ARVCF

Summary

ARVCF (ARVCF delta catenin family member, HGNC:728) is a protein-coding gene on chromosome 22q11.21, encoding Splicing regulator ARVCF (O00192). Contributes to the regulation of alternative splicing of pre-mRNAs.

Armadillo Repeat gene deleted in Velo-Cardio-Facial syndrome (ARVCF) is a member of the catenin family. This family plays an important role in the formation of adherens junction complexes, which are thought to facilitate communication between the inside and outside environments of a cell. The ARVCF gene was isolated in the search for the genetic defect responsible for the autosomal dominant Velo-Cardio-Facial syndrome (VCFS), a relatively common human disorder with phenotypic features including cleft palate, conotruncal heart defects and facial dysmorphology. The ARVCF gene encodes a protein containing two motifs, a coiled coil domain in the N-terminus and a 10 armadillo repeat sequence in the midregion. Since these sequences can facilitate protein-protein interactions ARVCF is thought to function in a protein complex. In addition, ARVCF contains a predicted nuclear-targeting sequence suggesting that it may have a function as a nuclear protein.

Source: NCBI Gene 421 — RefSeq curated summary.

At a glance

• GWAS associations: 29 (top 4% of genes corpus-wide)
• Clinical variants (ClinVar): 486 total — 65 pathogenic, 2 likely-pathogenic (top 7% of genes corpus-wide)
• GTEx eGene: eQTL in 31 tissues, sQTL in 33 (q < 0.05)
• Phenotypes (HPO): 131
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.03 (unconstrained)
• MANE Select transcript: NM_001670
• Notable: 486 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:728
Approved symbol	ARVCF
Name	ARVCF delta catenin family member
Location	22q11.21
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000099889
Ensembl biotype	protein_coding
OMIM	602269
Entrez	421

Gene structure

Transcript identifiers

Ensembl transcripts: 31 — 15 protein_coding, 9 nonsense_mediated_decay, 5 protein_coding_CDS_not_defined, 2 retained_intron

MANE Select: ENST00000263207

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 2: 3, TSL 3: 4, TSL 5: 3

ENST00000263207, ENST00000401994, ENST00000406259, ENST00000406522, ENST00000462319, ENST00000467828, ENST00000473551, ENST00000480792, ENST00000487793, ENST00000492625, ENST00000495096, ENST00000852538, ENST00000934103, ENST00000992162, ENST00000992163, ENST00001018228, ENST00001018229, ENST00001018230, ENST00001018231, ENST00001018232, ENST00001018234, ENST00001018235, ENST00001018236, ENST00001089163, ENST00001089164, ENST00001089165, ENST00001089166, ENST00001089167, ENST00001089168, ENST00001124359, ENST00001131855

RefSeq mRNA: 9 — MANE Select: NM_001670 NM_001410839, NM_001438683, NM_001438684, NM_001438685, NM_001438687, NM_001438690, NM_001438693, NM_001438694, NM_001670

CCDS: CCDS13771, CCDS93120

Canonical transcript exons

ENST00000263207 — 20 exons

Exon	Start	End
ENSE00001305102	20010455	20010508
ENSE00001305650	19971216	19971335
ENSE00001644901	19979743	19980242
ENSE00001728584	19981211	19981737
ENSE00001759472	19978897	19979080
ENSE00001766679	19976706	19976723
ENSE00001881837	19969896	19970743
ENSE00001927738	20016589	20016823
ENSE00002308607	19990585	19990812
ENSE00003459452	19973643	19973793
ENSE00003471476	19977415	19977586
ENSE00003482965	19981933	19982091
ENSE00003487398	19977958	19978075
ENSE00003525882	19972358	19972411
ENSE00003552716	19972925	19973036
ENSE00003578295	19972737	19972827
ENSE00003636865	19973119	19973317
ENSE00003638782	19971886	19971971
ENSE00003678473	19975686	19975757
ENSE00003688873	19974112	19974239

Expression profiles

Bgee: expression breadth ubiquitous, 273 present calls, max score 97.75.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 5.0112 / max 76.8872, expressed in 1255 samples.

Highest expression (Bgee): cerebellar hemisphere, hemisphere of cerebellum, cerebellar cortex, cerebellum, type B pancreatic cell.

Genetic regulation across tissues (GTEx eQTL / sQTL)

ARVCF is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 31 tissues and its splicing (sQTL) in 33 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 64 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Artery Tibial	sqtl	2.8e-56	+0.89	22:19969258:G:A
Artery Aorta	sqtl	4.8e-48	+0.96	22:19971146:G:A
Thyroid	eqtl	1.1e-43	+0.38	22:19972675:G:C
Artery Aorta	eqtl	8.3e-41	-0.56	22:19984595:C:A
Nerve Tibial	sqtl	9.6e-41	+0.73	22:19969258:G:A
Nerve Tibial	eqtl	1.3e-38	-0.28	22:19995588:C:A
Thyroid	sqtl	4.7e-33	+0.68	22:19969258:G:A
Colon Sigmoid	eqtl	1.5e-27	-0.34	22:20000722:G:A
Cells Cultured fibroblasts	eqtl	4.4e-27	-0.37	22:20017181:C:T
Muscle Skeletal	sqtl	1.1e-26	-0.67	22:19973083:G:C
Esophagus Muscularis	eqtl	2.5e-26	-0.33	22:20000722:G:A
Esophagus Gastroesophageal Junction	eqtl	2.8e-23	-0.42	22:20000722:G:A
Artery Tibial	eqtl	2.5e-22	-0.30	22:19996688:C:T
Lung	eqtl	8.3e-22	+0.30	22:19995588:C:A
Esophagus Muscularis	sqtl	9.7e-21	+0.73	22:19969258:G:A
Colon Sigmoid	sqtl	3.2e-20	+0.84	22:19969258:G:A
Skin Sun Exposed Lower leg	sqtl	1.0e-18	+0.58	22:19971146:G:A
Brain Cerebellum	eqtl	4.5e-17	-0.30	22:19995588:C:A
Colon Transverse	eqtl	5.9e-17	+0.27	22:19986509:T:C
Lung	sqtl	2.2e-16	+0.54	22:19969258:G:A

FANTOM5 promoters

5 alternative TSS:

Promoter ID	TPM avg	Samples expressed
193175	2.9814	1041
193178	0.8147	230
193180	0.7704	292
193179	0.2386	86
193176	0.2062	100

Top tissues by expression

showing 100 of 297 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
cerebellar hemisphere	UBERON:0002245	97.75	gold quality
right hemisphere of cerebellum	UBERON:0014890	97.71	gold quality
cerebellar cortex	UBERON:0002129	97.70	gold quality
cerebellum	UBERON:0002037	96.65	gold quality
type B pancreatic cell	CL:0000169	96.44	silver quality
olfactory bulb	UBERON:0002264	95.72	silver quality
right lobe of thyroid gland	UBERON:0001119	95.23	gold quality
ventricular zone	UBERON:0003053	94.71	gold quality
ascending aorta	UBERON:0001496	94.54	gold quality
thoracic aorta	UBERON:0001515	94.43	gold quality
vena cava	UBERON:0004087	94.13	gold quality
apex of heart	UBERON:0002098	94.07	gold quality
sural nerve	UBERON:0015488	93.84	gold quality
nerve	UBERON:0001021	93.82	gold quality
left lobe of thyroid gland	UBERON:0001120	93.82	gold quality
tibial nerve	UBERON:0001323	93.82	gold quality
aorta	UBERON:0000947	93.78	gold quality
ganglionic eminence	UBERON:0004023	93.78	gold quality
popliteal artery	UBERON:0002250	93.36	gold quality
tibial artery	UBERON:0007610	93.35	gold quality
thyroid gland	UBERON:0002046	93.30	gold quality
right coronary artery	UBERON:0001625	93.19	gold quality
descending thoracic aorta	UBERON:0002345	93.10	gold quality
pancreatic ductal cell	CL:0002079	92.06	silver quality
cerebellar vermis	UBERON:0004720	91.90	silver quality
embryo	UBERON:0000922	91.87	gold quality
triceps brachii	UBERON:0001509	91.86	gold quality
diaphragm	UBERON:0001103	91.72	gold quality
metanephros cortex	UBERON:0010533	91.68	gold quality
tongue squamous epithelium	UBERON:0006919	91.38	silver quality
adenohypophysis	UBERON:0002196	91.33	gold quality
coronary artery	UBERON:0001621	91.22	gold quality
pituitary gland	UBERON:0000007	91.16	gold quality
spleen	UBERON:0002106	91.06	gold quality
left coronary artery	UBERON:0001626	91.05	gold quality
gluteal muscle	UBERON:0002000	90.94	gold quality
lateral nuclear group of thalamus	UBERON:0002736	90.80	gold quality
cortical plate	UBERON:0005343	90.64	gold quality
parotid gland	UBERON:0001831	90.54	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	90.05	gold quality
pericardium	UBERON:0002407	89.97	silver quality
pons	UBERON:0000988	89.89	gold quality
subthalamic nucleus	UBERON:0001906	89.49	gold quality
hindlimb stylopod muscle	UBERON:0004252	89.47	gold quality
cardia of stomach	UBERON:0001162	89.43	silver quality
pylorus	UBERON:0001166	89.37	gold quality
dorsal plus ventral thalamus	UBERON:0001897	89.18	silver quality
body of tongue	UBERON:0011876	89.15	gold quality
left ventricle myocardium	UBERON:0006566	89.10	silver quality
nasal cavity epithelium	UBERON:0005384	88.94	gold quality
heart left ventricle	UBERON:0002084	88.90	gold quality
cardiac ventricle	UBERON:0002082	88.89	gold quality
cervix squamous epithelium	UBERON:0006922	88.84	silver quality
saphenous vein	UBERON:0007318	88.84	gold quality
vastus lateralis	UBERON:0001379	88.83	silver quality
tendon of biceps brachii	UBERON:0008188	88.81	silver quality
ventral tegmental area	UBERON:0002691	88.75	gold quality
right frontal lobe	UBERON:0002810	88.74	gold quality
inferior vagus X ganglion	UBERON:0005363	88.38	silver quality
amygdala	UBERON:0001876	88.29	gold quality
buccal mucosa cell	CL:0002336	88.20	gold quality
nipple	UBERON:0002030	88.15	gold quality
right lobe of liver	UBERON:0001114	88.14	gold quality
pharyngeal mucosa	UBERON:0000355	88.13	silver quality
quadriceps femoris	UBERON:0001377	88.04	silver quality
substantia nigra pars compacta	UBERON:0001965	87.96	gold quality
heart	UBERON:0000948	87.94	gold quality
upper arm skin	UBERON:0004263	87.94	silver quality
lateral globus pallidus	UBERON:0002476	87.87	gold quality
tongue	UBERON:0001723	87.80	silver quality
medulla oblongata	UBERON:0001896	87.75	gold quality
fundus of stomach	UBERON:0001160	87.71	gold quality
hypothalamus	UBERON:0001898	87.63	gold quality
right atrium auricular region	UBERON:0006631	87.56	gold quality
cardiac atrium	UBERON:0002081	87.52	gold quality
renal medulla	UBERON:0000362	87.51	gold quality
trigeminal ganglion	UBERON:0001675	87.42	gold quality
cingulate cortex	UBERON:0003027	87.42	gold quality
Brodmann (1909) area 9	UBERON:0013540	87.34	gold quality
anterior cingulate cortex	UBERON:0009835	87.31	gold quality
substantia nigra pars reticulata	UBERON:0001966	87.25	gold quality
lower esophagus muscularis layer	UBERON:0035833	87.21	gold quality
lower esophagus	UBERON:0013473	87.14	gold quality
endometrium epithelium	UBERON:0004811	87.12	gold quality
inferior olivary complex	UBERON:0002127	86.99	gold quality
superior vestibular nucleus	UBERON:0007227	86.97	gold quality
saliva-secreting gland	UBERON:0001044	86.95	gold quality
brain	UBERON:0000955	86.86	gold quality
endocervix	UBERON:0000458	86.84	gold quality
right lung	UBERON:0002167	86.80	gold quality
central nervous system	UBERON:0001017	86.76	gold quality
skeletal muscle tissue	UBERON:0001134	86.74	gold quality
minor salivary gland	UBERON:0001830	86.72	gold quality
granulocyte	CL:0000094	86.70	gold quality
muscle layer of sigmoid colon	UBERON:0035805	86.57	gold quality
myocardium	UBERON:0002349	86.45	gold quality
trachea	UBERON:0003126	86.27	silver quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	86.25	gold quality
CA1 field of hippocampus	UBERON:0003881	86.18	silver quality
muscle organ	UBERON:0001630	86.15	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.86

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 78 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Corpus callosum	tissue	26.3
Spinal cord	tissue	20.4
Midbrain	tissue	19.2
Substantia nigra	tissue	19.1
Locus coeruleus	tissue	18.1
Medulla oblongata	tissue	17.6
Thalamus	tissue	17.4
Hypothalamus	tissue	17.2
Cerebral cortex	tissue	16.8	medium
Somatosensory cortex	tissue	16.8
Motor cortex	tissue	16.1
Pons	tissue	16.0
Prefrontal cortex	tissue	15.7
Hippocampal formation	tissue	15.7
Entorhinal cortex	tissue	15.7
Insular cortex	tissue	15.7
Periaqueductal gray	tissue	15.4
Superior colliculi	tissue	15.0
Retrosplenial and cingulate cortex	tissue	15.0
Temporal cortex	tissue	15.0
Hippocampus	tissue	14.8	low
Retrosplenial cortex	tissue	14.7
Septum	tissue	14.1
Amygdala	tissue	14.0
Occipital cortex	tissue	13.6
Ventral forebrain	tissue	13.3
Cerebellum	tissue	12.8	medium
Putamen	tissue	11.5
Olfactory bulb	tissue	11.5
Frontal cortex	tissue	11.4
Basal ganglia	tissue	10.6	low
Nucleus accumbens	tissue	10.0
Postcentral gyrus	tissue	9.8
Caudate putamen	tissue	8.8
Pituitary gland	tissue	8.7
Choroid plexus	tissue	8.4
Skeletal muscle	tissue	6.4	medium
Spleen	tissue	6.2	not detected
Salivary gland	tissue	3.7	not detected
Pancreas	tissue	3.6	medium
Thyroid gland	tissue	3.4	medium
Epididymis	tissue	3.0	high
Bone marrow	tissue	3.0	not detected
Heart muscle	tissue	2.6	high
Vagina	tissue	2.6	not detected
Adrenal gland	tissue	2.5	low
Prostate	tissue	2.4	low
Skin 1	tissue	2.2	not detected
Testis	tissue	2.0	low
Stomach 1	tissue	2.0	not detected
Kidney	tissue	1.8	medium
Seminal vesicle	tissue	1.6	low
Parathyroid gland	tissue	1.6	low
Lung	tissue	1.5	low
Small intestine	tissue	1.4	not detected
Retina	tissue	1.3
Adipose tissue	tissue	1.3	not detected
Endometrium 1	tissue	1.3	low
Liver	tissue	1.3	not detected
Colon	tissue	1.2	low

Brain sub-regions (HPA Brain Atlas): detected in 190; highest nTPM — Vermis (43.8), Flocculonodular lobe (42.9), Cerebellar cortex (41.4), White matter (26.3), Habenula (23.4).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TAL1

miRNA regulators (miRDB)

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

showing 30 of 36 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-767-5P	99.95	70.85	993
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-3065-3P	99.87	70.25	1407
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-6752-3P	99.72	66.71	1587
HSA-MIR-545-5P	99.66	70.18	2308
HSA-MIR-4690-5P	99.65	66.24	813
HSA-MIR-6715B-5P	99.64	69.63	1420
HSA-MIR-6132	99.60	65.83	1554
HSA-MIR-762	99.58	66.61	1994
HSA-MIR-4269	99.55	69.89	1373
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-2392	99.43	67.50	708
HSA-MIR-3182	99.40	68.15	2454
HSA-MIR-155-5P	99.35	70.16	1509
HSA-MIR-328-5P	99.08	64.65	1000
HSA-MIR-5001-5P	99.05	66.76	1972
HSA-MIR-3619-5P	99.00	68.87	2308
HSA-MIR-761	98.71	68.07	2051

Functional genomics

gnomAD constraint: pLI 2.83e-19, LOEUF 1.03, missense Z -1.88 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000263207 — one region, missense o/e 1.06.

Literature-anchored findings (GeneRIF, showing 14)

• Evidence was found for association of illness to rs165849 in ARVCF, and a stronger signal from three-marker haplotypes spanning the 3’ portions of COMT and ARVCF. Val(108/158)Met was in linkage disequilibrium with the markers in ARVCF. (PMID:15340358)
• Interactions with zona occludens-1 and zona occludens-2, in particular, may mediate recruitment of ARVCF to the plasma membrane and the nucleus (PMID:15456900)
• Results implicate a very close association of ARVCF with migrating neurons from the ganglionic eminence. (PMID:15509897)
• Two haplotypes covering the catechol-O-methyltransferase-ARVCF region show significant transmission disequilibrium in anorexia nervosa-restricting Israeli-Jewish families (PMID:16118784)
• Differential expression pattern of protein ARVCF in nephron segments of human kidney. (PMID:18600340)
• Single nucleotide polymorphisms in the ARVGF gene are associated with the risk of schizophrenia. (PMID:19508883)
• Over-expression of TXNRD2, COMT and ARVCF affects incentive learning and working memory in transgenic mice. (PMID:19617637)
• The functional variant rs165815, which affects a critical region of ARVCF, is a considerable source of the genetic variability associated with the risk of developing schizophrenia. (PMID:20333729)
• Five SNPs were validated as being significantly associated with prostate cancer mortality, one each in the LEPR, CRY1, RNASEL, IL4, and ARVCF genes. (PMID:21846818)
• Schizophrenic patients with more copies of the haplotype T-G-A-T-T-G-G-C-T-G-T (ARVCF-Hap1) have lower white matter integrity in caudate nucleus and greater perseverative errors. (PMID:22053977)
• Data indicate that armadillo repeat protein ARVCF interacts with the splicing factors the splicing factor SRSF1 (SF2/ASF), the RNA helicase p68 (DDX5), and the heterogeneous nuclear ribonucleoprotein hnRNP H2. (PMID:24644279)
• Carriage of the minor allele at rs2518824 in the armadillo repeat gene deleted in velocardiofacial syndrome (ARVCF) gene was associated with white matter abnormality. (PMID:24819575)
• observed ARVCF-dependent changes in small GTPase (mainly RhoA) activity in lung cancer cells. We confirmed that ARVCF plays an important role in the malignant phenotype (PMID:25683624)
• p53-induced ARVCF modulates the splicing landscape and supports the tumor suppressive function of p53. (PMID:31827232)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	arvcfb	ENSDARG00000061688
danio_rerio	arvcfa	ENSDARG00000074329
mus_musculus	Arvcf	ENSMUSG00000118669
rattus_norvegicus	Arvcf	ENSRNOG00000001888

Paralogs (6): PKP2 (ENSG00000057294), PKP1 (ENSG00000081277), PKP4 (ENSG00000144283), CTNND2 (ENSG00000169862), PKP3 (ENSG00000184363), CTNND1 (ENSG00000198561)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:109620) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 18 distinct phenotype terms.

Mouse phenotype (MP)	Records
cataract	2
hyperactivity	2
abnormal gait	2
decreased bone mineral density	1
tremors	1
abnormal lens morphology	1
abnormal retina morphology	1
decreased anxiety-related response	1
increased startle reflex	1
increased mean platelet volume	1
increased circulating alkaline phosphatase level	1
abnormal bone structure	1
abnormal behavior	1
absent testes	1
abnormal optic disk morphology	1
decreased prepulse inhibition	1
decreased grip strength	1
decreased total retina thickness	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
Bos taurus	Q08DQ0	92.7%	Diamond
Arabidopsis thaliana	Q9C9A6	74.1%	Diamond
Xenopus laevis	Q8AXM9	49.7%	Diamond
Caenorhabditis elegans	Q9U308	42.6%	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
MIR1306	ncRNA	100302197
MIR6816	ncRNA	102465490
TANGO2	protein-coding	128989
TRMT2A	protein-coding	27037
MIR185	ncRNA	406961
DGCR8	protein-coding	54487
TXNRD2	protein-coding	10587
COMT	protein-coding	1312
MIR4761	ncRNA	100616414
GNB1L	protein-coding	54584
RTL10	protein-coding	79680
MIR3618	ncRNA	100500860
SNORA77B	snoRNA	109617010
RANBP1	protein-coding	5902

Protein

Protein identifiers

Splicing regulator ARVCF — O00192 (reviewed: O00192)

Alternative names: Armadillo repeat protein deleted in velo-cardio-facial syndrome

All UniProt accessions (3): O00192, C9JJX6, E9PDC3

UniProt curated annotations — full annotation on UniProt →

Function. Contributes to the regulation of alternative splicing of pre-mRNAs.

Subunit / interactions. Component of a ribonucleoprotein complex containing mRNAs and RNA-binding proteins including DDX5, HNRNPH2 and SRSF1 as well as ARVCF. Interacts (via the extreme C-terminus) with FRMPD2 (via the PDZ 2 domain). Interacts with CCDC85B.

Subcellular location. Cell junction. Adherens junction. Nucleus. Cytoplasm.

Tissue specificity. Found in all the examined tissues including heart, brain, liver and kidney. Found at low level in lung. Expressed in dermal connective tissue, salivary gland duct and in the corneal layer (at protein level). Expressed in arrector pili muscle (at protein level). High levels detected in epithelial cells with lower levels found in fibroblasts and T lymphocytes.

Similarity. Belongs to the beta-catenin family.

Isoforms (2)

UniProt ID	Names	Canonical?
O00192-1	Long	yes
O00192-2	Short

RefSeq proteins (9): NP_001397768, NP_001425612, NP_001425613, NP_001425614, NP_001425616, NP_001425619, NP_001425622, NP_001425623, NP_001661* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000225	Armadillo	Repeat
IPR011989	ARM-like	Homologous_superfamily
IPR016024	ARM-type_fold	Homologous_superfamily
IPR028435	Plakophilin/d_Catenin	Family

Pfam: PF00514

UniProt features (46 total): modified residue 14, repeat 10, sequence variant 7, region of interest 6, compositionally biased region 5, chain 1, coiled-coil region 1, short sequence motif 1, splice variant 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O00192-F1	65.73	0.41

Human Protein Atlas

Protein class: Predicted intracellular proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): cell junctions; plasma membrane

Antibody reliability (HPA): IH enhanced · IF enhanced

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 (14)

Type	Positions
Phosphothreonine	102, 104, 642, 872
Omega-n-methylarginine	170
Phosphoserine	267, 332, 335, 343, 345, 606, 864, 871, 915

Function

Pathways and Gene Ontology

Reactome pathways

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

MSigDB gene sets: 397 (showing top): GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_UP, TGGTGCT_MIR29A_MIR29B_MIR29C, TGCGCANK_UNKNOWN, CCAWYNNGAAR_UNKNOWN, BASSO_B_LYMPHOCYTE_NETWORK, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GOBP_CELL_CELL_ADHESION, KOYAMA_SEMA3B_TARGETS_UP, DOANE_RESPONSE_TO_ANDROGEN_DN, GOBP_RNA_SPLICING, AACTTT_UNKNOWN, MORF_PDPK1, E12_Q6

GO Biological Process (4): mRNA processing (GO:0006397), cell adhesion (GO:0007155), RNA splicing (GO:0008380), cell-cell adhesion (GO:0098609)

GO Molecular Function (2): cadherin binding (GO:0045296), protein binding (GO:0005515)

GO Cellular Component (5): nucleus (GO:0005634), cytoplasm (GO:0005737), plasma membrane (GO:0005886), adherens junction (GO:0005912), cell junction (GO:0030054)

GO top-level categories

12 GO namespaces:

Category	Terms
RNA processing	2
cellular anatomical structure	2
mRNA metabolic process	1
cellular process	1
cell adhesion	1
cell adhesion molecule binding	1
binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
membrane	1
cell periphery	1
cell-cell junction	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 7 of 11 annotations. The rest are phylogenetic / computational / electronic (IEA).

7 experimentally-supported GO terms:

GO term	NS	Evidence
RNA splicing	BP	mutant phenotype
adherens junction	CC	direct assay
cell junction	CC	direct assay
cytoplasm	CC	direct assay
nucleus	CC	direct assay
plasma membrane	CC	direct assay
cadherin binding	MF	physical interaction

Protein interactions and networks

STRING

showing 15 of 826 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ARVCF	COMT	P21964	886
ARVCF	TXNRD2	Q9NNW7	846
ARVCF	FRMPD2	Q68DX3	728
ARVCF	ATP6V1E1	P36543	677
ARVCF	GP1BB	P13224	668
ARVCF	GNB1L	Q9BYB4	634
ARVCF	ZBTB33	Q86T24	609
ARVCF	TANGO2	Q6ICL3	598
ARVCF	TAAR6	Q96RI8	495
ARVCF	PPP3CC	P48454	492
ARVCF	ZDHHC8	Q9ULC8	490
ARVCF	CLDN5	O00501	487
ARVCF	TRMT2A	Q8IZ69	483
ARVCF	STX7	O15400	478
ARVCF	DSP	P15924	477

IntAct

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

showing 30 of 87 partners by confidence:

Partner	Interaction type	MIscore	Records
TAX1BP3	association	0.690	5
ERBIN	physical association	0.610	2
CDH8	association	0.530	3
SCML1	association	0.530	2
PATJ	direct interaction	0.440	6
GRIP1	direct interaction	0.440	5
GRIP2	direct interaction	0.440	5
MAGI2	direct interaction	0.440	5
DLG1	direct interaction	0.440	3
DLG3	direct interaction	0.440	3
DLG4	direct interaction	0.440	3
FRMPD2	direct interaction	0.440	3
IL16	direct interaction	0.440	3
LNX1	direct interaction	0.440	3
MPDZ	direct interaction	0.440	3
NHERF4	direct interaction	0.440	3
PDZK1	direct interaction	0.440	3
WHRN	direct interaction	0.440	3
APBA1	direct interaction	0.440	2
APBA2	direct interaction	0.440	2
DLG2	direct interaction	0.440	2
GRID2IP	direct interaction	0.440	2
LNX2	direct interaction	0.440	2
MAGI1	direct interaction	0.440	2
SCRIB	direct interaction	0.440	2
AHNAK	direct interaction	0.440	1
APBA3	direct interaction	0.440	1
ARHGAP21	direct interaction	0.440	1
ARHGEF11	direct interaction	0.440	1
ARHGEF12	direct interaction	0.440	1

BioGRID (74 interactions; top human partners by supporting records): CDH15 (Two-hybrid; 3 records), CTNNB1 (Affinity Capture-MS; 3 records), CDH5 (Affinity Capture-MS; 2 records), CDH8 (Affinity Capture-MS; 2 records), CPA5 (Affinity Capture-MS; 2 records), CTNNA3 (Affinity Capture-MS; 2 records), CYP2S1 (Affinity Capture-MS; 2 records), ERBB2IP (Reconstituted Complex; 2 records), GJB7 (Affinity Capture-MS; 2 records), S1PR2 (Affinity Capture-MS; 2 records), SDC1 (Affinity Capture-MS; 2 records), TACR1 (Affinity Capture-MS; 2 records), ANK3 (Proximity Label-MS), ANLN (Affinity Capture-MS), C11orf52 (Proximity Label-MS)

SIGNOR signaling

7 signaling interactions:

A	Effect	B	Mechanism
ARVCF	“up-regulates activity”	ERBIN	binding
ARVCF	“up-regulates quantity by stabilization”	CDH3	binding
ARVCF	“up-regulates quantity by stabilization”	CDH2	binding
ARVCF	“up-regulates quantity by stabilization”	CDH5	binding
ARVCF	“up-regulates quantity by stabilization”	CDH1	binding
TJP1	“up-regulates activity”	ARVCF	binding
TJP2	“down-regulates activity”	ARVCF	relocalization

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 87 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	47.6×	3e-06
Unblocking of NMDA receptors, glutamate binding and activation	5	45.3×	3e-06
Negative regulation of NMDA receptor-mediated neuronal transmission	5	45.3×	3e-06
Assembly and cell surface presentation of NMDA receptors	10	42.3×	3e-12
Dopamine Neurotransmitter Release Cycle	5	41.4×	4e-06
Long-term potentiation	5	39.6×	5e-06
Neurexins and neuroligins	11	36.1×	2e-12
Protein-protein interactions at synapses	7	31.0×	2e-07

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	11	76.1×	5e-16
protein localization to synapse	6	54.7×	1e-07
receptor clustering	7	52.0×	1e-08
regulation of postsynaptic membrane neurotransmitter receptor levels	7	41.3×	5e-08
cell-cell adhesion	13	15.7×	6e-10
protein-containing complex assembly	9	12.2×	4e-06
regulation of small GTPase mediated signal transduction	5	8.6×	7e-03
chemical synaptic transmission	8	7.4×	6e-04

Disease & clinical

Genetic variants

Variant evidence for ARVCF: 486 ClinVar records (67 pathogenic / likely pathogenic); 29 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	65
Likely pathogenic	2
Uncertain significance	229
Likely benign	24
Benign	59

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 67 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
57452	GRCh38/hg38 22q11.21(chr22:18178957-20324240)x3	Pathogenic	criteria provided, single submitter	1
57570	GRCh38/hg38 22q11.21(chr22:18886943-20318794)x1	Pathogenic	criteria provided, single submitter	1
57571	GRCh38/hg38 22q11.21(chr22:18902758-20340590)x1	Pathogenic	criteria provided, single submitter	1
57590	GRCh38/hg38 22q11.21(chr22:18339130-20343532)x1	Pathogenic	criteria provided, single submitter	1
58196	GRCh38/hg38 22q11.21(chr22:18339130-20588575)x3	Pathogenic	criteria provided, single submitter	1
59199	GRCh38/hg38 22q11.21(chr22:18339130-20671425)x1	Pathogenic	criteria provided, single submitter	1
59204	GRCh38/hg38 22q11.21(chr22:18950648-20241494)x1	Pathogenic	criteria provided, single submitter	1
59209	GRCh38/hg38 22q11.21(chr22:18339130-20641963)x1	Pathogenic	criteria provided, single submitter	1
160932	GRCh38/hg38 22q11.21(chr22:18932429-20324240)x1	Pathogenic	criteria provided, single submitter	1
160954	GRCh38/hg38 22q11.21(chr22:18339130-20343532)x3	Pathogenic	criteria provided, single submitter	1
161049	GRCh38/hg38 22q11.21(chr22:18339130-20354644)x1	Pathogenic	criteria provided, single submitter	1
161087	GRCh38/hg38 22q11.21(chr22:18339130-20343532)x1	Pathogenic	criteria provided, single submitter	1
236379	Single allele	Pathogenic	criteria provided, single submitter	1
253570	GRCh37/hg19 22q11.21(chr22:18894339-21032422)x3	Pathogenic	criteria provided, single submitter	1
253589	GRCh37/hg19 22q11.21(chr22:18661724-21025713)x3	Pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore ARVCF’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; 37 predictions of 2,148):

Position(s)	Effect	Δscore	Sites
22:19971884–19971885	donor_loss	1.0000	4
22:19971972–19971973	acceptor_loss	1.0000	5
22:19972356–19972357	donor_loss	1.0000	3
22:19972735–19972736	donor_loss	1.0000	5
22:19972828–19972829	acceptor_loss	1.0000	5
22:19972835	acceptor_gain	1.0000
22:19972923–19972924	donor_loss	1.0000	3
22:19973037–19973038	acceptor_loss	1.0000	5
22:19973318–19973319	acceptor_loss	1.0000	5
22:19973795	acceptor_loss	1.0000

AlphaMissense

2,013 missense substitutions predicted likely pathogenic (of 6,150 scored), across 500 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
M366	9	0.933	0.998
N577	8	0.999	1.000
N689	8	0.999	1.000
N470	8	0.998	1.000
N528	8	0.998	1.000
N570	8	0.998	1.000
H384	8	0.997	0.999
N426	8	0.996	1.000
N521	8	0.989	0.999
N735	8	0.989	0.999
S530	8	0.986	1.000
F23	8	0.974	0.999
D739	8	0.974	0.991
F519	8	0.972	0.998
N377	8	0.958	0.999
N742	8	0.953	0.998
F849	8	0.923	0.991
D959	8	0.913	0.973
D372	8	0.895	0.969
N676	8	0.891	0.991

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

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

5 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	1.91e-07
Kidney Renal Papillary Cell Carcinoma (TCGA)	favorable	8.97e-05
Rectum Adenocarcinoma (TCGA)	favorable	0.000517
Glioblastoma Multiforme (validation)	favorable	0.000722
Lung Adenocarcinoma (TCGA)	favorable	0.000829

Disease associations

OMIM: gene MIM:602269 | disease phenotypes: MIM:181500, MIM:209850

GenCC curated gene-disease

Mondo (3): autism spectrum disorder (MONDO:0005258), schizophrenia (MONDO:0005090), autism (MONDO:0005260)

Orphanet (2): NON RARE IN EUROPE: Autism (Orphanet:106), NON RARE IN EUROPE: Schizophrenia (Orphanet:3140)

HPO phenotypes

showing 60 of 131 phenotypes (HPO-id order):

HPO	Term
HP:0000023	Inguinal hernia
HP:0000028	Cryptorchidism
HP:0000047	Hypospadias
HP:0000076	Vesicoureteral reflux
HP:0000089	Renal hypoplasia
HP:0000113	Polycystic kidney dysplasia
HP:0000130	Abnormality of the uterus
HP:0000160	Narrow mouth
HP:0000164	Abnormality of the dentition
HP:0000175	Cleft palate
HP:0000238	Hydrocephalus
HP:0000252	Microcephaly
HP:0000262	Turricephaly
HP:0000272	Malar flattening
HP:0000276	Long face
HP:0000286	Epicanthus
HP:0000316	Hypertelorism
HP:0000322	Short philtrum
HP:0000343	Long philtrum
HP:0000347	Micrognathia
HP:0000365	Hearing impairment
HP:0000369	Low-set ears
HP:0000385	Small earlobe
HP:0000389	Chronic otitis media
HP:0000396	Overfolded helix
HP:0000405	Conductive hearing impairment
HP:0000414	Bulbous nose
HP:0000426	Prominent nasal bridge
HP:0000431	Wide nasal bridge
HP:0000453	Choanal atresia
HP:0000470	Short neck
HP:0000486	Strabismus
HP:0000492	Abnormal eyelid morphology
HP:0000494	Downslanted palpebral fissures
HP:0000501	Glaucoma
HP:0000506	Telecanthus
HP:0000508	Ptosis
HP:0000518	Cataract
HP:0000568	Microphthalmia
HP:0000582	Upslanted palpebral fissure
HP:0000600	Abnormality of the pharynx
HP:0000627	Posterior embryotoxon
HP:0000648	Optic atrophy
HP:0000670	Carious teeth
HP:0000682	Abnormal dental enamel morphology
HP:0000708	Atypical behavior
HP:0000716	Depression
HP:0000717	Autism
HP:0000739	Anxiety
HP:0000765	Abnormal thorax morphology
HP:0000778	Hypoplasia of the thymus
HP:0000821	Hypothyroidism
HP:0000829	Hypoparathyroidism
HP:0000836	Hyperthyroidism
HP:0000929	Abnormal skull morphology
HP:0000979	Purpura
HP:0001051	Seborrheic dermatitis
HP:0001053	Hypopigmented skin patches
HP:0001061	Acne
HP:0001081	Cholelithiasis

GWAS associations

29 associations:

Study	Trait	p-value
GCST90002400_724	Plateletcrit	8e-26
GCST90002407_559	White blood cell count	6e-22
GCST90002402_661	Platelet count	1e-21
GCST90002388_408	Lymphocyte count	2e-21
GCST90002393_153	Monocyte count	8e-18
GCST90002401_324	Platelet distribution width	7e-17
GCST007269_273	Pulse pressure	4e-14
GCST90000025_702	Appendicular lean mass	5e-14
GCST004775_46	Pulse pressure	1e-13
GCST004278_86	Pulse pressure	6e-12
GCST004603_152	Platelet count	1e-11
GCST90000654_74	Central corneal thickness	3e-11
GCST004610_21	White blood cell count	9e-11
GCST004627_108	Lymphocyte count	1e-10
GCST007705_14	Pulse pressure	2e-10
GCST004625_194	Monocyte count	1e-9
GCST90002398_243	Neutrophil count	1e-9
GCST005667_15	Central corneal thickness	3e-9
GCST007096_65	Pulse pressure	3e-9
GCST007926_1	Medication use (antihypertensives)	4e-9
GCST007267_238	Systolic blood pressure	8e-9
GCST001337_55	Platelet count	3e-8
GCST006434_6	Systolic blood pressure x alcohol consumption interaction (2df test)	3e-8
GCST007929_22	Medication use (calcium channel blockers)	5e-8
GCST007703_73	Systolic blood pressure	3e-7
GCST004775_13	Pulse pressure	4e-7
GCST007705_5	Pulse pressure	4e-7
GCST007099_186	Systolic blood pressure	1e-6
GCST007705_23	Pulse pressure	1e-6

EFO canonical traits (from GWAS)

13 canonical traits:

EFO ID	Trait name
EFO:0004309	platelet count
EFO:0005763	pulse pressure measurement
EFO:0005091	monocyte count
EFO:0004587	lymphocyte count
EFO:0005213	central corneal thickness
EFO:0004329	alcohol drinking
EFO:0006335	systolic blood pressure
EFO:0009927	Antihypertensive use measurement
EFO:0009930	Calcium channel blocker use measurement
EFO:0004980	appendicular lean mass
EFO:0004833	neutrophil count
EFO:0007985	platelet crit
EFO:0007984	platelet component distribution width

MeSH disease descriptors

1 disease descriptors:

Descriptor	Name	Tree numbers
D001321	Autistic Disorder	F03.625.164.113.500

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

PharmGKB variants

2 variants:

Variant	Genes	Level	Score	#Clin annots	Drugs
rs165599	ARVCF, COMT	3	2.75	2	risperidone;bupropion
rs9332377	ARVCF, COMT	3	2.75	2	cisplatin

PharmGKB variant annotations

Per-publication pharmacogenomic findings for this gene (significant associations).

2 published findings:

Variant	Drug(s)	Category	Finding	PMID
rs174699	morphine	Dosage, Efficacy	Allele T is associated with decreased dose of morphine in people with Neoplasms as compared to allele C.	PMID:19094200
rs165728	morphine	Dosage, Efficacy	Allele T is associated with decreased dose of morphine in people with Neoplasms as compared to allele C.	PMID:19094200

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
methacrylaldehyde	increases expression, increases oxidation, increases abundance, affects cotreatment	2
Acetaminophen	increases expression	2
Acrolein	increases oxidation, increases abundance, affects cotreatment, increases expression	2
Benzo(a)pyrene	increases expression, increases methylation	2
Estradiol	affects expression, affects cotreatment, decreases expression	2
Ozone	increases oxidation, increases abundance, affects cotreatment, increases expression	2
Rotenone	decreases expression	2
Tobacco Smoke Pollution	decreases expression	2
Aflatoxin B1	increases expression	2
FR900359	affects phosphorylation	1
bufotalin	increases expression	1
methyleugenol	increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases expression, increases oxidation, increases abundance	1
propionaldehyde	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
nutlin 3	affects cotreatment, increases expression	1
abrine	increases expression	1
eprenetapopt	affects expression, affects reaction	1
jinfukang	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Fulvestrant	increases methylation	1
Air Pollutants	affects cotreatment, increases abundance, increases expression, increases oxidation	1
Caffeine	affects phosphorylation	1
Camptothecin	increases expression	1
Cisplatin	affects cotreatment, increases expression	1
Dactinomycin	affects cotreatment, increases expression	1
N-Nitrosopyrrolidine	increases expression	1

Clinical trials (associated diseases)

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

showing 60 of 300 trials:

NCT	Phase	Status	Title
NCT00000374	Phase 4	COMPLETED	Treatment for First-Episode Schizophrenia
NCT00001656	Phase 4	COMPLETED	Comparison of Clozapine vs Olanzapine in Childhood-Onset Psychotic Disorders
NCT00007774	Phase 4	COMPLETED	To Determine if Olanzapine is More Cost Effective Than Haloperidol for the Treatment of Schizophrenia
NCT00014001	Phase 4	COMPLETED	CATIE- Schizophrenia Trial
NCT00018668	Phase 4	COMPLETED	Antipsychotic Response in Schizophrenia
NCT00034801	Phase 4	COMPLETED	Olanzapine Versus Active Comparator in the Treatment of Depression in Patients With Schizophrenia
NCT00034905	Phase 4	COMPLETED	A Comparison of Seroquel vs. Risperidone in Schizophrenia
NCT00036088	Phase 4	COMPLETED	Olanzapine Versus An Active Comparator in the Treatment of Schizophrenia
NCT00044187	Phase 4	COMPLETED	The Assessment of a Weight-Gain Agent for the Treatment of Olanzapine-Associated Anti-Obesity Agent in Patients With Schizophrenia, Schizophreniform Disorder, Schizoaffective Disorder, and Bipolar I Disorder
NCT00044655	Phase 4	COMPLETED	Switching Medication to Treat Schizophrenia
NCT00048828	Phase 4	COMPLETED	Treating Drug-Resistant Childhood Schizophrenia
NCT00053703	Phase 4	COMPLETED	Treatment of Early Onset Schizophrenia Spectrum Disorders (TEOSS)
NCT00056498	Phase 4	COMPLETED	Risperidone Treatment in Schizophrenia Patients Who Are Currently Taking Clozapine
NCT00061802	Phase 4	COMPLETED	Efficacy and Safety of Two Atypical Antipsychotics vs. Placebo in Patients With an Acute Exacerbation of Either Schizophrenia or Schizoaffective Disorder
NCT00080327	Phase 4	COMPLETED	Study of Three Doses of Aripiprazole in Patients With Acute Schizophrenia
NCT00088049	Phase 4	COMPLETED	Study of Olanzapine vs. Aripiprazole in the Treatment of Schizophrenia
NCT00090012	Phase 4	COMPLETED	Comparison of Continuing Olanzapine to Switching to Quetiapine in Overweight or Obese Patients With Schizophrenia and Schizoaffective Disorder
NCT00100776	Phase 4	COMPLETED	Efficacy of High Dose Olanzapine for the Treatment of Schizophrenia and Schizoaffective Disorder
NCT00103571	Phase 4	COMPLETED	Olanzapine Versus Aripiprazole in the Treatment of Acutely Ill Patients With Schizophrenia
NCT00108368	Phase 4	COMPLETED	The Effects of Risperidone and Olanzapine on Thinking
NCT00114595	Phase 4	COMPLETED	Ethyl-Eicosapentaenoic Acid and Tardive Dyskinesia
NCT00130923	Phase 4	COMPLETED	Risperidone Long-acting Versus Oral Risperidone in Patients With Schizophrenia and Alcohol Use Disorder
NCT00137020	Phase 4	COMPLETED	Clinical Effect Of Cross Titration Of Antipsychotics With Ziprasidone In Schizophrenia Or Schizoaffective Disorder
NCT00140166	Phase 4	COMPLETED	Treatment of Acute Schizophrenia With Vitamin Therapy
NCT00145847	Phase 4	COMPLETED	Naltrexone Treatment of Alcohol Abuse in Schizophrenia
NCT00148564	Phase 4	COMPLETED	Energy Homeostasis Under Treatment With Atypical Antipsychotics
NCT00156715	Phase 4	COMPLETED	Efficacy of Quetiapine in the Treatment of Patients With Schizophrenia and a Comorbid Substance Use Disorder
NCT00158223	Phase 4	COMPLETED	Effectiveness of Pimozide in Augmenting the Effects of Clozapine in the Treatment of Schizophrenia
NCT00159081	Phase 4	COMPLETED	One Year Drug Treatment in First-Episode Schizophrenia
NCT00159120	Phase 4	COMPLETED	Maintenance Treatment vs. Stepwise Drug Discontinuation in First-Episode Schizophrenia
NCT00159133	Phase 4	COMPLETED	Prodrome-Based Early Intervention With Antipsychotics vs. Benzodiazepines in First-Episode Schizophrenia
NCT00159757	Phase 4	TERMINATED	12 Week Open, Non-Comparative Switch Study Of Oral Ziprazidone In Previously Treated Schizophrenic Patients
NCT00167817	Phase 4	COMPLETED	Effect of Switch to Aripiprazole on Health and Smoking Parameters in Patients With Schizophrenia: A Pilot Study
NCT00169026	Phase 4	TERMINATED	Alcoholism and Schizophrenia: Effects of Clozapine
NCT00169039	Phase 4	TERMINATED	Clozapine Versus Chlorpromazine for Treatment-Unresponsive Schizophrenia
NCT00169065	Phase 4	COMPLETED	Effectiveness of Clozapine Versus Olanzapine for Treatment-resistant Schizophrenia
NCT00169091	Phase 4	TERMINATED	Clozapine Versus Haloperidol for Treating the First Episode of Schizophrenia
NCT00176423	Phase 4	COMPLETED	Efficacy Study of Galantamine for Cognitive Impairments in Schizophrenia
NCT00176436	Phase 4	COMPLETED	Atomoxetine for Treatment of Weight Gain in Olanzapine or Clozapine Patients
NCT00177008	Phase 4	COMPLETED	Aripiprazole for the Treatment of Schizophrenia With Co-Morbid Social Anxiety
NCT00177580	Phase 4	COMPLETED	Improving Symptoms of Schizophrenia and Schizoaffective Disorder by Supplementing Medications With Pravastatin
NCT00182442	Phase 4	COMPLETED	Cognition, Functioning and Quality of Life
NCT00182494	Phase 4	UNKNOWN	Diabetes Prevention Program in Schizophrenia [DPPS]
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