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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
KRIT1
KRIT1 ankyrin repeat containing
Chromosome 7 Β· 7q21.2
NCBI Gene: 889Ensembl: ENSG00000001631.18HGNC: HGNC:1573UniProt: A4D1F7
145PubMed Papers
21Diseases
0Drugs
353Pathogenic Variants
RESEARCH IMPACT
Variant-Rich
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
negative regulation of endothelial cell apoptotic processplasma membraneGO:0005615cell-cell junctioncerebral cavernous malformation 1famililal cerebral cavernous malformationscerebral cavernous malformationgenetic disorder
✦AI Summary

KRIT1 is a 75 kDa scaffolding protein that functions as a critical regulator of vascular integrity and endothelial cell homeostasis 1. As a component of the CCM signaling pathway, KRIT1 maintains endothelial barrier function by limiting inflammatory responses and promoting a quiescent endothelial phenotype 1. Mechanistically, KRIT1 inhibits endothelial proliferation and migration while suppressing pathological angiogenesis through activation of the NOTCH-dependent KLF2/KLF4 signaling cascade 2. KRIT1 establishes proper endothelial cell polarity and vascular lumen formation by recruiting the Par polarity complex and regulating integrin signaling 1. Additionally, KRIT1 maintains intracellular reactive oxygen species homeostasis through FOXO1 and SOD2-mediated antioxidant pathways, preventing oxidative damage and facilitating cell cycle arrest 3. Loss-of-function mutations in KRIT1 cause cerebral cavernous malformations (CCM1), characterized by abnormal vessel formation, barrier dysfunction, increased endothelial proliferation, and altered gene expression 4. KRIT1 is widely expressed beyond endothelial tissue, suggesting roles in non-vascular contexts 1. These multifaceted functions make KRIT1 essential for maintaining vascular homeostasis and preventing pathological vascular remodeling.

Sources cited
1
KRIT1 is a 75 kDa scaffolding protein regulating endothelial cell phenotype, maintaining quiescent barrier function, and having roles beyond endothelial cells
PMID: 38980708
2
KRIT1 regulates intracellular ROS homeostasis and interacts with HEG1 in endothelial flow response pathways
PMID: 38099436
3
Loss of KRIT1 triggers pathophysiological MAPK-KLF2 signaling cascade in CCM disease
PMID: 39402138
4
KRIT1 loss-of-function mutations cause CCM1, characterized by abnormal vessel formation, barrier dysfunction, and increased endothelial proliferation
PMID: 38749279
5
KRIT1 deficiency leads to KLF2- and KLF4-dependent elevation of eNOS in endothelium, contributing to CCM pathogenesis
PMID: 34043589
Disease Associationsβ“˜21
cerebral cavernous malformation 1Open Targets
0.78Strong
famililal cerebral cavernous malformationsOpen Targets
0.71Strong
cerebral cavernous malformationOpen Targets
0.68Moderate
genetic disorderOpen Targets
0.50Moderate
Cavernous HemangiomaOpen Targets
0.41Moderate
asthmaOpen Targets
0.28Weak
Abnormal cerebral vascular morphologyOpen Targets
0.27Weak
angiokeratoma corporis diffusum with arteriovenous fistulasOpen Targets
0.19Weak
hemangiomaOpen Targets
0.14Weak
lymphangiomaOpen Targets
0.14Weak
vascular dementiaOpen Targets
0.11Weak
familial long QT syndromeOpen Targets
0.10Weak
Alzheimer diseaseOpen Targets
0.10Suggestive
catecholaminergic polymorphic ventricular tachycardiaOpen Targets
0.09Suggestive
glioblastoma multiformeOpen Targets
0.09Suggestive
Miyoshi myopathyOpen Targets
0.09Suggestive
atrial fibrillationOpen Targets
0.08Suggestive
posterior cortical atrophyOpen Targets
0.08Suggestive
head and neck squamous cell carcinomaOpen Targets
0.08Suggestive
hepatocellular carcinomaOpen Targets
0.08Suggestive
Cerebral cavernous malformations 1UniProt
Pathogenic Variants353
NM_194454.3(KRIT1):c.1363C>T (p.Gln455Ter)Pathogenic
Cerebral cavernous malformation 1|Cerebral cavernous malformation|not provided|KRIT1-related disorder|Inborn genetic diseases
β˜…β˜…β˜†β˜†2026β†’ Residue 455
NM_194454.3(KRIT1):c.1255-1G>APathogenic
not provided|Cerebral cavernous malformation
β˜…β˜…β˜†β˜†2026
NM_194454.3(KRIT1):c.268C>T (p.Arg90Ter)Pathogenic
not provided|Cerebral cavernous malformation
β˜…β˜…β˜†β˜†2026β†’ Residue 90
NM_194454.3(KRIT1):c.1267C>T (p.Arg423Ter)Pathogenic
not provided|Cerebral cavernous malformation|KRIT1-related disorder
β˜…β˜…β˜†β˜†2026β†’ Residue 423
NM_194454.3(KRIT1):c.1360_1363del (p.Ser454fs)Pathogenic
not provided|Cerebral cavernous malformation
β˜…β˜…β˜†β˜†2026β†’ Residue 454
NM_194454.3(KRIT1):c.1A>G (p.Met1Val)Pathogenic
Cerebral cavernous malformation|not provided
β˜…β˜…β˜†β˜†2026β†’ Residue 1
NM_194454.3(KRIT1):c.1730+4_1730+7delPathogenic
not provided|Cerebral cavernous malformation
β˜…β˜…β˜†β˜†2026
NM_194454.3(KRIT1):c.1146+1G>APathogenic
not provided|Cerebral cavernous malformation
β˜…β˜…β˜†β˜†2026
NM_194454.3(KRIT1):c.1890G>A (p.Trp630Ter)Pathogenic
not specified|Cerebral cavernous malformation|not provided
β˜…β˜…β˜†β˜†2026β†’ Residue 630
NM_194454.3(KRIT1):c.1336C>T (p.Gln446Ter)Pathogenic
Cerebral cavernous malformation|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 446
NM_194454.3(KRIT1):c.1730+5G>APathogenic
not provided|Cerebral cavernous malformation
β˜…β˜…β˜†β˜†2025
NM_194454.3(KRIT1):c.1201_1204del (p.Gln401fs)Pathogenic
not provided|Cerebral cavernous malformation|Hereditary cavernous hemangioma of brain
β˜…β˜…β˜†β˜†2025β†’ Residue 401
NM_194454.3(KRIT1):c.646_647del (p.Lys216fs)Pathogenic
Cerebral cavernous malformation|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 216
NM_194454.3(KRIT1):c.707C>G (p.Ser236Ter)Pathogenic
not provided|Cerebral cavernous malformation
β˜…β˜…β˜†β˜†2025β†’ Residue 236
NM_194454.3(KRIT1):c.880C>T (p.Arg294Ter)Pathogenic
not provided|Cerebral cavernous malformation
β˜…β˜…β˜†β˜†2025β†’ Residue 294
NM_194454.3(KRIT1):c.152_155del (p.Lys51fs)Pathogenic
not provided|Cerebral cavernous malformation|Hereditary cavernous hemangioma of brain|KRIT1-related disorder|Inborn genetic diseases
β˜…β˜…β˜†β˜†2025β†’ Residue 51
NM_194454.3(KRIT1):c.1905T>A (p.Tyr635Ter)Pathogenic
not provided|Cerebral cavernous malformation
β˜…β˜…β˜†β˜†2025β†’ Residue 635
NM_194454.3(KRIT1):c.1333C>T (p.Gln445Ter)Pathogenic
Cerebral cavernous malformation|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 445
NM_194454.3(KRIT1):c.2025+1G>APathogenic
Cerebral cavernous malformation
β˜…β˜…β˜†β˜†2025
NM_194454.3(KRIT1):c.418C>T (p.Arg140Ter)Pathogenic
not provided|Cerebral cavernous malformation
β˜…β˜…β˜†β˜†2025β†’ Residue 140
View on ClinVar β†—
Related Genes
ITGB1BP1Protein interaction100%SNX17Protein interaction100%ROCK2Protein interaction98%CTNNB1Protein interaction95%RAP1BProtein interaction94%RAP1AProtein interaction91%
Tissue Expression6 tissues
Ovary
100%
Liver
89%
Brain
75%
Lung
75%
Heart
37%
Bone Marrow
19%
Gene Interaction Network
Click a node to explore
KRIT1ITGB1BP1SNX17ROCK2CTNNB1RAP1BRAP1A
PROTEIN STRUCTURE
Preparing viewer…
PDB4HDO Β· 1.67 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.69LoF Tolerant
pLIβ“˜
0.11Tolerant
Observed/Expected LoF0.44 [0.29–0.69]
RankingsWhere KRIT1 stands among ~20K protein-coding genes
  • #3,141of 20,598
    Most Researched145 Β· top quartile
  • #162of 5,498
    Most Pathogenic Variants353 Β· top 5%
  • #5,201of 17,882
    Most Constrained (LOEUF)0.69
Genes detectedKRIT1
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
HEG1 Protects Against Atherosclerosis by Regulating Stable Flow-Induced KLF2/4 Expression in Endothelial Cells.
PMID: 38099436
Circulation Β· 2024
1.00
2
KRIT1 in vascular biology and beyond.
PMID: 38980708
Biosci Rep Β· 2024
0.90
3
Cerebral cavernous malformations - An overview on genetics, clinical aspects and therapeutic strategies.
PMID: 38749279
J Neurol Sci Β· 2024
0.80
4
Epigenetic regulation by polycomb repressive complex 1 promotes cerebral cavernous malformations.
PMID: 39402138
EMBO Mol Med Β· 2024
0.70
5
Astrocytes propel neurovascular dysfunction during cerebral cavernous malformation lesion formation.
PMID: 34043589
J Clin Invest Β· 2021
0.60