ROCK2

Rho associated coiled-coil containing protein kinase 2, the group of AGC family kinases|Pleckstrin homology domain containing

Basic information

Region (hg38): 2:11179759-11348330

Links

ENSG00000134318 ∙ NCBI:9475 ∙ OMIM:604002 ∙ HGNC:10252 ∙ Uniprot:O75116 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ROCK2 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ROCK2 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				4	2	6
missense			49	3	2	54
nonsense			3			3
start loss						0
frameshift			1			1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				2	2	4
non coding				1	1	2
Total	0	0	53	8	5

Variants in ROCK2

This is a list of pathogenic ClinVar variants found in the ROCK2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
2-11192181-C-T		not specified	Uncertain significance (Feb 28, 2023)
2-11192296-T-G		not specified	Uncertain significance (Dec 14, 2023)
2-11192480-T-C		not specified	Uncertain significance (Dec 01, 2022)
2-11192580-A-G		not specified	Uncertain significance (Jul 15, 2021)
2-11192631-A-C		not specified	Uncertain significance (Jul 30, 2023)
2-11192676-G-A		Dextrocardia	Uncertain significance (May 28, 2018)
2-11192717-G-A		ROCK2-related disorder	Likely benign (Jun 18, 2024)
2-11193868-T-G		not specified	Benign (Mar 29, 2016)
2-11194258-T-G		ROCK2-related disorder	Benign (Mar 07, 2019)
2-11197248-T-G		not specified	Uncertain significance (Jun 11, 2021)
2-11197675-G-A		Non-immune hydrops fetalis	Uncertain significance (Jun 18, 2020)
2-11198538-C-T		not specified	Uncertain significance (Oct 27, 2021)
2-11198553-C-T		not specified	Uncertain significance (Mar 28, 2023)
2-11198762-T-TA			Uncertain significance (Nov 01, 2023)
2-11200982-G-A		not specified	Uncertain significance (Sep 20, 2023)
2-11200989-C-G			not provided (-)
2-11201037-T-A		ROCK2-related disorder	Uncertain significance (Oct 03, 2023)
2-11201058-A-G		not specified	Uncertain significance (Dec 15, 2022)
2-11201391-C-G		not specified	Uncertain significance (Jun 17, 2022)
2-11201419-T-C		ROCK2-related disorder	Benign (Apr 05, 2019)
2-11202083-T-G		ROCK2-related disorder	Uncertain significance (Jun 05, 2023)
2-11202088-C-T		ROCK2-related disorder	Likely benign (Feb 28, 2024)
2-11202129-G-C		ROCK2-related disorder	Likely benign (Mar 08, 2022)
2-11207815-T-G		ROCK2-related disorder	Benign (Aug 13, 2019)
2-11207897-G-A		ROCK2-related disorder	Uncertain significance (Feb 12, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ROCK2	protein_coding	protein_coding	ENST00000315872	33	168570

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.00000247	124870	0	22	124892	0.0000881

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	4.38	369	694	0.532	0.0000344	9233
Missense in Polyphen		81	268.27	0.30193		3416
Synonymous	1.79	201	236	0.852	0.0000113	2374
Loss of Function	7.41	11	84.6	0.130	0.00000468	1068

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000253	0.000252
Ashkenazi Jewish	0.000203	0.000199
East Asian	0.0000556	0.0000553
Finnish	0.0000466	0.0000464
European (Non-Finnish)	0.000108	0.000106
Middle Eastern	0.0000556	0.0000553
South Asian	0.0000349	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• 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 ADD1, BRCA2, CNN1, EZR, DPYSL2, EP300, MSN, MYL9/MLC2, NPM1, RDX, PPP1R12A and VIM. Phosphorylates SORL1 and IRF4. Acts as a negative regulator of VEGF-induced angiogenic endothelial cell activation. Positively regulates the activation of p42/MAPK1-p44/MAPK3 and of p90RSK/RPS6KA1 during myogenic differentiation. Plays an important role in the timely initiation of centrosome duplication. Inhibits keratinocyte terminal differentiation. May regulate closure of the eyelids and ventral body wall through organization of actomyosin bundles. Plays a critical role in the regulation of spine and synaptic properties in the hippocampus. Plays an important role in generating the circadian rhythm of the aortic myofilament Ca(2+) sensitivity and vascular contractility by modulating the myosin light chain phosphorylation. {ECO:0000269|PubMed:10579722, ECO:0000269|PubMed:15699075, ECO:0000269|PubMed:16574662, ECO:0000269|PubMed:17015463, ECO:0000269|PubMed:19131646, ECO:0000269|PubMed:19997641, ECO:0000269|PubMed:21084279, ECO:0000269|PubMed:21147781}.
• Pathway: Platelet activation - Homo sapiens (human);Focal adhesion - Homo sapiens (human);Oxytocin 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);Pathways in cancer - Homo sapiens (human);Wnt signaling pathway - 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;Pathogenic Escherichia coli infection;Spinal Cord Injury;JAK-STAT;Focal Adhesion;Association Between Physico-Chemical Features and Toxicity Associated Pathways;VEGFA-VEGFR2 Signaling Pathway;Chemokine signaling pathway;Wnt Signaling Pathway;Regulation of Actin Cytoskeleton;G13 Signaling Pathway;Developmental Biology;Signaling by GPCR;Signal Transduction;ccr3 signaling in eosinophils;VEGFA-VEGFR2 Pathway;EPH-Ephrin signaling;EPHA-mediated growth cone collapse;EPHB-mediated forward signaling;RHO GTPases Activate ROCKs;RHO GTPase Effectors;Signaling by Rho GTPases;Sema4D induced cell migration and growth-cone collapse;Sema4D in semaphorin signaling;Semaphorin interactions;Signaling by VEGF;Axon guidance;G alpha (12/13) signalling events;Signaling by Receptor Tyrosine Kinases;GPCR downstream signalling;Osteopontin-mediated events;PAR4-mediated thrombin signaling events;PAR1-mediated thrombin signaling events;Signaling events mediated by focal adhesion kinase;PLK1 signaling events;Plasma membrane estrogen receptor signaling;RhoA signaling pathway (Consensus)

Recessive Scores

• pRec: 0.312

Intolerance Scores

• loftool: 0.316
• rvis_EVS: -1.02
• rvis_percentile_EVS: 8.04

Haploinsufficiency Scores

• pHI: 0.749
• hipred: Y
• hipred_score: 0.786
• ghis: 0.616

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.965

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	High
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Rock2
• 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); 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); embryo phenotype; immune system 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); vision/eye phenotype; growth/size/body region phenotype; homeostasis/metabolism phenotype; cellular phenotype; muscle phenotype

Zebrafish Information Network

• Gene name: rock2b
• Affected structure: cell
• Phenotype tag: abnormal
• Phenotype quality: increased size

Gene ontology

• Biological process: positive regulation of protein phosphorylation;aortic valve morphogenesis;protein phosphorylation;smooth muscle contraction;G protein-coupled receptor signaling pathway;I-kappaB kinase/NF-kappaB signaling;Rho protein signal transduction;positive regulation of endothelial cell migration;positive regulation of cardiac muscle hypertrophy;positive regulation of gene expression;positive regulation of centrosome duplication;negative regulation of angiogenesis;peptidyl-serine phosphorylation;peptidyl-threonine phosphorylation;regulation of cell adhesion;positive regulation of cell migration;cortical actin cytoskeleton organization;positive regulation of connective tissue growth factor production;regulation of actin cytoskeleton organization;negative regulation of myosin-light-chain-phosphatase activity;viral RNA genome replication;regulation of circadian rhythm;positive regulation of MAPK cascade;regulation of keratinocyte differentiation;vascular endothelial growth factor receptor signaling pathway;ephrin receptor signaling pathway;rhythmic process;regulation of protein metabolic process;centrosome duplication;regulation of stress fiber assembly;positive regulation of stress fiber assembly;regulation of focal adhesion assembly;negative regulation of biomineral tissue development;cellular response to testosterone stimulus;response to transforming growth factor beta;protein localization to plasma membrane;positive regulation of fibroblast growth factor production;regulation of angiotensin-activated signaling pathway;negative regulation of protein localization to lysosome;positive regulation of amyloid-beta formation;positive regulation of aspartic-type endopeptidase activity involved in amyloid precursor protein catabolic process;positive regulation of protein localization to early endosome;positive 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: nucleus;centrosome;cytosol;plasma membrane;cytoplasmic ribonucleoprotein granule
• Molecular function: RNA binding;protein serine/threonine kinase activity;structural molecule activity;protein binding;ATP binding;Rho GTPase binding;metal ion binding;tau protein binding;tau-protein kinase activity;Rho-dependent protein serine/threonine kinase activity