MYPN

myopalladin, the group of I-set domain containing

Basic information

Region (hg38): 10:68087897-68212017

Links

ENSG00000138347 ∙ NCBI:84665 ∙ OMIM:608517 ∙ HGNC:23246 ∙ Uniprot:Q86TC9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Transcripts

Transcript IDs starting with ENST are treated as Ensembl, all others as RefSeq. Showing 4 of 27.

Transcript ID	Protein ID	Coding exons	MANE Select	MANE Plus Clinical
NM_032578.4	NP_115967.2	19	yes	-
ENST00000358913.10	ENSP00000351790.5	19	yes	-
NM_001256267.2	NP_001243196.1	19	-	-
NM_001256268.2	NP_001243197.1	19	-	-

Phenotypes

GenCC

Source: genCC

• hypertrophic cardiomyopathy (Disputed Evidence), mode of inheritance: AD
• dilated cardiomyopathy (Limited), mode of inheritance: AD
• MYPN-related myopathy (Definitive), mode of inheritance: AR
• dilated cardiomyopathy 1KK (Limited), mode of inheritance: AD
• MYPN-related myopathy (Strong), mode of inheritance: AR
• familial isolated dilated cardiomyopathy (Supportive), mode of inheritance: AD
• familial isolated restrictive cardiomyopathy (Supportive), mode of inheritance: AD
• childhood-onset nemaline myopathy (Supportive), mode of inheritance: AD
• cap myopathy (Supportive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cardiomyopathy, dilated, 1KK; Cardiomyopathy, familial hypertrophic, 22; Cardiomyopathy, dilated, 1KK	AD	Cardiovascular	Surveillance (eg, including echocardiogram and electrocardiogram) and preventive measures related to cardiac manifestations may allow early diagnosis and management, which may reduce morbidity and mortality	Cardiovascular; Neurologic	18006477; 22286171; 22892539; 28017374

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MYPN gene.

• Dilated_cardiomyopathy_1KK (1194 variants)
• Cardiovascular_phenotype (980 variants)
• not_provided (446 variants)
• not_specified (169 variants)
• MYPN-related_myopathy (138 variants)
• MYPN-related_disorder (55 variants)
• Primary_dilated_cardiomyopathy (15 variants)
• Primary_familial_hypertrophic_cardiomyopathy (10 variants)
• Hypertrophic_cardiomyopathy (10 variants)
• Cardiomyopathy (8 variants)
• Primary_familial_dilated_cardiomyopathy (4 variants)
• Dilated_cardiomyopathy_1A (3 variants)
• Restrictive_cardiomyopathy (2 variants)
• Left_ventricular_noncompaction_cardiomyopathy (2 variants)
• Familial_hypertrophic_cardiomyopathy_22 (2 variants)
• See_cases (2 variants)
• Sudden_unexplained_death (1 variants)
• Long_QT_syndrome (1 variants)
• Left_ventricular_hypertrophy (1 variants)
• Nemaline_myopathy (1 variants)
• Left_ventricular_noncompaction_1 (1 variants)
• Hypertrophic_cardiomyopathy_1 (1 variants)
• Cardiomyopathy,_familial_restrictive,_4 (1 variants)
• Hypertrophic_cardiomyopathy_2 (1 variants)
• Cap_myopathy (1 variants)
• Cardiomyopathy,_familial_restrictive,_1 (1 variants)
• Arrhythmogenic_right_ventricular_cardiomyopathy (1 variants)
• Heart_failure (1 variants)
• Congenital_myopathy (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MYPN gene is commonly pathogenic or not. These statistics are base on transcript: NM_032578.4. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			8	476	3	487
missense		3	915	81	4	1003
nonsense	17	12	3			32
start loss			1			1
frameshift	27	13	6			46
splice donor/acceptor (+/-2bp)	4	12	5			21
Total	48	40	938	557	7

Highest pathogenic variant AF is 0.000016727381

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MYPN	protein_coding	protein_coding	ENST00000358913	19	105863

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
		125696	0	52	125748	0.000207

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.129	716	726	0.986	0.0000422	8620
Missense in Polyphen		261	284.24	0.91823		3471
Synonymous	-0.804	292	275	1.06	0.0000170	2669
Loss of Function	4.65	21	59.8	0.351	0.00000347	677

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000322	0.000322
Ashkenazi Jewish	0.00	0.00
East Asian	0.000489	0.000489
Finnish	0.000139	0.000139
European (Non-Finnish)	0.000229	0.000229
Middle Eastern	0.000489	0.000489
South Asian	0.0000653	0.0000653
Other	0.000326	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Component of the sarcomere that tethers together nebulin (skeletal muscle) and nebulette (cardiac muscle) to alpha-actinin, at the Z lines. {ECO:0000269|PubMed:11309420}.
• Disease: DISEASE: 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. {ECO:0000269|PubMed:18006477, ECO:0000269|PubMed:22286171, ECO:0000269|PubMed:22892539}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: 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. {ECO:0000269|PubMed:22286171}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: 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. {ECO:0000269|PubMed:22286171}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Integrin-mediated Cell Adhesion (Consensus)

Recessive Scores

• pRec: 0.111

Intolerance Scores

• loftool: 0.578
• rvis_EVS: 0.81
• rvis_percentile_EVS: 87.76

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.559

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High

Gene ontology

• Biological process: homophilic cell adhesion via plasma membrane adhesion molecules;axon guidance;sarcomere organization;dendrite self-avoidance
• Cellular component: nucleus;plasma membrane;Z disc;axon;I band
• Molecular function: actin binding;protein binding;cytoskeletal protein binding;SH3 domain binding;muscle alpha-actinin binding;cell-cell adhesion mediator activity