MYPN

Summary

MYPN (myopalladin, HGNC:23246) is a protein-coding gene on chromosome 10q21.3, encoding Myopalladin (Q86TC9). Component of the sarcomere that tethers together nebulin (skeletal muscle) and nebulette (cardiac muscle) to alpha-actinin, at the Z lines.

Striated muscle in vertebrates comprises large proteins which must be organized properly to contract efficiently. Z-lines in striated muscle are a sign of this organization, representing the ends of actin thin filaments, titin, nebulin or nebulette and accessory proteins required for structure and function. This gene encodes a protein which interacts with nebulin in skeletal muscle or nebulette in cardiac muscle and alpha-actinin. In addition, this gene product can interact with a protein with the I-band indicating it has a regulatory as well as structural function. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 84665 — RefSeq curated summary.

At a glance

• Gene–disease (curated): MYPN-related myopathy (Definitive, ClinGen) — +7 more curated relationships
• GWAS associations: 25
• Clinical variants (ClinVar): 1,943 total — 48 pathogenic, 26 likely-pathogenic
• Phenotypes (HPO): 117
• MANE Select transcript: NM_032578

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23246
Approved symbol	MYPN
Name	myopalladin
Location	10q21.3
Locus type	gene with protein product
Status	Approved
Aliases	MYOP
Ensembl gene	ENSG00000138347
Ensembl biotype	protein_coding
OMIM	608517
Entrez	84665

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 11 protein_coding, 6 nonsense_mediated_decay, 3 protein_coding_CDS_not_defined, 3 retained_intron

ENST00000354393, ENST00000358913, ENST00000373675, ENST00000540630, ENST00000613327, ENST00000685006, ENST00000685060, ENST00000685154, ENST00000685627, ENST00000686268, ENST00000686289, ENST00000687572, ENST00000687705, ENST00000688812, ENST00000689002, ENST00000689218, ENST00000689484, ENST00000689797, ENST00000690544, ENST00000692038, ENST00000692953, ENST00000692979, ENST00000693699

RefSeq mRNA: 3 — MANE Select: NM_032578 NM_001256267, NM_001256268, NM_032578

CCDS: CCDS7275

Canonical transcript exons

ENST00000358913 — 20 exons

Exon	Start	End
ENSE00000933624	68174066	68174656
ENSE00000933625	68175323	68175461
ENSE00000933626	68188905	68189126
ENSE00000933627	68194363	68194512
ENSE00000933628	68195450	68195532
ENSE00000933629	68197352	68197478
ENSE00000933630	68199368	68199575
ENSE00000933631	68201829	68201994
ENSE00000933632	68206770	68206903
ENSE00000986322	68121438	68122340
ENSE00000993822	68142940	68143115
ENSE00000993823	68145475	68145526
ENSE00000993824	68166294	68166666
ENSE00000993826	68150040	68150111
ENSE00000993828	68158486	68158627
ENSE00000993829	68148353	68148467
ENSE00001383703	68161729	68161752
ENSE00001384933	68165702	68165818
ENSE00001461213	68109488	68109723
ENSE00001461223	68210286	68212017

Expression profiles

Bgee: expression breadth ubiquitous, 116 present calls, max score 97.80.

FANTOM5 (CAGE): breadth broad, TPM avg 4.3965 / max 403.8288, expressed in 368 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
105219	1.6749	136
105218	0.9762	181
105217	0.6608	195
105215	0.3354	119
105220	0.3167	54
105222	0.1595	35
105214	0.1081	65
105216	0.0890	51
105221	0.0758	27

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
hindlimb stylopod muscle	UBERON:0004252	97.80	gold quality
gastrocnemius	UBERON:0001388	97.73	gold quality
vastus lateralis	UBERON:0001379	97.40	gold quality
quadriceps femoris	UBERON:0001377	97.28	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	96.85	gold quality
deltoid	UBERON:0001476	96.81	gold quality
skeletal muscle tissue	UBERON:0001134	96.71	gold quality
tibialis anterior	UBERON:0001385	96.37	gold quality
muscle of leg	UBERON:0001383	96.03	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	96.02	gold quality
biceps brachii	UBERON:0001507	95.58	gold quality
left ventricle myocardium	UBERON:0006566	93.77	gold quality
heart left ventricle	UBERON:0002084	92.85	gold quality
cardiac ventricle	UBERON:0002082	92.55	gold quality
apex of heart	UBERON:0002098	91.57	gold quality
myocardium	UBERON:0002349	91.46	gold quality
right atrium auricular region	UBERON:0006631	91.43	gold quality
muscle tissue	UBERON:0002385	91.03	gold quality
cardiac atrium	UBERON:0002081	90.84	gold quality
heart right ventricle	UBERON:0002080	90.03	gold quality
cardiac muscle of right atrium	UBERON:0003379	89.73	silver quality
heart	UBERON:0000948	86.47	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	75.17	gold quality
body of tongue	UBERON:0011876	72.57	gold quality
tongue	UBERON:0001723	69.47	gold quality
layer of synovial tissue	UBERON:0007616	68.50	silver quality
synovial joint	UBERON:0002217	68.28	gold quality
superficial temporal artery	UBERON:0001614	67.05	gold quality
sperm	CL:0000019	66.98	gold quality
oocyte	CL:0000023	66.33	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.17
E-MTAB-11268	no	883.60
E-GEOD-83139	no	3.23

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

58 targeting MYPN, 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-6740-5P	100.00	65.64	932
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-629-3P	99.85	67.99	1875
HSA-MIR-659-3P	99.85	70.69	1620
HSA-MIR-4713-5P	99.78	67.80	1794
HSA-MIR-498-5P	99.76	69.64	1807
HSA-MIR-4530	99.69	66.47	1509
HSA-MIR-6513-3P	99.59	69.77	1102
HSA-MIR-3616-5P	99.55	67.02	989
HSA-MIR-573	99.55	67.44	955
HSA-MIR-12117	99.50	67.57	868
HSA-MIR-330-3P	99.41	69.95	2521
HSA-MIR-377-3P	99.37	70.18	1905
HSA-MIR-1244	99.33	68.38	832
HSA-MIR-4263	99.18	69.25	2236
HSA-MIR-4504	99.10	69.14	1328
HSA-MIR-452-3P	99.01	66.25	1241
HSA-MIR-1257	98.97	68.02	1133
HSA-MIR-154-5P	98.92	66.65	733
HSA-MIR-3074-5P	98.82	66.56	1414
HSA-MIR-519A-2-5P	98.78	71.74	1401
HSA-MIR-520B-5P	98.78	71.74	1401
HSA-MIR-502-5P	98.77	66.51	906
HSA-MIR-500A-5P	98.76	69.13	1241
HSA-MIR-4742-3P	98.73	69.82	1803
HSA-MIR-548S	98.50	67.17	1213

Literature-anchored findings (GeneRIF, showing 10)

• myopalladin plays a signaling role in targeting and orienting nebulin during sarcomere assembly (PMID:12482578)
• myopalladin gene is a new gene associated with dilated cardiomyopathy and observed mutations in 3-4% of cases in a population. of European descent. (PMID:18006477)
• mutations in PDLIM3 and MYPN are infrequent in hypertrophic cardiomyopathies (PMID:20801532)
• Two nonsense and 13 missense MYPN variants were identified in subjects with hypertrophic, dilated and/or restrictive cardiomyopathy. (PMID:22286171)
• the clinical significance of myopalladin for the functional integrity of the sarcomeric apparatus and the protection against dilated cardiomyopathy (PMID:22892539)
• Heterozygote Mypn(WT/Q526X) knock-in mice develop RCM due to persistence of mutant Mypn(Q526X) protein in the nucleus. (PMID:25541130)
• results suggest that MYPN screening should be considered in individuals with mild nemaline myopathy, especially when cardiac problems or intranuclear rods are present (PMID:28017374)
• Homozygous truncating mutations in MYPN in 2 unrelated families with a slowly progressive congenital cap myopathy. (PMID:28220527)
• Targeted sequencing revealed trigenic mutations: c.700G>A/p.E234K in DES, c.2966G>A/p.R989H in MYPN, and c.5918G>C/p.R1973P in CACNA1C in a family of hypertrophic cardiomyopathy with early repolarization and short QT syndrome. (PMID:28427417)
• A consanguineous family with congenital to adult-onset muscle weakness and hanging big toe was reported. Muscle biopsy showed minimal changes with internal nuclei, type 1 fiber predominance, and ultrastructural defects of Z line. Cardiac involvement was demonstrated by magnetic resonance imaging and late gadolinium enhancement. (PMID:31133047)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio		ENSDARG00000109262
mus_musculus	Mypn	ENSMUSG00000020067
rattus_norvegicus	Mypn	ENSRNOG00000000383
drosophila_melanogaster	bt	FBGN0005666
caenorhabditis_elegans		WBGENE00001000
caenorhabditis_elegans		WBGENE00006759

Paralogs (9): SPEG (ENSG00000072195), MYOT (ENSG00000120729), PALLD (ENSG00000129116), ALPK3 (ENSG00000136383), HMCN1 (ENSG00000143341), OBSCN (ENSG00000154358), IGFN1 (ENSG00000163395), CCDC141 (ENSG00000163492), SPEGNB (ENSG00000286095)

Protein

Protein identifiers

Myopalladin — Q86TC9 (reviewed: Q86TC9)

Alternative names: 145 kDa sarcomeric protein

All UniProt accessions (14): A0A087WX60, A0A804CFL5, A0A8I5KRJ0, A0A8I5KSE3, A0A8I5KT31, A0A8I5KV65, A0A8I5KVD9, Q86TC9, A0A8I5KW69, A0A8I5KWT3, A0A8I5KX00, A0A8I5QKN9, A0A8I5QL13, A0A8J9ASZ5

UniProt curated annotations — full annotation on UniProt →

Function. Component of the sarcomere that tethers together nebulin (skeletal muscle) and nebulette (cardiac muscle) to alpha-actinin, at the Z lines.

Subunit / interactions. Interacts with TTN/titin, NEB, NEBL, ACTN2 and CARP.

Subcellular location. Cytoplasm. Nucleus. Myofibril. Sarcomere. Z line.

Tissue specificity. Expressed in adult skeletal muscle and fetal heart.

Disease relevance. Congenital myopathy 24 (CMYO24) [MIM:617336] An autosomal recessive muscular disorder characterized by slowly progressive muscle weakness and atrophy, mainly affecting the lower limbs and neck. Some patients may have mild cardiac or respiratory involvement, but they do not have respiratory failure. Muscle biopsy shows nemaline bodies. The disease is caused by variants affecting the gene represented in this entry. Cardiomyopathy, dilated, 1KK (CMD1KK) [MIM:615248] A disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death. The disease is caused by variants affecting the gene represented in this entry. Cardiomyopathy, familial hypertrophic, 22 (CMH22) [MIM:615248] A hereditary heart disorder characterized by ventricular hypertrophy, which is usually asymmetric and often involves the interventricular septum. The symptoms include dyspnea, syncope, collapse, palpitations, and chest pain. They can be readily provoked by exercise. The disorder has inter- and intrafamilial variability ranging from benign to malignant forms with high risk of cardiac failure and sudden cardiac death. The disease is caused by variants affecting the gene represented in this entry. Cardiomyopathy, familial restrictive 4 (RCM4) [MIM:615248] A heart disorder characterized by impaired filling of the ventricles with reduced diastolic volume, in the presence of normal or near normal wall thickness and systolic function. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the myotilin/palladin family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q86TC9-1	1	yes
Q86TC9-2	2

RefSeq proteins (3): NP_001243196, NP_001243197, NP_115967* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003598	Ig_sub2	Domain
IPR003599	Ig_sub	Domain
IPR007110	Ig-like_dom	Domain
IPR013098	Ig_I-set	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily

Pfam: PF07679

UniProt features (79 total): sequence variant 29, compositionally biased region 10, modified residue 10, region of interest 9, sequence conflict 9, domain 5, disulfide bond 3, splice variant 2, chain 1, coiled-coil region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86TC9-F1	52.71	0.07

Functional residue map

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

Post-translational modifications (10): 101, 131, 251, 644, 759, 813, 818, 867, 907, 928

Disulfide bonds (3): 290–341, 456–515, 1094–1146

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 338 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_DN, GOBP_NEURON_RECOGNITION, LFA1_Q6, GCANCTGNY_MYOD_Q6, GOBP_STRIATED_MUSCLE_CELL_DIFFERENTIATION, GOBP_NEUROGENESIS, chr10q21, GOBP_SARCOMERE_ORGANIZATION, CAGCTG_AP4_Q5, GOBP_CELL_CELL_ADHESION, GOBP_CELLULAR_COMPONENT_ASSEMBLY_INVOLVED_IN_MORPHOGENESIS, GOBP_MUSCLE_STRUCTURE_DEVELOPMENT, GOBP_ACTOMYOSIN_STRUCTURE_ORGANIZATION, GOBP_ORGANELLE_ASSEMBLY, LYF1_01

GO Biological Process (4): homophilic cell-cell adhesion (GO:0007156), axon guidance (GO:0007411), sarcomere organization (GO:0045214), dendrite self-avoidance (GO:0070593)

GO Molecular Function (6): actin binding (GO:0003779), cytoskeletal protein binding (GO:0008092), SH3 domain binding (GO:0017124), muscle alpha-actinin binding (GO:0051371), cell-cell adhesion mediator activity (GO:0098632), protein binding (GO:0005515)

GO Cellular Component (10): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytosol (GO:0005829), plasma membrane (GO:0005886), Z disc (GO:0030018), axon (GO:0030424), I band (GO:0031674), cytoplasm (GO:0005737), membrane (GO:0016020), sarcomere (GO:0030017)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	7
cell-cell adhesion	2
axonogenesis	1
neuron projection guidance	1
myofibril assembly	1
actomyosin structure organization	1
neuron recognition	1
cytoskeletal protein binding	1
protein binding	1
protein domain specific binding	1
alpha-actinin binding	1
cell adhesion mediator activity	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cytoplasm	1
membrane	1
cell periphery	1
I band	1
neuron projection	1
sarcomere	1
intracellular anatomical structure	1
myofibril	1

Protein interactions and networks

STRING

1586 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MYPN	NEB	P20929	979
MYPN	ANKRD1	Q15327	964
MYPN	NEBL	O76041	939
MYPN	ACTN2	P35609	902
MYPN	TMOD4	Q9NZQ9	810
MYPN	TMOD1	P28289	799
MYPN	CAPN3	P20807	799
MYPN	TCAP	O15273	798
MYPN	TMOD2	Q9NZR1	787
MYPN	CSRP3	P50461	767
MYPN	TMOD3	Q9NYL9	724
MYPN	MYOZ1	Q9NP98	720
MYPN	ANKRD23	Q86SG2	701
MYPN	ANKRD2	Q9GZV1	692
MYPN	TTN	Q8WZ42	677

IntAct

137 interactions, top by confidence:

A	B	Type	Score
YES1	MYPN	psi-mi:“MI:0407”(direct interaction)	0.440
MYPN	PDZK1	psi-mi:“MI:0407”(direct interaction)	0.440
MYPN	PDLIM1	psi-mi:“MI:0407”(direct interaction)	0.440
MYPN	LDB3	psi-mi:“MI:0407”(direct interaction)	0.440
MAST2	MYPN	psi-mi:“MI:0407”(direct interaction)	0.440
MYPN	NHERF4	psi-mi:“MI:0407”(direct interaction)	0.440
MYPN	SNX27	psi-mi:“MI:0407”(direct interaction)	0.440
MYPN	TAMALIN	psi-mi:“MI:0407”(direct interaction)	0.440
MYPN	PTPN3	psi-mi:“MI:0407”(direct interaction)	0.440
MYPN	GRIP2	psi-mi:“MI:0407”(direct interaction)	0.440
MAGI2	MYPN	psi-mi:“MI:0407”(direct interaction)	0.440
APBA3	MYPN	psi-mi:“MI:0407”(direct interaction)	0.440
MYPN	MAST1	psi-mi:“MI:0407”(direct interaction)	0.440
MYPN	PICK1	psi-mi:“MI:0407”(direct interaction)	0.440
MYPN	MPP2	psi-mi:“MI:0407”(direct interaction)	0.440
MYPN	HTRA4	psi-mi:“MI:0407”(direct interaction)	0.440
MYPN	PCLO	psi-mi:“MI:0407”(direct interaction)	0.440
MYPN	RAPGEF6	psi-mi:“MI:0407”(direct interaction)	0.440
MYPN	DLG3	psi-mi:“MI:0407”(direct interaction)	0.440
MYPN	TIAM2	psi-mi:“MI:0407”(direct interaction)	0.440
MYPN	PALS2	psi-mi:“MI:0407”(direct interaction)	0.440
MYPN	MAGI3	psi-mi:“MI:0407”(direct interaction)	0.440
MYPN	IL16	psi-mi:“MI:0407”(direct interaction)	0.440
DLG1	MYPN	psi-mi:“MI:0407”(direct interaction)	0.440
MYPN	SNTB1	psi-mi:“MI:0407”(direct interaction)	0.440
MYPN	PATJ	psi-mi:“MI:0407”(direct interaction)	0.440
MYPN	GRIP1	psi-mi:“MI:0407”(direct interaction)	0.440
MPDZ	MYPN	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (41): MYPN (Two-hybrid), ACTN2 (Two-hybrid), MTA2 (Co-fractionation), MYPN (Affinity Capture-MS), MYPN (Affinity Capture-MS), MYPN (Affinity Capture-MS), MYPN (Affinity Capture-MS), MYPN (Affinity Capture-MS), MYPN (Affinity Capture-MS), ACTN3 (Two-hybrid), MYPN (Affinity Capture-RNA), MYPN (Two-hybrid), TTN (Two-hybrid), ANKRD1 (Two-hybrid), ANKRD23 (Two-hybrid)

ESM2 similar proteins: A0A1L8H8C0, A0A1L8HFX9, A0A2K1J5A5, A0A2R6X6S3, A0JM08, A2RUV4, B1AZP2, F1QIC4, O14490, O61366, P46012, P46582, P70047, P83510, P97836, P97839, Q01538, Q08D57, Q09314, Q09599, Q0KIC3, Q18221, Q1LY77, Q498L0, Q501J7, Q52KW0, Q5F3P8, Q5RAU1, Q5SW79, Q5TZ18, Q5XHF3, Q66J90, Q69Z38, Q6A065, Q6DFG0, Q6PEI3, Q71M21, Q80TN7, Q86TC9, Q8CFC2

Diamond homologs: A2ASS6, A2CG49, A4IFM7, A8C984, A8X6H4, E9PT87, F1M0Z1, O02827, O14936, O43293, O44997, O49717, O54784, O60229, O70589, O75962, O80673, O88764, O94768, P07313, P08414, P0C5E3, P11801, P13234, P20689, P25323, P53355, P53681, P53684, P70402, P93759, P97924, Q05623, Q06850, Q0KL02, Q0V7M1, Q10KY3, Q13203, Q14012, Q16566

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 98 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
Ras activation upon Ca2+ influx through NMDA receptor	5	46.0×	4e-06
Unblocking of NMDA receptors, glutamate binding and activation	5	43.9×	4e-06
Negative regulation of NMDA receptor-mediated neuronal transmission	5	43.9×	4e-06
Assembly and cell surface presentation of NMDA receptors	10	40.9×	4e-12
Dopamine Neurotransmitter Release Cycle	5	40.0×	6e-06
Long-term potentiation	5	38.4×	6e-06
Neurexins and neuroligins	11	34.9×	3e-12
Protein-protein interactions at synapses	7	30.0×	3e-07

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	11	71.8×	9e-16
protein localization to synapse	6	51.6×	2e-07
receptor clustering	7	49.1×	2e-08
regulation of postsynaptic membrane neurotransmitter receptor levels	7	39.0×	9e-08
protein-containing complex assembly	9	11.5×	6e-06
cell-cell adhesion	10	11.4×	2e-06
actin cytoskeleton organization	7	6.2×	4e-03
chemical synaptic transmission	7	6.1×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

1943 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	48
Likely pathogenic	26
Uncertain significance	952
Likely benign	643
Benign	130

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1070620	NC_000010.10:g.(?69918233)(69926433_?)del	Pathogenic
1354074	NM_032578.4(MYPN):c.1722del (p.Lys575fs)	Pathogenic
1362406	NM_032578.4(MYPN):c.3403_3404del (p.Pro1135fs)	Pathogenic
1374949	NM_032578.4(MYPN):c.1910dup (p.Thr639fs)	Pathogenic
1448371	NM_032578.4(MYPN):c.1990C>T (p.Gln664Ter)	Pathogenic
1455552	NM_032578.4(MYPN):c.2689A>T (p.Arg897Ter)	Pathogenic
1526172	NM_032578.4(MYPN):c.608C>A (p.Ser203Ter)	Pathogenic
1771933	NM_032578.4(MYPN):c.1407T>A (p.Tyr469Ter)	Pathogenic
1795014	NM_032578.4(MYPN):c.2709C>G (p.Tyr903Ter)	Pathogenic
1941324	NM_032578.4(MYPN):c.211G>T (p.Glu71Ter)	Pathogenic
2025137	NM_032578.4(MYPN):c.781_784del (p.Tyr261fs)	Pathogenic
2112550	NM_032578.4(MYPN):c.3409dup (p.Thr1137fs)	Pathogenic
2177807	NM_032578.4(MYPN):c.1465C>T (p.Arg489Ter)	Pathogenic
2427044	NC_000010.10:g.(?69961566)(69961771_?)del	Pathogenic
2563969	NM_032578.4(MYPN):c.1105dup (p.Asp369fs)	Pathogenic
2563975	NM_032578.4(MYPN):c.1511del (p.Glu504fs)	Pathogenic
2574646	NM_032578.4(MYPN):c.1973+1G>C	Pathogenic
2574647	NM_032578.4(MYPN):c.1974-2A>C	Pathogenic
2723595	NM_032578.4(MYPN):c.2084del (p.Val694_Leu695insTer)	Pathogenic
2756706	NM_032578.4(MYPN):c.1714del (p.Gln572fs)	Pathogenic
2760763	NM_032578.4(MYPN):c.3327_3328del (p.Asn1109fs)	Pathogenic
2809474	NM_032578.4(MYPN):c.3244_3245dup (p.Met1082fs)	Pathogenic
2985336	NM_032578.4(MYPN):c.1204C>T (p.Gln402Ter)	Pathogenic
3030334	NM_032578.4(MYPN):c.444dup (p.Val149fs)	Pathogenic
31816	NM_032578.4(MYPN):c.1585C>T (p.Gln529Ter)	Pathogenic
3228160	NM_032578.4(MYPN):c.2445del (p.Pro816fs)	Pathogenic
3233263	NM_032578.4(MYPN):c.3158+1G>A	Pathogenic
3298139	NM_032578.4(MYPN):c.2779G>T (p.Glu927Ter)	Pathogenic
3626813	NM_032578.4(MYPN):c.2470C>T (p.Gln824Ter)	Pathogenic
3650465	NM_032578.4(MYPN):c.3242_3261del (p.Asp1081fs)	Pathogenic

SpliceAI

3775 predictions. Top by Δscore:

Variant	Effect	Δscore
10:68142937:CA:C	acceptor_loss	1.0000
10:68142938:A:AC	acceptor_loss	1.0000
10:68142938:A:AG	acceptor_gain	1.0000
10:68142938:AG:A	acceptor_gain	1.0000
10:68142938:AGGT:A	acceptor_gain	1.0000
10:68142938:AGGTG:A	acceptor_gain	1.0000
10:68142939:G:GT	acceptor_gain	1.0000
10:68142939:GG:G	acceptor_gain	1.0000
10:68142939:GGT:G	acceptor_gain	1.0000
10:68142939:GGTG:G	acceptor_gain	1.0000
10:68142939:GGTGG:G	acceptor_gain	1.0000
10:68143047:G:GT	donor_gain	1.0000
10:68143116:G:GC	donor_loss	1.0000
10:68145465:A:AG	acceptor_gain	1.0000
10:68145466:T:G	acceptor_gain	1.0000
10:68145471:CCAGG:C	acceptor_loss	1.0000
10:68145472:CAGGG:C	acceptor_loss	1.0000
10:68145473:A:AG	acceptor_gain	1.0000
10:68145473:AG:A	acceptor_gain	1.0000
10:68145473:AGG:A	acceptor_gain	1.0000
10:68145474:G:GT	acceptor_gain	1.0000
10:68145474:GG:G	acceptor_gain	1.0000
10:68145474:GGG:G	acceptor_gain	1.0000
10:68145513:G:GT	donor_gain	1.0000
10:68145525:CGGTA:C	donor_loss	1.0000
10:68145526:GGTA:G	donor_loss	1.0000
10:68145527:G:GA	donor_loss	1.0000
10:68145527:G:GG	donor_gain	1.0000
10:68145528:T:A	donor_loss	1.0000
10:68158623:GAAAA:G	donor_gain	1.0000

AlphaMissense

8649 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:68142941:T:A	W302R	1.000
10:68142941:T:C	W302R	1.000
10:68143014:T:C	L326P	1.000
10:68158570:T:A	W468R	1.000
10:68158570:T:C	W468R	1.000
10:68122250:T:C	F271S	0.999
10:68122308:C:G	C290W	0.999
10:68142942:G:C	W302S	0.999
10:68142943:G:C	W302C	0.999
10:68142943:G:T	W302C	0.999
10:68143052:T:G	Y339D	0.999
10:68143060:C:G	C341W	0.999
10:68143065:C:A	A343D	0.999
10:68143072:C:A	N345K	0.999
10:68143072:C:G	N345K	0.999
10:68150104:T:C	F437S	0.999
10:68158571:G:C	W468S	0.999
10:68158572:G:C	W468C	0.999
10:68158572:G:T	W468C	0.999
10:68165717:T:C	L500S	0.999
10:68165756:T:C	F513S	0.999
10:68165763:T:G	C515W	0.999
10:68165775:C:A	N519K	0.999
10:68165775:C:G	N519K	0.999
10:68194369:T:A	W978R	0.999
10:68194369:T:C	W978R	0.999
10:68194448:T:C	L1004P	0.999
10:68199398:T:A	W1106R	0.999
10:68199398:T:C	W1106R	0.999
10:68199474:T:C	L1131P	0.999

dbSNP variants (sampled 300 via entrez): RS1000000080 (10:68199959 T>C), RS1000019646 (10:68115996 C>G), RS1000065832 (10:68184002 A>G,T), RS1000198722 (10:68208029 C>G,T), RS1000208230 (10:68159440 A>G,T), RS1000210813 (10:68105498 AT>A), RS1000211706 (10:68202103 G>A), RS1000255340 (10:68108969 C>G,T), RS1000278256 (10:68200262 C>T), RS1000304649 (10:68187819 C>A,G,T), RS1000312149 (10:68130825 A>G), RS1000345790 (10:68124216 A>G), RS1000348974 (10:68171659 T>C), RS1000382045 (10:68131108 G>C), RS1000385373 (10:68103092 CA>C)

Disease associations

OMIM: gene MIM:608517 | disease phenotypes: MIM:615248, MIM:617336, MIM:117000, MIM:192600, MIM:115210, MIM:115200, MIM:256030, MIM:115195, MIM:604169

GenCC curated gene-disease

Disease	Classification	Inheritance
MYPN-related myopathy	Definitive	Autosomal recessive
hypertrophic cardiomyopathy	Strong	Autosomal dominant
dilated cardiomyopathy	Strong	Autosomal dominant
familial isolated dilated cardiomyopathy	Supportive	Autosomal dominant
childhood-onset nemaline myopathy	Supportive	Autosomal dominant
cap myopathy	Supportive	Autosomal dominant
familial isolated restrictive cardiomyopathy	Supportive	Autosomal dominant
dilated cardiomyopathy 1KK	Limited	Autosomal dominant

ClinGen Gene-Disease Validity (3)

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

Disease	Classification	Inheritance
MYPN-related myopathy	Definitive	AR
hypertrophic cardiomyopathy	Disputed	AD
dilated cardiomyopathy 1KK	Limited	AD

Mondo (22): dilated cardiomyopathy 1KK (MONDO:0014100), MYPN-related myopathy (MONDO:0015023), hypertrophic cardiomyopathy (MONDO:0005045), congenital myopathy (MONDO:0019952), familial hypertrophic cardiomyopathy (MONDO:0024573), hypertrophic cardiomyopathy 1 (MONDO:0008647), dilated cardiomyopathy (MONDO:0005021), cardiomyopathy (MONDO:0004994), cardiomyopathy, familial restrictive, 1 (MONDO:0007270), dilated cardiomyopathy 1A (MONDO:0007269), cap myopathy (MONDO:0015753), heart failure (MONDO:0005252), familial dilated cardiomyopathy (MONDO:0016333), nemaline myopathy (MONDO:0018958), hypertrophic cardiomyopathy 2 (MONDO:0007266)

Orphanet (15): Familial isolated dilated cardiomyopathy (Orphanet:154), Familial isolated restrictive cardiomyopathy (Orphanet:75249), Rare hypertrophic cardiomyopathy (Orphanet:217569), Congenital myopathy (Orphanet:97245), Rare familial disorder with hypertrophic cardiomyopathy (Orphanet:99739), Dilated cardiomyopathy (Orphanet:217604), Rare cardiomyopathy (Orphanet:167848), Familial dilated cardiomyopathy with conduction defect due to LMNA mutation (Orphanet:300751), Cap myopathy (Orphanet:171881), Familial dilated cardiomyopathy (Orphanet:217607), Nemaline myopathy (Orphanet:607), Restrictive cardiomyopathy (Orphanet:217632), Left ventricular noncompaction (Orphanet:54260), Inherited arrhythmogenic cardiomyopathy (Orphanet:247), NON RARE IN EUROPE: Familial isolated hypertrophic cardiomyopathy (Orphanet:155)

HPO phenotypes

117 total (30 of 117 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000218	High palate
HP:0000275	Narrow face
HP:0000276	Long face
HP:0000316	Hypertelorism
HP:0000347	Micrognathia
HP:0000407	Sensorineural hearing impairment
HP:0000467	Neck muscle weakness
HP:0000508	Ptosis
HP:0000767	Pectus excavatum
HP:0000774	Narrow chest
HP:0000969	Edema
HP:0001265	Hyporeflexia
HP:0001270	Motor delay
HP:0001279	Syncope
HP:0001284	Areflexia
HP:0001288	Gait disturbance
HP:0001290	Generalized hypotonia
HP:0001297	Stroke
HP:0001315	Reduced tendon reflexes
HP:0001324	Muscle weakness
HP:0001349	Facial diplegia
HP:0001371	Flexion contracture
HP:0001533	Slender build
HP:0001561	Polyhydramnios
HP:0001611	Hypernasal speech
HP:0001623	Breech presentation
HP:0001634	Mitral valve prolapse
HP:0001635	Congestive heart failure

GWAS associations

25 associations (top):

Study	Trait	p-value
GCST000657_2	Optic nerve measurement (disc area)	2.000000e-07
GCST002647_36	Height	4.000000e-13
GCST004184_8	Lung function (FVC)	9.000000e-15
GCST005984_50	Glomerular filtration rate	3.000000e-16
GCST005985_29	Creatinine levels	1.000000e-16
GCST006014_16	Creatine kinase levels	4.000000e-18
GCST006414_136	Atrial fibrillation	5.000000e-08
GCST007344_56	Estimated glomerular filtration rate	9.000000e-19
GCST007429_140	Lung function (FVC)	2.000000e-21
GCST007430_116	Peak expiratory flow	4.000000e-07
GCST007432_187	FEV1	4.000000e-20
GCST007876_92	Estimated glomerular filtration rate	7.000000e-19
GCST008058_178	Estimated glomerular filtration rate	7.000000e-32
GCST008059_71	Estimated glomerular filtration rate	3.000000e-22
GCST008060_39	Estimated glomerular filtration rate	6.000000e-11
GCST008064_14	Chronic kidney disease	7.000000e-06
GCST008479_26	Psoriasis	9.000000e-07
GCST008526_60	Coffee consumption	3.000000e-08
GCST008745_75	Estimated glomerular filtration rate in non-diabetics	4.000000e-09
GCST008747_184	Estimated glomerular filtration rate	7.000000e-15
GCST008747_69	Estimated glomerular filtration rate	5.000000e-13
GCST90000025_436	Appendicular lean mass	4.000000e-21
GCST90000026_35	Appendicular lean mass	4.000000e-14
GCST90000027_15	Appendicular lean mass	4.000000e-09
GCST90020028_47	Hip circumference adjusted for BMI	4.000000e-08

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0004312	vital capacity
EFO:0004534	creatine kinase measurement
EFO:0009718	peak expiratory flow
EFO:0004314	forced expiratory volume
EFO:0006781	coffee consumption measurement
EFO:0004980	appendicular lean mass
EFO:0008039	BMI-adjusted hip circumference

MeSH disease descriptors (13)

Descriptor	Name	Tree numbers
D019571	Arrhythmogenic Right Ventricular Dysplasia	C14.240.400.145; C14.280.238.028; C14.280.400.145; C16.131.240.400.145
D009202	Cardiomyopathies	C14.280.238
D002311	Cardiomyopathy, Dilated	C14.280.195.160; C14.280.238.070; C16.320.488.750
D002312	Cardiomyopathy, Hypertrophic	C14.280.238.100; C14.280.484.048.750.070.160
D024741	Cardiomyopathy, Hypertrophic, Familial	C14.280.238.100.500; C14.280.484.048.750.070.160.500; C16.320.160
D002313	Cardiomyopathy, Restrictive	C14.280.238.160
D006333	Heart Failure	C14.280.434
D008133	Long QT Syndrome	C14.280.067.565; C14.280.123.625; C16.131.240.400.715; C23.550.073.547
D017696	Myopathies, Nemaline	C05.651.575.290; C10.668.491.550.290
C579969	Cap Myopathy (supp.)
C566171	Cardiomyopathy, Familial Hypertrophic, 2 (supp.)
C566168	Cardiomyopathy, Familial Restrictive, 1 (supp.)
C536231	familial dilated cardiomyopathy (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases methylation, affects cotreatment, decreases expression	3
sodium arsenite	increases abundance, increases expression, decreases expression	3
aristolochic acid I	increases expression	1
bisphenol F	affects cotreatment, decreases expression	1
propionaldehyde	increases expression	1
dimethylselenide	increases expression, increases oxidation	1
sulforaphane	decreases expression	1
manganese chloride	increases abundance, increases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
nickel sulfate	increases expression	1
coumarin	decreases phosphorylation	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
ICG 001	decreases expression	1
abrine	increases expression	1
bisphenol S	affects cotreatment, decreases expression	1
jinfukang	affects cotreatment, decreases expression	1
incobotulinumtoxinA	decreases expression	1
(+)-JQ1 compound	decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Dasatinib	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Sunitinib	decreases expression	1
Arsenic	increases abundance, increases expression	1
Benzo(a)pyrene	decreases expression	1
Cisplatin	decreases expression, affects cotreatment	1
Copper	affects cotreatment, decreases expression	1
Dexamethasone	decreases expression, affects cotreatment	1
Doxorubicin	decreases expression	1
Indomethacin	affects cotreatment, decreases expression	1
Manganese	increases abundance, increases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1Y3	Abcam HeLa MYPN KO	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00879060	PHASE4	COMPLETED	Clinical and Therapeutic Implications of Fibrosis in Hypertrophic Cardiomyopathy
NCT01721967	PHASE4	COMPLETED	Ranolazine for the Treatment of Chest Pain in HCM Patients
NCT02948998	PHASE4	UNKNOWN	Evaluating the Effect of Spironolactone on Hypertrophic Cardiomyopathy
NCT03249272	PHASE4	TERMINATED	Microvascular Dysfunction in Nonischemic Cardiomyopathy: Insights From CMR Assessment of Coronary Flow Reserve
NCT04133532	PHASE4	COMPLETED	Effect of Metoprolol in Post Alcohol Septal Ablation Patients With Hypertrophic Cardiomyopathy
NCT06401343	PHASE4	RECRUITING	Use of SGLT2i in noHCM With HFpEF
NCT07103655	PHASE4	NOT_YET_RECRUITING	The Therapeutic Value of Mavacamten in Hypertrophic Cardiomyopathy With Mid-to-Apical Left Ventricular Obstruction
NCT07600177	PHASE4	RECRUITING	Mavacamten to Aficamten Transition in Patients With Obstructive Hypertrophic Cardiomyopathy
NCT00374465	PHASE4	UNKNOWN	Therapy With Verapamil or Carvedilol in Chronic Heart Failure
NCT01293903	PHASE4	COMPLETED	Study of Qiliqiangxin Capsule to Treat Dilated Cardiomyopathy
NCT01557140	PHASE4	COMPLETED	A Randomized Trial of Carvedilol in Chronic Chagas Cardiomyopathy
NCT01917149	PHASE4	COMPLETED	Supramaximal Titrated Inhibition of RAAS in Dilated Cardiomyopathy
NCT02115581	PHASE4	COMPLETED	Coenzyme Q10 Supplementation in Children With Idiopathic Dilated Cardiomyopathy
NCT06236022	PHASE4	RECRUITING	The Effects of Sirolimus in Patients With Dilated Cardiomyopathy Infected With Kaposi Sarcoma-associated Virus
NCT00317967	PHASE3	COMPLETED	Study to Determine if Atorvastatin Reduces Size and Stiffness of Muscle in the Left Ventricle of the Heart
NCT00698074	PHASE3	UNKNOWN	Diastolic Ventricular Interaction and the Effects of Biventricular Pacing in Hypertrophic Cardiomyopathy
NCT00821353	PHASE3	COMPLETED	Antiarrhythmic Therapy Versus Catheter Ablation for Atrial Fibrillation in Hypertrophic Cardiomyopathy
NCT02431221	PHASE3	WITHDRAWN	Efficacy, Safety, and Tolerability of Perhexiline in Subjects With Hypertrophic Cardiomyopathy and Heart Failure
NCT03470545	PHASE3	COMPLETED	Clinical Study to Evaluate Mavacamten (MYK-461) in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy
NCT05174416	PHASE3	COMPLETED	A Study to Evaluate the Efficacy and Safety of Mavacamten in Chinese Adults With Symptomatic Obstructive HCM
NCT05182658	PHASE3	ACTIVE_NOT_RECRUITING	Empagliflozin in Hypertrophic Cardiomyopathy
NCT05186818	PHASE3	COMPLETED	Phase 3 Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Placebo in Adults With Symptomatic oHCM
NCT05767346	PHASE3	COMPLETED	Phase 3 Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Metoprolol Succinate in Adults With Symptomatic oHCM
NCT06116968	PHASE3	COMPLETED	An Open-Label Study of Aficamten for Chinese Patients With Symptomatic oHCM
NCT06873828	PHASE3	NOT_YET_RECRUITING	Evaluation of the Efficacy and Safety of Wearable ECG (AT-Patch) in Patients With Hypertrophic Cardiomyopathy Requiring 48-Hour Holter MonitoringEvaluation of the Efficacy and Safety of Wearable ECG (AT-Patch) in Patients With Hypertrophic Cardiomyopathy Requiring 48-Hour Holter Monitoring
NCT07021976	PHASE3	RECRUITING	A Phase III Trial of HRS-1893 in Patients With Obstructive Hypertrophic Cardiomyopathy
NCT07023341	PHASE3	ACTIVE_NOT_RECRUITING	A Study to Learn More About How Well Aficamten Works in Japanese Participants With Symptomatic Obstructive Hypertrophic Cardiomyopathy
NCT07202897	PHASE3	NOT_YET_RECRUITING	LA-HCM Study : Rivaroxaban for Antithrombotic Prevention in Hypertrophic Cardiomyopathy Patients With Abnormal Left Atrial Strain.
NCT00333827	PHASE3	COMPLETED	Cell Therapy In Dilated Cardiomyopathy
NCT00505154	PHASE3	COMPLETED	Effect of Rosuvastatin on Left Ventricular Remodeling
NCT01223703	PHASE3	COMPLETED	PUFAs and Left Ventricular Function in Heart Failure
NCT01583114	PHASE3	TERMINATED	PREclinical Mutation CARriers From Families With DIlated Cardiomyopathy and ACE Inhibitors
NCT01914081	PHASE3	UNKNOWN	Resveratrol: A Potential Anti- Remodeling Agent in Heart Failure, From Bench to Bedside
NCT02989181	PHASE3	UNKNOWN	Continues Positive Airway Pressure Treatment for Patients With Dilated Cardiomyopathy and Obstructive Sleep Apnea
NCT03439514	PHASE3	TERMINATED	A Study of ARRY-371797 (PF-07265803) in Patients With Symptomatic Dilated Cardiomyopathy Due to a Lamin A/C Gene Mutation
NCT05237323	PHASE3	COMPLETED	Micophenolate Mofetil Versus Azathioprine in Myocarditis
NCT05849766	PHASE3	COMPLETED	Effect of Dapagliflozin on Cardiac Structure, Function and Secondary Mitral Regurgitation in Patients with Left Ventricle Dysfunction
NCT06250257	PHASE3	RECRUITING	Bromocriptine in Dilated Cardiomyopathy Among Women of Reproductive Age
NCT00001631	PHASE2	COMPLETED	Study of Blood Flow in Heart Muscle
NCT00001894	PHASE2	COMPLETED	A Comparison of Two Treatments: Pacemaker and Percutaneous Transluminal Septal Ablation for Hypertrophic Cardiomyopathy