MYO1E

protein-coding

myosin IE, the group of Myosin heavy chains, class I|MicroRNA protein coding host genes

Gene summary

This gene encodes a member of the nonmuscle class I myosins which are a subgroup of the unconventional myosin protein family. The unconventional myosin proteins function as actin-based molecular motors. Class I myosins are characterized by a head (motor) domain, a regulatory domain and a either a short or long tail domain. Among the class I myosins, this protein is distinguished by a long tail domain that is involved in crosslinking actin filaments. This protein localizes to the cytoplasm and may be involved in intracellular movement and membrane trafficking. Mutations in this gene are the cause of focal segmental glomerulosclerosis-6. This gene has been referred to as myosin IC in the literature but is distinct from the myosin IC gene located on chromosome 17. [provided by RefSeq, Jan 2012]

MANE transcript

NM_004998.4

Inheritance

AR, AD

ClinVar variants

P:31U:318B:104

Top phenotype

Focal segmental glomerulosclerosis 6

gnomAD constraint

pLI —, LoF o/e 0.31

Max pathogenic AF

—

Genomic locus

chr15:59,132,434-59,372,871

External References & Databases

Ensembl (ENSG00000157483)

Transcript & Mutation Effects

hg38 • Region Span ~240.4 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

focal segmental glomerulosclerosis 6STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0013589

Submitter: Ambry Genetics

familial idiopathic steroid-resistant nephrotic syndromeSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0019006

Submitter: Orphanet

focal segmental glomerulosclerosis 6STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0013589

Submitter: PanelApp Australia

focal segmental glomerulosclerosis 6STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0013589

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Focal segmental glomerulosclerosis 6AR

Manifestation: Renal

Intervention: Renal

Rationale: The condition can involve early-onset renal disease, and awareness may allow prompt diagnosis and management (eg, glucocorticoid and cyclosporine use has been descvribed as beneficial); Renal transplant has been described

Refs: 21756023

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to MYO1E variants in ClinVar

10 Conditions Cataloged

not providedTotal: 348

Focal segmental glomerulosclerosis 6Total: 212

Inborn genetic diseasesTotal: 148

not specifiedTotal: 138

MYO1E-related disorderTotal: 34

Corticosteroids responseTotal: 10

Nephrotic syndromeTotal: 5

Kidney disorderTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004998.4. 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			16 clinvar	87 clinvar	1 clinvar	104
missense	1 clinvar	4 clinvar	298 clinvar	15 clinvar	1 clinvar	319
nonsense	9 clinvar	8 clinvar	1 clinvar			18
start loss						0
frameshift	1 clinvar	6 clinvar				7
splice donor/acceptor (+/-2bp)	1 clinvar	1 clinvar	3 clinvar			5
Total	12	19	318	102	2	453

Highest pathogenic variant AF is 0.000006201812

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 34 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_004998.4	RefSeq	NP_004989.2	28	MANE Select
ENST00000288235.9	Ensembl	ENSP00000288235.4	28	MANE Select
ENST00000558571.1	Ensembl	ENSP00000453811.1	5	Standard
ENST00000559269.5	Ensembl	ENSP00000453232.1	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

miR-targeted genes in epithelium - TarBase
miR-targeted genes in lymphocytes - TarBase
miR-targeted genes in muscle cell - TarBase
Primary Focal Segmental Glomerulosclerosis FSGS

Biological Process

vasculogenesis
in utero embryonic development
glomerular filtration
nitrogen compound metabolic process
endocytosis

Molecular Function

microfilament motor activity
motor activity
protein binding
calmodulin binding
ATP binding

Cellular Component

cytoplasm
cytoskeleton
brush border
cell-cell junction
adherens junction

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000288235
Coding exons: 28
Length: 237987
Individuals with no LoFs: 125716
Homozygous LoFs: 0
Heterozygous LoFs: 32
Defined: 125748
p: 0.000127

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.169	600	612	0.981	0.0000364	7363
Missense (PolyPhen)		261	298.5	0.87436		3582
Synonymous	-1.61	265	234	1.13	0.0000152	1995
Loss of Function	5.32	21	68.5	0.307	0.00000386	772

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00018	0.00018	rare
Latino/Admixed American	0.00023	0.00023	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00011	0.00011	rare
South Asian	0.00013	0.00013	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Myosins are actin-based motor molecules with ATPase activity. Unconventional myosins serve in intracellular movements. Their highly divergent tails bind to membranous compartments, which are then moved relative to actin filaments. Binds to membranes containing anionic phospholipids via its tail domain. Required for normal morphology of the glomerular basement membrane, normal development of foot processes by kidney podocytes and normal kidney function. In dendritic cells, may control the movement of class II-containing cytoplasmic vesicles along the actin cytoskeleton by connecting them with the actin network via ARL14EP and ARL14. {ECO:0000269|PubMed:11940582, ECO:0000269|PubMed:17257598, ECO:0000269|PubMed:20860408}.;

Recessive Scores

pRec: 0.132

Intolerance Scores

LoFtool: 0.0965
RVIS EVS: -1.14
RVIS percentile EVS: 6.38

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.846

Gene Damage Prediction

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