KRIT1

Summary

KRIT1 (KRIT1 ankyrin repeat containing, HGNC:1573) is a protein-coding gene on chromosome 7q21.2, encoding Krev interaction trapped protein 1 (O00522). Component of the CCM signaling pathway which is a crucial regulator of heart and vessel formation and integrity.

This gene encodes a protein containing four ankyrin repeats, a band 4.1/ezrin/radixin/moesin (FERM) domain, and multiple NPXY sequences. The encoded protein is localized in the nucleus and cytoplasm. It binds to integrin cytoplasmic domain-associated protein-1 alpha (ICAP1alpha), and plays a critical role in beta1-integrin-mediated cell proliferation. It associates with junction proteins and RAS-related protein 1A (Rap1A), which requires the encoded protein for maintaining the integrity of endothelial junctions. It is also a microtubule-associated protein and may play a role in microtubule targeting. Mutations in this gene result in cerebral cavernous malformations. Multiple alternatively spliced transcript variants have been found for this gene.

Source: NCBI Gene 889 — RefSeq curated summary.

At a glance

• Gene–disease (curated): cerebral cavernous malformation 1 (Definitive, GenCC) — +1 more curated relationship
• GWAS associations: 2
• Clinical variants (ClinVar): 833 total — 279 pathogenic, 65 likely-pathogenic
• Phenotypes (HPO): 33
• MANE Select transcript: NM_194454

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1573
Approved symbol	KRIT1
Name	KRIT1 ankyrin repeat containing
Location	7q21.2
Locus type	gene with protein product
Status	Approved
Aliases	CAM
Ensembl gene	ENSG00000001631
Ensembl biotype	protein_coding
OMIM	604214
Entrez	889

Gene structure

Transcript identifiers

Ensembl transcripts: 81 — 33 protein_coding, 28 retained_intron, 17 nonsense_mediated_decay, 3 protein_coding_CDS_not_defined

ENST00000340022, ENST00000394503, ENST00000394505, ENST00000394507, ENST00000412043, ENST00000413688, ENST00000422347, ENST00000425073, ENST00000425919, ENST00000430102, ENST00000433016, ENST00000440209, ENST00000444960, ENST00000445516, ENST00000452773, ENST00000454017, ENST00000458177, ENST00000466166, ENST00000470309, ENST00000475770, ENST00000486261, ENST00000487168, ENST00000489087, ENST00000684808, ENST00000685285, ENST00000685431, ENST00000686043, ENST00000686094, ENST00000686149, ENST00000686233, ENST00000686527, ENST00000686619, ENST00000686785, ENST00000687135, ENST00000687517, ENST00000687627, ENST00000687876, ENST00000688180, ENST00000688196, ENST00000688314, ENST00000688404, ENST00000688580, ENST00000688665, ENST00000688766, ENST00000688781, ENST00000689082, ENST00000689411, ENST00000689539, ENST00000689556, ENST00000689778, ENST00000689789, ENST00000690292, ENST00000690529, ENST00000690720, ENST00000690751, ENST00000690904, ENST00000690908, ENST00000691222, ENST00000691239, ENST00000691622, ENST00000691827, ENST00000691890, ENST00000692000, ENST00000692157, ENST00000692205, ENST00000692361, ENST00000692428, ENST00000692690, ENST00000692807, ENST00000693563, ENST00000905037, ENST00000905038, ENST00000905039, ENST00000905040, ENST00000905041, ENST00000905042, ENST00000936491, ENST00000967258, ENST00000967259, ENST00000967260, ENST00000967261

RefSeq mRNA: 34 — MANE Select: NM_194454 NM_001013406, NM_001350669, NM_001350670, NM_001350671, NM_001350672, NM_001350673, NM_001350674, NM_001350675, NM_001350676, NM_001350677, NM_001350678, NM_001350679, NM_001350680, NM_001350681, NM_001350682, NM_001350683, NM_001350684, NM_001350685, NM_001350686, NM_001350687, NM_001350688, NM_001350689, NM_001350690, NM_001350691, NM_001350692, NM_001350693, NM_001350694, NM_001350695, NM_001350696, NM_001350697, NM_004912, NM_194454, NM_194455, NM_194456

CCDS: CCDS34679, CCDS5624

Canonical transcript exons

ENST00000394505 — 19 exons

Exon	Start	End
ENSE00001170047	92236413	92236542
ENSE00001170062	92240993	92241152
ENSE00001170077	92244002	92244149
ENSE00001518667	92245790	92245914
ENSE00001518669	92244902	92245171
ENSE00003468592	92214611	92214777
ENSE00003473862	92234449	92234592
ENSE00003501181	92201307	92201423
ENSE00003527201	92237667	92237759
ENSE00003532623	92234808	92234923
ENSE00003551421	92213195	92213401
ENSE00003567675	92213892	92213979
ENSE00003611468	92225720	92225827
ENSE00003631381	92226526	92226682
ENSE00003631960	92221902	92222053
ENSE00003656911	92199413	92200804
ENSE00003694626	92222822	92222978
ENSE00003788179	92235403	92235646
ENSE00003926925	92242034	92242137

Expression profiles

Bgee: expression breadth ubiquitous, 138 present calls, max score 95.27.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 12.1617 / max 311.1728, expressed in 1755 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
84784	10.9122	1734
84783	0.5187	258
84786	0.3262	92
84781	0.3050	63
84782	0.0665	16
84785	0.0333	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	95.27	gold quality
colonic epithelium	UBERON:0000397	95.02	gold quality
corpus callosum	UBERON:0002336	94.32	gold quality
mucosa of stomach	UBERON:0001199	93.39	gold quality
endometrium	UBERON:0001295	93.27	gold quality
body of pancreas	UBERON:0001150	92.56	gold quality
tonsil	UBERON:0002372	92.43	gold quality
bone marrow cell	CL:0002092	91.76	gold quality
adrenal tissue	UBERON:0018303	91.33	gold quality
ventricular zone	UBERON:0003053	91.30	gold quality
pancreas	UBERON:0001264	90.99	gold quality
uterine cervix	UBERON:0000002	90.97	gold quality
primary visual cortex	UBERON:0002436	90.87	gold quality
ovary	UBERON:0000992	90.78	gold quality
right uterine tube	UBERON:0001302	90.75	gold quality
pituitary gland	UBERON:0000007	90.72	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	90.68	gold quality
urinary bladder	UBERON:0001255	90.66	gold quality
thyroid gland	UBERON:0002046	90.63	gold quality
left ovary	UBERON:0002119	90.55	gold quality
adenohypophysis	UBERON:0002196	90.48	gold quality
right lobe of thyroid gland	UBERON:0001119	90.42	gold quality
right ovary	UBERON:0002118	90.41	gold quality
endocervix	UBERON:0000458	90.38	gold quality
left lobe of thyroid gland	UBERON:0001120	90.32	gold quality
cortex of kidney	UBERON:0001225	90.26	gold quality
gall bladder	UBERON:0002110	90.13	gold quality
sural nerve	UBERON:0015488	90.12	gold quality
fundus of stomach	UBERON:0001160	90.10	gold quality
smooth muscle tissue	UBERON:0001135	90.03	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.27

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

161 targeting KRIT1, 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-4768-5P	100.00	69.49	2861
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-6778-3P	99.96	67.29	2693

Literature-anchored findings (GeneRIF, showing 40)

• Experimentally determined additional 5’ UTR variants and additional mutations (in CCM1 study families) in coding exons that lead to frameshifts and premature truncations in the protein. (PMID:11161805)
• Experimentally determined additional 5’ UTR alternatively spliced variants. Determined gene contains 20 exons. (PMID:11342228)
• KRIT1/CCM1 mutation in a patient with retinal and cerebral cavernous angiomas. (PMID:11831930)
• Integrin-binding protein also interacts with Krit 1 protein, cause of CCM1. (ICAP-1, integrin cytoplasmic domain-associated protein 1) (PMID:11854171)
• In familial CCM1 samples, two new Krit1 mutations have been reported in four new upstream exons and six additional mutations have been discovered in the previously identified exons, demonstrating a mutation frequency of 47% in the 27 families studied. (PMID:11914398)
• RNA analysis reveals that two point mutations actually activate cryptic splice-donor sites, causing aberrant splicing and leading to a frameshift and protein truncation (PMID:11941540)
• Experimentally determined alternatively spliced variants in the 5’ coding region that alter the open reading frame and lead to premature translation termination codons. Determined that the 3’ UTR is larger than previously found. (PMID:12172908)
• Krit1 mRNA expression in adult tissues (PMID:12204286)
• Mutations in Krit1 are associated with familial cerebral cavernous malformations, but seldom a cause of sporadic cavernomas (PMID:12682320)
• Identification of a novel KRIT1 mutation in an Italian family with cerebral cavernous malformation by the protein truncation test. (PMID:12810002)
• We report a mutation causing a premature termination triplet in exon 17 of the Krit1 gene in a family with diagnoses of cerebral cavernous angioma (PMID:12877753)
• KRIT1 is also present in cells and structures integral to the cerebral angiogenesis and formation of the blood-brain barrier, namely, endothelial cells and astrocytic foot processes, as well as pyramidal neurons in the cerebral cortex. (PMID:15046662)
• The CCM1 gene was screened in 35 sporadic cases with either single or multiple CCM. It was found that 29% of the individuals with multiple CCM have a CCM1 mutation, whereas cases with only one malformation have none (PMID:15079030)
• biallelic CCM1 somatic and germ line truncating mutation identification strongly supports the “two-hit” mechanism in this cerebral cavernous malformation lesion (PMID:15718512)
• KRIT1, Malcavernin, and PDCD10 are differentially expressed in cerebral venous malformations and cerebral cavernous malformations (PMID:16239636)
• CCM1 and CCM2 have similar expression patterns during development and are involved in the same pathway important for central nervous system vascular development (PMID:16373645)
• Results confirm the conclusion that KRIT1 haploinsufficiency may be the underlying mechanism of cerebral cavernous malformations. (PMID:16529293)
• SNX17 has a role in the indicated KRIT1 function in cell adhesion processes by integrin signaling (PMID:16712798)
• Five percent of patients with familial cerebral cavernomas have retinal cavernomas. These lesions are clinically asymptomatic. They can be associated with any of the 3 cerebral cavernous malformation genes. (PMID:16769843)
• Two new mutations in the KRIT1 gene in two Italian families affected by cerebral cavernous malformations. (PMID:17043900)
• Mutations in CCM1/KRIT1 may be found in asymptomatic patients with retinal cavernous hemangioma. (PMID:17148043)
• Krit1 interacts with malcavernin and may shuttle it through the nucleus via nuclear export signals, thereby regulating cellular function. (PMID:17290187)
• we found a novel CCM1 gene mutation (Q66X) in a family with apparently asymptomatic old-aged mutation carriers and patients who either had skin angiomas alone or the full association of cerebral, spinal, and skin lesions (PMID:17440989)
• Three novel and 2 described mutations were found in KRIT1. The families included 33 KRIT1 mutation carriers, 57.6% of whom had no symptoms. (PMID:17562932)
• Rap1 increases KRIT-1 targeting to endothelial cell-cell junctions where it suppresses stress fibers and stabilizes junctional integrity. (PMID:17954608)
• data are in agreement with a loss-of-function mechanism for CCM mutations, uncover an N-terminal CCM2 domain required for CCM1 binding, and demonstrate full-length CCM2 as the essential core protein in the CCM1/CCM2/CCM3 complex (PMID:18300272)
• Krit1 and integrin cytoplasmic domain-associated protein-1 alpha (icap1alpha) act concordantly to play a critical role in beta 1-integrin-mediated cell proliferation. (PMID:18812969)
• Biallelic germline and somatic mutations were identified in CCM1, CCM2 or PDCD10 from all forms of inherited cerebral cavernous malformations. (PMID:19088123)
• Complete localized loss of either CCM1, CCM2 or CCM3 protein expression depend on the inherited mutation in cerebral cavernous malformations. (PMID:19088124)
• Sequencing of KRIT1 identified a novel frameshift mutation in exon 15 (c.1561delC or p.Leu551X) which cosegregated with the phenotype observed in a family with cerebral cavernous malformations. (PMID:19092252)
• mutations in the KRIT1 gene may cause phenotypically heterogeneous cutaneous vascular lesions other than those previously described as HCCVMs. (PMID:19182478)
• The Multiplex Ligation-dependent Probe Amplification analysis revealed a new mutation, a heterozygous exon 9/10 deletion of Krit1, in the proband and in all affected family members. (PMID:19199464)
• CCM1 is the most frequently mutated gene in cutaneous vascular malformations-familial cerebral cavernous malformations patients. (PMID:19453802)
• C329X in KRIT1 is a founder mutation among CCM patients in Sardinia. (PMID:19454328)
• Familial CCM1 cavernous malformations are unlikely to be associated with developmental venous anomalies, and sporadic malformations have a high rate of association with them (PMID:19833796)
• We have identified a novel mutation in the KRIT1/CCM1 gene in a patient with both CCM and retinal cavernous hemangioma. (PMID:20306072)
• The KRIT1-CCM2 interaction regulates endothelial junctional stability and vascular barrier function by suppressing activation of the RhoA/ROCK signaling pathway. This pathway is dysregulated in human cerebral cavernous malformation endothelium. (PMID:20308363)
• Genetic variations could interfere with the proper CCM1/CCM2/CCM3 protein complex, thus explaining the observed clinical variability in cerebral cavernous malformations in a large family. (PMID:20419355)
• Frame shift mutation in KRIT1 gene is associated with cerebral and multiple spinal cavernous malformations. (PMID:20689144)
• We described the complete loss of 7q21.2 locus encompassing the KRIT1 gene and 4 flanking genes in a CCM family by using a dense set of 12 microsatellite markers. (PMID:20798775)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	krit1	ENSDARG00000098916
mus_musculus	Krit1	ENSMUSG00000000600
rattus_norvegicus	Krit1	ENSRNOG00000007937
caenorhabditis_elegans	kri-1	WBGENE00013955

Paralogs (1): FRMD8 (ENSG00000126391)

Protein

Protein identifiers

Krev interaction trapped protein 1 — O00522 (reviewed: O00522)

Alternative names: Cerebral cavernous malformations 1 protein

All UniProt accessions (20): A0A0C4DG23, A0A8I5KQD8, A0A8I5KQH3, A0A8I5KRK7, A0A8I5KUF9, A0A8I5KVW5, O00522, A0A8I5KVY1, A0A8I5KVY4, A0A8I5KW41, A0A8I5KWG2, A0A8I5KX77, A4D1F7, C9J718, C9JD43, C9JEW7, C9JF32, C9JIY2, C9JJM9, C9JXI9

UniProt curated annotations — full annotation on UniProt →

Function. Component of the CCM signaling pathway which is a crucial regulator of heart and vessel formation and integrity. Negative regulator of angiogenesis. Inhibits endothelial proliferation, apoptosis, migration, lumen formation and sprouting angiogenesis in primary endothelial cells. Promotes AKT phosphorylation in a NOTCH-dependent and independent manner, and inhibits ERK1/2 phosphorylation indirectly through activation of the DELTA-NOTCH cascade. Acts in concert with CDH5 to establish and maintain correct endothelial cell polarity and vascular lumen and these effects are mediated by recruitment and activation of the Par polarity complex and RAP1B. Required for the localization of phosphorylated PRKCZ, PARD3, TIAM1 and RAP1B to the cell junction, and cell junction stabilization. Plays a role in integrin signaling via its interaction with ITGB1BP1; this prevents the interaction between ITGB1 and ITGB1BP1. Microtubule-associated protein that binds to phosphatidylinositol 4,5-bisphosphate (PIP2)-containing membranes in a GTP-bound RAP1-dependent manner. Plays an important role in the maintenance of the intracellular reactive oxygen species (ROS) homeostasis to prevent oxidative cellular damage. Regulates the homeostasis of intracellular ROS through an antioxidant pathway involving FOXO1 and SOD2. Facilitates the down-regulation of cyclin-D1 (CCND1) levels required for cell transition from proliferative growth to quiescence by preventing the accumulation of intracellular ROS through the modulation of FOXO1 and SOD2 levels. May play a role in the regulation of macroautophagy through the down-regulation of the mTOR pathway.

Subunit / interactions. Interacts with CDH5. Found in a complex, at least composed of ITGB1BP1, KRIT1 and RAP1A. Interacts (via C-terminus FERM domain) with RAP1A (active GTP-bound form preferentially); the interaction does not induce the opening conformation of KRIT1. Interacts (via FERM domain) with RAP1B. Interacts (via N-terminus NPXY motif) with ITGB1BP1; the interaction induces the opening conformation of KRIT1 and competes with ITGB1 for ITGB1BP1 interaction. Interacts with HEG1 and CCM2; greatly facilitates CCM2-binding to HEG1. Associates (via N-terminus and C-terminus regions) with microtubules; the interaction is inhibited in presence of ITGB1BP1 and active GTP-bound RAP1A.

Subcellular location. Cytoplasm. Cytoskeleton. Cell membrane. Cell junction.

Tissue specificity. Low levels in brain. Very weak expression found in heart and muscle.

Disease relevance. Cerebral cavernous malformations 1 (CCM1) [MIM:116860] A form of cerebral cavernous malformations, a congenital vascular anomaly of the central nervous system that can result in hemorrhagic stroke, seizures, recurrent headaches, and focal neurologic deficits. The lesions are characterized by grossly enlarged blood vessels consisting of a single layer of endothelium and without any intervening neural tissue, ranging in diameter from a few millimeters to several centimeters. CCM1 inheritance is autosomal dominant. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The FERM domain mediates binding to RAP1A and RAP1B and is necessary for binding to phosphatidylinositol 4,5-bisphosphate (PIP2). The N-terminal domain has structural similarity to the nudix hydrolase domain, despite the absence of a nudix box and low sequence similarity with nudix hydrolase domains. The N-terminus and the C-terminus part associate together via the NPAY binding motif and adopt a lose conformation that is disrupted by ITGB1BP1, but not by RAP1A. Contains 4 ANK repeats that precede the FERM domain.

Isoforms (3)

UniProt ID	Names	Canonical?
O00522-1	1	yes
O00522-2	2
O00522-3	3

RefSeq proteins (34): NP_001013424, NP_001337598, NP_001337599, NP_001337600, NP_001337601, NP_001337602, NP_001337603, NP_001337604, NP_001337605, NP_001337606, NP_001337607, NP_001337608, NP_001337609, NP_001337610, NP_001337611, NP_001337612, NP_001337613, NP_001337614, NP_001337615, NP_001337616, NP_001337617, NP_001337618, NP_001337619, NP_001337620, NP_001337621, NP_001337622, NP_001337623, NP_001337624, NP_001337625, NP_001337626, NP_004903, NP_919436, NP_919437, NP_919438 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000299	FERM_domain	Domain
IPR002110	Ankyrin_rpt	Repeat
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR014352	FERM/acyl-CoA-bd_prot_sf	Homologous_superfamily
IPR019748	FERM_central	Domain
IPR019749	Band_41_domain	Domain
IPR032022	NUDIX	Domain
IPR035963	FERM_2	Homologous_superfamily
IPR036770	Ankyrin_rpt-contain_sf	Homologous_superfamily
IPR041791	KRIT1_FERM_C	Domain
IPR043058	NUDIX_sf	Homologous_superfamily
IPR051594	KRIT1/FRMD8	Family
IPR056485	ARM_KRIT1	Domain
IPR057096	KRIT1_FRMD8_FERM_C	Domain

Pfam: PF00373, PF16705, PF24521, PF24522

UniProt features (90 total): helix 31, strand 22, mutagenesis site 14, turn 7, repeat 4, sequence conflict 3, region of interest 3, splice variant 2, sequence variant 2, chain 1, domain 1

Structure

Experimental structures (PDB)

15 structures.

PDB	Method	Resolution (Å)
4HDO	X-RAY DIFFRACTION	1.67
4JIF	X-RAY DIFFRACTION	1.7
6OQ4	X-RAY DIFFRACTION	1.75
6OQ3	X-RAY DIFFRACTION	1.85
6UZK	X-RAY DIFFRACTION	1.92
4DXA	X-RAY DIFFRACTION	1.95
4HDQ	X-RAY DIFFRACTION	1.95
8SU8	X-RAY DIFFRACTION	2.01
8T09	X-RAY DIFFRACTION	2.15
8T7V	X-RAY DIFFRACTION	2.25
3U7D	X-RAY DIFFRACTION	2.49
4DX8	X-RAY DIFFRACTION	2.54
5D68	X-RAY DIFFRACTION	2.91
4TKN	X-RAY DIFFRACTION	3
9PVG	X-RAY DIFFRACTION	3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O00522-F1	83.01	0.57

Functional residue map

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

Mutagenesis-validated functional residues (14):

Position	Phenotype
47–50	reduces interaction with microtubules, but not with itgb1bp1.
176	strongly reduces itgb1bp1 binding; when associated with d-182.
179	strongly reduces itgb1bp1 binding; when associated with a-179.
182	strongly reduces itgb1bp1 binding; when associated with d-176.
185	strongly reduces itgb1bp1 binding; when associated with a-179.
192–195	reduces interaction with itgb1bp1.
192	reduces itgb1bp1 binding; when associated with a-195.
195	reduces itgb1bp1 binding; when associated with a-192.
430	impairs interaction with rap1b.
432	impairs interaction with rap1b.
452	40-fold-reduced affinity for rap1a.
452	impairs interaction with rap1b.
717	strongly reduced affinity for heg1; when associated with a-721.
721	strongly reduced affinity for heg1; when associated with a-717.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 298 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_UP, GOBP_NEGATIVE_REGULATION_OF_EPITHELIAL_CELL_PROLIFERATION, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, GOBP_EPITHELIUM_DEVELOPMENT, WANG_CLIM2_TARGETS_UP, GGTGTGT_MIR329, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_CELL_POLARITY, TGACCTY_ERR1_Q2, MORF_HDAC2, GGGTGGRR_PAX4_03, MORF_TERF1, GOBP_ESTABLISHMENT_OF_CELL_POLARITY, GOBP_NEGATIVE_REGULATION_OF_MULTICELLULAR_ORGANISMAL_PROCESS, GOBP_CELL_REDOX_HOMEOSTASIS, GOBP_REGULATION_OF_ENDOTHELIAL_CELL_MIGRATION

GO Biological Process (13): angiogenesis (GO:0001525), negative regulation of endothelial cell proliferation (GO:0001937), endothelium development (GO:0003158), small GTPase-mediated signal transduction (GO:0007264), negative regulation of endothelial cell migration (GO:0010596), negative regulation of angiogenesis (GO:0016525), integrin activation (GO:0033622), cell redox homeostasis (GO:0045454), regulation of angiogenesis (GO:0045765), regulation of establishment of cell polarity (GO:2000114), negative regulation of endothelial cell apoptotic process (GO:2000352), negative regulation of developmental process (GO:0051093), regulation of multicellular organismal development (GO:2000026)

GO Molecular Function (4): phosphatidylinositol-4,5-bisphosphate binding (GO:0005546), microtubule binding (GO:0008017), GTPase regulator activity (GO:0030695), protein binding (GO:0005515)

GO Cellular Component (8): obsolete extracellular space (GO:0005615), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), plasma membrane (GO:0005886), cell-cell junction (GO:0005911), protein-containing complex (GO:0032991), membrane (GO:0016020), anchoring junction (GO:0070161)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
angiogenesis	2
regulation of developmental process	2
cellular anatomical structure	2
blood vessel morphogenesis	1
anatomical structure formation involved in morphogenesis	1
endothelial cell proliferation	1
regulation of endothelial cell proliferation	1
negative regulation of epithelial cell proliferation	1
epithelium development	1
intracellular signaling cassette	1
regulation of endothelial cell migration	1
negative regulation of cell migration	1
endothelial cell migration	1
regulation of angiogenesis	1
negative regulation of blood vessel morphogenesis	1
protein-containing complex assembly	1
cellular homeostasis	1
regulation of anatomical structure morphogenesis	1
regulation of vasculature development	1
establishment of cell polarity	1
regulation of establishment or maintenance of cell polarity	1
negative regulation of apoptotic process	1
endothelial cell apoptotic process	1
regulation of endothelial cell apoptotic process	1
developmental process	1
negative regulation of biological process	1
multicellular organism development	1
regulation of multicellular organismal process	1
phosphatidylinositol phosphate binding	1
phosphatidylinositol bisphosphate binding	1
tubulin binding	1
GTPase activity	1
nucleoside-triphosphatase regulator activity	1
binding	1
intracellular anatomical structure	1
intracellular membraneless organelle	1
membrane	1
cell periphery	1
anchoring junction	1
cellular_component	1

Protein interactions and networks

STRING

1182 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KRIT1	CCM2	Q9BSQ5	998
KRIT1	RAP1A	P10113	996
KRIT1	PDCD10	Q9BUL8	996
KRIT1	ITGB1BP1	O14713	992
KRIT1	SNX17	Q15036	967
KRIT1	HEG1	Q9ULI3	966
KRIT1	STK25	O00506	847
KRIT1	MAP3K3	Q99759	821
KRIT1	CDH5	P33151	773
KRIT1	RAP1B	P09526	768
KRIT1	RASIP1	Q5U651	754
KRIT1	RAP2A	P10114	727
KRIT1	RHOA	P06749	709
KRIT1	ACVRL1	P37023	706
KRIT1	MYL2	P10916	700

IntAct

45 interactions, top by confidence:

A	B	Type	Score
CCM2	KRIT1	psi-mi:“MI:0915”(physical association)	0.960
KRIT1	CCM2	psi-mi:“MI:0915”(physical association)	0.960
KRIT1	CCM2	psi-mi:“MI:0914”(association)	0.960
KRIT1	CCM2	psi-mi:“MI:0407”(direct interaction)	0.960
CCM2	KRIT1	psi-mi:“MI:0914”(association)	0.960
ITGB1BP1	KRIT1	psi-mi:“MI:0915”(physical association)	0.740
KRIT1	ITGB1BP1	psi-mi:“MI:0915”(physical association)	0.740
HEG1	KRIT1	psi-mi:“MI:0915”(physical association)	0.730
HEG1	KRIT1	psi-mi:“MI:0407”(direct interaction)	0.730
KRIT1	UBE2K	psi-mi:“MI:0915”(physical association)	0.560
TLNRD1	KRIT1	psi-mi:“MI:0914”(association)	0.530
CCM2	KRIT1	psi-mi:“MI:0914”(association)	0.500

BioGRID (63): KRIT1 (Affinity Capture-RNA), RAP1A (Two-hybrid), KRIT1 (Two-hybrid), KRIT1 (Two-hybrid), CCM2 (Two-hybrid), ITGB1BP1 (Two-hybrid), KRIT1 (Affinity Capture-MS), ITGB1BP1 (Affinity Capture-MS), HEG1 (Affinity Capture-MS), SLC34A2 (Affinity Capture-MS), UBFD1 (Affinity Capture-MS), KRIT1 (Synthetic Lethality), UBE2K (Two-hybrid), ITGB1BP1 (Two-hybrid), ITGB1BP1 (Reconstituted Complex)

ESM2 similar proteins: A0A1B0GW35, A6QNM3, B0R034, B1ANS9, B9EK06, D2KC46, D3ZY60, F1MS15, F1P065, F1REV3, O00522, O15091, O75747, P10911, P58069, Q008S8, Q14449, Q14D04, Q15283, Q32NR9, Q45GW3, Q4R366, Q4R6T7, Q5H9U9, Q5K651, Q5PQS3, Q5XGX5, Q5XIZ9, Q5ZLD2, Q60862, Q63713, Q69Z37, Q6DCF6, Q6S5J6, Q6TNJ1, Q75PQ8, Q80W71, Q86VD1, Q86YR7, Q8C5W4

Diamond homologs: F1REV3, O00522, Q10728, Q6S5J6, Q6TNJ1, Q9DBR7, A2AQH4, A4II29, B2RR83, G3I6Z6, O13987, O14974, O60237, P46531, P83757, Q01705, Q02979, Q03017, Q07008, Q0VC93, Q18297, Q1RJ94, Q28FJ2, Q337A0, Q3SX00, Q3UES3, Q3UMT1, Q3V096, Q4FE45, Q4JHE0, Q5H9F3, Q5I1X5, Q5R746, Q5R8C8, Q5U5A6, Q61982, Q6DRG7, Q6KAE5, Q7T3X9, Q7T3Y0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	279
Likely pathogenic	65
Uncertain significance	265
Likely benign	102
Benign	22

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1068679	NM_194454.3(KRIT1):c.1333C>T (p.Gln445Ter)	Pathogenic
1068705	NM_194454.3(KRIT1):c.1616T>G (p.Leu539Ter)	Pathogenic
1069273	NM_194454.3(KRIT1):c.1297del (p.Ser433fs)	Pathogenic
1070438	NM_194454.3(KRIT1):c.1446dup (p.His483fs)	Pathogenic
1070522	NM_194454.3(KRIT1):c.206T>A (p.Leu69Ter)	Pathogenic
1071790	NM_194454.3(KRIT1):c.1099dup (p.His367fs)	Pathogenic
1071796	NM_194454.3(KRIT1):c.382G>T (p.Gly128Ter)	Pathogenic
1072402	NC_000007.13:g.(?91829918)(91851387_?)del	Pathogenic
1072403	NC_000007.13:g.(?91863743)(91871469_?)del	Pathogenic
1073009	NM_194454.3(KRIT1):c.1162C>T (p.Gln388Ter)	Pathogenic
1074210	NM_194454.3(KRIT1):c.250C>T (p.Gln84Ter)	Pathogenic
1074229	NM_194454.3(KRIT1):c.2113A>T (p.Lys705Ter)	Pathogenic
1074264	NC_000007.13:g.(?91851196)(91871469_?)del	Pathogenic
1074265	NC_000007.13:g.(?91866961)(91871469_?)del	Pathogenic
1074639	NM_194454.3(KRIT1):c.2049T>G (p.Tyr683Ter)	Pathogenic
1074766	NM_194454.3(KRIT1):c.1389_1390del (p.Ile463fs)	Pathogenic
1075474	NM_194454.3(KRIT1):c.1980_1981delinsGT (p.Gly661Ter)	Pathogenic
1075800	NM_194454.3(KRIT1):c.1212G>A (p.Trp404Ter)	Pathogenic
1187060	NM_194454.3(KRIT1):c.1146+1G>T	Pathogenic
1252052	NM_194454.3(KRIT1):c.992A>G (p.Tyr331Cys)	Pathogenic
1254168	NM_194454.3(KRIT1):c.699del (p.Leu233fs)	Pathogenic
1284973	NM_194454.3(KRIT1):c.1166del (p.Gly389fs)	Pathogenic
1285155	NM_194454.3(KRIT1):c.1412-1G>C	Pathogenic
1285206	NM_194454.3(KRIT1):c.1287del (p.Ser430fs)	Pathogenic
1299386	NM_194454.3(KRIT1):c.1664C>T (p.Ala555Val)	Pathogenic
1320113	NM_194454.3(KRIT1):c.1444C>T (p.Gln482Ter)	Pathogenic
1331022	NM_194454.3(KRIT1):c.1287dup (p.Ser430fs)	Pathogenic
1333479	NM_194454.3(KRIT1):c.1097del (p.Gly366fs)	Pathogenic
1355783	NC_000007.14:g.92201424dup	Pathogenic
1358522	NM_194454.3(KRIT1):c.2100_2101dup (p.Ser701fs)	Pathogenic

SpliceAI

3108 predictions. Top by Δscore:

Variant	Effect	Δscore
7:92213886:GCTTA:G	donor_loss	1.0000
7:92213887:CTTA:C	donor_loss	1.0000
7:92213888:TTA:T	donor_loss	1.0000
7:92213889:TAC:T	donor_loss	1.0000
7:92213975:CTTCA:C	acceptor_gain	1.0000
7:92213978:CA:C	acceptor_gain	1.0000
7:92213980:C:CC	acceptor_gain	1.0000
7:92214609:A:AC	donor_gain	1.0000
7:92214610:C:CA	donor_gain	1.0000
7:92214779:T:C	acceptor_gain	1.0000
7:92221915:T:TA	donor_gain	1.0000
7:92221931:CATCT:C	donor_gain	1.0000
7:92222689:T:C	acceptor_gain	1.0000
7:92222691:A:C	acceptor_gain	1.0000
7:92222693:A:C	acceptor_gain	1.0000
7:92222820:A:AC	donor_gain	1.0000
7:92222821:C:CC	donor_gain	1.0000
7:92222821:CTGA:C	donor_gain	1.0000
7:92222821:CTGAG:C	donor_gain	1.0000
7:92222975:CATA:C	acceptor_gain	1.0000
7:92222977:TA:T	acceptor_gain	1.0000
7:92222979:C:CC	acceptor_gain	1.0000
7:92225714:TCTTA:T	donor_loss	1.0000
7:92225715:CTTA:C	donor_loss	1.0000
7:92225716:TTA:T	donor_loss	1.0000
7:92225717:TACTG:T	donor_loss	1.0000
7:92225718:A:AC	donor_gain	1.0000
7:92225718:ACTGG:A	donor_loss	1.0000
7:92225719:C:A	donor_loss	1.0000
7:92225719:C:CT	donor_gain	1.0000

AlphaMissense

4868 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:92234903:A:C	N250K	1.000
7:92234903:A:T	N250K	1.000
7:92237684:A:T	V113D	1.000
7:92242089:C:G	R16P	1.000
7:92213214:A:G	L669P	0.999
7:92213346:A:G	F625S	0.999
7:92221935:T:A	R510S	0.999
7:92221935:T:G	R510S	0.999
7:92221936:C:A	R510I	0.999
7:92222006:A:G	W487R	0.999
7:92222006:A:T	W487R	0.999
7:92222044:A:G	L474P	0.999
7:92222843:A:G	W464R	0.999
7:92222843:A:T	W464R	0.999
7:92222845:A:T	I463K	0.999
7:92222951:C:G	D428H	0.999
7:92222962:A:T	I424K	0.999
7:92226551:A:G	L374P	0.999
7:92226584:G:T	A363D	0.999
7:92226587:G:T	A362D	0.999
7:92226599:G:T	P358H	0.999
7:92226616:A:C	N352K	0.999
7:92226616:A:T	N352K	0.999
7:92234451:G:C	C329W	0.999
7:92234452:C:T	C329Y	0.999
7:92234453:A:G	C329R	0.999
7:92234467:G:C	P324R	0.999
7:92234467:G:T	P324H	0.999
7:92234474:A:G	W322R	0.999
7:92234474:A:T	W322R	0.999

dbSNP variants (sampled 300 via entrez): RS1000131072 (7:92221064 C>T), RS1000153086 (7:92236254 G>C), RS1000242654 (7:92221478 T>C), RS1000300337 (7:92199006 T>C,G), RS1000384813 (7:92233763 C>A), RS1000449073 (7:92227981 C>A,T), RS1000505571 (7:92236642 A>G), RS1000513814 (7:92243940 T>A,C), RS1000539467 (7:92215068 G>A), RS1000602788 (7:92233595 C>T), RS1000635953 (7:92228253 G>A,C), RS1000648626 (7:92246102 G>C), RS1000756633 (7:92203777 C>G,T), RS1000786709 (7:92202789 T>C), RS1000843107 (7:92209609 T>C)

Disease associations

OMIM: gene MIM:604214 | disease phenotypes: MIM:116860, MIM:600419

GenCC curated gene-disease

Disease	Classification	Inheritance
cerebral cavernous malformation 1	Definitive	Autosomal dominant
famililal cerebral cavernous malformations	Supportive	Autosomal dominant

Mondo (6): cerebral cavernous malformation (MONDO:0000820), cerebral cavernous malformation 1 (MONDO:0020724), angiokeratoma corporis diffusum with arteriovenous fistulas (MONDO:0010885), famililal cerebral cavernous malformations (MONDO:0031037), cavernous hemangioma (MONDO:0003155), vascular dementia (MONDO:0004648)

Orphanet (2): Familial cerebral cavernous malformation (Orphanet:221061), NON RARE IN EUROPE: Cerebral cavernous malformations (Orphanet:164)

HPO phenotypes

33 total (30 of 33 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000951	Abnormality of the skin
HP:0001028	Hemangioma
HP:0001048	Cavernous hemangioma
HP:0001250	Seizure
HP:0001324	Muscle weakness
HP:0001342	Cerebral hemorrhage
HP:0002170	Intracranial hemorrhage
HP:0002315	Headache
HP:0002514	Cerebral calcification
HP:0002516	Increased intracranial pressure
HP:0002572	Episodic vomiting
HP:0002650	Scoliosis
HP:0002858	Meningioma
HP:0003011	Abnormality of the musculature
HP:0003401	Paresthesia
HP:0003829	Typified by incomplete penetrance
HP:0006576	Hepatic vascular malformations
HP:0007797	Developmental retinal vascular malformation
HP:0007872	Choroidal hemangioma
HP:0009588	Vestibular schwannoma
HP:0009592	Astrocytoma
HP:0010512	Adrenal calcification
HP:0011276	Vascular skin abnormality
HP:0011513	Retinal cavernous hemangioma
HP:0012721	Venous malformation
HP:0012748	Focal T2 hyperintense brainstem lesion
HP:0012749	Focal T2 hypointense brainstem lesion
HP:0030430	Neuroma
HP:0033522	Cerebral cavernous malformation

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST006993_10	Hippocampal volume in Alzheimer’s disease dementia	2.000000e-07
GCST008526_36	Coffee consumption	1.000000e-07

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0005035	hippocampal volume
EFO:0006781	coffee consumption measurement

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D015140	Dementia, Vascular	C10.228.140.300.400; C10.228.140.300.510.800.500; C10.228.140.380.230; C10.228.140.695.500; C14.907.137.126.372.500; C14.907.253.560.350.500; F03.615.400.350
D006392	Hemangioma, Cavernous	C04.557.645.375.385; C10.228.140.232.625; C14.907.454.385; C15.378.463.515.385
C563940	Angiokeratoma Corporis Diffusum with Arteriovenous Fistulas (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	affects cotreatment, increases abundance, increases expression, decreases expression	3
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases expression, increases abundance	1
bisphenol A	increases expression	1
beta-lapachone	decreases expression, increases expression	1
sodium arsenite	decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
methacrylaldehyde	increases abundance, affects cotreatment, increases expression	1
beta-methylcholine	affects expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
pentanal	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	increases reaction, affects binding	1
K 7174	increases expression	1
jinfukang	decreases expression	1
Bortezomib	increases expression	1
Irinotecan	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Acetaminophen	decreases expression	1
Acrolein	affects cotreatment, increases expression, increases abundance	1
Atrazine	decreases expression	1
Coal	decreases expression, increases abundance	1
Cocaine	increases expression	1
Diethylhexyl Phthalate	decreases expression	1
Folic Acid	decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_C1V1	NFHHMUi001-A	Induced pluripotent stem cell	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00165763	PHASE4	COMPLETED	Efficacy and Safety of Donepezil Hydrochloride (Aricept) in Vascular Dementia
NCT00847860	PHASE4	COMPLETED	Cilostazol Verse Asprin for Vascular Dementia in Poststroke Patients With White Matter Lesions
NCT00947531	PHASE4	COMPLETED	A Clinical Trial to Evaluate the Safety and Efficacy of 20 ml Cerebrolysin in Patients With Vascular Dementia
NCT00950430	PHASE4	ENROLLING_BY_INVITATION	Imaging of Brain Amyloid Plaques in the Aging Population
NCT00099216	PHASE3	COMPLETED	Efficacy and Safety of Rivastigmine Capsules in Patients With Probable Vascular Dementia
NCT00130338	PHASE3	COMPLETED	Rivastigmine Capsules in Patients With Probable Vascular Dementia
NCT00209456	PHASE3	COMPLETED	Dopamine Transporter Scintigraphy Imaging (DAT-Imaging) in Patients With Lewy Body Dementia
NCT00249158	PHASE3	COMPLETED	A Study of the Effectiveness and Safety of Risperidone in the Treatment of Behavioral Disturbances in Patients With Dementia
NCT00261573	PHASE3	COMPLETED	A Study of the Safety and Effectiveness of Galantamine Versus Placebo in the Treatment of Patients With Vascular Dementia or Mixed Dementia
NCT00621647	PHASE3	COMPLETED	Seroquel- Agitation Associated With Dementia
NCT02453932	PHASE3	COMPLETED	Efficacy and Safety of Tianzhi Granule in Mild to Moderate Vascular Dementia
NCT03682185	PHASE3	COMPLETED	The Healthy Patterns Sleep Study
NCT03789760	PHASE3	COMPLETED	The Clinical Trial of Chinese Herbal Medicine (SaiLuoTong) Capsule
NCT03804229	PHASE3	ACTIVE_NOT_RECRUITING	Efficacy and Safety of Butylphthalide Soft Capsule for the Treatment of Vascular Dementia
NCT03986424	PHASE3	COMPLETED	Local Study of Akatinol Memantine in VaD in Russia
NCT04552041	PHASE3	COMPLETED	Prospekta in the Treatment of Cognitive, Behavioral and Psychiatric Disorders in Patients With Vascular Dementia.
NCT03474614	PHASE2	TERMINATED	Effect of Oral Propranolol on mRNA Expresssion in Symptomatic Cavernous Malformation
NCT03589014	PHASE2	COMPLETED	Treat_CCM: Propranolol in Familial Cerebral Cavernous Malformation
NCT05085561	PHASE2	COMPLETED	The Symptomatic Cerebral Cavernous Malformation Trial of REC-994
NCT01466543	PHASE2	UNKNOWN	Effect of Zydena (Udenafil) on Cerebral Blood Flow and Peripheral Blood Viscosity
NCT01475578	PHASE2	COMPLETED	Study of STA-1 Capsule in Patients With Vascular Dementia (Marrow-Sea Deficiency)
NCT01608217	PHASE2	COMPLETED	Delta-THC in Dementia
NCT01761227	PHASE2	COMPLETED	Efficacy and Safety of Fufangdanshen Tablets in Mild to Moderate Vascular Dementia
NCT01953705	PHASE2	UNKNOWN	n-3 PUFA for Vascular Cognitive Aging
NCT01965756	PHASE2	COMPLETED	Effect of Insulin Sensitizer Metformin on AD Biomarkers
NCT01978730	PHASE2	UNKNOWN	The Clinical Trial of Chinese Herbal Medicine SaiLuoTong Capsule
NCT02467413	PHASE2	WITHDRAWN	BAC in Patient With Alzheimer’s Disease or Vascular Dementia
NCT03230071	PHASE2	COMPLETED	Efficacy and Safety of TMBCZG in Mild to Moderate Vascular Dementia
NCT04109963	PHASE2	UNKNOWN	Trial of Remote Ischemic Pre-conditioning in Vascular Cognitive Impairment
NCT05371639	PHASE2	UNKNOWN	Efficacy and Safety of Tian Ma Bian Chun Zhi Gan Tablets in Mild to Moderate Vascular Dementia
NCT00783523	PHASE1	COMPLETED	Influence of MMP on Brain AVM Hemorrhage
NCT00457769	PHASE1	UNKNOWN	Aricept to Improve Functional Tasks in Vascular Dementia
NCT03702543	PHASE1	UNKNOWN	Managing Vascular Dementia Risk Factors With SymTrend
NCT04567745	PHASE1	COMPLETED	Automated Retinal Image Analysis System (EyeQuant) for Computation of Vascular Biomarkers
NCT01764451	EARLY_PHASE1	TERMINATED	Permeability MRI in Cerebral Cavernous Malformations Type 1 in New Mexico: Effects of Statins
NCT01764529	Not specified	ACTIVE_NOT_RECRUITING	Modifiers of Disease Severity in Cerebral Cavernous Malformations
NCT03467295	Not specified	UNKNOWN	Treatments and Outcomes of Untreated Cerebral Cavernous Malformations in CHina.
NCT03652181	Not specified	COMPLETED	CASH (Cavernous Angiomas With Symptomatic Hemorrhage) Trial Readiness
NCT06983132	Not specified	RECRUITING	Natural History of Familial Cerebral Cavernous Malformations: the CCM_Italia Cohort Study
NCT02603328	PHASE1/PHASE2	COMPLETED	Atorvastatin Treatment of Cavernous Angiomas With Symptomatic Hemorrhage Exploratory Proof of Concept (AT CASH EPOC) Trial