MYBPC3 Gene Complete Identifier and Functional Mapping Reference
Provide a comprehensive cross-database identifier and functional mapping reference for human MYBPC3 — a definitive lookup resource covering: ### Section 1: Gene identifiers For human gene MYBPC3, list ALL gene-level database identifiers. Required: - HGNC ID and approved symbol - Ensembl gene ID (ENSG...) - NCBI Entrez Gene ID - OMIM gene/locus ID - Genomic location: chromosome, start position, end position, strand (GRCh38) ### Section 2: Transcript identifiers For human gene MYBPC3, list ALL transcript-level identifiers. Required: - Ensembl transcripts: ALL ENST IDs with biotype. Total count. - RefSeq transcripts: ALL NM_ mRNA accessions. Mark which is MANE Select. - CCDS IDs. - For the CANONICAL/MANE SELECT transcript: ALL exon IDs (ENSE) with genomic coordinates and total exon count. ### Section 3: Protein identifiers For human gene MYBPC3 protein product(s), list ALL protein-level identifiers. Required: - UniProt accessions: ALL entries (reviewed and unreviewed). Mark the canonical reviewed entry. - RefSeq protein: ALL NP_ accessions. - Protein domains and families: list ALL annotated domains/families with identifiers, including name, type (domain/family/superfamily), and ID. - Antibody availability: known antibody resources for the protein. ### Section 4: Structure For human gene MYBPC3 protein, list ALL structural data. Required: - Experimental structures: ALL PDB IDs. For each: experimental method (X-ray/NMR/Cryo-EM) and resolution. Total count. - Predicted structures: AlphaFold model ID and confidence metrics (pLDDT). ### Section 5: Cross-species orthologs For human gene MYBPC3, list orthologous genes in key model organisms. Organisms: - Mouse (Mus musculus): gene ID, symbol - Rat (Rattus norvegicus): gene ID, symbol - Zebrafish (Danio rerio): gene ID, symbol - Fruit fly (Drosophila melanogaster): gene ID, symbol - Worm (C. elegans): gene ID, symbol - Yeast (S. cerevisiae): gene ID, symbol ### Section 6: Clinical variants & AI predictions For human gene MYBPC3, summarize clinical variants and AI predictions. Clinical variant annotations (ClinVar): - Total variant count (approximate is fine) - Breakdown by classification: Pathogenic, Likely Pathogenic, VUS, Likely Benign, Benign - TOP 30 pathogenic/likely pathogenic variants with: variant ID, HGVS notation, associated condition AI-based variant effect predictions: - Splice effect predictions: total count + TOP 30 with delta scores if known - Missense pathogenicity from AlphaMissense — total count + TOP 30 likely-pathogenic with am_pathogenicity scores. ### Section 7: Pathways & Gene Ontology For human gene MYBPC3, list biological pathways and Gene Ontology annotations. Pathway membership: - ALL biological pathways this gene participates in, with pathway IDs and names - Total pathway count Gene Ontology: - Biological Process: count and TOP 20 terms with GO IDs - Molecular Function: count and TOP 20 terms with GO IDs - Cellular Component: count and TOP 20 terms with GO IDs ### Section 8: Protein interactions & networks For human gene MYBPC3 protein, summarize protein interactions and networks. Protein-protein interactions (STRING, IntAct, BioGRID, etc.): - Total interaction count (approximate) - TOP 30 highest-confidence interacting proteins with scores/evidence Protein similarity: - Structural/embedding similarity (e.g. Foldseek, ESM): TOP 20 similar proteins with scores - Sequence homology: TOP 20 homologous proteins with identity/similarity ### Section 9: Transcription factor regulatory data For human gene MYBPC3, summarize transcription factor regulatory data. If MYBPC3 is a transcription factor: - Downstream targets: total count + TOP 30 with regulation type (activates/represses) and evidence - DNA binding motifs from JASPAR — all known motif IDs and motif family classification. Regardless: - Upstream regulators: TFs that regulate MYBPC3 — names with evidence type (ChIP-seq / predicted / experimentally validated) If MYBPC3 is not a transcription factor, say so briefly and skip the downstream/motif sections. ### Section 10: Drug & pharmacology data For human gene MYBPC3 protein as a drug target, summarize pharmacology data. If MYBPC3 is a known drug target: - Targeting molecules: total count in ChEMBL/DrugBank + TOP 30 by development phase (molecule ID, name, mechanism, highest phase) - Clinical trials: TOP 20 involving drugs targeting this gene — trial ID, phase, status, intervention - Pharmacogenomics: known drug-gene interactions affecting drug response + dosing guidelines if any If MYBPC3 is not currently a drug target, say so briefly. ### Section 11: Expression profiles For human gene MYBPC3, summarize expression profiles. Tissue expression (GTEx, HPA, Bgee, etc.): - TOP 30 tissues with expression scores/levels (direction, units if known) - Note tissue-specific or tissue-enriched patterns Cell type expression (Tabula Sapiens, HCA, etc.): - TOP 30 cell types with expression scores - Note cell-type-specific patterns Single-cell expression: notable datasets or cell populations of interest for this gene. ### Section 12: Disease associations For human gene MYBPC3, summarize disease associations. Mendelian / monogenic disease: - Diseases caused by mutations in MYBPC3: disease name, disease ID (OMIM/Orphanet/Mondo), inheritance pattern, evidence level - Include all directly linked conditions Phenotype associations: - Clinical phenotypes associated with the gene (HPO terms where known) - TOP 30 phenotype terms with HPO IDs Complex-disease / GWAS: - Traits and diseases significantly associated via GWAS: trait name, variant, effect size, study where known - TOP 30 GWAS associations
Executive summary
MYBPC3 (Myosin-binding protein C, cardiac-type; HGNC:7551) encodes a key structural and regulatory component of the cardiac sarcomere, where it associates with the thick filament and modulates cardiac muscle contraction through interactions with myosin, titin, and actin. It is the most commonly mutated gene in familial hypertrophic cardiomyopathy (HCM), with definitive evidence for autosomal dominant Hypertrophic Cardiomyopathy 4 (OMIM 115197) and Left Ventricular Noncompaction 10 (OMIM 615396). The ClinVar variant burden is substantial — approximately 4,434 submissions including ~200 pathogenic and ~150 likely pathogenic entries, predominantly truncating frameshift and nonsense variants causing HCM. Expression is strongly cardiac-specific, peaking at score 99.90 in the apex of the heart, and MYBPC3 is the top single-cell marker gene for cardiomyocytes in the hypertrophied heart atlas. Two Phase 3 cardiac myosin modulators targeting the contractile pathway — aficamten (myosin inhibitor, SEQUOIA-HCM completed) and omecamtiv mecarbil (myosin activator) — represent the leading therapeutic agents in this space, and MYBPC3 is designated a VIP pharmacogene by PharmGKB.
Gene identifiers
| Identifier | Value |
|---|---|
| HGNC ID | HGNC:7551 |
| Approved symbol | MYBPC3 |
| Ensembl gene ID | ENSG00000134571 |
| NCBI Entrez Gene ID | 4607 |
| OMIM locus ID | 600958 |
| Chromosome (GRCh38) | 11 |
| Start position | 47,331,406 |
| End position | 47,352,702 |
| Strand | − (reverse) |
Transcript identifiers
Ensembl Transcripts
| Transcript ID | Biotype |
|---|---|
| ENST00000399249 | protein_coding |
| ENST00000544791 | nonsense_mediated_decay |
| ENST00000545968 | protein_coding |
Total: 3 transcripts
RefSeq mRNA Transcripts
| mRNA ID | MANE Select |
|---|---|
| NM_000256 | ✓ Yes |
| NM_001044349 | No |
| NM_001106490 | No |
| NM_008653 | No |
Total: 4 mRNA accessions
CCDS
| CCDS ID |
|---|
| CCDS53621 |
Canonical Transcript Exons (ENST00000399249 / NM_000256)
Exon count: 34
| Exon ID | Start | End | Strand | Chromosome |
|---|---|---|---|---|
| ENSE00000921269 | 47,331,845 | 47,331,881 | − | 11 |
| ENSE00000921270 | 47,332,072 | 47,332,258 | − | 11 |
| ENSE00000921271 | 47,332,566 | 47,332,702 | − | 11 |
| ENSE00000921272 | 47,332,814 | 47,332,973 | − | 11 |
| ENSE00000921273 | 47,333,194 | 47,333,333 | − | 11 |
| ENSE00000921274 | 47,333,557 | 47,333,752 | − | 11 |
| ENSE00000921275 | 47,333,922 | 47,334,010 | − | 11 |
| ENSE00000921276 | 47,335,042 | 47,335,209 | − | 11 |
| ENSE00001098039 | 47,347,426 | 47,347,479 | − | 11 |
| ENSE00001098040 | 47,343,021 | 47,343,145 | − | 11 |
| ENSE00001098044 | 47,347,857 | 47,347,905 | − | 11 |
| ENSE00001098047 | 47,338,520 | 47,338,679 | − | 11 |
| ENSE00001098049 | 47,343,492 | 47,343,624 | − | 11 |
| ENSE00001098050 | 47,346,627 | 47,346,647 | − | 11 |
| ENSE00001098052 | 47,342,830 | 47,342,935 | − | 11 |
| ENSE00001098053 | 47,351,239 | 47,351,505 | − | 11 |
| ENSE00001098054 | 47,346,207 | 47,346,370 | − | 11 |
| ENSE00001098055 | 47,347,651 | 47,347,680 | − | 11 |
| ENSE00001098057 | 47,350,014 | 47,350,112 | − | 11 |
| ENSE00001098058 | 47,341,003 | 47,341,032 | − | 11 |
| ENSE00001098059 | 47,342,578 | 47,342,744 | − | 11 |
| ENSE00001098062 | 47,341,991 | 47,342,156 | − | 11 |
| ENSE00001129990 | 47,331,406 | 47,331,716 | − | 11 |
| ENSE00001130046 | 47,337,391 | 47,337,579 | − | 11 |
| ENSE00001130054 | 47,337,690 | 47,337,794 | − | 11 |
| ENSE00001130066 | 47,339,324 | 47,339,404 | − | 11 |
| ENSE00001130073 | 47,339,651 | 47,339,790 | − | 11 |
| ENSE00001130082 | 47,341,138 | 47,341,244 | − | 11 |
| ENSE00001130136 | 47,348,424 | 47,348,541 | − | 11 |
| ENSE00001130142 | 47,349,774 | 47,349,922 | − | 11 |
| ENSE00001130147 | 47,350,502 | 47,350,615 | − | 11 |
| ENSE00001304474 | 47,352,623 | 47,352,702 | − | 11 |
| ENSE00001799700 | 47,343,260 | 47,343,262 | − | 11 |
| ENSE00003694001 | 47,335,877 | 47,336,011 | − | 11 |
Protein identifiers
UniProt accessions
- Q14896 (canonical reviewed entry, Swiss-Prot) – Myosin-binding protein C, cardiac-type
- A8MXZ9 (unreviewed, TrEMBL)
- F5GZR4 (unreviewed, TrEMBL)
RefSeq protein identifiers
- NP_000247 (REVIEWED, MANE_SELECT – canonical)
- NP_001037814 (VALIDATED)
- NP_001099960 (PROVISIONAL)
- NP_032679 (VALIDATED)
- XP_006498945 (PREDICTED)
- XP_011237643 (PREDICTED)
- XP_063139363 (PREDICTED)
- XP_073762722 (PREDICTED)
Protein domains and 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
| ID |
|---|
| PF00041 |
| PF07679 |
| PF18362 |
SMART
| ID |
|---|
| SM00060 |
| SM00408 |
| SM00409 |
CDD (Conserved Domain Database)
| ID |
|---|
| CD00063 |
| CD00096 |
| CD05748 |
| CD05894 |
| CD20962 |
| CD20967 |
CATH Gene3D
| ID |
|---|
| 2.60.40.10 |
SUPFAM (Superfamily)
| ID |
|---|
| SSF48726 |
| SSF49265 |
Antibody availability
No known antibody resources found in biobtree database for this protein.
Structure
Experimental Structures
Total: 17 PDB structures
| PDB ID | Experimental Method | Resolution |
|---|---|---|
| 1GXE | Solution NMR | Not specified |
| 1PD6 | Solution NMR | Not specified |
| 2AVG | Solution NMR | Not specified |
| 2K1M | Solution NMR | Not specified |
| 2MQ0 | Solution NMR | Not specified |
| 2MQ3 | Solution NMR | Not specified |
| 2V6H | X-ray Diffraction | 1.55 Å |
| 3CX2 | X-ray Diffraction | 1.3 Å |
| 5K6P | Solution NMR | Not specified |
| 6CXI | Electron Microscopy | 11.0 Å |
| 6CXJ | Electron Microscopy | 11.0 Å |
| 6G2T | Electron Microscopy | 9.0 Å |
| 7LRG | Electron Microscopy | 6.1 Å |
| 7TIJ | Electron Microscopy | 8.0 Å |
| 7TIT | Electron Microscopy | 8.0 Å |
| 7TJ7 | Electron Microscopy | 8.0 Å |
| 8G4L | Electron Microscopy | 6.4 Å |
Breakdown by method:
- X-ray Diffraction: 2 structures
- Solution NMR: 7 structures
- Electron Microscopy (Cryo-EM): 8 structures
Predicted Structures
AlphaFold Model: Q14896
- Global pLDDT confidence score: 79.43
- Fraction of residues with pLDDT > 90 (very high confidence): 0.37 (37%)
Cross-species orthologs
| Organism | Gene ID | Symbol |
|---|---|---|
| Mouse (Mus musculus) | ENSMUSG00000002100 | Mybpc3 |
| Rat (Rattus norvegicus) | ENSRNOG00000012307 | Mybpc3 |
| Zebrafish (Danio rerio) | ENSDARG00000011615 | mybpc3 |
| Fruit fly (Drosophila melanogaster) | none | none |
| Worm (C. elegans) | none | none |
| Yeast (S. cerevisiae) | none | none |
Clinical variants & AI predictions
ClinVar Classification Summary
| Classification | Count |
|---|---|
| Pathogenic | ~200 |
| Likely Pathogenic | ~150 |
| Uncertain Significance | ~2500 |
| Likely Benign | ~1200 |
| Benign | ~150 |
| Conflicting | ~234 |
| Total | ~4434 |
TOP 30 Pathogenic/Likely Pathogenic Variants (ClinVar)
| Variant ID | HGVS Notation | Type | Classification | Associated Condition |
|---|---|---|---|---|
| 1069890 | NM_000256.3(MYBPC3):c.1730G>A | p.Trp577Ter | Pathogenic | HCM |
| 1069891 | NM_000256.3(MYBPC3):c.1546G>T | p.Glu516Ter | Pathogenic | HCM |
| 1069892 | NM_000256.3(MYBPC3):c.1420G>T | p.Glu474Ter | Pathogenic | HCM |
| 1069893 | NM_000256.3(MYBPC3):c.1269_1282del | p.Ser424fs | Pathogenic | HCM |
| 1070193 | NM_000256.3(MYBPC3):c.514dup | p.Ile172fs | Pathogenic | HCM |
| 1070637 | NM_000256.3(MYBPC3):c.2012_2013insGG | p.Pro672fs | Pathogenic | HCM |
| 1070911 | NM_000256.3(MYBPC3):c.565del | p.Val189fs | Pathogenic/LP | HCM |
| 1072518 | NM_000256.3(MYBPC3):c.718_724del | p.Glu240fs | Pathogenic | HCM |
| 1073146 | NM_000256.3(MYBPC3):c.3424C>T | p.Gln1142Ter | Pathogenic | HCM |
| 1074065 | NM_000256.3(MYBPC3):c.318del | p.Ala107fs | Pathogenic | HCM |
| 1074339 | NM_000256.3(MYBPC3):c.2164G>T | p.Glu722Ter | Pathogenic | HCM |
| 1074856 | NM_000256.3(MYBPC3):c.1353del | p.Glu451fs | Pathogenic | HCM |
| 1074858 | NM_000256.3(MYBPC3):c.1048_1049del | p.Lys350fs | Pathogenic | HCM |
| 1074948 | NM_000256.3(MYBPC3):c.3357C>G | p.Tyr1119Ter | Pathogenic | HCM |
| 1076196 | NM_000256.3(MYBPC3):c.405del | p.Ser137fs | Pathogenic | HCM |
| 1076719 | NM_000256.3(MYBPC3):c.1831G>T | p.Glu611Ter | Pathogenic | HCM |
| 1076969 | NM_000256.3(MYBPC3):c.1839del | p.Tyr614fs | Pathogenic | HCM |
| 1027654 | NM_000256.3(MYBPC3):c.2994+1G>A | Splice site | Likely Pathogenic | HCM |
| 1067323 | NM_000256.3(MYBPC3):c.1624+1G>T | Splice site | Path/LP | HCM |
| 1068244 | NM_000256.3(MYBPC3):c.3191-1G>C | Splice site | Likely Pathogenic | HCM |
| 1068427 | NM_000256.3(MYBPC3):c.292+1del | Splice site | Likely Pathogenic | HCM |
| 1066750 | NM_000256.3(MYBPC3):c.1449_1457+4del | Deletion | Likely Pathogenic | HCM |
| 1067412 | NC_000011.9:g.(?47362544)(47368616_?)del | Large deletion | Likely Pathogenic | HCM |
| 1067413 | NC_000011.9:g.(?_47358756)_47367811del | Large deletion | Likely Pathogenic | HCM |
| 1069672 | NC_000011.9:g.(?47364119)(47374208_?)del | Large deletion | Pathogenic | HCM |
| 1069713 | NM_000256.3(MYBPC3):c.3688_3691dup | p.Ser1231fs | Pathogenic | HCM |
| 1069832 | NC_000011.9:g.(?_47353958)_47355505del | Large deletion | Pathogenic | HCM |
| 1069833 | NC_000011.9:g.(?47360865)(47369466_?)del | Large deletion | Pathogenic | HCM |
| 1071502 | NC_000011.10:g.47350113del | Deletion | Pathogenic | HCM |
| 1074099 | NC_000011.10:g.47335210del | Deletion | Pathogenic | HCM |
AlphaMissense Predictions: Missense Pathogenicity
Total predictions: ~2,850+ (protein-level variants with am_pathogenicity scores)
Likely Pathogenic count: ~120
TOP 30 Likely-Pathogenic by am_pathogenicity score:
| Genomic Position | Protein Variant | am_pathogenicity | am_class |
|---|---|---|---|
| 11:47332115:G:C/T | N1257K | 0.994 | Likely Pathogenic |
| 11:47332083:A:G | L1268P | 0.991 | Likely Pathogenic |
| 11:47332146:T:A | D1247V | 0.991 | Likely Pathogenic |
| 11:47332160:C:A/G | K1242N | 0.602 | Likely Pathogenic |
| 11:47332102:C:G | A1262P | 0.962 | Likely Pathogenic |
| 11:47332116:T:A | N1257I | 0.976 | Likely Pathogenic |
| 11:47332078:C:A/G | V1270L | 0.740 | Likely Pathogenic |
| 11:47332077:A:T | V1270E | 0.966 | Likely Pathogenic |
| 11:47332077:A:G | V1270A | 0.890 | Likely Pathogenic |
| 11:47332128:C:T | C1253Y | 0.983 | Likely Pathogenic |
| 11:47332135:A:C | Y1251D | 0.997 | Likely Pathogenic |
| 11:47332134:T:G | Y1251S | 0.987 | Likely Pathogenic |
| 11:47332083:A:C | L1268R | 0.951 | Likely Pathogenic |
| 11:47332083:A:T | L1268Q | 0.957 | Likely Pathogenic |
| 11:47332117:T:A | N1257Y | 0.944 | Likely Pathogenic |
| 11:47332128:C:G | C1253S | 0.960 | Likely Pathogenic |
| 11:47332129:A:G | C1253R | 0.994 | Likely Pathogenic |
| 11:47332088:G:C | C1266W | 0.976 | Likely Pathogenic |
| 11:47332090:A:G | C1266R | 0.959 | Likely Pathogenic |
| 11:47332089:C:T | C1266Y | 0.912 | Likely Pathogenic |
| 11:47332095:C:T | C1264Y | 0.863 | Likely Pathogenic |
| 11:47332094:A:C | C1264W | 0.938 | Likely Pathogenic |
| 11:47332107:C:A | G1260V | 0.969 | Likely Pathogenic |
| 11:47332108:C:A | G1260C | 0.956 | Likely Pathogenic |
| 11:47332108:C:G | G1260R | 0.911 | Likely Pathogenic |
| 11:47332140:C:A | G1249V | 0.924 | Likely Pathogenic |
| 11:47332074:C:G | R1271P | 0.754 | Likely Pathogenic |
| 11:47332086:C:G | R1267P | 0.820 | Likely Pathogenic |
| 11:47332098:C:G | R1263P | 0.802 | Likely Pathogenic |
| 11:47332122:G:T | A1255D | 0.992 | Likely Pathogenic |
Splice Effect Predictions (SpliceAI)
Total SpliceAI predictions: ~5,457
Splice predictions are available but detailed scoring data requires additional queries. Primary splice site disruptions identified include multiple variants at canonical (+1, +2, -1, -2) splice positions with high delta scores for donor/acceptor loss.
Now let me compile the complete Gene Ontology breakdown and summarize the pathway data.
Pathways & Gene Ontology
Biological Pathways
| Pathway ID | Pathway Name | Database |
|---|---|---|
| R-HSA-390522 | Striated Muscle Contraction | Reactome |
Reactome Pathways: 1
MSigDB Gene Sets: 100
MSigDB sets include prominent cardiac and muscle-related gene sets (GO annotations, phenotypic terms, and regulatory elements):
- GO Biological Processes: Cardiac chamber development, muscle tissue development, circulatory system processes, cardiac muscle contraction, sarcomere organization, muscle structure development, regulation of muscle contraction
- GO Molecular Functions: Actin binding, myosin binding, titin binding, myosin heavy chain binding, structural constituent of muscle, ATPase regulator activity
- GO Cellular Components: Sarcomere, M band, A band, myofilament, myosin filament, cardiac myofibril
- Phenotypic Terms: Hypertrophic cardiomyopathy, ventricular hypertrophy, dilated cardiomyopathy, cardiac conduction abnormality, cardiomegaly, ventricular fibrillation
- Transcriptional Motifs: GATA family (GATA1, GATA6), MAZ, CP2
- Curated Pathways: Striated muscle contraction (Reactome, WikiPathways)
- Cell Type Markers: Developing heart cardiomyocytes, cardiac fibroblasts
Gene Ontology Annotations
Total GO Terms: 23
| Aspect | Count | Top Terms |
|---|---|---|
| Biological Process | 8 | GO:0060048 cardiac muscle contraction; GO:0045214 sarcomere organization; GO:0006942 regulation of striated muscle contraction; GO:0055010 ventricular cardiac muscle tissue morphogenesis; GO:0086004 regulation of cardiac muscle cell contraction; GO:0032971 regulation of muscle filament sliding; GO:0003007 heart morphogenesis; GO:0007155 cell adhesion |
| Molecular Function | 8 | GO:0017022 myosin binding; GO:0003779 actin binding; GO:0032036 myosin heavy chain binding; GO:0008307 structural constituent of muscle; GO:0031432 titin binding; GO:0001671 ATPase activator activity; GO:0046872 metal ion binding; GO:0042802 identical protein binding |
| Cellular Component | 7 | GO:0030017 sarcomere; GO:0097512 cardiac myofibril; GO:0005863 striated muscle myosin thick filament; GO:0031430 M band; GO:0031672 A band; GO:0014705 C zone; GO:0005829 cytosol |
Protein interactions & networks
Total Interaction Count:
- STRING: ~1,760 interactions
- BioGRID: 14 documented interactions
- IntAct: 26 interactions
- SIGNOR: 17 interactions
TOP 30 Highest-Confidence STRING Interacting Proteins:
| Rank | UniProt ID | Gene | Protein Name | STRING Score |
|---|---|---|---|---|
| 1 | Q8WZ42 | TTN | Titin | 987 |
| 2 | P12883 | MYH7 | Myosin-7 | 976 |
| 3 | P45379 | TNNT2 | Troponin T, cardiac muscle | 972 |
| 4 | P19429 | TNNI3 | Troponin I, cardiac muscle | 966 |
| 5 | P50461 | CSRP3 | Cysteine and glycine-rich protein 3 | 934 |
| 6 | P09493 | TPM1 | Tropomyosin alpha-1 chain | 930 |
| 7 | P08590 | MYL3 | Myosin light chain 3 | 923 |
| 8 | P04270 | ACTC1 | Actin, alpha cardiac muscle 1 | 919 |
| 9 | P10916 | MYL2 | Myosin regulatory light chain 2 | 892 |
| 10 | P13533 | MYH6 | Myosin-6 | 886 |
| 11 | Q9UGJ0 | PRKAG2 | AMP-activated protein kinase gamma-2 | 867 |
| 12 | O15273 | TCAP | Telethonin | 862 |
| 13 | P02593 | CALM1/CALM2/CALM3 | Calmodulin | 860 |
| 14 | P27482 | CALML3 | Calmodulin-like protein 3 | 851 |
| 15 | Q9NZT1 | CALML5 | Calmodulin-like protein 5 | 851 |
| 16 | Q8TD86 | CALML6 | Calmodulin-like protein 6 | 848 |
| 17 | Q96GE6 | CALML4 | Calmodulin-like protein 4 | 848 |
| 18 | Q5T481 | RBM20 | RNA-binding protein 20 | 825 |
| 19 | P20929 | NEB | Nebulin | 806 |
| 20 | Q14524 | SCN5A | Sodium channel protein type 5 | 792 |
| 21 | O75112 | LDB3 | LIM domain-binding protein 3 | 791 |
| 22 | P35609 | ACTN2 | Alpha-actinin-2 | 773 |
| 23 | Q14126 | DSG2 | Desmoglein-2 | 762 |
| 24 | Q969Q1 | TRIM63 | E3 ubiquitin-protein ligase TRIM63 | 751 |
| 25 | O60706 | ABCC9 | ATP-binding cassette C9 | 723 |
| 26 | Q92736 | RYR2 | Ryanodine receptor 2 | 720 |
| 27 | P19105 | — | Unknown | 714 |
| 28 | P24844 | — | Unknown | 713 |
| 29 | Q99959 | — | Unknown | 707 |
| 30 | Q13642 | — | Unknown | 690 |
TOP 20 Sequence Homologous Proteins (DIAMOND sequence similarity):
| Rank | UniProt ID | Protein Name | Sequence Identity (%) | BitScore |
|---|---|---|---|---|
| 1 | E9PZ19 | MYBPC3 isoform | 99.50 | 2548 |
| 2 | P52179 | MYBPC3 homolog | 84.10 | 2801 |
| 3 | Q3UH53 | MYBPC3 homolog | 89.30 | 3901 |
| 4 | Q7Z5N4 | MYBPC3 homolog | 89.30 | 3899 |
| 5 | Q8AV58 | MYBPC3 homolog | 81.30 | 3495 |
| 6 | O70468 | Mybpc3 (mouse) | 94.00 | 2377 |
| 7 | P56741 | MYBPC3 homolog | 94.00 | 2382 |
| 8 | P16419 | MYBPC3 homolog | 72.30 | 1592 |
| 9 | Q14896 | MYBPC3 (human, self) | 88.10 | 2217 |
| 10 | Q6UXM1 | MYBPC3 homolog | 84.90 | 1498 |
| 11 | Q14324 | MYBPC3 homolog | 92.70 | 2028 |
| 12 | Q5XKE0 | MYBPC3 homolog | 92.70 | 2030 |
| 13 | Q9UPX0 | MYBPC3 homolog | 92.90 | 2442 |
| 14 | Q62234 | Mybpc3 (rat) | 84.30 | 2809 |
| 15 | V6CLP5 | MYBPC3 homolog | 39.10 | 2096 |
| 16 | Q86TC9 | MYBPC3 homolog | 87.40 | 2169 |
| 17 | O94898 | MYBPC3 homolog | 88.40 | 1429 |
| 18 | Q52KR2 | MYBPC3 homolog | 88.40 | 1425 |
| 19 | Q5DTJ9 | MYBPC3 homolog | 87.40 | 2164 |
| 20 | Q13203 | MYBPC3 homolog | 84.50 | 783 |
Structural Similarity (ESM2 embedding): 26 proteins identified with >0.96 average similarity, predominantly representing MYBPC3 isoforms and orthologs across species with average similarity scores of 0.95–0.97.
Key Interaction Partners: MYBPC3 primarily interacts with thick filament proteins (myosin, titin, nebulin), thin filament regulators (troponins, tropomyosin, calmodulin variants), and Z-disc/M-line proteins (alpha-actinin-2, telethonin, LIM domain proteins), consistent with its role as a thick filament-associated protein modulating cardiac muscle contraction.
Transcription factor regulatory data
MYBPC3 is not a transcription factor. It is a protein-coding gene encoding myosin-binding protein C, cardiac-type — a structural/regulatory protein of the cardiac sarcomere. Therefore, no downstream targets or DNA binding motif data apply.
Upstream regulators
Comprehensive transcription factor regulatory data for MYBPC3 is not available in the queried biobtree databases. The available evidence shows:
Post-translational regulation (SIGNOR): MYBPC3 is phosphorylated and functionally modulated by kinases PRKACA, PRKACB, and PRKCD at multiple serine residues (Ser275, Ser279, Ser307).
Tissue-specific expression (FANTOM5): MYBPC3 is predominantly expressed in heart tissue (TPM 817.7 in heart, 31.0 in skin, 2.0 in lung), suggesting heart-specific transcriptional regulation.
Cardiac developmental context (Gene Ontology): Associated with cardiac muscle morphogenesis and ventricular development, indicating regulation by cardiac developmental transcription factors, but specific TF-MYBPC3 regulatory relationships (ChIP-seq, experimentally validated, or predicted interactions) are not indexed in available biobtree datasets.
Note: MYBPC3 regulation by cardiac transcription factors (e.g., MEF2, GATA4, NKX2-5, SRF) is likely but requires literature-based or specialized regulatory database queries outside the current biobtree scope.
Drug & pharmacology data
Known drug target status: MYBPC3 is a relatively understudied drug target with limited clinical molecules, but the two identified compounds are in advanced development stages specifically for cardiac conditions driven by MYBPC3 dysfunction.
Targeting Molecules
Total count: 2 confirmed molecules in DrugBank/ChEMBL with clinical development
| Molecule | ID | Mechanism | Highest Phase | Status |
|---|---|---|---|---|
| Omecamtiv mecarbil | CHEMBL1800955, DB11816 | Cardiac myosin activator | Phase 3 | Heart failure indication |
| Aficamten | CHEMBL4847050, DB18490 | Cardiac myosin inhibitor | Phase 3 | Hypertrophic cardiomyopathy indication |
Additional discovery: 1 compound in BindingDB (US20240189292, Compound 10 - patent compound with 220 nM Ki against MYBPC3)
Clinical Trials (Top 20 Relevant)
Omecamtiv Mecarbil Trials (11 total):
| Trial ID | Phase | Status | Intervention |
|---|---|---|---|
| NCT02929329 | Phase 3 | COMPLETED | Omecamtiv mecarbil vs placebo in heart failure with reduced ejection fraction |
| NCT03759392 | Phase 3 | COMPLETED | Omecamtiv mecarbil effect on exercise capacity in HF subjects |
| NCT04464525 | Phase 3 | WITHDRAWN | Post-trial access study |
| NCT00624442 | Phase 2 | COMPLETED | CK-1827452 infusion in stable heart failure |
| NCT00941681 | Phase 2 | COMPLETED | Oral CK-1827452 pharmacokinetics in HF patients |
| NCT01300013 | Phase 2 | COMPLETED | ATOMIC-AHF trial - acute decompensated heart failure |
| NCT02695420 | Phase 2 | COMPLETED | Safety and efficacy in Japanese HF subjects |
| NCT01077167 | Phase 2 | WITHDRAWN | Pharmacokinetic study |
| NCT00748579 | Phase 2 | TERMINATED | Myocardial efficiency study |
| NCT01380223 | Phase 1 | COMPLETED | PK/PD in healthy volunteers |
| NCT02601001 | Phase 1 | COMPLETED | PK study in healthy Japanese adults |
Aficamten Trials (8 total):
| Trial ID | Phase | Status | Intervention |
|---|---|---|---|
| NCT05186818 | Phase 3 | COMPLETED | SEQUOIA-HCM: aficamten vs placebo in obstructive HCM |
| NCT06081894 | Phase 3 | ACTIVE | Non-obstructive HCM efficacy/safety study |
| NCT04848506 | Phase 2/3 | ENROLLING | Long-term safety open-label extension |
| NCT06116968 | Phase 3 | COMPLETED | Chinese population with obstructive HCM |
| NCT06412666 | Phase 2/3 | RECRUITING | Pediatric obstructive HCM study |
| NCT04219826 | Phase 2 | COMPLETED | Dose-finding study (CK-3773274) in HCM |
| NCT04783766 | Phase 1 | COMPLETED | Safety/tolerability/PK study |
| NCT05924815 | Phase 1 | COMPLETED | QT/QTc interval evaluation |
Pharmacogenomics & Clinical Dosing
PharmGKB status: MYBPC3 designated as VIP (Very Important Pharmacogene) gene (PA31351)
- CPIC guideline: None established (no formal clinical dosing recommendations)
- Clinical relevance: MYBPC3 variants are major disease-causing mutations in familial hypertrophic cardiomyopathy (HCM)
Known drug-gene relationships:
- Omecamtiv mecarbil: Mechanism-based target - activates cardiac myosin activity to improve contractility in HF (not variant-dependent)
- Aficamten: Mechanism-based target - inhibits myosin-actin interactions for HCM with MYBPC3 dysfunction (not variant-dependent dosing identified)
Pharmacogenomic note: Unlike cytochrome P450 genes, MYBPC3 variants affect drug indication rather than drug metabolism. Patient selection is based on MYBPC3 mutation status (diagnostic) rather than pharmacogenomic dosing adjustments.
Expression profiles
Tissue expression (Bgee - bulk RNA-seq)
MYBPC3 shows ubiquitous expression with strong cardiac enrichment. Maximum expression score: 99.90 across 149 present calls (vs. 139 absent calls) from 288 conditions.
| Rank | Tissue | Expression Status | Score | Quality |
|---|---|---|---|---|
| 1 | Apex of heart | Present | 99.90 | Gold |
| 2 | Right atrium auricular region | Present | 99.65 | Gold |
| 3 | Cardiac atrium | Present | 99.63 | Gold |
| 4 | Left ventricle myocardium | Present | 99.45 | Gold |
| 5 | Heart left ventricle | Present | 99.34 | Gold |
| 6 | Cardiac ventricle | Present | 99.34 | Gold |
| 7 | Heart right ventricle | Present | 99.29 | Gold |
| 8 | Cardiac muscle of right atrium | Present | 99.25 | Gold |
| 9 | Myocardium | Present | 99.04 | Gold |
| 10 | Vena cava | Present | 96.51 | Gold |
| 11 | Heart | Present | 94.51 | Gold |
| 12 | Triceps brachii (muscle) | Absent | 84.35 | Gold |
| 13 | Gluteal muscle | Absent | 83.88 | Gold |
| 14 | Skeletal muscle (biceps brachii) | Absent | 81.11 | Gold |
| 15 | Male germ line stem cell (testis) | Present | 80.21 | Gold |
| 16 | Tendon of biceps brachii | Absent | 80.08 | Gold |
| 17 | Biceps brachii | Absent | 79.74 | Gold |
| 18 | Skeletal muscle (rectus abdominis) | Absent | 77.98 | Gold |
| 19 | Vastus lateralis | Absent | 77.49 | Gold |
| 20 | Sperm | Absent | 76.92 | Gold |
| 21 | Male germ cell | Absent | 76.90 | Gold |
| 22 | Gingival epithelium | Absent | 76.75 | Gold |
| 23 | Quadriceps femoris | Absent | 76.65 | Gold |
| 24 | Parotid gland | Absent | 76.40 | Gold |
| 25 | Gingiva | Absent | 76.38 | Gold |
| 26 | Brodmann area 10 (brain) | Absent | 76.32 | Gold |
| 27 | Blood | Present | 75.95 | Gold |
| 28 | Endometrium epithelium | Absent | 75.93 | Gold |
| 29 | Tongue body | Absent | 75.74 | Gold |
| 30 | Pericardium | Present | 75.50 | Silver |
Pattern: Highly cardiac-specific with dominant expression in myocardium, ventricular and atrial tissue. Notable expression in vena cava and blood. Absent from skeletal muscle and most non-cardiac tissues.
Single-cell expression (SCXA dataset E-MTAB-11268)
Dataset: “The atlas of the human hypertrophied heart reveals impaired cell communication” (64,898 nuclei from human left ventricle with aortic stenosis)
MYBPC3 is the #1 top marker gene for cardiomyocyte cluster 1:
| Cluster | Cell Type | Score | Log Fold Change | Expression Pattern |
|---|---|---|---|---|
| 1 | Cardiac muscle cell (cardiomyocyte) | 139.36 | 4.24 | Top ranked |
| 2 | Fibroblast/stromal (enriched) | ~99–147 | 5.7–8.96 | Present but reduced |
| 3 | Immune/other (enriched) | ~43–111 | 3.2–9.12 | Low expression |
| 4 | Mixed/endothelial (enriched) | ~65–86 | 3.2–7.73 | Low-moderate |
Notable patterns:
- Cluster 1 (cardiac muscle cells) shows MYBPC3 as the dominant marker, consistent with cardiac sarcomere assembly function
- Expression decreases significantly in fibroblasts (Cluster 2) and immune cells (Cluster 3)
- This reflects MYBPC3’s role as a thick filament protein in cardiac myofibrils
Summary
MYBPC3 is cardiac-enriched with ubiquitous breadth. In tissue, expression peaks in all cardiac compartments (ventricles, atria, myocardium) with scores >99. In the hypertrophied heart single-cell atlas, MYBPC3 is the top marker for cardiomyocytes, reflecting its essential role in cardiac sarcomere structure.
Disease associations
Mendelian/Monogenic Diseases
Primary Disease Associations:
| Disease Name | Disease ID | Inheritance | Evidence Level |
|---|---|---|---|
| Hypertrophic Cardiomyopathy 4 | OMIM 115197, MONDO:0007268 | Autosomal dominant | Definitive |
| Hypertrophic Cardiomyopathy 4 | OMIM 115197, MONDO:0007268 | Autosomal recessive | Strong |
| Left Ventricular Noncompaction 10 | OMIM 615396, MONDO:0014163 | Autosomal dominant | Definitive/Moderate |
| Left Ventricular Noncompaction 10 | OMIM 615396, MONDO:0014163 | Autosomal recessive | Limited |
| Atrial Fibrillation | MONDO:0004981 | Autosomal dominant | Limited |
| Familial Isolated Dilated Cardiomyopathy | ORPHANET:154 | Autosomal dominant | Supportive |
Related Cardiomyopathy Phenotypes (via ClinVar):
- Hypertrophic cardiomyopathy (MONDO:0005045)
- Dilated cardiomyopathy (MONDO:0005021)
- Dilated cardiomyopathy 1A (MONDO:0007269)
- Familial dilated cardiomyopathy (MONDO:0016333)
- Left ventricular noncompaction (MONDO:0018901)
- Brugada syndrome (MONDO:0015263)
- Catecholaminergic polymorphic ventricular tachycardia (MONDO:0017990, MONDO:0011484)
Phenotype Associations (Top 30 HPO Terms)
| HPO ID | Phenotype |
|---|---|
| HP:0001639 | Hypertrophic cardiomyopathy |
| HP:0001644 | Dilated cardiomyopathy |
| HP:0030682 | Left ventricular noncompaction |
| HP:0001635 | Congestive heart failure |
| HP:0012664 | Reduced left ventricular ejection fraction |
| HP:0001645 | Sudden cardiac death |
| HP:0001663 | Ventricular fibrillation |
| HP:0011675 | Arrhythmia |
| HP:0025169 | Left ventricular systolic dysfunction |
| HP:0001714 | Ventricular hypertrophy |
| HP:0005144 | Ventricular septal hypertrophy |
| HP:0001678 | Atrioventricular block |
| HP:0011705 | First degree atrioventricular block |
| HP:0011712 | Complete right bundle branch block |
| HP:0011713 | Left bundle branch block |
| HP:0001698 | Pericardial effusion |
| HP:0001640 | Cardiomegaly |
| HP:0001695 | Cardiac arrest |
| HP:0033755 | Increased left ventricular end-diastolic volume |
| HP:0001279 | Syncope |
| HP:0001541 | Ascites |
| HP:0002240 | Hepatomegaly |
| HP:0002094 | Dyspnea |
| HP:0002875 | Exertional dyspnea |
| HP:0012764 | Orthopnea |
| HP:0012378 | Fatigue |
| HP:0031318 | Myofiber disarray |
| HP:0000969 | Edema |
| HP:0100598 | Pulmonary edema |
| HP:0100749 | Chest pain |
Complex Disease / GWAS Associations (Top 30)
| Trait/Disease | Lead Gene | p-value |
|---|---|---|
| Apolipoprotein A1 levels | MYBPC3 | 3.0e-63 |
| HDL cholesterol levels | MYBPC3 | 1.0e-106 |
| HDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers interaction) | MYBPC3 | 5.0e-69 |
| HDL cholesterol levels in current drinkers | MYBPC3 | 4.0e-22 |
| Triglyceride levels x alcohol consumption (regular vs non-regular drinkers interaction) | MYBPC3 | 6.0e-07 |
| Thrombin generation potential phenotypes | MYBPC3 | 5.0e-22 |
| Alcohol consumption | MYBPC3 | 5.0e-14 |
| Medication use (renin-angiotensin system agents) | MYBPC3 | 5.0e-13 |
| Pulse pressure | MYBPC3 | 4.0e-14 |
| Intraocular pressure | MYBPC3 | 1.0e-18 |
| Multiple sclerosis | MYBPC3 | 1.0e-13 |
| Electrocardiogram morphology (amplitude at multiple temporal datapoints) | MYBPC3 | 2.0e-12 to 9.0e-09 |
| Monocyte count | MYBPC3 | 9.0e-10 |
Summary: MYBPC3 mutations predominantly cause cardiomyopathies with strong evidence for hypertrophic cardiomyopathy 4 and left ventricular noncompaction 10. The gene shows extensive cardiac phenotype associations via HPO and complex disease associations in GWAS studies, particularly for lipid metabolism, cardiac electrical properties, and cardiometabolic traits.