MYL9

protein-coding

myosin light chain 9, the group of Myosin light chains, class 2

Gene summary

Myosin, a structural component of muscle, consists of two heavy chains and four light chains. The protein encoded by this gene is a myosin light chain that may regulate muscle contraction by modulating the ATPase activity of myosin heads. The encoded protein binds calcium and is activated by myosin light chain kinase. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

MANE transcript

NM_006097.5

Inheritance

ClinVar variants

P:2U:24B:1

Top phenotype

Megacystis-microcolon-intestinal hypoperistalsis syndrome 4

gnomAD constraint

pLI —, LoF o/e 0.6

Max pathogenic AF

—

Genomic locus

chr20:36,541,497-36,551,447

External References & Databases

Ensembl (ENSG00000101335)

Transcript & Mutation Effects

hg38 • Region Span ~10.0 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

megacystis-microcolon-intestinal hypoperistalsis syndrome 4STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0030296

Submitter: Labcorp Genetics (formerly Invitae)

megacystis-microcolon-intestinal hypoperistalsis syndrome 4STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0030296

Submitter: PanelApp Australia

megacystis-microcolon-intestinal hypoperistalsis syndrome 4STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0030296

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Megacystis-microcolon-intestinal hypoperistalsis syndrome 4AR

Manifestation: Gastrointestinal; Genitourinary; Musculoskeletal; Ophthalmologic; Renal

Intervention: Gastrointestinal; Renal

Rationale: Individuals have been described as benefiting from surgical interventions, including related to renal anomalies and nephrolithiasis; Multivisceral transplantation has been described

Refs: 27481187; 29453416; 33031641

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to MYL9 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 21

not providedTotal: 2

Visceral myopathy 1Total: 2

Megacystis-microcolon-intestinal hypoperistalsis syndrome 4Total: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_006097.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	1 clinvar		2
missense			21 clinvar			21
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)		2 clinvar	2 clinvar			4
Total	0	2	24	1	0	27

Highest pathogenic variant AF is 0.000008210866

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 37 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_006097.5	RefSeq	NP_006088.2	3	MANE Select
ENST00000279022.7	Ensembl	ENSP00000279022.2	3	MANE Select
NM_181526.3	RefSeq	NP_852667.1	2	Standard
ENST00000346786.2	Ensembl	ENSP00000217313.2	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Focal adhesion - Homo sapiens (human)
Oxytocin signaling pathway - Homo sapiens (human)
Tight junction - Homo sapiens (human)
Regulation of actin cytoskeleton - Homo sapiens (human)
cAMP signaling pathway - Homo sapiens (human)

Biological Process

muscle contraction
regulation of muscle contraction
regulation of megakaryocyte differentiation
platelet aggregation

Molecular Function

calcium ion binding
structural constituent of muscle
myosin heavy chain binding

Cellular Component

stress fiber
cytosol
muscle myosin complex
Z disc

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000279022
Coding exons: 3
Length: 8342
Individuals with no LoFs: 125728
Homozygous LoFs: 0
Heterozygous LoFs: 18
Defined: 125746
p: 0.0000716

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.17	83	119	0.698	0.00000773	1176
Missense (PolyPhen)		17	30.866	0.55077		364
Synonymous	0.375	43	46.2	0.930	0.00000332	301
Loss of Function	0.841	3	5.04	0.596	2.13e-7	63

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.00015	0.00014	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00028	0.00027	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000071	0.000070	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Myosin regulatory subunit that plays an important role in regulation of both smooth muscle and nonmuscle cell contractile activity via its phosphorylation. Implicated in cytokinesis, receptor capping, and cell locomotion. {ECO:0000269|PubMed:11942626, ECO:0000269|PubMed:2526655}.;

Recessive Scores

pRec: 0.149

Intolerance Scores

LoFtool: 0.626
RVIS EVS: -0.16
RVIS percentile EVS: 41.25

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.982

Gene Damage Prediction

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