MYBPC2

protein-coding

myosin binding protein C2, the group of I-set domain containing|Myosin binding proteins

Gene summary

This gene encodes a member of the myosin-binding protein C family. This family includes the fast-, slow- and cardiac-type isoforms, each of which is a myosin-associated protein found in the cross-bridge-bearing zone (C region) of A bands in striated muscle. The protein encoded by this locus is referred to as the fast-type isoform. Mutations in the related but distinct genes encoding the slow-type and cardiac-type isoforms have been associated with distal arthrogryposis, type 1 and hypertrophic cardiomyopathy, respectively. [provided by RefSeq, Jul 2012]

MANE transcript

NM_004533.4

Inheritance

—

ClinVar variants

U:229B:23

Top phenotype

MYBPC2-related disorder

gnomAD constraint

pLI —, LoF o/e 0.75

Max pathogenic AF

—

Genomic locus

chr19:50,432,892-50,466,321

External References & Databases

Ensembl (ENSG00000086967)

Transcript & Mutation Effects

hg38 • Region Span ~33.4 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to MYBPC2 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 223

not providedTotal: 14

MYBPC2-related disorderTotal: 8

Flexion contractureTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004533.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	9 clinvar		11
missense			220 clinvar	11 clinvar		231
nonsense			1 clinvar			1
start loss						0
frameshift			2 clinvar	2 clinvar		4
splice donor/acceptor (+/-2bp)			4 clinvar	1 clinvar		5
Total	0	0	229	23	0	252

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 31 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_004533.4	RefSeq	NP_004524.3	28	MANE Select
ENST00000357701.6	Ensembl	ENSP00000350332.4	28	MANE Select
ENST00000966351.1	Ensembl	ENSP00000636410.1	26	Standard
ENST00000966351.2	Ensembl	ENSP00000636410.1	26	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
mybpc2b	Danio rerio	Structure: skeletal muscle cell Quality: decondensed abnormal

Gene / Model

Organism

Observed Phenotype

mybpc2b

Danio rerio

Structure: skeletal muscle cell

Quality: decondensed

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Striated Muscle Contraction
Striated Muscle Contraction
Muscle contraction

Biological Process

muscle contraction
cell adhesion
muscle filament sliding
skeletal muscle thin filament assembly
skeletal muscle myosin thick filament assembly

Molecular Function

protein binding
structural constituent of muscle
actin filament binding
muscle alpha-actinin binding

Cellular Component

cytosol
striated muscle thin filament
sarcomere
Z disc
M band

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000357701
Coding exons: 28
Length: 33419
Individuals with no LoFs: 124030
Homozygous LoFs: 2
Heterozygous LoFs: 636
Defined: 124668
p: 0.00256

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.674	672	723	0.929	0.0000472	7376
Missense (PolyPhen)		253	274.15	0.92285		2781
Synonymous	-0.913	323	303	1.07	0.0000221	2183
Loss of Function	1.77	43	57.5	0.748	0.00000281	693

Population LoF Frequency

Population	CAF	p-value	Status
African	0.023	0.022	notable
Latino/Admixed American	0.0017	0.0016	notable
Ashkenazi Jewish	0.0021	0.0021	notable
East Asian	0.0011	0.0011	notable
Finnish	0.00028	0.00028	rare
European (Non-Finnish)	0.00080	0.00079	rare
South Asian	0.0030	0.0029	notable
Other	0.0025	0.0025	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Thick filament-associated protein located in the crossbridge region of vertebrate striated muscle a bands. In vitro it binds MHC, F-actin and native thin filaments, and modifies the activity of actin-activated myosin ATPase. It may modulate muscle contraction or may play a more structural role.;

Intolerance Scores

LoFtool: 0.970
RVIS EVS: 2.37
RVIS percentile EVS: 98.45

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.211

Gene Damage Prediction

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