MYBPC2

Summary

MYBPC2 (myosin binding protein C2, HGNC:7550) is a protein-coding gene on chromosome 19q13.33, encoding Myosin-binding protein C, fast-type (Q14324). Thick filament-associated protein located in the crossbridge region of vertebrate striated muscle a bands.

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.

Source: NCBI Gene 4606 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 252 total
• MANE Select transcript: NM_004533

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7550
Approved symbol	MYBPC2
Name	myosin binding protein C2
Location	19q13.33
Locus type	gene with protein product
Status	Approved
Aliases	MYBPCF, MGC163408, fsMyBP-C
Ensembl gene	ENSG00000086967
Ensembl biotype	protein_coding
OMIM	160793
Entrez	4606

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 12 protein_coding, 1 retained_intron

ENST00000357701, ENST00000597498, ENST00000966351, ENST00000966352, ENST00000966353, ENST00000966354, ENST00000966355, ENST00000966356, ENST00000966357, ENST00000966358, ENST00000966359, ENST00000966360, ENST00000966361

RefSeq mRNA: 1 — MANE Select: NM_004533 NM_004533

CCDS: CCDS46152

Canonical transcript exons

ENST00000357701 — 28 exons

Exon	Start	End
ENSE00000721593	50451280	50451309
ENSE00000721600	50450829	50450935
ENSE00000869259	50459111	50459306
ENSE00000869262	50458587	50458754
ENSE00000954625	50435776	50435862
ENSE00000954626	50436012	50436160
ENSE00000954627	50436617	50436734
ENSE00000954628	50437473	50437521
ENSE00000954629	50437659	50437718
ENSE00000954630	50440880	50441076
ENSE00000954631	50442181	50442313
ENSE00000954632	50443494	50443618
ENSE00000954633	50443711	50443816
ENSE00000954634	50445880	50446052
ENSE00000954635	50448225	50448390
ENSE00000954636	50451864	50452003
ENSE00000954637	50454020	50454179
ENSE00000954638	50454265	50454369
ENSE00000954639	50455108	50455296
ENSE00000954640	50455510	50455644
ENSE00000954641	50458918	50459006
ENSE00000954642	50460040	50460179
ENSE00000954643	50461542	50461701
ENSE00000954644	50461900	50462036
ENSE00001297081	50464346	50464532
ENSE00001301795	50435161	50435250
ENSE00001354328	50432892	50432972
ENSE00003146286	50466195	50466321

Expression profiles

Bgee: expression breadth ubiquitous, 175 present calls, max score 99.69.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 3.8296 / max 1801.6215, expressed in 115 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
177150	3.7967	109
177149	0.0328	13

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
vastus lateralis	UBERON:0001379	99.69	gold quality
hindlimb stylopod muscle	UBERON:0004252	99.63	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	99.60	gold quality
quadriceps femoris	UBERON:0001377	99.59	gold quality
triceps brachii	UBERON:0001509	99.47	gold quality
biceps brachii	UBERON:0001507	99.43	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	99.35	gold quality
gastrocnemius	UBERON:0001388	99.22	gold quality
diaphragm	UBERON:0001103	99.18	gold quality
gluteal muscle	UBERON:0002000	99.09	gold quality
skeletal muscle tissue	UBERON:0001134	99.06	gold quality
muscle organ	UBERON:0001630	97.60	gold quality
body of tongue	UBERON:0011876	97.54	gold quality
muscle of leg	UBERON:0001383	96.89	gold quality
deltoid	UBERON:0001476	96.45	gold quality
muscle tissue	UBERON:0002385	90.62	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.37	gold quality
tongue	UBERON:0001723	86.58	gold quality
tibialis anterior	UBERON:0001385	85.63	silver quality
pharyngeal mucosa	UBERON:0000355	79.28	gold quality
superior surface of tongue	UBERON:0007371	74.11	gold quality
trabecular bone tissue	UBERON:0002483	69.81	gold quality
minor salivary gland	UBERON:0001830	63.68	gold quality
cingulate cortex	UBERON:0003027	62.73	gold quality
anterior cingulate cortex	UBERON:0009835	62.43	gold quality
mouth mucosa	UBERON:0003729	61.73	gold quality
apex of heart	UBERON:0002098	61.37	gold quality
right frontal lobe	UBERON:0002810	61.37	gold quality
synovial joint	UBERON:0002217	59.59	gold quality
pituitary gland	UBERON:0000007	59.26	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

9 targeting MYBPC2, 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-6857-5P	99.87	65.32	985
HSA-MIR-1208	99.70	68.28	1533
HSA-MIR-7156-5P	99.64	68.81	1369
HSA-MIR-7150	99.62	66.80	1322
HSA-MIR-4273	99.45	67.93	1206
HSA-MIR-508-5P	99.41	64.25	1248
HSA-MIR-6799-5P	99.14	65.72	2093
HSA-MIR-4450	98.26	68.35	725
HSA-MIR-4736	97.96	65.89	1287

Literature-anchored findings (GeneRIF, showing 7)

• Identification of interactions between domains of Myosin binding protein-C that are modulated by hypertrophic cardiomyopathy missense mutations. (PMID:12386147)
• the CD-loop is a natively unfolded sequence with a likely coupling between folding and ligand binding. (PMID:17876814)
• Role and quaternary structure of MyBPC in skeletal muscle. (PMID:18201573)
• The distribution of MyBP-C in the A-bands of cardiac and skeletal muscles and compare this to the A-band structure in cardiac muscle of MyBP-C-deficient mice, was investigated. (PMID:18817784)
• The patients with a frameshift deletion mutation of MyBPC may develop LV systolic dysfunction and suffer from cardiovascular events through mid-life and beyond. (PMID:20605413)
• the mean methylation level of CpGs was significantly higher in MYBPC3 than MYBPC2. (PMID:20740642)
• MYBPC2 and MYL1 as Significant Gene Markers for Rhabdomyosarcoma. (PMID:33499774)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	mybpc2b	ENSDARG00000021265
mus_musculus	Mybpc2	ENSMUSG00000038670
rattus_norvegicus	Mybpc2	ENSRNOG00000019627
drosophila_melanogaster	mtgo	FBGN0259735
caenorhabditis_elegans		WBGENE00007944

Paralogs (11): MYOM2 (ENSG00000036448), FNDC3B (ENSG00000075420), MYOM1 (ENSG00000101605), FNDC3A (ENSG00000102531), OBSL1 (ENSG00000124006), MYBPH (ENSG00000133055), MYBPC3 (ENSG00000134571), MYOM3 (ENSG00000142661), IGSF22 (ENSG00000179057), MYBPC1 (ENSG00000196091), MYBPHL (ENSG00000221986)

Protein

Protein identifiers

Myosin-binding protein C, fast-type — Q14324 (reviewed: Q14324)

Alternative names: C-protein, skeletal muscle fast isoform

All UniProt accessions (2): Q14324, A0A140VJQ0

UniProt curated annotations — full annotation on UniProt →

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.

Similarity. Belongs to the immunoglobulin superfamily. MyBP family.

RefSeq proteins (1): NP_004524* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003598	Ig_sub2	Domain
IPR003599	Ig_sub	Domain
IPR003961	FN3_dom	Domain
IPR007110	Ig-like_dom	Domain
IPR013098	Ig_I-set	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR036116	FN3_sf	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR040849	MyBP-C_THB	Domain
IPR050964	Striated_Muscle_Regulatory	Family

Pfam: PF00041, PF07679, PF18362

UniProt features (55 total): strand 27, domain 10, sequence variant 7, turn 5, sequence conflict 2, chain 1, region of interest 1, compositionally biased region 1, helix 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
2E7C	SOLUTION NMR
2EDK	SOLUTION NMR
2EDN	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q14324-F1	81.61	0.41

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-390522	Striated Muscle Contraction
R-HSA-397014	Muscle contraction

MSigDB gene sets: 116 (showing top): GOBP_STRIATED_MUSCLE_CELL_DIFFERENTIATION, TGACCTY_ERR1_Q2, GOBP_SARCOMERE_ORGANIZATION, CHX10_01, GCM_PRKCG, GCM_RING1, GOBP_CELLULAR_COMPONENT_ASSEMBLY_INVOLVED_IN_MORPHOGENESIS, GOBP_MUSCLE_STRUCTURE_DEVELOPMENT, MODULE_202, AML_Q6, GOBP_ACTOMYOSIN_STRUCTURE_ORGANIZATION, GOBP_ORGANELLE_ASSEMBLY, MODULE_157, GOMF_ACTIN_BINDING, GCM_ATM

GO Biological Process (2): cell adhesion (GO:0007155), sarcomere organization (GO:0045214)

GO Molecular Function (3): actin binding (GO:0003779), structural constituent of muscle (GO:0008307), protein binding (GO:0005515)

GO Cellular Component (3): cytosol (GO:0005829), M band (GO:0031430), myosin filament (GO:0032982)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Muscle contraction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
cellular process	1
myofibril assembly	1
actomyosin structure organization	1
cytoskeletal protein binding	1
structural molecule activity	1
binding	1
cytoplasm	1
A band	1
myosin complex	1
supramolecular fiber	1

Protein interactions and networks

STRING

1208 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MYBPC2	TTN	Q8WZ42	919
MYBPC2	NEB	P20929	760
MYBPC2	TNNT3	P45378	697
MYBPC2	MYH1	P12882	694
MYBPC2	MYH6	P13533	683
MYBPC2	MYL9	P24844	682
MYBPC2	CSRP3	P50461	673
MYBPC2	ACTN3	Q08043	673
MYBPC2	MYL12A	P19105	662
MYBPC2	MYL2	P10916	648
MYBPC2	TMOD4	Q9NZQ9	646
MYBPC2	TPM1	P09493	634
MYBPC2	ACTA1	P02568	624
MYBPC2	TRIM63	Q969Q1	618
MYBPC2	ANKRD23	Q86SG2	604

IntAct

60 interactions, top by confidence:

A	B	Type	Score
SH3GL3	MYBPC2	psi-mi:“MI:0915”(physical association)	0.560
MYBPC2	MYBPC2	psi-mi:“MI:0407”(direct interaction)	0.440
MYBPC2	PA2G4	psi-mi:“MI:0915”(physical association)	0.400
MYBPC2	PCNA	psi-mi:“MI:0915”(physical association)	0.370
MECOM	ATP2A1	psi-mi:“MI:0914”(association)	0.350
RSPH6A	ATP2A1	psi-mi:“MI:0914”(association)	0.350
LATS1	ATP2A1	psi-mi:“MI:0914”(association)	0.350
TSPAN33	ATP2A1	psi-mi:“MI:0914”(association)	0.350
AMOT	MYBPC2	psi-mi:“MI:0915”(physical association)	0.000
MYBPC2	CCT6A	psi-mi:“MI:0915”(physical association)	0.000
MYBPC2	DYSF	psi-mi:“MI:0915”(physical association)	0.000
HSPA1A	MYBPC2	psi-mi:“MI:0915”(physical association)	0.000
ITGB5	MYBPC2	psi-mi:“MI:0915”(physical association)	0.000
MYBPC2	ACTN2	psi-mi:“MI:0915”(physical association)	0.000
MYBPC2	AOC3	psi-mi:“MI:0915”(physical association)	0.000
CMYA5	MYBPC2	psi-mi:“MI:0915”(physical association)	0.000
MYBPC2	COL12A1	psi-mi:“MI:0915”(physical association)	0.000
COL12A1	MYBPC2	psi-mi:“MI:0915”(physical association)	0.000
MYBPC2	DST	psi-mi:“MI:0915”(physical association)	0.000
FLNB	MYBPC2	psi-mi:“MI:0915”(physical association)	0.000
MYBPC2	FLNC	psi-mi:“MI:0915”(physical association)	0.000
FLNC	MYBPC2	psi-mi:“MI:0915”(physical association)	0.000
MYBPC2	FSD2	psi-mi:“MI:0915”(physical association)	0.000
MYBPC2	GABARAP	psi-mi:“MI:0915”(physical association)	0.000
MYBPC2	GAS7	psi-mi:“MI:0915”(physical association)	0.000
MYBPC2	MAD2L2	psi-mi:“MI:0915”(physical association)	0.000
MSN	MYBPC2	psi-mi:“MI:0915”(physical association)	0.000
MYBPC2	MYBPC1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (43): MYBPC2 (Affinity Capture-MS), MYBPC2 (Affinity Capture-RNA), PA2G4 (Proximity Label-MS), MYBPC2 (Two-hybrid), MYBPC2 (Two-hybrid), MYBPC2 (Two-hybrid), MYBPC2 (Two-hybrid), MYBPC2 (Two-hybrid), FLNC (Two-hybrid), MYBPC1 (Two-hybrid), PDE4DIP (Two-hybrid), TRIM63 (Two-hybrid), TTN (Two-hybrid), COL12A1 (Two-hybrid), GAS7 (Two-hybrid)

ESM2 similar proteins: A0A087WV53, A2AAJ9, A2ABU4, A2RUH7, E7F6H7, O00423, O01761, O14576, O54785, O70468, O88485, O88599, P16419, P22607, P26453, P52179, P53670, P53671, P54296, P56741, P70402, Q00872, Q02173, Q05623, Q05BC3, Q0DYP5, Q13203, Q14168, Q14324, Q14896, Q29RQ3, Q32L23, Q4V8C3, Q5FW53, Q5PQM4, Q5VST9, Q5VTT5, Q5XI81, Q5XKE0, Q60992

Diamond homologs: A0A087WV53, A2ASS6, A2CG49, A2RUH7, F1M0Z1, O08775, O60229, O70468, O75962, O88599, O94856, P11799, P16419, P35918, P56741, P70402, P97685, P97924, Q00872, Q05623, Q0KL02, Q13203, Q14324, Q14896, Q15746, Q5FW53, Q5PQM4, Q5VTT5, Q5XKE0, Q63518, Q696W0, Q6GMZ9, Q7T2H2, Q8N9C0, Q8WZ42, Q90688, Q9JIF9, B4P5Q9, D3Z7H8, D3ZEY0

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 38 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
Muscle contraction	5	12.4×	5e-03

GO biological processes:

GO term	Partners	Fold	FDR
sarcomere organization	5	53.2×	1e-05
actin cytoskeleton organization	5	11.0×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	217
Likely benign	22
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

4216 predictions. Top by Δscore:

Variant	Effect	Δscore
19:50435156:TACAG:T	acceptor_loss	1.0000
19:50435159:A:AG	acceptor_gain	1.0000
19:50435159:A:T	acceptor_loss	1.0000
19:50435159:AGC:A	acceptor_gain	1.0000
19:50435159:AGCG:A	acceptor_gain	1.0000
19:50435160:G:GA	acceptor_gain	1.0000
19:50435160:GC:G	acceptor_gain	1.0000
19:50435160:GCG:G	acceptor_gain	1.0000
19:50435160:GCGG:G	acceptor_gain	1.0000
19:50435769:T:A	acceptor_gain	1.0000
19:50435770:GAACA:G	acceptor_loss	1.0000
19:50435773:CA:C	acceptor_loss	1.0000
19:50435774:A:AG	acceptor_gain	1.0000
19:50435775:G:GC	acceptor_gain	1.0000
19:50435775:GA:G	acceptor_gain	1.0000
19:50435775:GAA:G	acceptor_gain	1.0000
19:50435775:GAAGC:G	acceptor_gain	1.0000
19:50435858:GACTG:G	donor_gain	1.0000
19:50436007:T:G	acceptor_gain	1.0000
19:50436007:TGTA:T	acceptor_loss	1.0000
19:50436008:GTAG:G	acceptor_loss	1.0000
19:50436009:TA:T	acceptor_loss	1.0000
19:50436010:A:AG	acceptor_gain	1.0000
19:50436010:AG:A	acceptor_gain	1.0000
19:50436010:AGG:A	acceptor_gain	1.0000
19:50436011:G:GA	acceptor_gain	1.0000
19:50436011:GG:G	acceptor_gain	1.0000
19:50436011:GGG:G	acceptor_gain	1.0000
19:50436011:GGGA:G	acceptor_gain	1.0000
19:50436156:GCAAT:G	donor_gain	1.0000

AlphaMissense

7511 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:50448329:T:A	W471R	1.000
19:50448329:T:C	W471R	1.000
19:50450840:T:C	L495P	1.000
19:50455228:G:C	R712P	1.000
19:50455244:T:A	N717K	1.000
19:50455244:T:G	N717K	1.000
19:50442276:T:A	W289R	0.999
19:50442276:T:C	W289R	0.999
19:50443529:T:C	L313P	0.999
19:50443613:T:A	V341D	0.999
19:50443815:T:A	W378R	0.999
19:50443815:T:C	W378R	0.999
19:50445880:G:C	W378C	0.999
19:50445880:G:T	W378C	0.999
19:50445963:T:C	L406P	0.999
19:50446001:T:G	Y419D	0.999
19:50448291:T:C	F458S	0.999
19:50451986:T:A	W578R	0.999
19:50451986:T:C	W578R	0.999
19:50454116:T:G	Y616D	0.999
19:50454136:C:A	N622K	0.999
19:50454136:C:G	N622K	0.999
19:50454174:T:A	V635D	0.999
19:50454330:T:A	W659R	0.999
19:50454330:T:C	W659R	0.999
19:50455110:T:G	Y673D	0.999
19:50455123:G:C	R677P	0.999
19:50455146:T:A	W685R	0.999
19:50455146:T:C	W685R	0.999
19:50455148:G:C	W685C	0.999

dbSNP variants (sampled 300 via entrez): RS1000004089 (19:50434081 A>G), RS1000122800 (19:50465409 C>T), RS1000360663 (19:50439340 C>G,T), RS1000525881 (19:50455060 C>A), RS1000672654 (19:50465974 C>T), RS1000860743 (19:50434340 G>A), RS1000958664 (19:50432661 T>A,G), RS1000998884 (19:50449474 G>A), RS1001009574 (19:50432849 G>A), RS1001041512 (19:50465709 G>C), RS1001238800 (19:50461350 T>C,G), RS1001281000 (19:50454694 G>A,C), RS1001300733 (19:50437932 A>G), RS1001520814 (19:50450047 C>A), RS1001602891 (19:50448180 C>T)

Disease associations

OMIM: gene MIM:160793 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST003129_10	Primary biliary cholangitis	1.000000e-20

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

11 total (human), top 11 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
entinostat	increases expression, affects cotreatment	2
aristolochic acid I	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
Benzo(a)pyrene	increases methylation, affects methylation	1
Cadmium	decreases expression	1
Doxorubicin	affects expression	1
Ethyl Methanesulfonate	increases expression	1
Methyl Methanesulfonate	increases expression	1
Aflatoxin B1	increases methylation	1

Clinical trials (associated diseases)

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