MYBPC1

myosin binding protein C1, the group of I-set domain containing|Myosin binding proteins

Basic information

Region (hg38): 12:101568353-101686028

Links

ENSG00000196091

∙ NCBI:4604 ∙ OMIM:160794 ∙ HGNC:7549 ∙ Uniprot:Q00872 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

lethal congenital contracture syndrome 4 (Strong), mode of inheritance: AR
myopathy, congenital, with tremor (Moderate), mode of inheritance: AD
digitotalar dysmorphism (Supportive), mode of inheritance: AD
lethal congenital contracture syndrome 3 (Supportive), mode of inheritance: AR
lethal congenital contracture syndrome 4 (Strong), mode of inheritance: AR
arthrogryposis, distal, type 1B (Strong), mode of inheritance: AD
myopathy, congenital, with tremor (Strong), mode of inheritance: AD
lethal congenital contracture syndrome 4 (Limited), mode of inheritance: AR
arthrogryposis, distal, type 1B (Moderate), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Arthrogryposis, distal, type 1B; Congenital myopathy 16; Lethal congenital contractural syndrome 4	AD/AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Musculoskeletal	20045868; 22610851; 31025394; 31264822

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MYBPC1 gene.

not_provided (172 variants)
Inborn_genetic_diseases (120 variants)
Arthrogryposis,_distal,_type_1B (64 variants)
MYBPC1-related_disorder (18 variants)
Myopathy,_congenital,_with_tremor (17 variants)
not_specified (16 variants)
Lethal_congenital_contracture_syndrome_4 (13 variants)
Distal_arthrogryposis (3 variants)
MYBPC1-related_autosomal_recessive_non-lethal_arthrogryposis_multiplex_congenita_syndrome (1 variants)
Abnormality_of_the_musculature (1 variants)
Intellectual_disability (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MYBPC1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000002465.4. 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	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			3 clinvar	15 clinvar	6 clinvar	24
missense	4 clinvar	5 clinvar	167 clinvar	23 clinvar	3 clinvar	202
nonsense		2 clinvar	1 clinvar			3
start loss						0
frameshift		1 clinvar	3 clinvar			4
splice donor/acceptor (+/-2bp)		1 clinvar	3 clinvar			4
Total	4	9	177	38	9

Highest pathogenic variant AF is 0.00000656901

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MYBPC1	protein_coding	protein_coding	ENST00000452455	30	117666

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000484	1.00	125717	0	31	125748	0.000123

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.02	556	628	0.885	0.0000326	7758
Missense in Polyphen		245	306.41	0.79957		3751
Synonymous	-0.477	222	213	1.04	0.0000112	2188
Loss of Function	5.03	20	63.2	0.317	0.00000296	809

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000116	0.000116
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.000141	0.000141
Middle Eastern	0.0000544	0.0000544
South Asian	0.000262	0.000261
Other	0.000327	0.000326

dbNSFP

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.;
Disease: DISEASE: Arthrogryposis, distal, 1B (DA1B) [MIM:614335]: A form of distal arthrogryposis, a disease characterized by congenital joint contractures that mainly involve two or more distal parts of the limbs, in the absence of a primary neurological or muscle disease. Distal arthrogryposis type 1 is characterized largely by camptodactyly and clubfoot. Hypoplasia and/or absence of some interphalangeal creases is common. The shoulders and hips are less frequently affected. {ECO:0000269|PubMed:20045868, ECO:0000269|PubMed:26661508}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Lethal congenital contracture syndrome 4 (LCCS4) [MIM:614915]: A form of lethal congenital contracture syndrome, an autosomal recessive disorder characterized by degeneration of anterior horn neurons, extreme skeletal muscle atrophy and congenital non-progressive joint contractures. The contractures can involve the upper or lower limbs and/or the vertebral column, leading to various degrees of flexion or extension limitations evident at birth. {ECO:0000269|PubMed:22610851}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway: Striated Muscle Contraction;Striated Muscle Contraction;Muscle contraction (Consensus)

Recessive Scores

pRec: 0.208

Intolerance Scores

loftool: 0.645
rvis_EVS: -1.17
rvis_percentile_EVS: 6.03

Haploinsufficiency Scores

pHI: 0.164
hipred: Y
hipred_score: 0.744
ghis: 0.549

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: N
gene_indispensability_score: 0.487

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Mybpc1
Phenotype

Zebrafish Information Network

Gene name: mybpc1
Affected structure: slow muscle cell
Phenotype tag: abnormal
Phenotype quality: has fewer parts of type

Gene ontology

Biological process: muscle contraction;cell adhesion;muscle filament sliding;skeletal muscle thin filament assembly;skeletal muscle myosin thick filament assembly;sarcomere organization;cardiac muscle fiber development;cardiac myofibril assembly;cardiac muscle tissue morphogenesis;striated muscle myosin thick filament assembly
Cellular component: cytosol;striated muscle thin filament;myofibril;sarcomere;Z disc;M band;myosin filament
Molecular function: protein binding;structural constituent of muscle;titin binding;actin filament binding;muscle alpha-actinin binding