected
Hypothalamus	tissue	0.1
Cerebellum	tissue	0.1	low
Adrenal gland	tissue	0.1	not detected
Cerebral cortex	tissue	0.0	low
Bronchus	tissue	-1.0	medium
Oral mucosa	tissue	-1.0	medium

Brain sub-regions (HPA Brain Atlas): detected in 187; highest nTPM — Periaquaductal grey, lateral (4.4), Periaquaductal grey, anterior (3.0), Flocculonodular lobe (2.7), Vermis (2.5), Cerebellar cortex (2.4).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ESR1, FOXC1, GRHL2, HNF4A, NFE2L2, SP1, STAT2, TFAP4, TWIST1, ZEB2

miRNA regulators (miRDB)

Targeting CLDN4 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 41 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-1296-3P	99.72	64.04	636
HSA-MIR-4530	99.69	66.47	1509
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-6887-3P	99.66	67.83	1778
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-497-3P	99.61	69.71	1990
HSA-MIR-186-3P	99.51	66.24	1685
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-582-5P	99.47	70.79	2635
HSA-MIR-3125	99.14	68.49	2269
HSA-MIR-491-5P	99.13	65.98	1468
HSA-MIR-5701	98.97	69.54	1502
HSA-MIR-939-3P	98.97	65.07	2347
HSA-MIR-4656	98.79	66.22	1306
HSA-MIR-6511A-5P	98.13	67.47	1770
HSA-MIR-649	97.96	67.21	704
HSA-MIR-6847-5P	97.93	66.74	1808
HSA-MIR-7113-5P	97.88	67.33	1735
HSA-MIR-1914-5P	97.83	66.21	807

Functional genomics

gnomAD constraint: pLI 0.000128, LOEUF 1.44, missense Z 1.14 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000340958 — one region, missense o/e 0.85.

Literature-anchored findings (GeneRIF, showing 40)

• Results support a model in which claudins 2 and 4 create paracellular channels and the first extracellular domain is sufficient to determine both paracellular charge selectivity and transepithelial electrical resistance. (PMID:12700140)
• CLDN4, clustered with CLDN3 at human chromosome 7q11, is a four-transmembrane protein with WWCC motif, defined by W-X(17-22)-W-X(2)-C-X(8-10)-C. (PMID:12736707)
• Claudin-4 is a potent inhibitor of the invasiveness and metastatic phenotype of pancreatic cancer cells, and a target of the transforming growth factor beta and Ras/Raf/extracellular signal-regulated kinase pathways. (PMID:14559813)
• The tail of claudin-2 could stabilize claudin-4, with a concomitant increase in both protein level and physiologic influence. (PMID:15366421)
• claudin 4 may play a role in the disruption of cell-to-cell adhesion in diffuse type gastric cancer and in a loss of differentiation. (PMID:15643498)
• loss of CLDN4 expression in areas of apocrine metaplasia and in the majority of grade 1 invasive carcinomas suggests a particular role for this protein in mammary glandular cell differentiation and carcinogenesis (PMID:15743508)
• tyrosine phosphorylation of claudin-4 attenuates association of claudin-4 with ZO-1, decreasing integration of claudin-4 into sites of cell-cell contact and enhancing paracellular permeability (PMID:16236711)
• The expression of claudin-1, -3 and -4 was upregulated 5.7-, 1.5- and 2.4-fold, respectively, in colorectal tumor tissues in comparison to the normal ones. (PMID:16253248)
• claudin 3 and claudin 4 may play a role in transformation of ovarian surface epithelium towards the malignant phenotype (PMID:16287068)
• Claudin-4 expression seems to be a useful marker in differentiating biliary tract cancers from hepatocellular carcinomas and could well become a potential diagnostic tool. (PMID:16439986)
• Sp1 epigenetic modifications have a critical role in regulation of the CLDN4 promoter in ovarian cancer cells (PMID:16714763)
• WNK1 increases paracellular chloride permeability and phosphorylation of claudin-4 (PMID:16949040)
• expression of claudin-4 is lower in diffuse-type gastric cancer than in intestinal-type gastric cancer (PMID:16969486)
• Overexpression of claudin-4 is associated with uterine serous papillary carcinoma (PMID:17326053)
• Tight junction proteins contribute to the permeability barrier in epidermal keratinocytes (PMID:17359339)
• When compared, small-cell-lung cancers and carcinoid tumors, adenocarcinomas, and squamous cell carcinomas in CLDN4 expression. (PMID:17418912)
• Loss of claudin expression may enhance the grade of malignancy of gastric cancer in vivo. (PMID:17459057)
• Claudin-3 and claudin-4 receptors are highly overexpressed in carcinosarcoma (PMID:17545541)
• Our data suggest that JUND and CLDN4 are critical mediators of the antiproliferative and antiviral effects of type I IFNs and further confirm the functional importance of the DNA-binding domain of Stat2. (PMID:17651017)
• The modulation of claudin-4 activity by PKCepsilon may not only provide a mechanism for disrupting TJ function in ovarian cancer, but may also be important in the regulation of TJ function in normal epithelial cells. (PMID:17678893)
• vinculin plays a role in growth regulation of neuroendocrine tumors and in expression of CLD4 (PMID:17709988)
• Reduced claudin-4 expression correlates with loss of differentiation in thyroid neoplasms. (PMID:17962811)
• Cdx2 plays an important role in the regulation of intestinal claudin expression not only in gastric mucosa with intestinal metaplasia but also gastric carcinoma. (PMID:18251778)
• MMP-2, MMP-9 and claudin-4 expression may be phenotypic features, distinguishing intestinal-type and diffuse-type gastric cancer. (PMID:18283635)
• Increased expression of claudin-3 and claudin-4 may contribute to aggressive phenotype of endometrial cancer of serous papillary or clear-cell histology. Possible targets for therapeutic intervention. (PMID:18313739)
• Down-regulated expression of claudin-3 and claudin-4 in ectopic endometrium suggests that claudin-3 and claudin-4 might play a pathogenic role in the formation of endometriosis. (PMID:18384777)
• Early gastric carcinomas demonstrating I-CLDN(+) phenotype have a high risk of synchronous and metachronous secondary gastric epithelial neoplasias. (PMID:18477216)
• Claudins 1 and 4 expression was significantly associated with stage in patients with urothelial carcinoma of the upper urinary tract. (PMID:18550469)
• Claudin-4, coding for an integral membrane cell-junction protein, was the most significantly (P<0.00001) upregulated marker in both primary and metastatic tumour specimens compared with benign prostatic hyperplasia at both RNA and protein levels (PMID:18648369)
• High CLDN4 is associated with basal-like breast carcinomas. (PMID:18752049)
• We found that claudin-4 contains a sequence which is phosphorylated by atypical PKC (aPKC). These findings suggest that aPKC regulates tight junction formation through the phosphorylation of claudin-4. (PMID:18786529)
• Claudin 4 is downregulated in lobular carcinoma in situ compated with normal breast epithelium and stroma. (PMID:18954444)
• Down-regulated expression of claudin-4 might play a pathogenic role in the formation of endometriosis. (PMID:19035134)
• The expression of claudins-2, -3 and -4 in 16 rectal well-differentiated endocrine neoplasms was studied (PMID:19082451)
• Down-regulation of claudin-4 might lead to altered tight junction structure and be related to the impaired epithelial function in active ulcerative colitis. (PMID:19120888)
• Increased claudin-4 expression is associated with breast cancer. (PMID:19142967)
• The expressions of PSCA and Claudin-4 are upregulated in the pancreatic carcinomas. (PMID:19180924)
• Tight junction proteins claudin-1, claudin-3, claudin-4, and the adherens junction protein beta-catenin are overexpressed in colorectal carcinoma. (PMID:19184060)
• claudin-4, in addition to 1 and 5, might be a useful differential diagnostic marker of lung cancer in Korean people. (PMID:19231096)
• CLDN4 has a role in the optimization of the endometrium for embryo implantation. (PMID:19374770)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Cldn13	ENSMUSG00000008843
rattus_norvegicus	Cldn4	ENSRNOG00000001476

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), CLDN5 (ENSG00000184113), CLDN6 (ENSG00000184697), CLDN24 (ENSG00000185758), CLDN9 (ENSG00000213937), CLDN25 (ENSG00000228607), CLDN34 (ENSG00000234469), CLDN23 (ENSG00000253958)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1313314) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 23 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal renal reabsorption	2
increased urine chloride ion level	2
decreased circulating calcium level	1
abnormal renal/urinary system morphology	1
hydronephrosis	1
ureter urothelium hyperplasia	1
decreased body weight	1
polyuria	1
premature death	1
increased hematocrit	1
increased circulating aldosterone level	1
increased circulating bicarbonate level	1
decreased circulating chloride level	1
alkalosis	1
abnormal ureter physiology	1
decreased mean systemic arterial blood pressure	1
increased urine calcium level	1
increased circulating potassium level	1
increased urine sodium level	1
abnormal renal sodium reabsorption	1
abnormal renal calcium reabsorption	1
abnormal kidney pelvis urothelium morphology	1
increased kidney cell proliferation	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Pongo abelii	Q5R8E5	99.6%	Diamond
Chlorocebus aethiops	O19005	99.0%	Diamond
Macaca fascicularis	Q4R3L1	98.1%	Diamond
Bos taurus	Q3MHK4	97.1%	Diamond
Canis lupus familiaris	Q95KM5	94.5%	Diamond
Sus scrofa	C3VMW3	85.8%	Diamond
Danio rerio	Q6DHP1	70.2%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
CLDN3	protein-coding	1365
METTL27	protein-coding	155368
ABHD11	protein-coding	83451
TMEM270	protein-coding	135886
ELN-AS1	ncRNA	107986809
ELN	protein-coding	2006
LIMK1	protein-coding	3984

Protein

Protein identifiers

Claudin-4 — O14493 (reviewed: O14493)

Alternative names: Clostridium perfringens enterotoxin receptor, Williams-Beuren syndrome chromosomal region 8 protein

All UniProt accessions (2): O14493, Q75L80

UniProt curated annotations — full annotation on UniProt →

Function. Can associate with other claudins to regulate tight junction structural and functional strand dynamics. May coassemble with CLDN8 into tight junction strands containing anion-selective channels that convey paracellular chloride permeability in renal collecting ducts. May integrate into CLDN3 strands to modulate localized tight junction barrier properties. May disrupt strand assembly of channel-forming CLDN2 and CLDN15 and inhibit cation conductance. Cannot form tight junction strands on its own.

Subunit / interactions. Can form heteropolymeric strands with other claudins. Interacts with CLDN8. Interacts with CLDN1. Directly interacts with TJP1/ZO-1. Interacts with TJP2/ZO-2 and TJP3/ZO-3. Interacts with EPHA2; phosphorylates CLDN4 and may regulate tight junctions. (Microbial infection) Interacts (via both extracellular domains) with Clostridium perfringens enterotoxin CPE; the interaction may disrupt claudin assembly in tight junctions.

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

Post-translational modifications. Phosphorylated. Phosphorylation by EPHA2 is stimulated by EFNA1 and alters interaction with TJP1.

Disease relevance. CLDN4 is located in the Williams-Beuren syndrome (WBS) critical region. WBS results from a hemizygous deletion of several genes on chromosome 7q11.23, thought to arise as a consequence of unequal crossing over between highly homologous low-copy repeat sequences flanking the deleted region.

Similarity. Belongs to the claudin family.

RefSeq proteins (1): NP_001296* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003550	Claudin4	Family
IPR004031	PMP22/EMP/MP20/Claudin	Family
IPR006187	Claudin	Family
IPR017974	Claudin_CS	Conserved_site

Pfam: PF00822

Catalyzed reactions (Rhea)

• chloride(in) = chloride(out) (RHEA:29823)
• iodide(out) = iodide(in) (RHEA:66324)
• bromide(in) = bromide(out) (RHEA:75383)
• fluoride(in) = fluoride(out) (RHEA:76159)

UniProt features (33 total): strand 9, mutagenesis site 6, topological domain 5, transmembrane region 4, helix 4, region of interest 2, chain 1, modified residue 1, disulfide bond 1

Structure

Experimental structures (PDB)

8 structures by resolution:

PDB	Title	Method	Resolution (Å)
9CMI	Cryo-EM structure of human claudin-4 complex with Clostridium perfringens enterotoxin …	ELECTRON MICROSCOPY	2.83
8U4V	Cryo-EM structure of human claudin-4 complex with Clostridium perfringens enterotoxin …	ELECTRON MICROSCOPY	2.99
7KP4	Crystal structure of human claudin-4 in complex with Clostridium perfringens enterotoxin …	X-RAY DIFFRACTION	3.37
5B2G	Crystal structure of human claudin-4 in complex with C-terminal fragment of Clostridium …	X-RAY DIFFRACTION	3.5
9CMH	Cryo-EM structure of human claudin-4 complex with Clostridium perfringens enterotoxin	ELECTRON MICROSCOPY	4
7TDN	CryoEM Structure of sFab COP-3 Complex with human claudin-4 and Clostridium perfringens …	ELECTRON MICROSCOPY	5
8U5B	Cryo-EM structure of human claudin-4 complex with Clostridium perfringens enterotoxin …	ELECTRON MICROSCOPY	5.3
7TDM	CryoEM Structure of sFab COP-2 Complex with human claudin-4 and Clostridium perfringens …	ELECTRON MICROSCOPY	6.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O14493-F1	84.50	0.54

Antibody-complex structures (SAbDab)

5 antibodies co-crystallized with this protein: 7TDM, 7TDN, 8U4V, 8U5B, 9CMI

Human Protein Atlas

Protein class: Transporters, Transporter channels and pores, Predicted membrane proteins, Cancer-related genes, Candidate cancer biomarkers, Disease related genes, Potential drug targets, Human disease related genes, Other congenital disorders, Chromosomal abnormalities

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): plasma membrane

Antibody reliability (HPA): IH enhanced · IF supported

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)

Type	Positions
Phosphotyrosine	208

Disulfide bonds (1)

Type	Positions
Disulfide bond	54–64

Mutagenesis-validated functional residues (6)

Position	Phenotype
35	decreases interaction with clostridium perfringens cpe.
35	abolishes interaction with clostridium perfringens cpe.
40	no effect on interaction with clostridium perfringens cpe.
40	strongly decreases interaction with clostridium perfringens cpe.
53	decreases interaction with clostridium perfringens cpe.
208	loss of phosphorylation by epha2.

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 4; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

4 pathways:

ID	Pathway	Evidence
R-HSA-446728	Cell junction organization	—
R-HSA-1500931	Cell-Cell communication	—
R-HSA-421270	Cell-cell junction organization	—
R-HSA-420029	Tight junction interactions	electronic

MSigDB gene sets: 240 (showing top): GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_DN, GOBP_CIRCADIAN_RHYTHM, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_REGULATION_OF_CELL_MORPHOGENESIS, GOBP_REGULATION_OF_WOUND_HEALING, ENK_UV_RESPONSE_KERATINOCYTE_UP, SHEPARD_CRASH_AND_BURN_MUTANT_UP, MODULE_64, IVANOVA_HEMATOPOIESIS_MATURE_CELL, MCBRYAN_PUBERTAL_TGFB1_TARGETS_DN, GOBP_INORGANIC_ANION_TRANSPORT, KEGG_TIGHT_JUNCTION, TGACCTY_ERR1_Q2, NAGASHIMA_NRG1_SIGNALING_UP, RODRIGUES_NTN1_TARGETS_DN

GO Biological Process (14): female pregnancy (GO:0007565), circadian rhythm (GO:0007623), calcium-independent cell-cell adhesion (GO:0016338), regulation of cell morphogenesis (GO:0022604), positive regulation of cell migration (GO:0030335), response to progesterone (GO:0032570), establishment of skin barrier (GO:0061436), renal absorption (GO:0070293), positive regulation of wound healing (GO:0090303), paracellular transport (GO:0160184), monoatomic ion transport (GO:0006811), chloride transport (GO:0006821), monoatomic ion transmembrane transport (GO:0034220), chloride transmembrane transport (GO:1902476)

GO Molecular Function (5): transmembrane signaling receptor activity (GO:0004888), structural molecule activity (GO:0005198), chloride channel activity (GO:0005254), identical protein binding (GO:0042802), protein binding (GO:0005515)

GO Cellular Component (10): plasma membrane (GO:0005886), cell-cell junction (GO:0005911), bicellular tight junction (GO:0005923), basal plasma membrane (GO:0009925), apical plasma membrane (GO:0016324), apicolateral plasma membrane (GO:0016327), lateral plasma membrane (GO:0016328), chloride channel complex (GO:0034707), tight junction (GO:0070160), membrane (GO:0016020)

Reactome top-level categories

3 top-level categories:

Category	Pathways
Cell-cell junction organization	1
Cell junction organization	1
Cell-Cell communication	1

GO top-level categories

41 GO namespaces:

Category	Terms
plasma membrane region	3
transport	2
cellular anatomical structure	2
multi-organism reproductive process	1
multi-multicellular organism process	1
rhythmic process	1
cell-cell adhesion	1
cell morphogenesis	1
regulation of anatomical structure morphogenesis	1
cell migration	1
regulation of cell migration	1
positive regulation of cell motility	1
response to steroid hormone	1
response to ketone	1
skin epidermis development	1
renal system process	1
wound healing	1
regulation of wound healing	1
positive regulation of response to wounding	1
monoatomic anion transport	1
inorganic anion transport	1
monoatomic ion transport	1
transmembrane transport	1
chloride transport	1
monoatomic anion transmembrane transport	1
signaling receptor activity	1
molecular_function	1
monoatomic anion channel activity	1
chloride transmembrane transporter activity	1
protein binding	1
binding	1
membrane	1
cell periphery	1
anchoring junction	1
apical junction complex	1
tight junction	1
basal part of cell	1
apical part of cell	1
plasma membrane	1
monoatomic ion channel complex	1
cell-cell junction	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 8 of 29 annotations. The rest are phylogenetic / computational / electronic (IEA).

8 experimentally-supported GO terms:

GO term	NS	Evidence
establishment of skin barrier	BP	mutant phenotype
positive regulation of cell migration	BP	mutant phenotype
positive regulation of wound healing	BP	mutant phenotype
regulation of cell morphogenesis	BP	mutant phenotype
bicellular tight junction	CC	direct assay
cell-cell junction	CC	direct assay
plasma membrane	CC	direct assay
tight junction	CC	direct assay

Protein interactions and networks

STRING

showing 15 of 1,460 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CLDN4	TJP1	Q07157	934
CLDN4	CLDN12	P56749	928
CLDN4	OCLN	Q16625	923
CLDN4	TJP2	Q9UDY2	747
CLDN4	MARVELD2	Q8N4S9	653
CLDN4	CDH1	P12830	650
CLDN4	TJP3	O95049	648
CLDN4	F11R	Q9Y624	645
CLDN4	KRT8	P05787	581
CLDN4	EPCAM	P16422	569
CLDN4	TUBB2A	Q13885	513
CLDN4	CGN	Q9P2M7	499
CLDN4	KRT5	P13647	498
CLDN4	IL1B	P01584	498
CLDN4	MUC2	Q02817	482

IntAct

Human interaction partners of CLDN4 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

showing 30 of 85 partners by confidence:

Partner	Interaction type	MIscore	Records
AQP6	physical association	0.560	3
ARL13B	physical association	0.560	3
CLEC14A	physical association	0.560	3
FAM209A	physical association	0.560	3
FFAR2	physical association	0.560	3
GJA8	physical association	0.560	3
GOLM1	physical association	0.560	3
HSD17B13	physical association	0.560	3
ICAM3	physical association	0.560	3
MFSD14B	physical association	0.560	3
SYT2	physical association	0.560	3
TMEM237	physical association	0.560	3
TMEM52B	physical association	0.560	3
TRIM59	physical association	0.560	3
TSPO2	physical association	0.560	3
PATJ	direct interaction	0.440	7
GRIP1	direct interaction	0.440	5
GRIP2	direct interaction	0.440	5
DLG1	direct interaction	0.440	3
DLG3	direct interaction	0.440	3
FRMPD2	direct interaction	0.440	3
IL16	direct interaction	0.440	3
MAGI2	direct interaction	0.440	3
MPDZ	direct interaction	0.440	3
PDZK1	direct interaction	0.440	3
SCRIB	direct interaction	0.440	3
WHRN	direct interaction	0.440	3
APBA2	direct interaction	0.440	2
DLG2	direct interaction	0.440	2
DLG4	direct interaction	0.440	2

BioGRID (72 interactions; top human partners by supporting records): ADD3 (Affinity Capture-MS), AHNAK (Affinity Capture-MS), AKAP12 (Affinity Capture-MS), AP1B1 (Affinity Capture-MS), AQP6 (Two-hybrid), ARL13B (Two-hybrid), ATP1A1 (Affinity Capture-MS), ATP2B1 (Affinity Capture-MS), BAIAP2 (Affinity Capture-MS), CLEC14A (Two-hybrid), CPD (Affinity Capture-MS), CTNND1 (Affinity Capture-MS), CXADR (Affinity Capture-MS), DCBLD2 (Affinity Capture-MS), DLG1 (Affinity Capture-MS)

SIGNOR signaling

3 signaling interactions:

A	Effect	B	Mechanism
SNAI1	“down-regulates quantity by repression”	CLDN4	“transcriptional regulation”
CLDN4	down-regulates	Epithelial-mesenchymal_transition
EPHA2	“down-regulates activity”	CLDN4	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 85 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
Ras activation upon Ca2+ influx through NMDA receptor	5	52.9×	1e-06
Unblocking of NMDA receptors, glutamate binding and activation	5	50.4×	1e-06
Negative regulation of NMDA receptor-mediated neuronal transmission	5	50.4×	1e-06
Assembly and cell surface presentation of NMDA receptors	10	47.0×	7e-13
Dopamine Neurotransmitter Release Cycle	5	46.0×	2e-06
Long-term potentiation	5	44.1×	2e-06
Neurexins and neuroligins	12	43.8×	5e-15
Protein-protein interactions at synapses	8	39.4×	1e-09

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	9	64.6×	4e-12
protein localization to synapse	6	56.7×	1e-07
receptor clustering	7	53.9×	9e-09
regulation of postsynaptic membrane neurotransmitter receptor levels	6	36.7×	1e-06
cell-cell adhesion	9	11.3×	6e-06
protein-containing complex assembly	8	11.2×	3e-05
chemical synaptic transmission	7	6.7×	3e-03

Disease & clinical

Genetic variants

Variant evidence for CLDN4: 30 ClinVar records (1 pathogenic / likely pathogenic). Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	27
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (1)

Showing all 1 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
978415	NC_000007.14:g.73773313_74086695del	Pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore CLDN4’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 10 predictions of 36):

Position(s)	Effect	Δscore	Sites
7:73832663	acceptor_gain	0.4800
7:73832661	acceptor_gain	0.4700
7:73831679	donor_gain	0.3800
7:73831827	donor_gain	0.3700
7:73831788	donor_gain	0.3600
7:73832666	acceptor_gain	0.3500
7:73832214	acceptor_gain	0.3300
7:73831822	donor_gain	0.3200
7:73831785	donor_gain	0.3100
7:73831833	donor_gain	0.2900

AlphaMissense

611 missense substitutions predicted likely pathogenic (of 1,340 scored), across 174 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M52	8	0.811	0.961
D68	8	0.775	0.915
C54	7	0.991	0.994
C64	7	0.988	0.997
F147	7	0.984	0.998
W30	7	0.980	0.996
W51	7	0.978	0.996
F35	7	0.961	0.994
W168	7	0.935	0.997
W47	7	0.890	0.968
W138	7	0.853	0.959
E159	7	0.843	0.953
F125	7	0.784	0.881
G49	6	0.986	0.998
G161	6	0.980	0.996
P28	6	0.969	0.988
R81	6	0.943	0.994
S58	6	0.932	0.974
G60	6	0.929	0.986
G17	6	0.917	0.995

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

3 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	1.95e-09
Kidney Renal Clear Cell Carcinoma (validation)	favorable	5.05e-05
Ovary Serous Cystadenocarcinoma (TCGA)	unfavorable	0.00023

Disease associations

OMIM: gene MIM:602909 | disease phenotypes: MIM:194050

GenCC curated gene-disease

Mondo (1): Williams syndrome (MONDO:0008678)

Orphanet (1): Williams syndrome (Orphanet:904)

MeSH disease descriptors

1 disease descriptors:

Descriptor	Name	Tree numbers
D018980	Williams Syndrome	C10.597.606.360.970; C14.280.484.048.750.535.960; C16.131.260.970; C16.320.180.970

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases methylation, increases expression, decreases expression	7
Valproic Acid	affects cotreatment, increases expression	5
deoxynivalenol	affects localization, decreases expression, increases expression	3
trichostatin A	affects cotreatment, increases expression	3
sodium arsenite	decreases expression, increases expression	3
Estradiol	affects cotreatment, decreases expression	3
Tobacco Smoke Pollution	increases expression	3
Cadmium Chloride	increases expression	3
ochratoxin A	affects reaction, decreases expression	2
mercuric bromide	increases expression, affects cotreatment	2
trans-10,cis-12-conjugated linoleic acid	increases expression	2
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	affects expression, affects reaction, decreases expression, affects cotreatment	2
Panobinostat	increases expression, affects cotreatment	2
Air Pollutants	increases abundance, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Quercetin	affects localization, increases expression	2
Smoke	decreases expression, increases abundance, increases expression	2
Cyclosporine	increases expression	2
Okadaic Acid	increases expression	2
aristolochic acid I	increases expression	1
propionaldehyde	decreases expression, increases expression	1
sanguinarine	decreases expression	1
bisphenol A	decreases expression	1
2,5,2’,5’-tetrachlorobiphenyl	increases expression	1
quercitrin	affects expression	1
butyraldehyde	increases expression	1
tetrathiomolybdate	decreases expression	1
benzo(e)pyrene	increases methylation	1
diallyl disulfide	decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, decreases expression	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_C3VA	HT-1080/hCLDN-4	Cancer cell line	Male
CVCL_D3PN	CHO/CLDN4	Transformed cell line	Female

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

28 trials:

NCT	Phase	Status	Title
NCT00768820	Phase 4	RECRUITING	The Psychiatric and Cognitive Phenotypes in Velocardiofacial Syndrome
NCT04807517	Phase 4	COMPLETED	Buspirone Treatment of Anxiety in Williams Syndrome
NCT00876200	Phase 2	COMPLETED	Efficacy of Minoxidil in Children With Williams-Beuren Syndrome
NCT06087757	Phase 2	ACTIVE_NOT_RECRUITING	Clemastine Treatment in Individuals With Williams Syndrome
NCT06315699	Phase 2	COMPLETED	Clemastine Fumarate in the Treatment of Neurodevelopmental Delays in Williams Syndrome
NCT00004351	Not specified	COMPLETED	Study of Phenotype and Genotype Correlations in Patients With Contiguous Gene Deletion Syndromes
NCT00013962	Not specified	COMPLETED	Vitamin D Metabolism and the Williams Syndrome
NCT01132885	Not specified	RECRUITING	Defining the Brain Phenotype of Children With Williams Syndrome
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
NCT01864304	Not specified	COMPLETED	Fat Distribution and Glucose Metabolism in Williams Syndrome
NCT02212314	Not specified	COMPLETED	Response Inhibition Training for Children With Williams Syndrome
NCT02692846	Not specified	COMPLETED	WS-SAVE Study (Williams Syndrome Skin and Vessel Elasticity Study)
NCT02706639	Not specified	COMPLETED	Williams Syndrome (WS) and Supravalvar Aortic Stenosis (SVAS) DNA and Tissue Bank
NCT02840448	Not specified	COMPLETED	Impact of Elastin Mediated Vascular Stiffness on End Organs
NCT03758651	Not specified	COMPLETED	Williams Syndrome Strength, Hormones, Activity & Adiposity, DNA Programming, Eating Study
NCT03827525	Not specified	UNKNOWN	Cognitive and Behavioral Therapy of Anxiety in Williams Syndrome
NCT03836300	Not specified	ENROLLING_BY_INVITATION	Parent and Infant Inter(X)Action Intervention (PIXI)
NCT04051086	Not specified	UNKNOWN	Quantification of Elastin Markers Synthesis in Williams-Beuren Syndrome and 7q11.23 Micro-duplication Syndrome
NCT04095585	Not specified	COMPLETED	Molecular Characterization of Patients Affected by Williams Syndrome and Autism.
NCT04463316	Not specified	RECRUITING	GROWing Up With Rare GENEtic Syndromes
NCT04610424	Not specified	UNKNOWN	Cooperative Parent Mediated Therapy in Children With Fragile X Syndrome and Williams Syndrome
NCT05430763	Not specified	WITHDRAWN	Motor Deficits and Signal Conduction in Individuals With Williams Syndrome
NCT06740162	Not specified	RECRUITING	Physical Activity and Community EmPOWERment Project
NCT06930417	Not specified	RECRUITING	Characterization and Natural History of Williams Syndrome and Other Chromosome 7q11.23 Variants
NCT07285720	Not specified	RECRUITING	Phonological Constraints on Language Development in Individuals With Williams Syndrome
NCT07493096	Not specified	RECRUITING	Intensive Multimodal Neurorehabilitation Targeting Neuroplasticity in Pediatric Neurodevelopmental and Chromosomal Disorders
NCT07509879	Not specified	NOT_YET_RECRUITING	Research on the Molecular Mechanism of Cognitive Differences Between Williams Syndrome and Autism Spectrum Disorder
NCT07537374	Not specified	NOT_YET_RECRUITING	A Case-Control Observational Study of Peripheral Blood-Derived iPSC Models to Investigate Oligodendrocyte Lineage Development in Children With Williams Syndrome and Healthy Controls