MYLK

myosin light chain kinase, the group of Myosin light chain kinase family|Fibronectin type III domain containing|I-set domain containing

Basic information

Region (hg38): 3:123610048-123884332

Links

ENSG00000065534 ∙ NCBI:4638 ∙ OMIM:600922 ∙ HGNC:7590 ∙ Uniprot:Q15746 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• connective tissue disorder (Moderate), mode of inheritance: AD
• aortic aneurysm, familial thoracic 7 (Moderate), mode of inheritance: AD
• megacystis-microcolon-intestinal hypoperistalsis syndrome (Limited), mode of inheritance: AR
• megacystis-microcolon-intestinal hypoperistalsis syndrome (Supportive), mode of inheritance: AD
• familial thoracic aortic aneurysm and aortic dissection (Supportive), mode of inheritance: AD
• aortic aneurysm, familial thoracic 7 (Strong), mode of inheritance: AD
• familial thoracic aortic aneurysm and aortic dissection (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Aortic aneurysm, familial thoracic 7; Megacystis-microcolon-intestinal hypoperistalsis syndrome 1	AD/AR	Cardiovascular; Gastrointestinal; Renal	In Aortic aneurysm, familial thoracic, preventive measures and medical management may be helpful to help decrease morbidity; Individuals with Megacystis-microcolon-intestinal hypoperistalsis syndrome may have intestinal anomalies and hydronephrosis, and awareness may allow prompt surgical and medical management; Multivisceral, liver-small bowel, and bowel transplant has been described in Megacystis-microcolon-intestinal hypoperistalsis syndrome	Cardiovascular; Gastrointestinal; Renal	21055718; 20301299; 28602422

ClinVar

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

• Aortic aneurysm, familial thoracic 7 (1350 variants)
• Familial thoracic aortic aneurysm and aortic dissection (780 variants)
• not provided (489 variants)
• not specified (240 variants)
• Aortic aneurysm, familial thoracic 7;Megacystis-microcolon-intestinal hypoperistalsis syndrome 1 (91 variants)
• Megacystis-microcolon-intestinal hypoperistalsis syndrome 1;Aortic aneurysm, familial thoracic 7 (54 variants)
• Inborn genetic diseases (40 variants)
• Connective tissue disorder (37 variants)
• MYLK-related condition (9 variants)
• Megacystis, microcolon, hypoperistalsis syndrome (6 variants)
• Megacystis-microcolon-intestinal hypoperistalsis syndrome 1 (2 variants)
• Congenital aneurysm of ascending aorta (2 variants)
• Familial thoracic aortic aneurysm and aortic dissection;Disproportionate tall stature (2 variants)
• Visceral myopathy 1 (1 variants)
• Megacystis, microcolon, hypoperistalsis syndrome;Familial thoracic aortic aneurysm and aortic dissection (1 variants)
• See cases (1 variants)
• Marfan syndrome (1 variants)
• Aortic aneurysm, familial abdominal, 1 (1 variants)
• Atrial septal defect (1 variants)
• Cardiovascular phenotype (1 variants)
• Aortic aneurysm, familial thoracic 6 (1 variants)
• Loeys-Dietz syndrome (1 variants)
• Stroke disorder;Carotid artery dissection;Internal carotid artery dissection;Carotid artery occlusion;Aortic dissection (1 variants)
• Familial aortic aneurysms (1 variants)
• Isolated thoracic aortic aneurysm (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MYLK 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			14	394	12	420
missense			803	30	5	838
nonsense	6	3	13			22
start loss			1			1
frameshift	12	3	17	1		33
inframe indel			18	2		20
splice donor/acceptor (+/-2bp)	1	8	8			17
splice region	1		38	58	3	100
non coding			48	113	11	172
Total	19	14	922	540	28

Highest pathogenic variant AF is 0.00000657

Variants in MYLK

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

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

Position	Type	Phenotype	Significance	ClinVar
3-123612296-T-C		Aortic aneurysm, familial thoracic 7	Benign (Jul 03, 2018)
3-123612434-T-A		Familial thoracic aortic aneurysm and aortic dissection	Uncertain significance (Jun 14, 2016)
3-123612452-C-T		Aortic aneurysm, familial thoracic 7 • Aortic aneurysm, familial thoracic 7;Megacystis-microcolon-intestinal hypoperistalsis syndrome 1	Uncertain significance (Sep 01, 2021)
3-123612458-C-G		Aortic aneurysm, familial thoracic 7	Uncertain significance (Jan 13, 2018)
3-123612475-C-T		Aortic aneurysm, familial thoracic 7	Uncertain significance (Jan 13, 2018)
3-123612529-C-T		Aortic aneurysm, familial thoracic 7	Uncertain significance (Jan 13, 2018)
3-123612567-T-C		Aortic aneurysm, familial thoracic 7	Benign (Jan 13, 2018)
3-123612579-G-T		Familial thoracic aortic aneurysm and aortic dissection	Uncertain significance (Jun 14, 2016)
3-123612586-A-G		Aortic aneurysm, familial thoracic 7	Uncertain significance (Jan 12, 2018)
3-123612593-A-ATAT		Familial thoracic aortic aneurysm and aortic dissection	Likely benign (Jun 14, 2016)
3-123612596-T-C		Aortic aneurysm, familial thoracic 7	Uncertain significance (Jan 12, 2018)
3-123612803-A-G		Familial thoracic aortic aneurysm and aortic dissection	Uncertain significance (Jun 14, 2016)
3-123612839-TACAC-T		Familial thoracic aortic aneurysm and aortic dissection	Uncertain significance (Jun 14, 2016)
3-123612895-A-G		Aortic aneurysm, familial thoracic 7	Uncertain significance (Jan 13, 2018)
3-123612914-A-G		Aortic aneurysm, familial thoracic 7 • Aortic aneurysm, familial thoracic 7;Megacystis-microcolon-intestinal hypoperistalsis syndrome 1	Uncertain significance (Aug 09, 2021)
3-123612927-T-TTAAG		Familial thoracic aortic aneurysm and aortic dissection	Conflicting classifications of pathogenicity (Jun 14, 2016)
3-123612928-TA-T		Familial thoracic aortic aneurysm and aortic dissection	Likely benign (Jun 14, 2016)
3-123612970-C-T		Aortic aneurysm, familial thoracic 7	Likely benign (Jan 13, 2018)
3-123612971-G-A		Aortic aneurysm, familial thoracic 7	Likely benign (Jan 12, 2018)
3-123613015-T-C		Aortic aneurysm, familial thoracic 7	Likely benign (Jan 12, 2018)
3-123613035-A-T		Aortic aneurysm, familial thoracic 7	Likely benign (Jan 13, 2018)
3-123613064-C-A		Familial thoracic aortic aneurysm and aortic dissection	Uncertain significance (Jun 14, 2016)
3-123613065-C-T		Aortic aneurysm, familial thoracic 7	Uncertain significance (Jan 13, 2018)
3-123613074-G-T		Familial thoracic aortic aneurysm and aortic dissection	Uncertain significance (Jun 14, 2016)
3-123613124-T-C		Aortic aneurysm, familial thoracic 7	Uncertain significance (Jan 13, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MYLK	protein_coding	protein_coding	ENST00000360304	31	274283

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
9.17e-12	1.00	125667	0	81	125748	0.000322

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.13	967	1.07e+3	0.903	0.0000667	12484
Missense in Polyphen		108	136.61	0.79055		1672
Synonymous	-0.258	450	443	1.02	0.0000308	3780
Loss of Function	5.23	35	87.9	0.398	0.00000450	1056

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000511	0.000449
Ashkenazi Jewish	0.0000996	0.0000992
East Asian	0.000272	0.000272
Finnish	0.00	0.00
European (Non-Finnish)	0.000427	0.000422
Middle Eastern	0.000272	0.000272
South Asian	0.000490	0.000490
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Calcium/calmodulin-dependent myosin light chain kinase implicated in smooth muscle contraction via phosphorylation of myosin light chains (MLC). Also regulates actin-myosin interaction through a non-kinase activity. Phosphorylates PTK2B/PYK2 and myosin light-chains. Involved in the inflammatory response (e.g. apoptosis, vascular permeability, leukocyte diapedesis), cell motility and morphology, airway hyperreactivity and other activities relevant to asthma. Required for tonic airway smooth muscle contraction that is necessary for physiological and asthmatic airway resistance. Necessary for gastrointestinal motility. Implicated in the regulation of endothelial as well as vascular permeability, probably via the regulation of cytoskeletal rearrangements. In the nervous system it has been shown to control the growth initiation of astrocytic processes in culture and to participate in transmitter release at synapses formed between cultured sympathetic ganglion cells. Critical participant in signaling sequences that result in fibroblast apoptosis. Plays a role in the regulation of epithelial cell survival. Required for epithelial wound healing, especially during actomyosin ring contraction during purse-string wound closure. Mediates RhoA- dependent membrane blebbing. Triggers TRPC5 channel activity in a calcium-dependent signaling, by inducing its subcellular localization at the plasma membrane. Promotes cell migration (including tumor cells) and tumor metastasis. PTK2B/PYK2 activation by phosphorylation mediates ITGB2 activation and is thus essential to trigger neutrophil transmigration during acute lung injury (ALI). May regulate optic nerve head astrocyte migration. Probably involved in mitotic cytoskeletal regulation. Regulates tight junction probably by modulating ZO-1 exchange in the perijunctional actomyosin ring. Mediates burn-induced microvascular barrier injury; triggers endothelial contraction in the development of microvascular hyperpermeability by phosphorylating MLC. Essential for intestinal barrier dysfunction. Mediates Giardia spp.-mediated reduced epithelial barrier function during giardiasis intestinal infection via reorganization of cytoskeletal F-actin and tight junctional ZO-1. Necessary for hypotonicity-induced Ca(2+) entry and subsequent activation of volume-sensitive organic osmolyte/anion channels (VSOAC) in cervical cancer cells. Responsible for high proliferative ability of breast cancer cells through anti-apoptosis. {ECO:0000269|PubMed:11113114, ECO:0000269|PubMed:11976941, ECO:0000269|PubMed:15020676, ECO:0000269|PubMed:15825080, ECO:0000269|PubMed:16284075, ECO:0000269|PubMed:16723733, ECO:0000269|PubMed:18587400, ECO:0000269|PubMed:18710790, ECO:0000269|PubMed:19826488, ECO:0000269|PubMed:20139351, ECO:0000269|PubMed:20181817, ECO:0000269|PubMed:20375339, ECO:0000269|PubMed:20453870}.
• Disease: DISEASE: Aortic aneurysm, familial thoracic 7 (AAT7) [MIM:613780]: A disease characterized by permanent dilation of the thoracic aorta usually due to degenerative changes in the aortic wall. It is primarily associated with a characteristic histologic appearance known as 'medial necrosis' or 'Erdheim cystic medial necrosis' in which there is degeneration and fragmentation of elastic fibers, loss of smooth muscle cells, and an accumulation of basophilic ground substance. {ECO:0000269|PubMed:21055718}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Platelet activation - Homo sapiens (human);Focal adhesion - Homo sapiens (human);Oxytocin signaling pathway - Homo sapiens (human);Gastric acid secretion - Homo sapiens (human);Regulation of actin cytoskeleton - Homo sapiens (human);Calcium signaling pathway - Homo sapiens (human);Apelin signaling pathway - Homo sapiens (human);Vascular smooth muscle contraction - Homo sapiens (human);cGMP-PKG signaling pathway - Homo sapiens (human);Disopyramide Action Pathway;Procainamide (Antiarrhythmic) Action Pathway;Phenytoin (Antiarrhythmic) Action Pathway;Fosphenytoin (Antiarrhythmic) Action Pathway;Bopindolol Action Pathway;Timolol Action Pathway;Carteolol Action Pathway;Intracellular Signalling Through Prostacyclin Receptor and Prostacyclin;Bevantolol Action Pathway;Practolol Action Pathway;Dobutamine Action Pathway;Isoprenaline Action Pathway;Arbutamine Action Pathway;Amiodarone Action Pathway;Levobunolol Action Pathway;Metipranolol Action Pathway;Mexiletine Action Pathway;Lidocaine (Antiarrhythmic) Action Pathway;Quinidine Action Pathway;Sotalol Action Pathway;Epinephrine Action Pathway;Betaxolol Action Pathway;Atenolol Action Pathway;Alprenolol Action Pathway;Acebutolol Action Pathway;Muscle/Heart Contraction;Diltiazem Action Pathway;Propranolol Action Pathway;Pindolol Action Pathway;Penbutolol Action Pathway;Oxprenolol Action Pathway;Metoprolol Action Pathway;Esmolol Action Pathway;Bisoprolol Action Pathway;Bupranolol Action Pathway;Nebivolol Action Pathway;Amlodipine Action Pathway;Verapamil Action Pathway;Nitrendipine Action Pathway;Nisoldipine Action Pathway;Nimodipine Action Pathway;Ibutilide Action Pathway;Tocainide Action Pathway;Flecainide Action Pathway;Isradipine Action Pathway;Nifedipine Action Pathway;Felodipine Action Pathway;Nadolol Action Pathway;Carvedilol Action Pathway;Labetalol Action Pathway;MicroRNAs in cardiomyocyte hypertrophy;Endothelin Pathways;Focal Adhesion;Association Between Physico-Chemical Features and Toxicity Associated Pathways;Regulation of Actin Cytoskeleton;Smooth Muscle Contraction;Signal Transduction;bioactive peptide induced signaling pathway;erk and pi-3 kinase are necessary for collagen binding in corneal epithelia;pkc-catalyzed phosphorylation of inhibitory phosphoprotein of myosin phosphatase;mcalpain and friends in cell motility;rho cell motility signaling pathway;rac1 cell motility signaling pathway;RHO GTPases activate PAKs;Muscle contraction;RHO GTPase Effectors;Signaling by Rho GTPases;Aurora B signaling (Consensus)

Intolerance Scores

• loftool: 0.734
• rvis_EVS: -0.32
• rvis_percentile_EVS: 30.93

Haploinsufficiency Scores

• pHI: 0.236
• hipred: Y
• hipred_score: 0.590
• ghis: 0.529

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.935

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Mylk
• 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); normal 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); renal/urinary system phenotype; skeleton phenotype; immune system phenotype; digestive/alimentary phenotype; muscle phenotype; growth/size/body region phenotype; homeostasis/metabolism phenotype

Zebrafish Information Network

• Gene name: mylka
• Affected structure: thrombocyte
• Phenotype tag: abnormal
• Phenotype quality: shape

Gene ontology

• Biological process: protein phosphorylation;muscle contraction;smooth muscle contraction;tonic smooth muscle contraction;positive regulation of cell migration;bleb assembly;positive regulation of calcium ion transport;aorta smooth muscle tissue morphogenesis;cellular hypotonic response;cardiovascular system development;positive regulation of wound healing
• Cellular component: stress fiber;cytoplasm;cytosol;plasma membrane;actin cytoskeleton;lamellipodium;cleavage furrow
• Molecular function: actin binding;protein kinase activity;myosin light chain kinase activity;protein binding;calmodulin binding;ATP binding;metal ion binding