ROCK1
Rho associated coiled-coil containing protein kinase 1, the group of Pleckstrin homology domain containing|AGC family kinases
Basic information
Region (hg38): 18:20944612-21111813
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the ROCK1 gene is commonly pathogenic or not.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 6 | |||||
| missense | 17 | 18 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 1 | 1 | 2 | |||
| non coding | 0 | |||||
| Total | 0 | 0 | 18 | 4 | 3 |
Variants in ROCK1
This is a list of pathogenic ClinVar variants found in the ROCK1 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 18-20954789-A-T | not specified | Uncertain significance (May 30, 2023) | ||
| 18-20955181-G-A | Lung carcinoma • Breast neoplasm | Likely pathogenic (May 13, 2016) | ||
| 18-20959844-T-C | not specified | Uncertain significance (May 23, 2023) | ||
| 18-20959904-T-C | not specified | Uncertain significance (Nov 02, 2023) | ||
| 18-20969192-C-T | not specified | Uncertain significance (Mar 28, 2024) | ||
| 18-20970350-G-A | not specified | Uncertain significance (Jun 22, 2023) | ||
| 18-20970392-T-G | Benign (Jun 20, 2018) | |||
| 18-20970418-G-A | not specified | Uncertain significance (Oct 06, 2021) | ||
| 18-20970516-G-A | Benign (Apr 04, 2018) | |||
| 18-20982804-G-T | Likely benign (Apr 01, 2023) | |||
| 18-20984360-T-C | not specified | Uncertain significance (Feb 05, 2024) | ||
| 18-20984460-C-T | not specified | Uncertain significance (Jun 29, 2023) | ||
| 18-20984522-G-C | Benign (Mar 01, 2024) | |||
| 18-20987033-A-G | not specified | Uncertain significance (May 08, 2023) | ||
| 18-20987056-C-T | not specified | Uncertain significance (May 02, 2024) | ||
| 18-20991322-T-C | not specified | Uncertain significance (Mar 18, 2024) | ||
| 18-20992888-G-A | not specified | Likely benign (Feb 28, 2024) | ||
| 18-21006451-A-C | Benign (Aug 16, 2018) | |||
| 18-21006551-A-G | not specified | Uncertain significance (May 16, 2024) | ||
| 18-21023673-A-G | not specified | Uncertain significance (Nov 30, 2022) | ||
| 18-21028785-C-T | not specified | Uncertain significance (May 05, 2023) | ||
| 18-21039464-A-G | Benign/Likely benign (Jan 01, 2024) | |||
| 18-21042172-T-A | not specified | Uncertain significance (Nov 15, 2021) | ||
| 18-21042178-T-TA | See cases | Uncertain significance (Oct 31, 2022) | ||
| 18-21042578-G-A | Likely benign (Nov 01, 2022) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| ROCK1 | protein_coding | protein_coding | ENST00000399799 | 33 | 164946 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 1.00 | 2.24e-7 | 125735 | 0 | 9 | 125744 | 0.0000358 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 4.59 | 327 | 658 | 0.497 | 0.0000328 | 9000 |
| Missense in Polyphen | 68 | 238.19 | 0.28549 | 3360 | ||
| Synonymous | 0.862 | 209 | 225 | 0.927 | 0.0000110 | 2272 |
| Loss of Function | 7.63 | 10 | 86.6 | 0.115 | 0.00000504 | 1073 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000930 | 0.0000904 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.0000930 | 0.0000924 |
| European (Non-Finnish) | 0.0000360 | 0.0000352 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.0000341 | 0.0000327 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Protein kinase which is a key regulator of actin cytoskeleton and cell polarity. Involved in regulation of smooth muscle contraction, actin cytoskeleton organization, stress fiber and focal adhesion formation, neurite retraction, cell adhesion and motility via phosphorylation of DAPK3, GFAP, LIMK1, LIMK2, MYL9/MLC2, PFN1 and PPP1R12A. Phosphorylates FHOD1 and acts synergistically with it to promote SRC-dependent non-apoptotic plasma membrane blebbing. Phosphorylates JIP3 and regulates the recruitment of JNK to JIP3 upon UVB-induced stress. Acts as a suppressor of inflammatory cell migration by regulating PTEN phosphorylation and stability. Acts as a negative regulator of VEGF-induced angiogenic endothelial cell activation. Required for centrosome positioning and centrosome-dependent exit from mitosis. Plays a role in terminal erythroid differentiation. May regulate closure of the eyelids and ventral body wall by inducing the assembly of actomyosin bundles. Promotes keratinocyte terminal differentiation. Involved in osteoblast compaction through the fibronectin fibrillogenesis cell-mediated matrix assembly process, essential for osteoblast mineralization. {ECO:0000269|PubMed:10436159, ECO:0000269|PubMed:10652353, ECO:0000269|PubMed:11018042, ECO:0000269|PubMed:11283607, ECO:0000269|PubMed:17158456, ECO:0000269|PubMed:18573880, ECO:0000269|PubMed:18694941, ECO:0000269|PubMed:19036714, ECO:0000269|PubMed:19131646, ECO:0000269|PubMed:19181962, ECO:0000269|PubMed:19997641, ECO:0000269|PubMed:21072057, ECO:0000269|PubMed:8617235, ECO:0000269|PubMed:9722579}.;
- Pathway
- Platelet activation - Homo sapiens (human);Focal adhesion - Homo sapiens (human);Oxytocin signaling pathway - Homo sapiens (human);TGF-beta signaling pathway - Homo sapiens (human);Salmonella infection - Homo sapiens (human);Tight junction - Homo sapiens (human);Chemokine signaling pathway - Homo sapiens (human);Regulation of actin cytoskeleton - Homo sapiens (human);Axon guidance - Homo sapiens (human);cAMP signaling pathway - Homo sapiens (human);Vascular smooth muscle contraction - Homo sapiens (human);Sphingolipid signaling pathway - Homo sapiens (human);Shigellosis - Homo sapiens (human);Pathogenic Escherichia coli infection - Homo sapiens (human);Proteoglycans in cancer - Homo sapiens (human);MicroRNAs in cancer - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);cGMP-PKG signaling pathway - Homo sapiens (human);Leukocyte transendothelial migration - Homo sapiens (human);Androgen receptor signaling pathway;MicroRNAs in cardiomyocyte hypertrophy;Integrin-mediated Cell Adhesion;Leptin signaling pathway;Regulation of Microtubule Cytoskeleton;Pathogenic Escherichia coli infection;AGE-RAGE pathway;JAK-STAT;Focal Adhesion;TGF-beta Signaling Pathway;VEGFA-VEGFR2 Signaling Pathway;Chemokine signaling pathway;EGF-EGFR Signaling Pathway;Regulation of Actin Cytoskeleton;G13 Signaling Pathway;Developmental Biology;Signaling by GPCR;RAGE;Neutrophil degranulation;Signal Transduction;erk and pi-3 kinase are necessary for collagen binding in corneal epithelia;integrin signaling pathway;pkc-catalyzed phosphorylation of inhibitory phosphoprotein of myosin phosphatase;VEGFA-VEGFR2 Pathway;rho cell motility signaling pathway;thrombin signaling and protease-activated receptors;EPH-Ephrin signaling;EPHA-mediated growth cone collapse;Apoptotic cleavage of cellular proteins;Innate Immune System;Immune System;EPHB-mediated forward signaling;Apoptotic execution phase;Apoptosis;Programmed Cell Death;RHO GTPases Activate ROCKs;RHO GTPase Effectors;Signaling by Rho GTPases;TGF_beta_Receptor;Sema4D induced cell migration and growth-cone collapse;Sema4D in semaphorin signaling;role of mal in rho-mediated activation of srf;Semaphorin interactions;Thromboxane A2 receptor signaling;Noncanonical Wnt signaling pathway;Signaling by VEGF;Axon guidance;G alpha (12/13) signalling events;Signaling by Receptor Tyrosine Kinases;GPCR downstream signalling;Stabilization and expansion of the E-cadherin adherens junction;PAR4-mediated thrombin signaling events;PAR1-mediated thrombin signaling events;N-cadherin signaling events;amb2 Integrin signaling;EPHB forward signaling;Signaling events mediated by VEGFR1 and VEGFR2;Integrins in angiogenesis;EPHA forward signaling;RhoA signaling pathway;Signaling events mediated by PRL
(Consensus)
Recessive Scores
- pRec
- 0.555
Intolerance Scores
- loftool
- 0.349
- rvis_EVS
- -0.57
- rvis_percentile_EVS
- 18.9
Haploinsufficiency Scores
- pHI
- hipred
- Y
- hipred_score
- 0.718
- ghis
- 0.626
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- K
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.864
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Rock1
- Phenotype
- cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype; renal/urinary system phenotype; immune system phenotype; vision/eye phenotype; muscle phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); homeostasis/metabolism phenotype; cellular phenotype;
Gene ontology
- Biological process
- aortic valve morphogenesis;apical constriction;protein phosphorylation;apoptotic process;smooth muscle contraction;leukocyte cell-cell adhesion;signal transduction;G protein-coupled receptor signaling pathway;I-kappaB kinase/NF-kappaB signaling;Rho protein signal transduction;regulation of autophagy;positive regulation of autophagy;positive regulation of cardiac muscle hypertrophy;positive regulation of gene expression;negative regulation of angiogenesis;peptidyl-serine phosphorylation;membrane to membrane docking;actin cytoskeleton organization;regulation of cell adhesion;cortical actin cytoskeleton organization;neuron projection development;bleb assembly;negative regulation of protein binding;regulation of actin cytoskeleton organization;negative regulation of myosin-light-chain-phosphatase activity;neutrophil degranulation;positive regulation of MAPK cascade;negative regulation of neuron apoptotic process;regulation of keratinocyte differentiation;regulation of neuron differentiation;vascular endothelial growth factor receptor signaling pathway;ephrin receptor signaling pathway;leukocyte migration;leukocyte tethering or rolling;negative regulation of membrane protein ectodomain proteolysis;myoblast migration;regulation of stress fiber assembly;regulation of focal adhesion assembly;positive regulation of focal adhesion assembly;negative regulation of biomineral tissue development;response to transforming growth factor beta;protein localization to plasma membrane;regulation of angiotensin-activated signaling pathway;neuron projection arborization;positive regulation of amyloid-beta clearance;regulation of synaptic vesicle endocytosis;regulation of amyloid-beta formation;negative regulation of amyloid-beta formation;negative regulation of amyloid precursor protein catabolic process;regulation of establishment of endothelial barrier;negative regulation of bicellular tight junction assembly;positive regulation of connective tissue replacement;response to angiotensin;regulation of establishment of cell polarity;regulation of cell motility
- Cellular component
- Golgi membrane;ruffle;extracellular region;centriole;cytosol;cytoskeleton;plasma membrane;cytoplasmic stress granule;lamellipodium;bleb;secretory granule lumen;amyloid-beta complex
- Molecular function
- protein kinase activity;protein serine/threonine kinase activity;protein binding;ATP binding;GTP-Rho binding;metal ion binding;tau protein binding;tau-protein kinase activity;Rho-dependent protein serine/threonine kinase activity