MYO1E

Summary

MYO1E (myosin IE, HGNC:7599) is a protein-coding gene on chromosome 15q22.2, encoding Unconventional myosin-Ie (Q12965). Actin-based motor molecule with ATPase activity.

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.

Source: NCBI Gene 4643 — RefSeq curated summary.

At a glance

• Gene–disease (curated): focal segmental glomerulosclerosis 6 (Strong, GenCC) — +3 more curated relationships
• GWAS associations: 16
• Clinical variants (ClinVar): 1,044 total — 11 pathogenic, 17 likely-pathogenic
• Phenotypes (HPO): 24
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_004998

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7599
Approved symbol	MYO1E
Name	myosin IE
Location	15q22.2
Locus type	gene with protein product
Status	Approved
Aliases	MYO1C, HuncM-IC, MGC104638
Ensembl gene	ENSG00000157483
Ensembl biotype	protein_coding
OMIM	601479
Entrez	4643

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 15 protein_coding, 2 protein_coding_CDS_not_defined, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000288235, ENST00000558182, ENST00000558571, ENST00000558646, ENST00000558814, ENST00000559269, ENST00000559412, ENST00000559489, ENST00000560642, ENST00000560749, ENST00000884338, ENST00000884339, ENST00000884340, ENST00000884341, ENST00000884342, ENST00000884343, ENST00000884344, ENST00000884345, ENST00000929057, ENST00000929058

RefSeq mRNA: 1 — MANE Select: NM_004998 NM_004998

CCDS: CCDS32254

Canonical transcript exons

ENST00000288235 — 28 exons

Exon	Start	End
ENSE00001099448	59208681	59208848
ENSE00001099451	59163157	59163303
ENSE00001099453	59178393	59178537
ENSE00001099455	59174126	59174240
ENSE00001099458	59161073	59161230
ENSE00001099468	59210514	59210600
ENSE00001099472	59214640	59214720
ENSE00001099476	59214228	59214314
ENSE00001099483	59217891	59218087
ENSE00001270803	59138198	59138367
ENSE00001270812	59153590	59153791
ENSE00001270819	59158287	59158379
ENSE00001270973	59261420	59261509
ENSE00001270979	59272306	59272449
ENSE00001270990	59132434	59137456
ENSE00001681842	59173746	59173915
ENSE00002548049	59372498	59372871
ENSE00003483460	59224689	59224823
ENSE00003490101	59231702	59231791
ENSE00003495170	59205400	59205485
ENSE00003497697	59188118	59188216
ENSE00003564402	59223059	59223191
ENSE00003587532	59256284	59256378
ENSE00003633210	59202326	59202407
ENSE00003634148	59227459	59227590
ENSE00003635043	59195461	59195567
ENSE00003669706	59236585	59236672
ENSE00003790049	59171897	59172042

Expression profiles

Bgee: expression breadth ubiquitous, 235 present calls, max score 98.54.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 24.5796 / max 271.3708, expressed in 1660 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
150274	19.3983	1650
150273	2.4271	1301
150271	1.1776	495
150272	1.1185	570
150266	0.2795	120
150268	0.1024	45
150267	0.0458	16
150275	0.0304	12

Top tissues by expression

281 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	98.54	gold quality
sural nerve	UBERON:0015488	97.17	gold quality
gall bladder	UBERON:0002110	96.32	gold quality
tibial artery	UBERON:0007610	96.14	gold quality
popliteal artery	UBERON:0002250	96.13	gold quality
rectum	UBERON:0001052	96.08	gold quality
stromal cell of endometrium	CL:0002255	95.85	gold quality
aorta	UBERON:0000947	95.30	gold quality
lower esophagus mucosa	UBERON:0035834	95.16	gold quality
skin of leg	UBERON:0001511	94.87	gold quality
descending thoracic aorta	UBERON:0002345	94.82	gold quality
mucosa of transverse colon	UBERON:0004991	94.67	gold quality
thoracic aorta	UBERON:0001515	94.60	gold quality
ascending aorta	UBERON:0001496	94.59	gold quality
ventricular zone	UBERON:0003053	94.41	gold quality
right coronary artery	UBERON:0001625	94.17	gold quality
colonic epithelium	UBERON:0000397	93.98	gold quality
islet of Langerhans	UBERON:0000006	93.77	gold quality
left coronary artery	UBERON:0001626	93.75	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	93.75	gold quality
nerve	UBERON:0001021	93.72	gold quality
tibial nerve	UBERON:0001323	93.72	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	93.61	gold quality
transverse colon	UBERON:0001157	93.28	gold quality
skin of abdomen	UBERON:0001416	93.17	gold quality
esophagus mucosa	UBERON:0002469	92.85	gold quality
ectocervix	UBERON:0012249	92.48	gold quality
coronary artery	UBERON:0001621	92.26	gold quality
right lobe of liver	UBERON:0001114	92.02	gold quality
small intestine Peyer’s patch	UBERON:0003454	91.93	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-CURD-119	yes	30.99
E-CURD-112	yes	14.83
E-ANND-3	yes	12.65
E-HCAD-25	yes	4.94

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): GLI1, TAL1

miRNA regulators (miRDB)

108 targeting MYO1E, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-23B-5P	99.98	66.07	587
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-23A-5P	99.94	65.39	468

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 14)

• The kinetic mechanism of Myo1e (human myosin-IC). (PMID:11940582)
• Two proteins with prominent functions in endocytosis, synaptojanin-1 and dynamin, bind to the SH3 domain of human Myo1E. (PMID:17257598)
• myo1e binds lipids through nonspecific electrostatic interactions rather than a stereospecific protein-phosphoinositide interaction. (PMID:20860408)
• Homozygosity mapping and exome sequencing in a consanguineous kindred identified MYO1E and NEIL1 as novel candidate genes for human autosomal recessive steroid-resistant nephrotic syndrome. (PMID:21697813)
• MYO1E mutations are associated with childhood-onset, glucocorticoid-resistant focal segmental glomerulosclerosis. (PMID:21756023)
• Myo1e is a key component contributing to the functional integrity of podocytes. (PMID:23977349)
• MYO1E mutations are not a major cause of Chinese familial Steroid-resistant nephrotic syndrome. (PMID:24750828)
• Coinheritance of COL4A5 and MYO1E mutations accentuate the severity of kidney disease. (PMID:25739341)
• our data suggests that MYO1E contributes to breast tumor malignancy and regulates the differentiation and proliferation state of breast tumor cells. (PMID:27329840)
• The ERK signaling pathway thus promotes cell motility through regulation of the subcellular localization of Myo1E. (PMID:27502487)
• TH12 domain of Myo1e serves as a regulatory component to connect phosphatidylinositol signaling to F-actin polymerization at the podosome. (PMID:30601698)
• Focal segmental glomerulosclerosis and proteinuria associated with Myo1E mutations: novel variants and histological phenotype analysis. (PMID:35723736)
• Steroid-Resistant Nephrotic Syndrome-Associated MYO1E Mutations Have Differential Effects on Myosin 1e Localization, Dynamics, and Activity. (PMID:36316095)
• Myo1e overexpression in lung adenocarcinoma is associated with increased risk of mortality. (PMID:36914720)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	myo1ea	ENSDARG00000036179
mus_musculus	Myo1e	ENSMUSG00000032220
rattus_norvegicus	Myo1e	ENSRNOG00000061928
caenorhabditis_elegans	hum-1	WBGENE00002035

Paralogs (44): MYH13 (ENSG00000006788), MYO16 (ENSG00000041515), MYO9A (ENSG00000066933), MYO3B (ENSG00000071909), MYH7B (ENSG00000078814), MYO15A (ENSG00000091536), MYH7 (ENSG00000092054), MYO3A (ENSG00000095777), MYO9B (ENSG00000099331), MYH9 (ENSG00000100345), MYH14 (ENSG00000105357), MYH1 (ENSG00000109061), MYH3 (ENSG00000109063), MYH2 (ENSG00000125414), MYO1B (ENSG00000128641), MYO5C (ENSG00000128833), CGNL1 (ENSG00000128849), MYH8 (ENSG00000133020), MYH10 (ENSG00000133026), MYH11 (ENSG00000133392), MYO18B (ENSG00000133454), CCDC102A (ENSG00000135736), MYO1G (ENSG00000136286), MYO7A (ENSG00000137474), MYO1F (ENSG00000142347), CGN (ENSG00000143375), TMF1 (ENSG00000144747), MYH15 (ENSG00000144821), MYO10 (ENSG00000145555), CCDC102B (ENSG00000150636), CCDC158 (ENSG00000163749), MYO1A (ENSG00000166866), MYO5B (ENSG00000167306), MYO7B (ENSG00000169994), MYO1H (ENSG00000174527), MYO1D (ENSG00000176658), MYO18A (ENSG00000196535), MYO6 (ENSG00000196586), MYO5A (ENSG00000197535), MYH6 (ENSG00000197616)

Protein

Protein identifiers

Unconventional myosin-Ie — Q12965 (reviewed: Q12965)

Alternative names: Myosin-Ic, Unconventional myosin 1E

All UniProt accessions (7): Q12965, H0YLE5, H0YLJ4, H0YN00, H0YNB0, H0YNQ8, Q4KMR3

UniProt curated annotations — full annotation on UniProt →

Function. Actin-based motor molecule 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. Involved in clathrin-mediated endocytosis and intracellular movement of clathrin-coated vesicles. 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.

Subunit / interactions. Interacts with CALM and F-actin. Interacts (via SH3 domain) with SYNJ1, DNM1 and DNM2. Interacts with ARL14EP. Interacts with CARMIL1.

Subcellular location. Cytoplasm. Cytoskeleton. Cytoplasmic vesicle. Clathrin-coated vesicle. Cell junction.

Tissue specificity. Expressed in the immune system. In the kidney, predominantly expressed in the glomerulus, including podocytes.

Disease relevance. Focal segmental glomerulosclerosis 6 (FSGS6) [MIM:614131] A renal pathology defined by the presence of segmental sclerosis in glomeruli and resulting in proteinuria, reduced glomerular filtration rate and progressive decline in renal function. Renal insufficiency often progresses to end-stage renal disease, a highly morbid state requiring either dialysis therapy or kidney transplantation. FSGS6 is a childhood-onset disorder resulting in nephrotic syndrome, which includes massive proteinuria, hypoalbuminemia, hyperlipidemia, and edema. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Myosin family.

RefSeq proteins (1): NP_004989* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001452	SH3_domain	Domain
IPR001609	Myosin_head_motor_dom-like	Domain
IPR010926	Myosin_TH1	Domain
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR035507	Ie/If_SH3	Domain
IPR036028	SH3-like_dom_sf	Homologous_superfamily
IPR036072	MYSc_Myo1	Domain
IPR036961	Kinesin_motor_dom_sf	Homologous_superfamily

Pfam: PF00018, PF00063, PF06017

UniProt features (28 total): sequence variant 11, domain 4, compositionally biased region 3, sequence conflict 3, region of interest 3, modified residue 2, chain 1, binding site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q12965-F1	80.46	0.42

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (1): 112–119

Post-translational modifications (2): 980, 1002

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 747 (showing top): GOBP_PLATELET_DERIVED_GROWTH_FACTOR_RECEPTOR_SIGNALING_PATHWAY, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, MULLIGHAN_NPM1_SIGNATURE_3_UP, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_VASCULAR_ENDOTHELIAL_GROWTH_FACTOR_SIGNALING_PATHWAY, GOBP_VESICLE_LOCALIZATION, GOBP_RESPONSE_TO_PEPTIDE, GOBP_EPITHELIAL_CELL_DEVELOPMENT, GCANCTGNY_MYOD_Q6, GOBP_APICAL_JUNCTION_ASSEMBLY, ASTON_MAJOR_DEPRESSIVE_DISORDER_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_PROTEIN_TARGETING

GO Biological Process (12): vasculogenesis (GO:0001570), in utero embryonic development (GO:0001701), glomerular filtration (GO:0003094), endocytosis (GO:0006897), actin filament organization (GO:0007015), glomerulus development (GO:0032835), glomerular basement membrane development (GO:0032836), post-embryonic hemopoiesis (GO:0035166), platelet-derived growth factor receptor signaling pathway (GO:0048008), podocyte development (GO:0072015), kidney development (GO:0001822), hemopoiesis (GO:0030097)

GO Molecular Function (11): microfilament motor activity (GO:0000146), calmodulin binding (GO:0005516), ATP binding (GO:0005524), ATP hydrolysis activity (GO:0016887), phosphatidylinositol binding (GO:0035091), actin filament binding (GO:0051015), nucleotide binding (GO:0000166), cytoskeletal motor activity (GO:0003774), actin binding (GO:0003779), protein binding (GO:0005515), lipid binding (GO:0008289)

GO Cellular Component (13): cytoplasm (GO:0005737), cytoskeleton (GO:0005856), plasma membrane (GO:0005886), microvillus (GO:0005902), brush border (GO:0005903), adherens junction (GO:0005912), actin cytoskeleton (GO:0015629), myosin complex (GO:0016459), clathrin-coated vesicle (GO:0030136), extracellular exosome (GO:0070062), cytoplasmic vesicle (GO:0031410), clathrin-coated endocytic vesicle (GO:0045334), anchoring junction (GO:0070161)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
anatomical structure development	2
ATP-dependent activity	2
binding	2
cell differentiation	1
blood vessel morphogenesis	1
chordate embryonic development	1
renal filtration	1
vesicle budding from membrane	1
membrane invagination	1
vesicle-mediated transport	1
import into cell	1
actin cytoskeleton organization	1
supramolecular fiber organization	1
nephron development	1
extracellular matrix organization	1
glomerulus development	1
post-embryonic development	1
hemopoiesis	1
cell surface receptor protein tyrosine kinase signaling pathway	1
podocyte differentiation	1
glomerular epithelial cell development	1
animal organ development	1
renal system development	1
cell development	1
cytoskeletal motor activity	1
polypeptide conformation or assembly isomerase activity	1
protein binding	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
ribonucleoside triphosphate phosphatase activity	1
anion binding	1
actin binding	1
protein-containing complex binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
molecular_function	1
cytoskeletal protein binding	1
intracellular anatomical structure	1
cellular anatomical structure	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

1688 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MYO1E	INF2	Q27J81	756
MYO1E	ACTN4	O43707	739
MYO1E	ARL14	Q8N4G2	586
MYO1E	NPHS2	Q9NP85	579
MYO1E	ANLN	Q9NQW6	567
MYO1E	ARL14EP	Q8N8R7	558
MYO1E	PTPRO	Q16827	532
MYO1E	PLCE1	Q9P212	514
MYO1E	NPHS1	O60500	512
MYO1E	COQ6	Q9Y2Z9	509
MYO1E	SYNJ1	O43426	490
MYO1E	TRPC6	Q9Y210	479
MYO1E	PTPRU	P78399	475
MYO1E	COQ8B	Q96D53	475
MYO1E	COQ2	Q96H96	475

IntAct

105 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
NCBP2	KPNA3	psi-mi:“MI:0914”(association)	0.640
OSTF1	RP2	psi-mi:“MI:0914”(association)	0.640
ZNF764	SH3PXD2B	psi-mi:“MI:0914”(association)	0.530
UNC45A	MYO9A	psi-mi:“MI:0914”(association)	0.530
OSTF1	CHMP2A	psi-mi:“MI:0914”(association)	0.530
ARL14EP	MYO1E	psi-mi:“MI:0915”(physical association)	0.520
MYO1E	ARL14EP	psi-mi:“MI:0915”(physical association)	0.520
DNM2	MYO1E	psi-mi:“MI:0915”(physical association)	0.520
Synj1	MYO1E	psi-mi:“MI:0915”(physical association)	0.520
Dnm1	MYO1E	psi-mi:“MI:0915”(physical association)	0.520
MYO1E	Synj1	psi-mi:“MI:0915”(physical association)	0.520
CFTR	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
rep	MYO1E	psi-mi:“MI:0915”(physical association)	0.480
ADAM10	MYO1E	psi-mi:“MI:0407”(direct interaction)	0.440
MYO1E	Dnm2	psi-mi:“MI:0915”(physical association)	0.400
SYNJ1	MYO1E	psi-mi:“MI:0915”(physical association)	0.400
DNM1	MYO1E	psi-mi:“MI:0915”(physical association)	0.400
MYO1E	LTB4R2	psi-mi:“MI:0915”(physical association)	0.370
SYNJ1	MYO1E	psi-mi:“MI:0915”(physical association)	0.370
Ppp1cb	MYO1C	psi-mi:“MI:0914”(association)	0.350
MYH9	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
ANLN	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
MYO18A	PLEKHG3	psi-mi:“MI:0914”(association)	0.350

BioGRID (247): MYO1E (Affinity Capture-RNA), MYO1E (Affinity Capture-RNA), MYO1E (Affinity Capture-RNA), MYO1E (Affinity Capture-RNA), ARPC4-TTLL3 (Co-fractionation), ARPC4 (Co-fractionation), CAND1 (Co-fractionation), MYH9 (Co-fractionation), MYO1E (Co-fractionation), MYO1E (Co-fractionation), MYO1E (Co-fractionation), MYO1E (Co-fractionation), MYO5A (Co-fractionation), PPA1 (Co-fractionation), MYO1E (Biochemical Activity)

ESM2 similar proteins: A0MP03, A3LYL7, A5DKH0, A5PF48, A6ZMG6, E7F9L8, E9Q634, F1PRN2, F4I460, F4JM19, O00159, O00160, O08638, O88329, O94832, P10568, P10587, P11055, P35748, P35749, P70248, P97479, Q01989, Q04439, Q076A3, Q12965, Q13402, Q17LW0, Q17R14, Q23979, Q27966, Q29P71, Q5SYD0, Q5ZLA6, Q62774, Q62812, Q63355, Q63356, Q63357, Q6BUQ2

Diamond homologs: A0MP03, A1C4A5, A1DBH2, A2R5J1, A3LYL7, A4RE77, A5DKH0, A5E4A8, A5PF48, A6SED8, A6ZMG6, A6ZZJ1, A7EK16, A7TDZ8, A8N2Y6, A8PWF6, B0CRJ3, B0I1T2, B0Y9Q4, D3ZJP6, E7F9L8, E9Q634, F1PRN2, F4HWY6, F4I5Q6, F4IUG9, F4IVR7, F4JM19, F4K5J1, K7U9N8, O00159, O00160, O43795, O88329, O94832, P0CP00, P0CP01, P10568, P10569, P19706

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
MYO1E	“up-regulates activity”	PTK2	binding
SYNJ1	“up-regulates activity”	MYO1E	binding
DNM1	“up-regulates activity”	MYO1E	binding
MYO1E	up-regulates	“Receptor_mediated_ endocytosis”
MYO1E	up-regulates	Endocytosis

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 115 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
RHO GTPases activate PAKs	6	47.3×	1e-06
VEGFR2 mediated vascular permeability	5	29.6×	2e-04
RHO GTPases activate IQGAPs	5	25.1×	3e-04

GO biological processes:

GO term	Partners	Fold	FDR
actin filament organization	8	10.3×	6e-04
endocytosis	8	8.3×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

1044 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	11
Likely pathogenic	17
Uncertain significance	469
Likely benign	235
Benign	193

Top pathogenic / likely-pathogenic (28)

Variant ID	HGVS	Classification
1179070	NM_004998.4(MYO1E):c.979C>T (p.Gln327Ter)	Pathogenic
2189935	NM_004998.4(MYO1E):c.1141G>T (p.Glu381Ter)	Pathogenic
2500430	NM_004998.4(MYO1E):c.141C>G (p.Tyr47Ter)	Pathogenic
2645383	NM_004998.4(MYO1E):c.2627+1G>T	Pathogenic
2980334	NM_004998.4(MYO1E):c.1849C>T (p.Arg617Ter)	Pathogenic
30191	NM_004998.4(MYO1E):c.475G>C (p.Ala159Pro)	Pathogenic
30192	NM_004998.4(MYO1E):c.2085T>G (p.Tyr695Ter)	Pathogenic
3632780	NM_004998.4(MYO1E):c.1050C>A (p.Tyr350Ter)	Pathogenic
3658719	NM_004998.4(MYO1E):c.1586_1587insCA (p.Leu530fs)	Pathogenic
4708454	NM_004998.4(MYO1E):c.519C>G (p.Tyr173Ter)	Pathogenic
974435	NM_004998.4(MYO1E):c.2908C>T (p.Gln970Ter)	Pathogenic
1344752	NM_004998.4(MYO1E):c.1228G>A (p.Glu410Lys)	Likely pathogenic
1344757	NM_004998.4(MYO1E):c.1978C>T (p.Gln660Ter)	Likely pathogenic
2994089	NM_004998.4(MYO1E):c.2627+1G>A	Likely pathogenic
3577505	NM_004998.4(MYO1E):c.2879del	Likely pathogenic
3577514	NM_004998.4(MYO1E):c.2692C>T (p.Gln898Ter)	Likely pathogenic
3577532	NM_004998.4(MYO1E):c.2145C>G (p.Tyr715Ter)	Likely pathogenic
3577545	NM_004998.4(MYO1E):c.1663A>T (p.Lys555Ter)	Likely pathogenic
3577547	NM_004998.4(MYO1E):c.1631_1634del (p.Ser544fs)	Likely pathogenic
3577552	NM_004998.4(MYO1E):c.1506del (p.Phe502fs)	Likely pathogenic
3577554	NM_004998.4(MYO1E):c.1462C>T (p.Gln488Ter)	Likely pathogenic
3577556	NM_004998.4(MYO1E):c.1423G>T (p.Glu475Ter)	Likely pathogenic
3577572	NM_004998.4(MYO1E):c.808G>T (p.Glu270Ter)	Likely pathogenic
4541954	NM_004998.4(MYO1E):c.1603C>T (p.Gln535Ter)	Likely pathogenic
4541955	NM_004998.4(MYO1E):c.1337T>A (p.Val446Glu)	Likely pathogenic
498551	NM_004998.4(MYO1E):c.1311del (p.Ile438fs)	Likely pathogenic
807636	NM_004998.4(MYO1E):c.2060T>C (p.Leu687Ser)	Likely pathogenic
988196	NM_004998.4(MYO1E):c.1567C>T (p.Arg523Trp)	Likely pathogenic

SpliceAI

5310 predictions. Top by Δscore:

Variant	Effect	Δscore
15:59153583:ATCTT:A	donor_loss	1.0000
15:59153584:TCTTA:T	donor_loss	1.0000
15:59153585:CTTAC:C	donor_loss	1.0000
15:59153586:TTACC:T	donor_loss	1.0000
15:59153587:TA:T	donor_loss	1.0000
15:59153588:AC:A	donor_gain	1.0000
15:59153589:CC:C	donor_gain	1.0000
15:59153589:CCCTG:C	donor_gain	1.0000
15:59153787:GTATC:G	acceptor_gain	1.0000
15:59153788:TATC:T	acceptor_gain	1.0000
15:59153789:ATC:A	acceptor_gain	1.0000
15:59153790:TC:T	acceptor_gain	1.0000
15:59153791:CC:C	acceptor_gain	1.0000
15:59153792:C:CC	acceptor_gain	1.0000
15:59153793:T:C	acceptor_loss	1.0000
15:59158378:ACCTG:A	acceptor_loss	1.0000
15:59161071:A:AC	donor_gain	1.0000
15:59161072:C:CC	donor_gain	1.0000
15:59161072:CGGGA:C	donor_gain	1.0000
15:59161226:CAAGC:C	acceptor_gain	1.0000
15:59163155:A:AC	donor_gain	1.0000
15:59163156:C:CC	donor_gain	1.0000
15:59163156:CGT:C	donor_gain	1.0000
15:59163156:CGTA:C	donor_gain	1.0000
15:59163299:TAGTA:T	acceptor_gain	1.0000
15:59163300:AGTA:A	acceptor_gain	1.0000
15:59163301:GTA:G	acceptor_gain	1.0000
15:59163302:TA:T	acceptor_gain	1.0000
15:59163302:TAC:T	acceptor_loss	1.0000
15:59163303:ACTG:A	acceptor_loss	1.0000

AlphaMissense

7391 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:59137435:C:T	G1091D	1.000
15:59137436:C:G	G1091R	1.000
15:59137445:A:G	W1088R	1.000
15:59137445:A:T	W1088R	1.000
15:59138239:A:G	L1070P	1.000
15:59163303:A:C	S827R	1.000
15:59163303:A:T	S827R	1.000
15:59171898:T:G	S827R	1.000
15:59171936:C:G	R814P	1.000
15:59173884:T:A	R732S	1.000
15:59173884:T:G	R732S	1.000
15:59178411:G:C	F677L	1.000
15:59178411:G:T	F677L	1.000
15:59178412:A:G	F677S	1.000
15:59178413:A:G	F677L	1.000
15:59178427:C:T	G672E	1.000
15:59188145:C:G	R626P	1.000
15:59188157:C:T	G622D	1.000
15:59188177:G:C	N615K	1.000
15:59188177:G:T	N615K	1.000
15:59188187:A:G	L612P	1.000
15:59188197:A:G	Y609H	1.000
15:59188202:A:T	V607D	1.000
15:59195508:G:C	C586W	1.000
15:59195513:G:T	R585S	1.000
15:59195539:A:G	L576P	1.000
15:59195551:A:G	L572P	1.000
15:59195560:G:T	A569D	1.000
15:59195561:C:G	A569P	1.000
15:59205448:C:G	R523P	1.000

dbSNP variants (sampled 300 via entrez): RS1000029351 (15:59169761 C>A,T), RS1000064154 (15:59337345 G>A), RS1000095331 (15:59306632 T>C), RS1000140564 (15:59211661 C>T), RS1000165123 (15:59250337 G>A,C), RS1000166152 (15:59206524 C>G), RS1000166543 (15:59172083 A>T), RS1000168802 (15:59238122 T>C,G), RS1000171152 (15:59202599 G>C), RS1000179690 (15:59140340 A>G), RS1000195977 (15:59284173 G>A,T), RS1000197760 (15:59356442 A>G), RS1000209460 (15:59306439 T>C), RS1000216699 (15:59276923 C>A,T), RS1000259714 (15:59192466 C>G)

Disease associations

OMIM: gene MIM:601479 | disease phenotypes: MIM:614131, MIM:181500, MIM:156000, MIM:247200

GenCC curated gene-disease

Disease	Classification	Inheritance
focal segmental glomerulosclerosis 6	Strong	Autosomal recessive
autosomal dominant nonsyndromic hearing loss	Supportive	Autosomal dominant
familial idiopathic steroid-resistant nephrotic syndrome	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
nonsyndromic genetic hearing loss	Disputed	AD

Mondo (8): focal segmental glomerulosclerosis 6 (MONDO:0013589), kidney disorder (MONDO:0005240), nephrotic syndrome (MONDO:0005377), schizophrenia (MONDO:0005090), Meniere disease (MONDO:0007972), Miller-Dieker lissencephaly syndrome (MONDO:0009532), autosomal dominant nonsyndromic hearing loss (MONDO:0019587), familial idiopathic steroid-resistant nephrotic syndrome (MONDO:0019006)

Orphanet (5): Hereditary steroid-resistant nephrotic syndrome (Orphanet:656), Microphthalmia-anophthalmia-coloboma (Orphanet:98555), Miller-Dieker syndrome (Orphanet:531), NON RARE IN EUROPE: Schizophrenia (Orphanet:3140), NON RARE IN EUROPE: Menière disease (Orphanet:45360)

HPO phenotypes

24 total (25 of 24 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000092	Renal tubular atrophy
HP:0000093	Proteinuria
HP:0000097	Focal segmental glomerulosclerosis
HP:0000100	Nephrotic syndrome
HP:0000707	Abnormality of the nervous system
HP:0000737	Irritability
HP:0000790	Hematuria
HP:0000969	Edema
HP:0001945	Fever
HP:0001967	Diffuse mesangial sclerosis
HP:0002027	Abdominal pain
HP:0002315	Headache
HP:0002586	Peritonitis
HP:0003073	Hypoalbuminemia
HP:0003621	Juvenile onset
HP:0003676	Progressive
HP:0003774	Stage 5 chronic kidney disease
HP:0011463	Childhood onset
HP:0011947	Respiratory tract infection
HP:0012579	Minimal change glomerulonephritis
HP:0012622	Chronic kidney disease
HP:0031504	Foamy urine
HP:0100539	Periorbital edema
HP:0100753	Schizophrenia

GWAS associations

16 associations (top):

Study	Trait	p-value
GCST001639_9	Metabolite levels	1.000000e-10
GCST002194_4	Social communication problems	1.000000e-07
GCST005175_37	Coronary artery calcified atherosclerotic plaque (90 or 130 HU threshold) in type 2 diabetes	2.000000e-06
GCST006414_32	Atrial fibrillation	3.000000e-09
GCST006629_104	Pulse pressure	5.000000e-11
GCST007269_299	Pulse pressure	6.000000e-13
GCST009240_364	Serum metabolite levels (CMS)	1.000000e-10
GCST009240_379	Serum metabolite levels (CMS)	9.000000e-13
GCST010988_554	Adult body size	5.000000e-09
GCST90000025_114	Appendicular lean mass	8.000000e-14
GCST90000026_42	Appendicular lean mass	6.000000e-06
GCST90000027_47	Appendicular lean mass	2.000000e-09
GCST90002395_234	Mean platelet volume	7.000000e-19
GCST90002398_258	Neutrophil count	2.000000e-19
GCST90002400_157	Plateletcrit	2.000000e-09
GCST90002407_565	White blood cell count	6.000000e-12

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0004723	coronary artery calcification
EFO:0005427	social communication impairment
EFO:0005763	pulse pressure measurement
EFO:0004980	appendicular lean mass
EFO:0004833	neutrophil count
EFO:0007985	platelet crit

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D007674	Kidney Diseases	C12.050.351.968.419; C12.200.777.419; C12.950.419
D008575	Meniere Disease	C09.218.568.217.500
D009404	Nephrotic Syndrome	C12.050.351.968.419.630.643; C12.200.777.419.630.643; C12.950.419.630.643

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

68 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression	5
Valproic Acid	increases expression, increases methylation, affects cotreatment	4
bisphenol A	affects cotreatment, increases methylation, decreases expression	2
cobaltous chloride	decreases expression	2
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression, increases expression	2
Acetaminophen	increases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	decreases expression	1
2,4,6-tribromophenol	decreases expression	1
triphenyl phosphate	affects expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, decreases expression, affects localization	1
decabromobiphenyl ether	decreases expression	1
trichostatin A	increases expression	1
beta-lapachone	increases expression	1
arsenite	affects binding, decreases reaction	1
sodium arsenite	decreases expression	1
tetrabromobisphenol A	decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
aflatoxin B2	decreases methylation	1
nickel sulfate	increases expression	1
coumarin	decreases phosphorylation	1
epigallocatechin gallate	decreases expression, affects cotreatment	1
perfluorooctane sulfonic acid	decreases expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	decreases ADP-ribosylation	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
bisphenol B	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
pentabrominated diphenyl ether 100	increases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
bisphenol S	affects cotreatment, increases methylation	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_C7Y0	HAP1 MYO1E (-)	Cancer cell line	Male

Clinical trials (associated diseases)

300 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00067990	PHASE4	COMPLETED	Angiotensin II Blockade for Chronic Allograft Nephropathy
NCT00117078	PHASE4	COMPLETED	Aranesp® Monthly Preference Study - 2
NCT00117130	PHASE4	COMPLETED	Study to Evaluate Effectiveness of Aranesp®
NCT00132431	PHASE4	COMPLETED	START: Sensipar Treatment Algorithm to Reach K/DOQI Targets in Chronic Kidney Disease Subjects With Secondary Hyperparathyroidism
NCT00140985	PHASE4	COMPLETED	Antiproteinuric Efficacy of Losartan Potassium in Patients With Non-Diabetic Proteinuric Renal Diseases (0954-213)
NCT00246129	PHASE4	COMPLETED	CamTac Trial:Campath-Tacrolimus vs IL2R MoAb/Tacrolimus/MMF in Renal Transplantation
NCT00275535	PHASE4	COMPLETED	The Comparison of Tacrolimus and Sirolimus Immunosuppression Based Drug Regimens in Kidney Transplant Recipients
NCT00282217	PHASE4	COMPLETED	Study Evaluating Sirolimus in the Treatment of Kidney Transplant
NCT00289614	PHASE4	COMPLETED	Patients With Renal Impairment and Diabetes Undergoing Computed Tomography (CT)
NCT00290069	PHASE4	UNKNOWN	Renal Function Optimization With Mycophenolate Mofetil (MMF) Immunosuppressor Regimes (ALHAMBRA)
NCT00338468	PHASE4	TERMINATED	A Study to Assess Disability in Anemic Elderly Patients With Kidney Disease Receiving PROCRIT (Epoetin Alfa)
NCT00368901	PHASE4	COMPLETED	STAAR-2 Clinical Study
NCT00369733	PHASE4	COMPLETED	STAAR-3 Clinical Study
NCT00369772	PHASE4	COMPLETED	STAAR-1 Clinical Study
NCT00379899	PHASE4	COMPLETED	ADVANCE: Study to Evaluate Cinacalcet Plus Low Dose Vitamin D on Vascular Calcification in Subjects With Chronic Kidney Disease Receiving Hemodialysis
NCT00443508	PHASE4	UNKNOWN	Reduction or Discontinuation of CNI’s With Conversion to Everolimus-Based Immunosuppresion
NCT00452478	PHASE4	TERMINATED	Conversion From Standard Phosphate Binder Therapy to Fosrenol® (Lanthanum Carbonate) in Chronic Kidney Disease Stage 5
NCT00492518	PHASE4	COMPLETED	Acetylcysteine, Theophylline, and a Combination of Both in the Prophylaxis of Contrast-Induced Nephropathy
NCT00505102	PHASE4	UNKNOWN	Safe Renal Function In Long Term Heart Transplanted Patients
NCT00526331	PHASE4	COMPLETED	Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
NCT00688480	PHASE4	COMPLETED	Do Xanthine Oxidase Inhibitors Reduce Both Left Ventricular Hypertrophy and Endothelial Dysfunction in Cardiovascular Patients With Renal Dysfunction?
NCT00863707	PHASE4	COMPLETED	A Study of the Safety and Tolerance of Regadenoson in Subjects With Renal Impairment
NCT01101698	PHASE4	UNKNOWN	Vitamin K2 and Vessel Calcification in Chronic Kidney Disease Patients
NCT01150201	PHASE4	COMPLETED	Aliskiren Combined With Losartan in Proteinuric, Non-diabetic Chronic Kidney Disease
NCT01155141	PHASE4	COMPLETED	Idiopathic Focal Segmental Glomerulosclerosis (FSGS) and Treatment With ACTH
NCT01228279	PHASE4	COMPLETED	Sympathetic Activity in Patients With End-stage Renal Disease on Peritoneal Dialysis
NCT01334333	PHASE4	COMPLETED	Comparison of Medication Adherence Between Once and Twice Daily Tacrolimus in Stable Renal Transplant Recipients
NCT01437943	PHASE4	TERMINATED	Effect of Short Term Aliskiren Treatment in Kidney Transplant Patients
NCT01545479	PHASE4	COMPLETED	Increased Renal Oxygenation and Angiotensin Converting Enzyme Inhibition
NCT01614431	PHASE4	COMPLETED	N Acetyl Cysteine for Cystinosis Patients
NCT01631149	PHASE4	COMPLETED	Effect of Deep BLock on Intraoperative Surgical Conditions
NCT01722513	PHASE4	UNKNOWN	Efficacy and Safety of Alprostadil Prevent Contrast Induced Nephropathy
NCT01985360	PHASE4	COMPLETED	ISCHEMIA-Chronic Kidney Disease Trial
NCT02311010	PHASE4	UNKNOWN	Practical Use of Advagraf de Novo After Kidney Transplantation According to Recipient Genetic Polymorphism
NCT02413073	PHASE4	COMPLETED	Whole Body Vibration in Kidney Disease
NCT02444013	PHASE4	UNKNOWN	Folic Acid for Prevention of Contrast Induced Nephropathy
NCT02663713	PHASE4	COMPLETED	A Randomized, Pharmacodynamic Comparison of Low Dose Ticagrelor to Clopidogrel in Patients With Prior Myocardial Infarction
NCT02707809	PHASE4	COMPLETED	Effects of Dexmedetomidine on Microcirculation of Kidney Transplant Recipient
NCT02761577	PHASE4	COMPLETED	A Prospective Study on Incidence and Prevention of Contrast-induced Nephropathy in Croatia
NCT03029351	PHASE4	TERMINATED	GLP-1 Receptor Agonist Therapy and Albuminuria in Patients With Type 2 Diabetes