MYOF

Summary

MYOF (myoferlin, HGNC:3656) is a protein-coding gene on chromosome 10q23.33, encoding Myoferlin (Q9NZM1). Calcium/phospholipid-binding protein that plays a role in the plasmalemma repair mechanism of endothelial cells that permits rapid resealing of membranes disrupted by mechanical stress.

Mutations in dysferlin, a protein associated with the plasma membrane, can cause muscle weakness that affects both proximal and distal muscles. The protein encoded by this gene is a type II membrane protein that is structurally similar to dysferlin. It is a member of the ferlin family and associates with both plasma and nuclear membranes. The protein contains C2 domains that play a role in calcium-mediated membrane fusion events, suggesting that it may be involved in membrane regeneration and repair. Two transcript variants encoding different isoforms have been found for this gene. Other possible variants have been detected, but their full-length nature has not been determined.

Source: NCBI Gene 26509 — RefSeq curated summary.

At a glance

• Gene–disease (curated): angioedema, hereditary, 7 (Limited, GenCC)
• GWAS associations: 43
• Clinical variants (ClinVar): 444 total — 1 pathogenic
• Phenotypes (HPO): 6
• Druggable target: yes
• MANE Select transcript: NM_013451

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3656
Approved symbol	MYOF
Name	myoferlin
Location	10q23.33
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1207
Ensembl gene	ENSG00000138119
Ensembl biotype	protein_coding
OMIM	604603
Entrez	26509

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 7 protein_coding, 3 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000358334, ENST00000359263, ENST00000371488, ENST00000371489, ENST00000463743, ENST00000474161, ENST00000475358, ENST00000485212, ENST00000488645, ENST00000941955, ENST00000941956, ENST00000941957

RefSeq mRNA: 2 — MANE Select: NM_013451 NM_013451, NM_133337

CCDS: CCDS41550, CCDS41551

Canonical transcript exons

ENST00000359263 — 54 exons

Exon	Start	End
ENSE00000932929	93323270	93323358
ENSE00001591952	93377323	93377429
ENSE00001597532	93399392	93399495
ENSE00001602452	93397247	93397290
ENSE00001607775	93372930	93373085
ENSE00001635278	93359833	93359978
ENSE00001644285	93369645	93369776
ENSE00001650844	93355628	93355736
ENSE00001651333	93401418	93401544
ENSE00001657218	93374763	93374955
ENSE00001658202	93349808	93349969
ENSE00001669811	93402860	93402890
ENSE00001685634	93351197	93351295
ENSE00001687908	93363961	93364075
ENSE00001690317	93343856	93343932
ENSE00001696852	93404157	93404219
ENSE00001699506	93404023	93404073
ENSE00001718884	93351665	93351846
ENSE00001721472	93396142	93396224
ENSE00001738173	93397388	93397456
ENSE00001741484	93337815	93337913
ENSE00001743861	93366392	93366555
ENSE00001753360	93335921	93336046
ENSE00001760561	93408787	93408915
ENSE00001764014	93361452	93361557
ENSE00001770834	93356675	93356848
ENSE00001775552	93402232	93402347
ENSE00001776338	93353811	93353888
ENSE00001778381	93392917	93392955
ENSE00001780017	93409573	93409739
ENSE00001791610	93387797	93387913
ENSE00001792572	93379863	93379987
ENSE00001796656	93389030	93389154
ENSE00001801029	93351413	93351571
ENSE00001801168	93347617	93347782
ENSE00002512650	93381219	93381396
ENSE00002516596	93340153	93340164
ENSE00003264674	93333221	93333312
ENSE00003269682	93333758	93333913
ENSE00003289603	93329664	93329834
ENSE00003474142	93316714	93316813
ENSE00003478117	93313020	93313210
ENSE00003478648	93325826	93325965
ENSE00003494463	93431408	93431516
ENSE00003504934	93426071	93426158
ENSE00003510105	93452050	93452141
ENSE00003513158	93456882	93456937
ENSE00003559504	93323078	93323173
ENSE00003605171	93328763	93328911
ENSE00003640266	93310534	93310643
ENSE00003652893	93319872	93320013
ENSE00003663477	93310020	93310167
ENSE00003847643	93306429	93307001
ENSE00003848007	93482107	93482334

Expression profiles

Bgee: expression breadth ubiquitous, 284 present calls, max score 98.74.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 32.2018 / max 523.6100, expressed in 1562 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
110692	16.3617	1503
110693	11.2008	1369
110691	1.9217	988
110694	1.3256	705
110676	0.3666	183
110678	0.3068	119
110679	0.2729	111
110680	0.2402	120
110677	0.2055	81

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
skin of hip	UBERON:0001554	98.74	gold quality
gingival epithelium	UBERON:0001949	98.33	gold quality
nasal cavity epithelium	UBERON:0005384	98.27	gold quality
gingiva	UBERON:0001828	98.24	gold quality
upper leg skin	UBERON:0004262	98.24	gold quality
stromal cell of endometrium	CL:0002255	98.22	gold quality
mucosa of paranasal sinus	UBERON:0005030	98.14	gold quality
epithelium of nasopharynx	UBERON:0001951	98.01	gold quality
urethra	UBERON:0000057	97.99	gold quality
palpebral conjunctiva	UBERON:0001812	97.95	gold quality
decidua	UBERON:0002450	97.94	gold quality
mammalian vulva	UBERON:0000997	97.93	gold quality
mammary duct	UBERON:0001765	97.70	gold quality
visceral pleura	UBERON:0002401	97.62	gold quality
upper arm skin	UBERON:0004263	97.61	gold quality
epithelium of mammary gland	UBERON:0003244	97.47	gold quality
placenta	UBERON:0001987	97.45	gold quality
urinary bladder	UBERON:0001255	97.28	gold quality
colonic epithelium	UBERON:0000397	97.25	gold quality
nasal cavity mucosa	UBERON:0001826	97.20	gold quality
pleura	UBERON:0000977	97.16	gold quality
cervix squamous epithelium	UBERON:0006922	97.15	gold quality
right uterine tube	UBERON:0001302	97.12	gold quality
mucosa of urinary bladder	UBERON:0001259	97.09	gold quality
tongue squamous epithelium	UBERON:0006919	97.09	gold quality
pericardium	UBERON:0002407	97.08	gold quality
squamous epithelium	UBERON:0006914	97.07	gold quality
parietal pleura	UBERON:0002400	97.06	gold quality
penis	UBERON:0000989	97.05	gold quality
cauda epididymis	UBERON:0004360	97.05	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-MTAB-11121	yes	85.26
E-MTAB-6819	yes	70.67
E-MTAB-6678	yes	8.35
E-ENAD-27	yes	7.16
E-GEOD-81383	no	1035.87
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NFATC2

miRNA regulators (miRDB)

44 targeting MYOF, 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-4283	100.00	66.42	2097
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-6744-5P	99.93	66.82	748
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-4694-3P	99.79	69.53	2640
HSA-MIR-320A-3P	99.77	69.73	2107
HSA-MIR-320B	99.77	69.73	2107
HSA-MIR-320C	99.77	69.73	2107
HSA-MIR-320D	99.77	69.73	2107
HSA-MIR-4429	99.77	69.62	2111
HSA-MIR-4517	99.76	69.19	1867
HSA-MIR-494-3P	99.70	71.45	2795
HSA-MIR-10393-5P	99.65	68.01	1368
HSA-MIR-6848-3P	99.64	66.49	885
HSA-MIR-4452	99.50	68.45	1493
HSA-MIR-4797-5P	99.39	68.01	1354
HSA-MIR-940	99.37	66.14	2064
HSA-MIR-3678-3P	99.31	67.10	1432
HSA-MIR-6808-5P	99.31	66.23	2150
HSA-MIR-6893-5P	99.31	66.25	2119
HSA-MIR-6843-3P	99.26	66.42	915
HSA-MIR-642A-3P	99.23	67.67	1258
HSA-MIR-642B-3P	99.23	67.67	1258

Literature-anchored findings (GeneRIF, showing 36)

• myoferlin forms a complex with dynamin-2 and VEGFR-2, which prevents CBL-dependent VEGFR-2 polyubiquitination and proteasomal degradation. (PMID:17702744)
• solution structure of the inner DysF domain of the dysferlin paralogue myoferlin, which has a unique fold held together by stacking of arginine and tryptophans, mutations that lead to clinical disease in dysferlin (PMID:18495154)
• interaction of myoferlin with EHD2 identifies molecular overlap between the endocytic recycling pathway and the machinery that regulates myoblast membrane fusion (PMID:18502764)
• In trophoblastic cells, there was a positive correlation between cell fusion and increased dysferlin expression but not myoferlin expression. (PMID:19228595)
• These data describe a new role for myoferlin in receptor-dependent endocytosis and an overlapping role for myoferlin-dynamin 2-caveolin 1 protein complexes in membrane fusion and fission events. (PMID:19494235)
• MYOF plays a previously unrecognized role in cancer cell invasion. (PMID:22135466)
• suggest a novel role of MYOF in breast tumor cell invasion and a potential reversion to an epithelial phenotype upon loss of MYOF (PMID:22761893)
• The effect of myoferlin on the expression of ZO-1 in airway epithelial cells indicates its role in membrane fusion events that regulate cell detachment and apoptosis within the airway epithelium. (PMID:22808170)
• These data provide the first evidence of myoferlin expression in solid human and mouse tumors. (PMID:23499551)
• Data indicate that dysferlin, otoferlin, and myoferlin do not merely passively adsorb to membranes but actively sculpt lipid bilayers. (PMID:23859474)
• High myoferlin expression is associated with breast cancer. (PMID:23864327)
• MYOF regulates cell adhesions and cell-substrate adhesion strength and may account for the high degree of motility in invasive breast cancer cells. (PMID:25631868)
• Myoferlin plays a key role in VEGFA secretion and impacts tumor-associated angiogenesis in human pancreas cancer. (PMID:26311411)
• Results demonstrate for the first time that nuclear myoferlin expression independently predicts poor clinical outcome in OPSCC patients. (PMID:26919244)
• A novel regulator, myoferlin, of ADAM12 is discovered in HeLa cells and this protein increases ADAM12 expression level, stability, and its enzymatic activity, leading to the reduction of its substrate, E-cadherin, which plays important roles in the regulation of cell adhesion and tumor metastasis. (PMID:27432471)
• Myoferlin is a general component of cancer cell derived exosomes from different breast and pancreatic cancer cell lines. (PMID:27845903)
• the cleavage of myoferlin, yielding a membrane-associated dual C2 domain ‘mini-myoferlin’, is reported. (PMID:28192161)
• This study is the first to report robust age associations for DNA methylation in MYOF and DDO, both of which have plausible functional roles in aging (PMID:28255110)
• Data show myoferlin depletion did not affect STAT3 transcription factor (STAT3) phosphorylation, but completely blocked STAT3 translocation to nucleus. (PMID:28745314)
• Data show that myoferlin (MYOF) plays an important role in VM and knockdown of MYOF suppresses vasculogenic mimicry (VM) formation via decreasing matrix metallopeptidase 2 (MMP-2) and inducing mesenchymal-to-epithelial transition (MET) in A375 melanoma cells. (PMID:29164766)
• The observed mitochondrial fission induced by myoferlin depletion led to a decrease of cell proliferation. (PMID:29720728)
• Results show that the FerA domain is a novel four-helix bundle fold with its own Ca(2+)-dependent phospholipid-binding activity which interaction with the membrane is enhanced by the presence of Ca(2+). (PMID:30026467)
• The initial C2 domains of dysferlin and myoferlin are 57% similar (42% identical). Unlike dysferlin C2A, myoferlin binds two Ca2+ with equivalent affinity. Unlike dysferlin C2A, the membrane binding loop 1 of myoferlin C2A is relatively rigid. (PMID:31004665)
• Myoferlin hyperexpression can be a useful marker for predicting the development of subsequent primary malignancies in patients with ccRCC. (PMID:31280198)
• Prognostic significance of immunohistochemical staining for myoferlin in clear cell renal cell carcinoma and its association with epidermal growth factor receptor expression. (PMID:31421995)
• The otoferlin enhances cancer cell proliferation, migration and metabolism by affecting various aspects of membrane biology. (PMID:31443490)
• Myoferlin silencing inhibits VEGFR2-mediated proliferation of metastatic clear cell renal cell carcinoma. (PMID:31477752)
• PINCH-1 interacts with myoferlin to promote breast cancer progression and metastasis. (PMID:31801973)
• This article reviews the physiological function of myoferlin (MYOF) as well as its role in cancer. (PMID:31828126)
• Lysosomal retargeting of Myoferlin mitigates membrane stress to enable pancreatic cancer growth. (PMID:33686253)
• Comprehensive Analysis of Myoferlin in Human Pancreatic Cancer via Bioinformatics. (PMID:34957301)
• Impairment of APPL1/Myoferlin facilitates adipogenic differentiation of mesenchymal stem cells by blocking autophagy flux in osteoporosis. (PMID:35984564)
• HBZ upregulates myoferlin expression to facilitate HTLV-1 infection. (PMID:36827461)
• Tetraspanin CD82 Associates with Trafficking Vesicle in Muscle Cells and Binds to Dysferlin and Myoferlin. (PMID:37434585)
• A missense variant in MYOF is associated with ARVC and sudden cardiac death. (PMID:38253296)
• Identification of myoferlin as a mitochondria-associated membranes component required for calcium signaling in PDAC cell lines. (PMID:38368370)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	myof	ENSDARG00000006112
danio_rerio	myofl	ENSDARG00000017128
mus_musculus	Myof	ENSMUSG00000048612
rattus_norvegicus	Myof	ENSRNOG00000016117
drosophila_melanogaster	mfr	FBGN0266757

Paralogs (4): OTOF (ENSG00000115155), DYSF (ENSG00000135636), FER1L6 (ENSG00000214814), FER1L5 (ENSG00000249715)

Protein

Protein identifiers

Myoferlin — Q9NZM1 (reviewed: Q9NZM1)

Alternative names: Fer-1-like protein 3

All UniProt accessions (2): Q9NZM1, H0YD14

UniProt curated annotations — full annotation on UniProt →

Function. Calcium/phospholipid-binding protein that plays a role in the plasmalemma repair mechanism of endothelial cells that permits rapid resealing of membranes disrupted by mechanical stress. Involved in endocytic recycling. Implicated in VEGF signal transduction by regulating the levels of the receptor KDR.

Subunit / interactions. Interacts with DNM2 and KDR. Interacts with EHD1. Interacts with EHD2; the interaction is direct. Interacts with RIPOR2.

Subcellular location. Cell membrane. Nucleus membrane. Cytoplasmic vesicle membrane. Late endosome membrane.

Tissue specificity. Expressed in myoblast and endothelial cells (at protein level). Highly expressed in cardiac and skeletal muscles. Also present in lung, and at very low levels in kidney, placenta and brain.

Disease relevance. Angioedema, hereditary, 7 (HAE7) [MIM:619366] A form of angioedema, a disorder characterized by episodic local swelling involving subcutaneous or submucous tissue of the upper respiratory and gastrointestinal tracts, face, extremities, and genitalia. HAE7 is an autosomal dominant form characterized by onset of recurrent swelling of the face, lips, and oral mucosa in the second decade. The disease may be caused by variants affecting the gene represented in this entry.

Cofactor. Binds Ca(2+). The ions are bound to the C2 1 domain.

Domain organisation. The C2 domain 1 associates with lipid membranes in a calcium-dependent manner.

Similarity. Belongs to the ferlin family.

Isoforms (8)

UniProt ID	Names	Canonical?
Q9NZM1-1	1	yes
Q9NZM1-2	2
Q9NZM1-3	3
Q9NZM1-4	4
Q9NZM1-5	5
Q9NZM1-6	6
Q9NZM1-7	7
Q9NZM1-8	8

RefSeq proteins (2): NP_038479, NP_579899 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000008	C2_dom	Domain
IPR006614	Peroxin/Ferlin	Domain
IPR012560	Ferlin_A-domain	Domain
IPR012561	Ferlin_B-domain	Domain
IPR012968	FerIin_dom	Domain
IPR032362	Ferlin_C	Domain
IPR035892	C2_domain_sf	Homologous_superfamily
IPR037720	C2B_Ferlin	Domain
IPR037721	Ferlin	Family
IPR037722	C2C_Ferlin	Domain
IPR037723	C2D_Ferlin	Domain
IPR037724	C2E_Ferlin	Domain
IPR037725	C2F_Ferlin	Domain
IPR037726	C2A_Ferlin	Domain
IPR055072	Ferlin_DSRM	Domain

Pfam: PF00168, PF08150, PF08151, PF08165, PF16165, PF22901

UniProt features (91 total): binding site 19, strand 18, sequence conflict 11, splice variant 10, domain 7, modified residue 6, sequence variant 6, region of interest 4, turn 3, topological domain 2, chain 1, compositionally biased region 1, transmembrane region 1, mutagenesis site 1, helix 1

Structure

Experimental structures (PDB)

8 structures.

PDB	Method	Resolution (Å)
6EEL	X-RAY DIFFRACTION	1.93
9H6X	ELECTRON MICROSCOPY	2.56
9QLF	ELECTRON MICROSCOPY	2.65
9QKV	ELECTRON MICROSCOPY	2.74
9QLE	ELECTRON MICROSCOPY	2.8
9QLN	ELECTRON MICROSCOPY	3.2
2DMH	SOLUTION NMR
2K2O	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NZM1-F1	80.04	0.33

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 (19): 390; 390; 396; 444; 444; 446; 446; 452; 1155; 1161; 1217; 1219 …

Post-translational modifications (6): 174, 553, 729, 884, 1507, 1915

Mutagenesis-validated functional residues (1):

Position	Phenotype
238–240	reduces interaction with ehd2.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 321 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_UP, TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_MONOCYTE_UP, GOBP_CIRCULATORY_SYSTEM_PROCESS, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_PLASMA_MEMBRANE_ORGANIZATION, GOBP_NEUROTRANSMITTER_TRANSPORT, TOMLINS_PROSTATE_CANCER_DN, HEIDENBLAD_AMPLICON_8Q24_DN, GOCC_MICROTUBULE_ORGANIZING_CENTER, RODRIGUES_NTN1_TARGETS_DN, GOBP_CELL_CELL_SIGNALING, GOBP_WOUND_HEALING, TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_ERYTHROCYTE_UP, ONKEN_UVEAL_MELANOMA_UP, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_1

GO Biological Process (4): plasma membrane repair (GO:0001778), muscle contraction (GO:0006936), blood circulation (GO:0008015), regulation of neurotransmitter secretion (GO:0046928)

GO Molecular Function (4): calcium ion binding (GO:0005509), phospholipid binding (GO:0005543), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (15): nuclear envelope (GO:0005635), plasma membrane (GO:0005886), caveola (GO:0005901), cilium (GO:0005929), synaptic vesicle membrane (GO:0030672), cytoplasmic vesicle (GO:0031410), late endosome membrane (GO:0031902), nuclear membrane (GO:0031965), centriolar satellite (GO:0034451), ciliary basal body (GO:0036064), extracellular exosome (GO:0070062), ciliary tip (GO:0097542), nucleus (GO:0005634), membrane (GO:0016020), cytoplasmic vesicle membrane (GO:0030659)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
nucleus	2
cilium	2
plasma membrane organization	1
wound healing	1
muscle system process	1
circulatory system process	1
neurotransmitter secretion	1
modulation of chemical synaptic transmission	1
regulation of neurotransmitter transport	1
regulation of secretion by cell	1
metal ion binding	1
lipid binding	1
binding	1
cation binding	1
endomembrane system	1
organelle envelope	1
membrane	1
cell periphery	1
plasma membrane raft	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1
synaptic vesicle	1
exocytic vesicle membrane	1
cytoplasm	1
intracellular vesicle	1
late endosome	1
endosome membrane	1
nuclear envelope	1
organelle membrane	1
centrosome	1
microtubule organizing center	1
extracellular vesicle	1
intracellular membrane-bounded organelle	1
vesicle membrane	1
cytoplasmic vesicle	1

Protein interactions and networks

STRING

1310 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MYOF	AHNAK	Q09666	813
MYOF	CAPN3	P20807	762
MYOF	EHD2	Q9NZN4	730
MYOF	EHD3	Q9NZN3	711
MYOF	LST1	O00453	654
MYOF	EPS15	P42566	609
MYOF	TRIM72	Q6ZMU5	607
MYOF	CAV3	P56539	604
MYOF	ANXA1	P04083	565
MYOF	DMD	P11532	511
MYOF	HS3ST6	Q96QI5	475
MYOF	EHD1	Q9H4M9	463
MYOF	EHBP1	Q8NDI1	460
MYOF	ITGB4	P16144	455
MYOF	AGFG1	P52594	455

IntAct

81 interactions, top by confidence:

A	B	Type	Score
CD9	ADAM10	psi-mi:“MI:0914”(association)	0.750
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
EBNA-LP	HAX1	psi-mi:“MI:0914”(association)	0.530
KCNE3	RIOK3	psi-mi:“MI:0914”(association)	0.530
CFTR	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
sseJ	AGPS	psi-mi:“MI:0914”(association)	0.460
Ehd2	MYOF	psi-mi:“MI:0407”(direct interaction)	0.440
	GNAT3	psi-mi:“MI:0915”(physical association)	0.400
	AGPS	psi-mi:“MI:0915”(physical association)	0.400
MYOF	YWHAZ	psi-mi:“MI:0915”(physical association)	0.400
MYOF		psi-mi:“MI:0915”(physical association)	0.370
TK	AP3B1	psi-mi:“MI:0914”(association)	0.350
		psi-mi:“MI:0914”(association)	0.350
	TAF4	psi-mi:“MI:0914”(association)	0.350
	IPO5	psi-mi:“MI:0914”(association)	0.350
	ESYT2	psi-mi:“MI:0914”(association)	0.350
E6	PLOD2	psi-mi:“MI:0914”(association)	0.350
E5	ESYT2	psi-mi:“MI:0914”(association)	0.350
	PGRMC1	psi-mi:“MI:0914”(association)	0.350
	SNAP23	psi-mi:“MI:0914”(association)	0.350

BioGRID (165): MYOF (Affinity Capture-Western), MYOF (Affinity Capture-MS), MYOF (Reconstituted Complex), MYOF (Affinity Capture-MS), MYOF (Affinity Capture-MS), MYOF (Affinity Capture-MS), MYOF (Affinity Capture-MS), MYOF (Affinity Capture-MS), MYOF (Affinity Capture-MS), MYOF (Affinity Capture-MS), MYOF (Affinity Capture-MS), MYOF (Affinity Capture-MS), MYOF (Affinity Capture-MS), MYOF (Affinity Capture-MS), MYOF (Affinity Capture-MS)

ESM2 similar proteins: A0AVI2, A0FGR9, A3KGK3, A6NCM1, A6QQP7, B0DOB4, B3DLH6, B7FF09, B7ZC32, D3ZGS3, F1S5L4, O00329, O35904, O70145, O75923, P0DM40, P32019, P58069, P97564, Q0VA04, Q15283, Q17I16, Q1LXZ7, Q2WGJ9, Q32PH0, Q5DTI8, Q5GJ77, Q5RE88, Q5T0N1, Q5XIZ9, Q61586, Q62240, Q63713, Q69ZN7, Q6DCF6, Q6P5U7, Q6PA97, Q86VS3, Q86YR7, Q8BWR4

Diamond homologs: A0AVI2, A3KGK3, A6QQP7, B3DLH6, O75923, P0DM40, Q69ZN7, Q8LFN9, Q9C6B7, Q9ESD7, Q9NZM1, Q9Z268, A0JJX5, A1CQG2, A1ZBD6, A2QQ28, A4IFJ5, A8KBH6, B1WAZ6, B8N7E5, G0S9J5, O14065, O14795, O43581, O75131, O94812, P04409, P05126, P05128, P05129, P05696, P05771, P05772, P0C869, P0C871, P10102, P10829, P13677, P17252, P20444

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
NFATC2	up-regulates	MYOF	“transcriptional regulation”
NFATC2	“up-regulates quantity by expression”	MYOF	“transcriptional regulation”
MYOF	up-regulates	Myoblast_fusion

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	314
Likely benign	40
Benign	15

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1162305	NM_013451.4(MYOF):c.651G>T (p.Arg217Ser)	Pathogenic

SpliceAI

7969 predictions. Top by Δscore:

Variant	Effect	Δscore
10:93306997:TAGTT:T	acceptor_gain	1.0000
10:93307002:C:CC	acceptor_gain	1.0000
10:93310018:A:AC	donor_gain	1.0000
10:93310018:ACCG:A	donor_loss	1.0000
10:93310019:C:CA	donor_loss	1.0000
10:93310019:C:CC	donor_gain	1.0000
10:93310019:CCGG:C	donor_gain	1.0000
10:93310144:C:CT	acceptor_gain	1.0000
10:93310145:A:T	acceptor_gain	1.0000
10:93310163:GTCGA:G	acceptor_gain	1.0000
10:93310164:TCGA:T	acceptor_gain	1.0000
10:93310165:CGA:C	acceptor_gain	1.0000
10:93310165:CGAC:C	acceptor_gain	1.0000
10:93310166:GA:G	acceptor_gain	1.0000
10:93310166:GAC:G	acceptor_loss	1.0000
10:93310167:ACTG:A	acceptor_loss	1.0000
10:93310168:C:CC	acceptor_gain	1.0000
10:93310168:C:CG	acceptor_loss	1.0000
10:93310173:T:TC	acceptor_gain	1.0000
10:93310528:TCTCA:T	donor_loss	1.0000
10:93310529:CTCA:C	donor_loss	1.0000
10:93310530:TCACT:T	donor_loss	1.0000
10:93310532:A:AC	donor_gain	1.0000
10:93310532:ACTTT:A	donor_loss	1.0000
10:93310533:C:CT	donor_gain	1.0000
10:93310533:CT:C	donor_gain	1.0000
10:93310533:CTT:C	donor_gain	1.0000
10:93310641:CCC:C	acceptor_gain	1.0000
10:93310642:CCC:C	acceptor_gain	1.0000
10:93310644:C:CC	acceptor_gain	1.0000

AlphaMissense

13602 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:93329793:A:G	L1618P	1.000
10:93351772:A:G	W1186R	1.000
10:93351772:A:T	W1186R	1.000
10:93359894:C:G	R1020P	1.000
10:93366414:A:G	W911R	1.000
10:93366414:A:T	W911R	1.000
10:93397417:A:G	W421R	1.000
10:93397417:A:T	W421R	1.000
10:93402327:A:G	W299R	1.000
10:93402327:A:T	W299R	1.000
10:93313061:A:G	W1950R	0.999
10:93313061:A:T	W1950R	0.999
10:93313064:A:G	W1949R	0.999
10:93313064:A:T	W1949R	0.999
10:93319930:C:G	R1847P	0.999
10:93319946:C:A	G1842W	0.999
10:93323084:A:T	V1817D	0.999
10:93323343:A:G	W1763R	0.999
10:93323343:A:T	W1763R	0.999
10:93323357:C:T	G1758E	0.999
10:93323358:C:G	G1758R	0.999
10:93323358:C:T	G1758R	0.999
10:93325857:A:G	L1747S	0.999
10:93325862:C:A	R1745S	0.999
10:93325862:C:G	R1745S	0.999
10:93329742:C:T	G1635E	0.999
10:93329743:C:G	G1635R	0.999
10:93329743:C:T	G1635R	0.999
10:93329781:A:T	V1622D	0.999
10:93335921:C:A	K1521N	0.999

dbSNP variants (sampled 300 via entrez): RS1000036991 (10:93384866 G>C), RS1000065338 (10:93429900 T>C), RS1000096143 (10:93451182 A>T), RS1000118523 (10:93373530 T>G), RS1000145067 (10:93412881 G>A), RS1000164129 (10:93356989 A>G), RS1000178622 (10:93442311 T>C), RS1000181346 (10:93314514 G>A), RS1000187717 (10:93404282 T>C), RS1000199951 (10:93316960 A>G), RS1000235729 (10:93395125 CAAT>C), RS1000266449 (10:93413195 T>A,C), RS1000273829 (10:93391374 T>C), RS1000274204 (10:93354437 T>C), RS1000292427 (10:93460733 C>CTCCAAT)

Disease associations

OMIM: gene MIM:604603 | disease phenotypes: MIM:619366

GenCC curated gene-disease

Disease	Classification	Inheritance
angioedema, hereditary, 7	Limited	Unknown

Mondo (1): angioedema, hereditary, 7 (MONDO:0025713)

Orphanet (0):

HPO phenotypes

6 total (6 of 6 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000282	Facial edema
HP:0030254	Nail bed hemorrhage
HP:0031244	Swollen lip
HP:0033250	Nailfold capillary tortuosity
HP:0100665	Angioedema

GWAS associations

43 associations (top):

Study	Trait	p-value
GCST005170_26	Intraocular pressure	5.000000e-11
GCST005407_1	Glaucoma (primary open-angle)	2.000000e-06
GCST005409_1	Open-angle glaucoma and vertical cup-disc ratio	6.000000e-10
GCST005580_136	Intraocular pressure	1.000000e-36
GCST005580_198	Intraocular pressure	9.000000e-27
GCST005989_21	Serum total protein levels	4.000000e-08
GCST005991_23	Platelet count	1.000000e-11
GCST006291_67	Spherical equivalent or myopia (age of diagnosis)	3.000000e-10
GCST006394_56	Intraocular pressure	8.000000e-09
GCST006395_26	Glaucoma	3.000000e-09
GCST006412_113	Intraocular pressure	4.000000e-11
GCST008070_32	HDL cholesterol levels	2.000000e-09
GCST008074_118	Triglyceride levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	4.000000e-12
GCST008074_3	Triglyceride levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	1.000000e-12
GCST008074_42	Triglyceride levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	3.000000e-25
GCST008075_110	HDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	1.000000e-16
GCST008075_125	HDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	4.000000e-06
GCST008075_202	HDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	4.000000e-06
GCST008075_74	HDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	1.000000e-08
GCST008076_25	Triglyceride levels	2.000000e-18
GCST008076_88	Triglyceride levels	7.000000e-12
GCST008078_124	LDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	1.000000e-08
GCST008078_46	LDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	9.000000e-07
GCST008079_120	LDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	6.000000e-11
GCST008079_69	LDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	5.000000e-08
GCST008083_2	Triglyceride levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	2.000000e-12
GCST008083_69	Triglyceride levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	4.000000e-13
GCST008083_81	Triglyceride levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	7.000000e-27
GCST008084_128	HDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	2.000000e-06
GCST008084_186	HDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	6.000000e-17

EFO canonical traits (10, from GWAS)

EFO ID	Trait name
EFO:0004695	intraocular pressure measurement
EFO:0006939	cup-to-disc ratio measurement
EFO:0004309	platelet count
EFO:0004847	age at onset
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004530	triglyceride measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004329	alcohol drinking
EFO:0004869	YKL40 measurement
EFO:0004615	apolipoprotein B measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4523476 (SINGLE PROTEIN)

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

ChEMBL bioactivities

3 potent at pChembl≥5 of 3 total, top 3 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.03	Kd	94	nM	CHEMBL4582168
6.77	Kd	170	nM	CHEMBL5403598
5.88	Kd	1330	nM	CHEMBL5423432

PubChem BioAssay actives

3 with measured affinity, of 15 total; 3 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
3-[3-ethyl-5-(5-methoxypyrimidin-2-yl)-1,2,4-triazol-1-yl]-N-(4-phenylbutyl)benzamide	1508802: Reversible binding affinity to recombinant human GST-tagged MYOF C2 domain (3445 to 3912 residues) expressed in Escherichia coli BL21 (DE3) by surface plasmon resonance analysis	kd	0.0940	uM
3-[3-ethyl-5-(4-methoxyphenyl)-1,2,4-triazol-1-yl]-N-[4-(triazol-2-yl)butyl]benzamide	2004491: Binding affinity to MYOF C2D (unknown origin) expressed in Escherichia coli BL21(DE3) by SPR analysis	kd	0.1700	uM
3-[3-(2-methoxyphenyl)-4-oxo-1,3-thiazolidin-2-yl]-N-(4-phenylbutyl)benzamide	2004484: Binding affinity to human MYOF C2D by SPR method	kd	1.3300	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects methylation, decreases expression	7
Benzo(a)pyrene	increases expression	5
Estradiol	decreases expression, increases expression, affects expression, affects cotreatment	4
Tetrachlorodibenzodioxin	affects cotreatment, affects expression, increases expression	4
bisphenol A	increases expression, affects cotreatment, decreases expression	3
trichostatin A	increases expression, affects cotreatment	3
Tobacco Smoke Pollution	affects expression, decreases expression, increases expression	3
Aflatoxin B1	affects expression, decreases methylation, increases expression, increases methylation	3
bisphenol F	affects cotreatment, decreases expression, increases expression	2
mercuric bromide	increases expression, affects cotreatment	2
entinostat	increases expression, affects cotreatment	2
Panobinostat	affects cotreatment, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Progesterone	affects cotreatment, increases expression, decreases expression	2
Tretinoin	increases expression	2
Cyclosporine	increases expression	2
FR900359	increases phosphorylation	1
TAK-243	decreases sumoylation	1
daidzein	increases expression, affects cotreatment	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
pyrogallol 1,3-dimethyl ether	increases expression, decreases expression, affects cotreatment, affects localization	1
tris(2-butoxyethyl) phosphate	affects expression	1
daidzin	affects cotreatment, increases expression	1
beta-lapachone	decreases expression, increases expression	1
arsenite	affects binding, decreases reaction	1
afimoxifene	decreases reaction, increases expression	1
cobaltous chloride	decreases expression	1
butyraldehyde	decreases expression	1
3,4,5,3’,4’-pentachlorobiphenyl	increases expression	1

ChEMBL screening assays

14 unique, capped per target: 14 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4304992	Binding	Reversible binding affinity to recombinant human GST-tagged MYOF C2 domain (3445 to 3912 residues) expressed in Escherichia coli BL21 (DE3) by surface plasmon resonance analysis	Modification and Biological Evaluation of a Series of 1,5-Diaryl-1,2,4-triazole Compounds as Novel Agents against Pancreatic Cancer Metastasis through Targeting Myoferlin. — J Med Chem

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1Y2	Abcam HeLa MYOF KO	Cancer cell line	Female

Clinical trials (associated diseases)

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