MYBPC1

Summary

MYBPC1 (myosin binding protein C1, HGNC:7549) is a protein-coding gene on chromosome 12q23.2, encoding Myosin-binding protein C, slow-type (Q00872). 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. Myosin-binding protein C family members are myosin-associated proteins found in the cross-bridge-bearing zone (C region) of A bands in striated muscle. The encoded protein is the slow skeletal muscle isoform of myosin-binding protein C and plays an important role in muscle contraction by recruiting muscle-type creatine kinase to myosin filaments. Mutations in this gene are associated with distal arthrogryposis type I. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene.

Source: NCBI Gene 4604 — RefSeq curated summary.

At a glance

• Gene–disease (curated): arthrogryposis, distal, type 1B (Strong, GenCC) — +6 more curated relationships
• GWAS associations: 2
• Clinical variants (ClinVar): 415 total — 5 pathogenic, 5 likely-pathogenic
• Phenotypes (HPO): 35
• MANE Select transcript: NM_002465

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7549
Approved symbol	MYBPC1
Name	myosin binding protein C1
Location	12q23.2
Locus type	gene with protein product
Status	Approved
Aliases	ssMyBP-C
Ensembl gene	ENSG00000196091
Ensembl biotype	protein_coding
OMIM	160794
Entrez	4604

Gene structure

Transcript identifiers

Ensembl transcripts: 41 — 32 protein_coding, 4 retained_intron, 4 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000361466, ENST00000361685, ENST00000392934, ENST00000452455, ENST00000536007, ENST00000541119, ENST00000545503, ENST00000547405, ENST00000547509, ENST00000547627, ENST00000548298, ENST00000548532, ENST00000548834, ENST00000549145, ENST00000549608, ENST00000550270, ENST00000550312, ENST00000550501, ENST00000550514, ENST00000550812, ENST00000551300, ENST00000552198, ENST00000553190, ENST00000673861, ENST00000971973, ENST00000971974, ENST00000971975, ENST00000971976, ENST00000971977, ENST00000971978, ENST00000971979, ENST00000971980, ENST00000971981, ENST00000971982, ENST00000971983, ENST00000971984, ENST00000971985, ENST00000971986, ENST00000971987, ENST00000971988, ENST00000971989

RefSeq mRNA: 17 — MANE Select: NM_002465 NM_001254718, NM_001254719, NM_001254720, NM_001254721, NM_001254722, NM_001254723, NM_001404675, NM_001404676, NM_001404677, NM_001404678, NM_001404679, NM_001404680, NM_001404681, NM_002465, NM_206819, NM_206820, NM_206821

CCDS: CCDS55877, CCDS58268, CCDS58269, CCDS58270, CCDS58271, CCDS58272, CCDS58273, CCDS9083, CCDS9084, CCDS9085

Canonical transcript exons

ENST00000361466 — 32 exons

Exon	Start	End
ENSE00000937702	101642419	101642585
ENSE00000937703	101644664	101644796
ENSE00000937704	101646763	101646887
ENSE00000937705	101648045	101648150
ENSE00000937706	101649260	101649426
ENSE00002207905	101663426	101663560
ENSE00002238757	101659672	101659831
ENSE00002246646	101662358	101662546
ENSE00002256370	101651231	101651393
ENSE00002258967	101652678	101652784
ENSE00002264957	101661158	101661262
ENSE00002306286	101653115	101653248
ENSE00003492930	101626872	101626910
ENSE00003527577	101617202	101617243
ENSE00003534697	101632021	101632138
ENSE00003535662	101636672	101636728
ENSE00003564730	101684382	101684424
ENSE00003568633	101594971	101595095
ENSE00003572980	101680343	101680529
ENSE00003579729	101677235	101677394
ENSE00003582745	101634554	101634605
ENSE00003586674	101614496	101614531
ENSE00003592509	101627769	101627804
ENSE00003595705	101629434	101629544
ENSE00003596790	101631571	101631719
ENSE00003601735	101673427	101673622
ENSE00003637650	101670321	101670409
ENSE00003651959	101678102	101678238
ENSE00003653274	101667732	101667899
ENSE00003657796	101682604	101682662
ENSE00003673833	101675292	101675431
ENSE00003894485	101685582	101686028

Expression profiles

Bgee: expression breadth ubiquitous, 225 present calls, max score 99.96.

FANTOM5 (CAGE): breadth broad, TPM avg 45.5600 / max 17937.6621, expressed in 228 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
127609	42.5984	172
127637	1.3221	96
127634	0.6897	84
127633	0.4589	78
127636	0.1132	62
127635	0.0805	51
127612	0.0787	23
127610	0.0646	17
127614	0.0637	15
127615	0.0452	16

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
biceps brachii	UBERON:0001507	99.96	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	99.96	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	99.95	gold quality
skeletal muscle tissue	UBERON:0001134	99.92	gold quality
deltoid	UBERON:0001476	99.92	gold quality
vastus lateralis	UBERON:0001379	99.91	gold quality
gastrocnemius	UBERON:0001388	99.91	gold quality
gluteal muscle	UBERON:0002000	99.91	gold quality
quadriceps femoris	UBERON:0001377	99.90	gold quality
triceps brachii	UBERON:0001509	99.90	gold quality
hindlimb stylopod muscle	UBERON:0004252	99.90	gold quality
diaphragm	UBERON:0001103	99.89	gold quality
tibialis anterior	UBERON:0001385	99.87	gold quality
body of tongue	UBERON:0011876	99.86	gold quality
muscle organ	UBERON:0001630	99.51	gold quality
muscle of leg	UBERON:0001383	99.35	gold quality
cranial nerve II	UBERON:0000941	98.13	gold quality
medial globus pallidus	UBERON:0002477	97.72	gold quality
globus pallidus	UBERON:0001875	97.51	gold quality
lateral globus pallidus	UBERON:0002476	97.32	gold quality
substantia nigra	UBERON:0002038	95.62	gold quality
midbrain	UBERON:0001891	94.97	gold quality
hypothalamus	UBERON:0001898	94.49	gold quality
ventral tegmental area	UBERON:0002691	94.30	gold quality
substantia nigra pars reticulata	UBERON:0001966	93.97	gold quality
tongue	UBERON:0001723	93.96	gold quality
nucleus accumbens	UBERON:0001882	93.48	gold quality
muscle tissue	UBERON:0002385	93.43	gold quality
pharyngeal mucosa	UBERON:0000355	93.32	gold quality
superior vestibular nucleus	UBERON:0007227	91.50	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)

22 targeting MYBPC1, 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-450B-5P	99.92	71.48	3175
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-4779	99.86	66.50	1583
HSA-MIR-4503	99.85	71.45	1869
HSA-MIR-6515-3P	99.82	68.19	1933
HSA-MIR-4658	99.77	64.94	514
HSA-MIR-6790-5P	99.77	65.24	505
HSA-MIR-766-5P	99.47	67.91	2225
HSA-MIR-330-3P	99.41	69.95	2521
HSA-MIR-3678-3P	99.31	67.10	1432
HSA-MIR-4695-5P	99.06	64.87	1151
HSA-MIR-16-1-3P	98.70	69.23	1538
HSA-MIR-4266	98.53	67.29	1035
HSA-MIR-676-5P	98.49	68.87	1492
HSA-MIR-3187-5P	98.36	65.74	1776
HSA-MIR-1285-3P	97.72	67.02	1932
HSA-MIR-5189-5P	97.72	66.96	1814
HSA-MIR-612	97.26	65.95	1597
HSA-MIR-6860	97.21	66.31	1656
HSA-MIR-3184-3P	96.96	66.91	845
HSA-MIR-6872-5P	95.60	67.57	55
HSA-MIR-6814-3P	93.66	66.98	50

Literature-anchored findings (GeneRIF, showing 16)

• Screening patients with dilated cardiomyopathy, as well as hypertrophic cardiomyopathy, for this mutation is of signifiant importance with this mutation diagnosing dilated cardiomyopathy. (PMID:12628722)
• The present study demonstrates slow skeletal muscle type C-protein in moderate amount in right atrium and interatrial septum of adult human, rabbit, rat and bovine hearts using both immunocytochemical and immunoblotting procedures. (PMID:16003462)
• to determine whether HCM mutations in beta myosin heavy chain located within the light meromyosin portion alter the binding of cMyBP-C, and to define the precise region of this binding. (PMID:16918501)
• These findings reveal that the MYBPC1 is a novel gene responsible for DA1, though the mechanism of disease may differ from how some cardiac MYBPC3 mutations cause hypertrophic cardiomyopathy. (PMID:20045868)
• Significant molecule MYBPC1 phosphoprotein network from 12 frontal cortex of HIV encephalitis (HIVE) control patients and 16 HIVE, was identified and constructed. (PMID:21061152)
• MyBPC1 acts as an adaptor to connect the ATP consumer (myosin) and the regenerator (muscle type creatine kinase) for efficient energy metabolism and homoeostasis. (PMID:21426302)
• Autosomal recessive lethal congenital contractural syndrome type 4 (LCCS4) caused by a mutation in MYBPC1 (PMID:22610851)
• Mutations in the MYH7 gene, rather than in the MYBPC3 gene, were also related to a worse prognosis. This is the first work characterizing HC molecular epidemiology in the Brazilian population for the 3 most important genes. (PMID:24093860)
• Two novel mutations in myosin binding protein C slow causing distal arthrogryposis type 2 were both found to occur in the C2 immunoglobulin domain, which constitutes part of the binding site for the S2 subfragment of myosin. (PMID:25679999)
• A novel milder MYBPC1 homozygous phenotype causes arthrogryposis multiplex congenita in a consanguineous Israeli Druze pedigree. (PMID:26661508)
• Ca(2+) modulates the interaction of cMyBP-C with the thin filament in the sarcomere. (PMID:26831109)
• Two novel missense mutations in MYBPC1 were linked to a dominant, mild skeletal myopathy associated with a distinctive tremor. (PMID:31025394)
• Data substantiate that damaging variants in MYBPC1 are associated with a new form of an early-onset myopathy with tremor, which is a defining and consistent characteristic in all affected individuals, with no contractures. Recognition of this expanded myopathic phenotype can enable identification of individuals with MYBPC1 variants without arthrogryposis. (PMID:31264822)
• MYBPC1 is a key regulator for laryngeal carcinoma formation. (PMID:36539363)
• A Case Series of Patients With MYBPC1 Gene Variants Featuring Undulating Tongue Movements as Myogenic Tremor. (PMID:37392669)
• Congenital tremor and myopathy secondary to novel MYBPC1 variant. (PMID:38185014)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	mybpc1	ENSDARG00000045560
mus_musculus	Mybpc1	ENSMUSG00000020061
rattus_norvegicus	Mybpc1	ENSRNOG00000056493
drosophila_melanogaster	mtgo	FBGN0259735
caenorhabditis_elegans		WBGENE00007944

Paralogs (11): MYOM2 (ENSG00000036448), FNDC3B (ENSG00000075420), MYBPC2 (ENSG00000086967), MYOM1 (ENSG00000101605), FNDC3A (ENSG00000102531), OBSL1 (ENSG00000124006), MYBPH (ENSG00000133055), MYBPC3 (ENSG00000134571), MYOM3 (ENSG00000142661), IGSF22 (ENSG00000179057), MYBPHL (ENSG00000221986)

Protein

Protein identifiers

Myosin-binding protein C, slow-type — Q00872 (reviewed: Q00872)

Alternative names: C-protein, skeletal muscle slow isoform

All UniProt accessions (7): A0A669KAR9, A0A669KB32, Q00872, F8VZE0, F8VZY0, F8W1Z9, G3V1V7

UniProt curated annotations — full annotation on UniProt →

Function. Thick filament-associated protein located in the crossbridge region of vertebrate striated muscle a bands. Slow skeletal protein that binds to both myosin and actin. In vitro, binds to native thin filaments and modifies the activity of actin-activated myosin ATPase. May modulate muscle contraction or may play a more structural role.

Subunit / interactions. Interacts with USP25 (isoform USP25m only); the interaction prevents proteasomal degradation of MYBPC1.

Disease relevance. 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. The disease is caused by variants affecting the gene represented in this entry. 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. The disease is caused by variants affecting the gene represented in this entry. Congenital myopathy 16 (CMYO16) [MIM:618524] An autosomal dominant muscular disorder characterized by muscle weakness, hypotonia associated with high-frequency postural tremor of the limbs, mildly delayed walking, and steppage gait. Additional features include skeletal deformities such as scoliosis, thoracic asymmetry and spinal rigidity. Some patients show mild facial dysmorphic features. Cognitive functions are normal. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the immunoglobulin superfamily. MyBP family.

Isoforms (10)

UniProt ID	Names	Canonical?
Q00872-1	1	yes
Q00872-2	2
Q00872-3	3
Q00872-4	4
Q00872-5	5
Q00872-6	6
Q00872-7	7
Q00872-8	8
Q00872-9	9
Q00872-10	10

RefSeq proteins (17): NP_001241647, NP_001241648, NP_001241649, NP_001241650, NP_001241651, NP_001241652, NP_001391604, NP_001391605, NP_001391606, NP_001391607, NP_001391608, NP_001391609, NP_001391610, NP_002456, NP_996555, NP_996556, NP_996557 (=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 (114 total): strand 45, sequence conflict 29, domain 10, splice variant 9, sequence variant 8, modified residue 4, turn 3, helix 3, chain 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

8 structures.

PDB	Method	Resolution (Å)
2YXM	X-RAY DIFFRACTION	1.51
1X44	SOLUTION NMR
2DAV	SOLUTION NMR
2YUV	SOLUTION NMR
2YUW	SOLUTION NMR
2YUX	SOLUTION NMR
2YUZ	SOLUTION NMR
9PFE	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q00872-F1	81.99	0.47

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (4): 406, 611, 798, 823

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: 213 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_DN, AAGCAAT_MIR137, KAAB_HEART_ATRIUM_VS_VENTRICLE_UP, GOBP_STRIATED_MUSCLE_CELL_DIFFERENTIATION, MODULE_329, GOBP_SARCOMERE_ORGANIZATION, CAGCTG_AP4_Q5, CEBPB_01, PAX8_B, GOBP_CELLULAR_COMPONENT_ASSEMBLY_INVOLVED_IN_MORPHOGENESIS, GOBP_MUSCLE_STRUCTURE_DEVELOPMENT, MODULE_202, BLALOCK_ALZHEIMERS_DISEASE_UP, GOBP_ACTOMYOSIN_STRUCTURE_ORGANIZATION, GOBP_ORGANELLE_ASSEMBLY

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

GO Molecular Function (6): actin binding (GO:0003779), structural constituent of muscle (GO:0008307), myosin binding (GO:0017022), titin binding (GO:0031432), structural molecule activity (GO:0005198), protein binding (GO:0005515)

GO Cellular Component (4): cytosol (GO:0005829), myofibril (GO:0030016), 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
cytoskeletal protein binding	3
cellular anatomical structure	2
cellular process	1
myofibril assembly	1
actomyosin structure organization	1
structural molecule activity	1
molecular_function	1
binding	1
cytoplasm	1
contractile muscle fiber	1
A band	1
myosin complex	1
supramolecular fiber	1

Protein interactions and networks

STRING

1736 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MYBPC1	FLNC	Q14315	828
MYBPC1	KY	Q8NBH2	771
MYBPC1	TNNT1	P13805	681
MYBPC1	TNNT3	P45378	659
MYBPC1	SNTB1	Q13884	658
MYBPC1	OBSCN	Q5VST9	647
MYBPC1	TNNI2	P48788	636
MYBPC1	MYL2	P10916	606
MYBPC1	MYH3	P11055	593
MYBPC1	SGCG	Q13326	581
MYBPC1	SGCB	Q16585	580
MYBPC1	SGCA	Q16586	573
MYBPC1	SGCD	Q92629	552
MYBPC1	TPM2	P06468	549
MYBPC1	MYH8	P13535	528

IntAct

34 interactions, top by confidence:

A	B	Type	Score
GABARAP	MYBPC1	psi-mi:“MI:0407”(direct interaction)	0.440
GABARAPL1	MYBPC1	psi-mi:“MI:0407”(direct interaction)	0.440
GABARAPL2	MYBPC1	psi-mi:“MI:0407”(direct interaction)	0.440
MYBPC1	PCNA	psi-mi:“MI:0915”(physical association)	0.370
NP	KPNA6	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
MFGE8	MYH7B	psi-mi:“MI:0914”(association)	0.350
MRPS23	MYH7B	psi-mi:“MI:0914”(association)	0.350
TTC4	MYH7B	psi-mi:“MI:0914”(association)	0.350
MYBPC1	ACO1	psi-mi:“MI:0915”(physical association)	0.000
MYBPC1	AMOT	psi-mi:“MI:0915”(physical association)	0.000
MYBPC1	ANKRD1	psi-mi:“MI:0915”(physical association)	0.000
MYBPC1	ASH2L	psi-mi:“MI:0915”(physical association)	0.000
C1QTNF9	MYBPC1	psi-mi:“MI:0915”(physical association)	0.000
MYBPC1	CAPN3	psi-mi:“MI:0915”(physical association)	0.000
MYBPC1	CLIP4	psi-mi:“MI:0915”(physical association)	0.000
MYBPC1	DNAJB5	psi-mi:“MI:0915”(physical association)	0.000
MYBPC1	DNAJB6	psi-mi:“MI:0915”(physical association)	0.000
MYBPC1	DYSF	psi-mi:“MI:0915”(physical association)	0.000
DYSF	MYBPC1	psi-mi:“MI:0915”(physical association)	0.000
FHL1	MYBPC1	psi-mi:“MI:0915”(physical association)	0.000
MYBPC1	KLHL41	psi-mi:“MI:0915”(physical association)	0.000
MYBPC2	MYBPC1	psi-mi:“MI:0915”(physical association)	0.000
MYBPC1	MYBPC2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (46): MYBPC1 (Two-hybrid), MYBPC1 (Two-hybrid), MYBPC1 (Two-hybrid), MYBPC1 (Two-hybrid), MYBPC1 (Affinity Capture-Western), FHL1 (Reconstituted Complex), MYBPC1 (Two-hybrid), MYBPC1 (Two-hybrid), MYBPC1 (Affinity Capture-Western), MYBPC1 (Affinity Capture-Western), MYBPC1 (Synthetic Growth Defect), MYBPC1 (Affinity Capture-MS), MYBPC1 (Affinity Capture-MS), MYBPC1 (Two-hybrid), MYBPC1 (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, A2AAJ9, A2ASS6, A2RUH7, O75147, O94856, O94898, P05548, P52179, P54296, P97685, Q00872, Q23551, Q52KR2, Q5VST9, Q62234, Q80W87, Q810U3, Q8WX93, Q92626, A2CG49, F1M0Z1, O08775, O60229, O70468, O75962, O88599, P11799, P16419, P35918, P56741, P70402, P97924, Q05623, Q0KL02, Q13203, Q14324, Q14896, Q15746, Q5FW53

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	5
Likely pathogenic	5
Uncertain significance	180
Likely benign	75
Benign	112

Top pathogenic / likely-pathogenic (10)

Variant ID	HGVS	Classification
29800	NM_002465.4(MYBPC1):c.706T>C (p.Trp236Arg)	Pathogenic
29801	NM_002465.4(MYBPC1):c.2566T>C (p.Tyr856His)	Pathogenic
4795471	NM_002465.4(MYBPC1):c.788T>C (p.Leu263Pro)	Pathogenic
635215	NM_002465.4(MYBPC1):c.788T>G (p.Leu263Arg)	Pathogenic
689419	NM_002465.4(MYBPC1):c.739T>C (p.Tyr247His)	Pathogenic
1180783	NM_002465.4(MYBPC1):c.122del (p.Pro41fs)	Likely pathogenic
1801331	NM_002465.4(MYBPC1):c.793C>G (p.Arg265Gly)	Likely pathogenic
3337339	NM_002465.4(MYBPC1):c.832+1G>C	Likely pathogenic
4082076	NM_002465.4(MYBPC1):c.795_803dup (p.Arg268_Met269insLeuLysArg)	Likely pathogenic
523451	NM_002465.4(MYBPC1):c.1678G>C (p.Val560Leu)	Likely pathogenic

SpliceAI

4046 predictions. Top by Δscore:

Variant	Effect	Δscore
12:101629424:T:A	acceptor_gain	1.0000
12:101629429:ATCAG:A	acceptor_loss	1.0000
12:101629430:TCAGA:T	acceptor_loss	1.0000
12:101629431:CAGAC:C	acceptor_loss	1.0000
12:101629432:A:AG	acceptor_gain	1.0000
12:101629432:AGACT:A	acceptor_gain	1.0000
12:101629433:G:GA	acceptor_gain	1.0000
12:101629433:GA:G	acceptor_gain	1.0000
12:101629433:GAC:G	acceptor_gain	1.0000
12:101629433:GACT:G	acceptor_gain	1.0000
12:101629433:GACTG:G	acceptor_gain	1.0000
12:101629541:GTTG:G	donor_gain	1.0000
12:101629545:G:GG	donor_gain	1.0000
12:101629545:G:T	donor_loss	1.0000
12:101629546:TGAG:T	donor_loss	1.0000
12:101629547:GA:G	donor_loss	1.0000
12:101631565:TTCTA:T	acceptor_loss	1.0000
12:101631566:TCTA:T	acceptor_loss	1.0000
12:101631568:TA:T	acceptor_loss	1.0000
12:101631569:A:AG	acceptor_gain	1.0000
12:101631570:G:GG	acceptor_gain	1.0000
12:101631677:G:GT	donor_gain	1.0000
12:101631677:G:T	donor_gain	1.0000
12:101631715:GTCGG:G	donor_gain	1.0000
12:101631717:CGGGT:C	donor_loss	1.0000
12:101631719:GGTAA:G	donor_loss	1.0000
12:101631720:G:GG	donor_gain	1.0000
12:101631720:GTAA:G	donor_loss	1.0000
12:101631721:T:TC	donor_loss	1.0000
12:101632099:GA:G	donor_gain	1.0000

AlphaMissense

7764 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:101661223:T:A	W640R	1.000
12:101661223:T:C	W640R	1.000
12:101662396:T:A	W666R	1.000
12:101662396:T:C	W666R	1.000
12:101662398:G:C	W666C	1.000
12:101662398:G:T	W666C	1.000
12:101662478:G:C	R693P	1.000
12:101663491:T:A	W738R	1.000
12:101663491:T:C	W738R	1.000
12:101667822:G:C	R809P	1.000
12:101675409:A:C	Q969P	1.000
12:101677317:G:C	R1004P	1.000
12:101631636:T:A	W94R	0.999
12:101631636:T:C	W94R	0.999
12:101644759:T:A	W285R	0.999
12:101644759:T:C	W285R	0.999
12:101648149:T:A	W374R	0.999
12:101648149:T:C	W374R	0.999
12:101651332:T:A	W464R	0.999
12:101651332:T:C	W464R	0.999
12:101653231:T:A	W559R	0.999
12:101653231:T:C	W559R	0.999
12:101659730:T:C	L584P	0.999
12:101659768:T:G	Y597D	0.999
12:101659826:T:A	V616D	0.999
12:101661164:C:A	P620H	0.999
12:101661224:G:C	W640S	0.999
12:101661225:G:C	W640C	0.999
12:101661225:G:T	W640C	0.999
12:101661245:G:A	G647E	0.999

dbSNP variants (sampled 300 via entrez): RS1000031946 (12:101649856 G>A), RS1000047576 (12:101609180 G>A), RS1000103246 (12:101614322 G>T), RS1000141491 (12:101619658 T>C), RS1000145227 (12:101643218 C>A), RS1000159486 (12:101656609 G>A), RS1000182050 (12:101603254 G>A,C), RS1000189816 (12:101687214 C>A), RS1000193694 (12:101594322 G>A), RS1000206886 (12:101638144 T>C), RS1000222680 (12:101675159 C>A,G,T), RS1000240129 (12:101620323 A>C), RS1000249707 (12:101681338 C>T), RS1000289613 (12:101636296 C>T), RS1000294696 (12:101674905 G>A)

Disease associations

OMIM: gene MIM:160794 | disease phenotypes: MIM:614335, MIM:614915, MIM:618524, MIM:108120

GenCC curated gene-disease

Disease	Classification	Inheritance
arthrogryposis, distal, type 1B	Strong	Autosomal dominant
lethal congenital contracture syndrome 4	Strong	Autosomal recessive
myopathy, congenital, with tremor	Strong	Autosomal dominant
myopathy	Strong	Autosomal dominant
arthrogryposis	Strong	Autosomal recessive
digitotalar dysmorphism	Supportive	Autosomal dominant
lethal congenital contracture syndrome 3	Supportive	Autosomal recessive

Mondo (10): arthrogryposis, distal, type 1B (MONDO:0013698), lethal congenital contracture syndrome 4 (MONDO:0013965), myopathy, congenital, with tremor (MONDO:0032797), MYBPC1-related autosomal recessive non-lethal arthrogryposis multiplex congenita syndrome (MONDO:0044682), intellectual disability (MONDO:0001071), distal arthrogryposis (MONDO:0019942), digitotalar dysmorphism (MONDO:0015240), lethal congenital contracture syndrome 3 (MONDO:0012656), myopathy (MONDO:0005336), arthrogryposis (MONDO:0008779)

Orphanet (4): Distal arthrogryposis type 1 (Orphanet:1146), MYBPC1-related autosomal recessive non-lethal arthrogryposis multiplex congenita syndrome (Orphanet:498693), Distal arthrogryposis (Orphanet:97120), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

35 total (30 of 35 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000160	Narrow mouth
HP:0000218	High palate
HP:0000347	Micrognathia
HP:0001181	Adducted thumb
HP:0001371	Flexion contracture
HP:0001387	Joint stiffness
HP:0001762	Talipes equinovarus
HP:0001838	Rocker bottom foot
HP:0001883	Talipes
HP:0002093	Respiratory insufficiency
HP:0002174	Postural tremor
HP:0002460	Distal muscle weakness
HP:0002650	Scoliosis
HP:0002804	Arthrogryposis multiplex congenita
HP:0002828	Multiple joint contractures
HP:0002938	Lumbar hyperlordosis
HP:0003202	Skeletal muscle atrophy
HP:0003272	Abnormal hip bone morphology
HP:0003306	Spinal rigidity
HP:0003327	Axial muscle weakness
HP:0003458	EMG: myopathic abnormalities
HP:0003577	Congenital onset
HP:0003691	Scapular winging
HP:0003701	Proximal muscle weakness
HP:0005272	Prominent nasolabial fold
HP:0005684	Distal arthrogryposis
HP:0008366	Foot joint contracture
HP:0009465	Ulnar deviation of finger

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST002165_8	Lung function (FEV1)	7.000000e-07
GCST010679_1	Memory decline	2.000000e-07

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004314	forced expiratory volume
EFO:0004874	memory performance
EFO:0007710	cognitive decline measurement

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D001176	Arthrogryposis	C05.550.150; C05.651.102; C05.660.077; C16.131.621.077
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
C565097	Digitotalar Dysmorphism (supp.)
C566961	Lethal Congenital Contractural Syndrome 3 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Nickel	decreases expression	2
Valproic Acid	affects expression, increases expression	2
bisphenol F	increases methylation, affects cotreatment	1
propionaldehyde	decreases expression	1
bisphenol A	decreases methylation	1
lead acetate	decreases expression	1
mono-(2-ethylhexyl)phthalate	increases abundance, increases methylation	1
cupric chloride	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	increases expression, affects cotreatment, affects response to substance	1
perfluorooctane sulfonic acid	increases expression	1
acyline	decreases expression	1
incobotulinumtoxinA	decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Arsenic	affects methylation	1
Vehicle Emissions	decreases methylation	1
Benzo(a)pyrene	affects methylation	1
Calcitriol	increases expression, affects cotreatment	1
Diethylhexyl Phthalate	increases abundance, increases methylation	1
Lipopolysaccharides	affects response to substance, increases expression, affects cotreatment	1
Dihydrotestosterone	increases expression	1
Testosterone	affects cotreatment, increases expression	1
Fluorescein-5-isothiocyanate	affects binding	1
Okadaic Acid	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00120055	PHASE4	COMPLETED	Association Between Systemic Exposure of Atorvastatin and Metabolites and Atorvastatin-induced Myotoxicity
NCT03633565	PHASE4	UNKNOWN	Comparative Study of Strategies for Management of Duchenne Myopathy (DM)
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT01225614	PHASE3	UNKNOWN	Efficacy and Tolerance of Early Launching of Nocturnal Non Invasive
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT01028833	PHASE2	COMPLETED	Effects of Power Mobility on Young Children With Severe Motor Impairments
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT00278564	PHASE1	TERMINATED	Stem Cell Transplantation in Idiopathic Inflammatory Myopathy Diseases
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT01642056	PHASE1/PHASE2	COMPLETED	EPI-743 for Metabolism or Mitochondrial Disorders
NCT02124070	PHASE1/PHASE2	WITHDRAWN	Therapeutic Effect of Recombinant Human Growth Hormone (rhGH) on the Myopathy of Cystinosis
NCT00549029	Not specified	UNKNOWN	The Association of Genetic Polymorphisms With Statin-Induced Myopathy.
NCT00767130	Not specified	UNKNOWN	DNA Diagnostic System for Statin Safety and Efficacy
NCT00922428	Not specified	COMPLETED	PASCOE-Agil HOM-Injektopas in the Treatment of Rheumatic Disorders
NCT00937001	Not specified	ACTIVE_NOT_RECRUITING	Critical Illness Myopathy as a Cause of Debilitating ICU-Acquired Weakness
NCT00990834	Not specified	WITHDRAWN	Muscle Characteristics Associated With Statin Therapy
NCT01022450	Not specified	UNKNOWN	Study of the Causes of the Breakdown of Muscle Fibers in Hospitalized Patients
NCT01040650	Not specified	TERMINATED	Metabolic Features of Post-Myopathy Patients Associated With Statin Treatment
NCT01047163	Not specified	COMPLETED	Maintenance of Muscle Mass in Older People: the Negative Impact of Statin Therapy
NCT01270269	Not specified	COMPLETED	ACT-ICU Study: Activity and Cognitive Therapy in the Intensive Care Unit
NCT01353430	Not specified	RECRUITING	Characterization of Inclusion Body Myopathy Associated With Paget’s Disease of Bone and Frontotemporal Dementia (IBMPFD)
NCT01395563	Not specified	WITHDRAWN	Strength Training on Pancreatic Cancer
NCT01530841	Not specified	COMPLETED	Efficacy and Tolerance of AVAPS Mode in Myotonic Dystrophy
NCT01547767	Not specified	COMPLETED	Investigations Into ISCU Myopathy or Iron Sulfur Scaffold U Protein Myopathy
NCT01702987	Not specified	COMPLETED	Evaluation of Ubiquinol on Mitochondrial Oxidative Capacity in Statin Patients Using 31PMRS
NCT01790178	Not specified	COMPLETED	Ultrasound in Muscle Biopsy
NCT02011282	Not specified	COMPLETED	Electro-Neuro-Muscular Stimulation in ICU
NCT02104921	Not specified	COMPLETED	Innovative Ultrasound Technology in Neuromuscular Disease
NCT02118805	Not specified	COMPLETED	Innovative Measures of Speech and Swallowing Dysfunction in Neurological Disorders
NCT02235220	Not specified	UNKNOWN	Reduction of Masticatory Muscle Activity by Restoring Canine Guidance