MYBPC1

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

Basic information

Region (hg38): 12:101568352-101686028

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 (235 variants)
• Arthrogryposis, distal, type 1B (74 variants)
• Inborn genetic diseases (41 variants)
• not specified (25 variants)
• Myopathy, congenital, with tremor (13 variants)
• Lethal congenital contracture syndrome 4 (10 variants)
• MYBPC1-related condition (5 variants)
• Distal arthrogryposis (5 variants)
• Arthrogryposis, distal, type 1B;Myopathy, congenital, with tremor;Lethal congenital contracture syndrome 4 (2 variants)
• Abnormality of the musculature (1 variants)
• Myopathy, congenital, with tremor;Arthrogryposis, distal, type 1B;Lethal congenital contracture syndrome 4 (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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	11	9	22
missense	2	4	74	5	4	89
nonsense		1	1			2
start loss						0
frameshift		1	2			3
inframe indel			1			1
splice donor/acceptor (+/-2bp)						0
splice region			5	2	3	10
non coding			9	69	108	186
Total	2	6	89	85	121

Variants in MYBPC1

This is a list of pathogenic ClinVar variants found in the MYBPC1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
12-101594747-C-T			Benign (Nov 12, 2018)
12-101594978-C-T		Arthrogryposis, distal, type 1B	Benign/Likely benign (Oct 30, 2019)
12-101594996-G-T		Arthrogryposis, distal, type 1B	Benign (Nov 12, 2018)
12-101595025-C-T		Arthrogryposis, distal, type 1B	Benign/Likely benign (Jun 17, 2020)
12-101595058-T-C		Arthrogryposis, distal, type 1B	Benign (Jan 12, 2018)
12-101595080-C-G		Inborn genetic diseases	Uncertain significance (Dec 27, 2022)
12-101595087-A-T		Arthrogryposis, distal, type 1B • MYBPC1-related disorder	Benign/Likely benign (Aug 08, 2019)
12-101595144-T-C			Likely benign (Nov 15, 2019)
12-101595222-C-T			Likely benign (Feb 22, 2020)
12-101614304-A-G			Likely benign (Aug 06, 2020)
12-101614323-TGTGAGA-T			Benign (Nov 15, 2019)
12-101614323-T-TGA			Likely benign (Dec 01, 2019)
12-101614325-T-A			Benign (Sep 04, 2019)
12-101614438-AG-A			Benign (Nov 15, 2019)
12-101614487-C-T		not specified • Arthrogryposis, distal, type 1B	Benign/Likely benign (Nov 30, 2020)
12-101614502-A-G		Lethal congenital contracture syndrome 4	Uncertain significance (-)
12-101614514-C-T		Inborn genetic diseases	Uncertain significance (Jan 04, 2024)
12-101614516-GCCCCAC-G		Distal arthrogryposis	Uncertain significance (Jun 14, 2016)
12-101614529-A-C			Uncertain significance (Jun 07, 2023)
12-101616908-G-T			Likely benign (Jun 18, 2020)
12-101616962-A-C			Benign (Nov 12, 2018)
12-101616975-G-A			Likely benign (Jul 26, 2020)
12-101617037-T-C			Benign (Nov 12, 2018)
12-101617224-C-T			Benign (Apr 18, 2018)
12-101617248-G-T		not specified	Uncertain significance (Dec 02, 2016)

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

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