HACD1

Summary

HACD1 (3-hydroxyacyl-CoA dehydratase 1, HGNC:9639) is a protein-coding gene on chromosome 10p12.33, encoding Very-long-chain (3R)-3-hydroxyacyl-CoA dehydratase 1 (B0YJ81). Catalyzes the third of the four reactions of the long-chain fatty acids elongation cycle.

The protein encoded by this gene contains a characteristic catalytic motif of the protein tyrosine phosphatases (PTPs) family. The PTP motif of this protein has the highly conserved arginine residue replaced by a proline residue; thus it may represent a distinct class of PTPs. Members of the PTP family are known to be signaling molecules that regulate a variety of cellular processes. This gene was preferentially expressed in both adult and fetal heart. A much lower expression level was detected in skeletal and smooth muscle tissues, and no expression was observed in other tissues. The tissue specific expression in the developing and adult heart suggests a role in regulating cardiac development and differentiation.

Source: NCBI Gene 9200 — RefSeq curated summary.

At a glance

• Gene–disease (curated): congenital myopathy (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 1
• Clinical variants (ClinVar): 192 total — 15 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 73
• MANE Select transcript: NM_014241

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9639
Approved symbol	HACD1
Name	3-hydroxyacyl-CoA dehydratase 1
Location	10p12.33
Locus type	gene with protein product
Status	Approved
Aliases	CAP
Ensembl gene	ENSG00000165996
Ensembl biotype	protein_coding
OMIM	610467
Entrez	9200

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 9 protein_coding, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000326961, ENST00000361271, ENST00000466335, ENST00000471481, ENST00000498812, ENST00000632169, ENST00000910450, ENST00000910451, ENST00000957760, ENST00000957761, ENST00000957762, ENST00000957763

RefSeq mRNA: 1 — MANE Select: NM_014241 NM_014241

CCDS: CCDS7121

Canonical transcript exons

ENST00000361271 — 7 exons

Exon	Start	End
ENSE00001121114	17589032	17590446
ENSE00001907350	17617083	17617374
ENSE00002453309	17603726	17603744
ENSE00002467042	17603560	17603648
ENSE00002529135	17603930	17604047
ENSE00003473310	17599290	17599411
ENSE00003688862	17594205	17594383

Expression profiles

Bgee: expression breadth ubiquitous, 257 present calls, max score 98.20.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 24.5649 / max 310.0936, expressed in 1689 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
108548	12.3894	1615
108549	12.1754	1614

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
heart right ventricle	UBERON:0002080	98.20	gold quality
heart left ventricle	UBERON:0002084	97.77	gold quality
cardiac ventricle	UBERON:0002082	97.71	gold quality
right atrium auricular region	UBERON:0006631	97.42	gold quality
cardiac atrium	UBERON:0002081	97.12	gold quality
heart	UBERON:0000948	97.10	gold quality
apex of heart	UBERON:0002098	97.04	gold quality
right coronary artery	UBERON:0001625	96.92	gold quality
popliteal artery	UBERON:0002250	96.89	gold quality
tibial artery	UBERON:0007610	96.88	gold quality
left ventricle myocardium	UBERON:0006566	96.73	gold quality
aorta	UBERON:0000947	96.65	gold quality
thoracic aorta	UBERON:0001515	96.53	gold quality
ascending aorta	UBERON:0001496	96.52	gold quality
myocardium	UBERON:0002349	96.49	gold quality
left coronary artery	UBERON:0001626	96.15	gold quality
descending thoracic aorta	UBERON:0002345	95.99	gold quality
lower esophagus muscularis layer	UBERON:0035833	95.90	gold quality
lower esophagus	UBERON:0013473	95.89	gold quality
blood vessel layer	UBERON:0004797	95.73	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	95.36	gold quality
coronary artery	UBERON:0001621	94.78	gold quality
muscle layer of sigmoid colon	UBERON:0035805	94.76	gold quality
cardiac muscle of right atrium	UBERON:0003379	94.28	gold quality
gastrocnemius	UBERON:0001388	94.23	gold quality
muscle of leg	UBERON:0001383	93.59	gold quality
hindlimb stylopod muscle	UBERON:0004252	93.25	gold quality
muscle organ	UBERON:0001630	92.96	gold quality
tibialis anterior	UBERON:0001385	91.96	gold quality
deltoid	UBERON:0001476	91.82	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-HCAD-6	yes	19.16
E-MTAB-6701	yes	10.02
E-MTAB-8271	yes	9.40
E-CURD-112	yes	8.88
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

37 targeting HACD1, 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-3613-3P	100.00	76.36	7965
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-498-3P	99.91	71.27	1114
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-369-3P	99.85	70.52	2264
HSA-MIR-4799-5P	99.82	70.60	2663
HSA-MIR-1299	99.77	71.24	2389
HSA-MIR-3680-3P	99.75	72.51	3095
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-3679-3P	99.64	69.88	1599
HSA-MIR-3128	99.50	67.85	1258
HSA-MIR-578	99.46	68.36	1787
HSA-MIR-488-5P	99.28	68.12	821
HSA-MIR-361-3P	99.19	66.45	1381
HSA-MIR-487A-5P	98.85	69.37	993
HSA-MIR-487B-5P	98.85	69.48	987
HSA-MIR-3145-3P	98.85	69.07	2031
HSA-MIR-374C-3P	98.47	67.93	451
HSA-MIR-34C-3P	98.11	65.60	858
HSA-MIR-3928-3P	97.61	66.53	1096

Literature-anchored findings (GeneRIF, showing 10)

• A loss-of-function mutation in the canine ortholog of HACD1 that was identified by genetic mapping in a French pedigree of Labrador retrievers causes a congenital myopathy named centronuclear myopathy (CNM) in Labrador retrievers. (PMID:15829503)
• PTPLA SNPs show genotypic association with Alzheimer disease. (PMID:19241460)
• HACD1 is 3-hydroxyacyl-CoA dehydratase involved in elongation of very long-chain fatty acids. HACD1 (K64Q) exhibits normal enzyme activity, intracellular localization and interaction with other VLCFA enzymes, with no negative effect on VLCFA elongation (PMID:20724468)
• PTPLA-CAP expression was limited to cementum cells; promoted gingival fibroblast attachment. PTPLA-CAP is splice variant of PTPLA, and that, in the periodontium, cementum and cementum cells express this variant. (PMID:22067203)
• Labrador retrievers carrying two copies of a unique canine HACD1 loss-of-function allele that recently disseminated worldwide, are all affected by a congenital myopathy, confirming its role in muscle development. (PMID:23071563)
• These data indicate that HACD1 is necessary for muscle function. (PMID:23933735)
• Longitudinal analyses in myopathic Labrador retrievers reveal several membrane-associated defects, including ultrastructural triads dysmorphogenesis and mitochondrial mislocalization in Labrador retrievers with deficiencies in the canine HACD1 gene. (PMID:27939133)
• Mutations in HACD1 can result in myopathies in humans; knockout mice lacking Hacd1 develop myopathic phenotypes. Data (including data from studies using knockout mice and cultured cells from knockout mice) suggest that HACD1 and HACD2 exhibit overlapping substrate specificities and thus appear to represent redundant activities in skeletal muscle. (PMID:28784662)
• Biallelic loss-of-function HACD1 variants are a bona fide cause of congenital myopathy. (PMID:33354762)
• The 3-hydroxyacyl-CoA dehydratase 1/2 form complex with trans-2-enoyl-CoA reductase involved in substrates transfer in very long chain fatty acid elongation. (PMID:38422897)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	hacd1	ENSDARG00000103744
mus_musculus	Hacd1	ENSMUSG00000063275
rattus_norvegicus	Hacd1	ENSRNOG00000043192
drosophila_melanogaster	Hacd1	FBGN0032394
caenorhabditis_elegans		WBGENE00020517

Paralogs (3): HACD3 (ENSG00000074696), HACD4 (ENSG00000188921), HACD2 (ENSG00000206527)

Protein

Protein identifiers

Very-long-chain (3R)-3-hydroxyacyl-CoA dehydratase 1 — B0YJ81 (reviewed: B0YJ81)

Alternative names: 3-hydroxyacyl-CoA dehydratase 1, Cementum-attachment protein, Protein-tyrosine phosphatase-like member A

All UniProt accessions (4): A6NP58, B0YJ81, J3KS69, J3KT94

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the third of the four reactions of the long-chain fatty acids elongation cycle. This endoplasmic reticulum-bound enzymatic process, allows the addition of two carbons to the chain of long- and very long-chain fatty acids/VLCFAs per cycle. This enzyme catalyzes the dehydration of the 3-hydroxyacyl-CoA intermediate into trans-2,3-enoyl-CoA, within each cycle of fatty acid elongation. Thereby, it participates in the production of VLCFAs of different chain lengths that are involved in multiple biological processes as precursors of membrane lipids and lipid mediators. In tooth development, may play a role in the recruitment and the differentiation of cells that contribute to cementum formation. May also bind hydroxyapatite and regulate its crystal nucleation to form cementum.

Subunit / interactions. May interact with enzymes of the ELO family (including ELOVL1); with those enzymes that mediate condensation, the first of the four steps of the reaction cycle responsible for fatty acids elongation, may be part of a larger fatty acids elongase complex. Homooligomer. Self-assembles into spheres which then aggregates to form strings and a meshwork that may support hydroxyapatite crystal nucleation. Interacts with TECR.

Subcellular location. Endoplasmic reticulum membrane.

Tissue specificity. Isoform 1 is highly expressed in the myocardium, and to a lesser extent in skeletal and smooth muscular tissues including those from stomach, jejunum, and bladder. Also detected in gingival fibroblasts, periodontal ligament cells, osteoblasts and cementoblasts. Isoform 2 is specifically expressed by cementoblasts but also detected in periodontal ligament cells, heart, liver and kidney (at protein level).

Post-translational modifications. N-glycosylated.

Disease relevance. Congenital myopathy 11 (CMYO11) [MIM:619967] An autosomal recessive skeletal muscle disorder characterized clinically by severe hypotonia apparent at birth, motor delay, and walking difficulties. The course of the disease is non-progressive, and affected individuals achieve independent ambulation and tend to show improvement of muscle weakness throughout childhood and early adulthood. The disease is caused by variants affecting the gene represented in this entry.

Pathway. Lipid metabolism; fatty acid biosynthesis.

Miscellaneous. Catalytically inactive since it lacks the active site but may have an alternative function.

Similarity. Belongs to the very long-chain fatty acids dehydratase HACD family.

Isoforms (2)

UniProt ID	Names	Canonical?
B0YJ81-1	1	yes
B0YJ81-2	2, CAP, cementum-attachment protein, PTPLA-CAP

RefSeq proteins (1): NP_055056* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007482	Tyr_Pase-like_PTPLA	Family

Pfam: PF04387

Catalyzed reactions (Rhea), 7 shown:

• (3R)-hydroxyoctadecanoyl-CoA = (2E)-octadecenoyl-CoA + H2O (RHEA:39155)
• (3R)-hydroxyhexadecanoyl-CoA = (2E)-hexadecenoyl-CoA + H2O (RHEA:39159)
• (3R)-hydroxyeicosanoyl-CoA = (2E)-eicosenoyl-CoA + H2O (RHEA:39175)
• (3R)-hydroxydocosanoyl-CoA = (2E)-docosenoyl-CoA + H2O (RHEA:39187)
• (3R)-hydroxytetracosanoyl-CoA = (2E)-tetracosenoyl-CoA + H2O (RHEA:39199)
• (3R)-hydroxyhexacosanoyl-CoA = (2E)-hexacosenoyl-CoA + H2O (RHEA:39211)
• a very-long-chain (3R)-3-hydroxyacyl-CoA = a very-long-chain (2E)-enoyl-CoA + H2O (RHEA:45812)

UniProt features (29 total): topological domain 7, transmembrane region 6, sequence variant 6, active site 2, splice variant 2, chain 1, region of interest 1, compositionally biased region 1, modified residue 1, glycosylation site 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-B0YJ81-F1	77.13	0.55

Functional residue map

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

Catalytic / active sites (2): 210; 217

Post-translational modifications (1): 22

Glycosylation sites (1): 243

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-75876	Synthesis of very long-chain fatty acyl-CoAs

MSigDB gene sets: 370 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_DN, REACTOME_SYNTHESIS_OF_VERY_LONG_CHAIN_FATTY_ACYL_COAS, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, MODULE_255, MODULE_317, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_NUCLEOSIDE_PHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_TOOTH_MINERALIZATION, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, KEGG_BIOSYNTHESIS_OF_UNSATURATED_FATTY_ACIDS, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_ORGANIC_ACID_BIOSYNTHETIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_CELL_ADHESION, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, GOBP_SMALL_MOLECULE_BIOSYNTHETIC_PROCESS

GO Biological Process (10): positive regulation of cell-substrate adhesion (GO:0010811), sphingolipid biosynthetic process (GO:0030148), fatty acid elongation (GO:0030497), long-chain fatty-acyl-CoA biosynthetic process (GO:0035338), very long-chain fatty acid biosynthetic process (GO:0042761), protein-containing complex assembly (GO:0065003), cementum mineralization (GO:0071529), lipid metabolic process (GO:0006629), fatty acid metabolic process (GO:0006631), fatty acid biosynthetic process (GO:0006633)

GO Molecular Function (6): 3-hydroxyacyl-CoA dehydratase activity (GO:0018812), enzyme binding (GO:0019899), hydroxyapatite binding (GO:0046848), very-long-chain (3R)-3-hydroxyacyl-CoA dehydratase activity (GO:0102158), protein binding (GO:0005515), lyase activity (GO:0016829)

GO Cellular Component (3): endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Fatty acyl-CoA biosynthesis	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
lipid biosynthetic process	2
fatty acid biosynthetic process	2
regulation of cell-substrate adhesion	1
cell-substrate adhesion	1
positive regulation of cell adhesion	1
sphingolipid metabolic process	1
long-chain fatty-acyl-CoA metabolic process	1
fatty-acyl-CoA biosynthetic process	1
very long-chain fatty acid metabolic process	1
cellular component assembly	1
protein-containing complex organization	1
tooth mineralization	1
primary metabolic process	1
lipid metabolic process	1
monocarboxylic acid metabolic process	1
fatty acid metabolic process	1
monocarboxylic acid biosynthetic process	1
enoyl-CoA hydratase activity	1
protein binding	1
small molecule binding	1
(2E)-enoyl-CoA hydratase activity	1
binding	1
catalytic activity	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1370 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HACD1	MTM1	Q13496	862
HACD1	CEMP1	Q6PRD7	813
HACD1	PTS	Q03393	754
HACD1	HSD17B12	Q53GQ0	638
HACD1	TECR	Q9NZ01	563
HACD1	IBSP	P21815	510
HACD1	ELOVL1	Q9BW60	484
HACD1	COASY	Q13057	468
HACD1	ELOVL6	Q9H5J4	452
HACD1	FN1	P02751	443
HACD1	BGLAP	P02818	432
HACD1	ELOVL4	Q9GZR5	426
HACD1	MTMR14	Q8NCE2	410
HACD1	TGFB3	P10600	387
HACD1	ELOVL7	A1L3X0	382

IntAct

34 interactions, top by confidence:

A	B	Type	Score
HACD1	TECR	psi-mi:“MI:0915”(physical association)	0.700
TECR	HACD1	psi-mi:“MI:0914”(association)	0.700
HACD1	TMEM106C	psi-mi:“MI:0915”(physical association)	0.600
HACD1	IL10RA	psi-mi:“MI:0915”(physical association)	0.560
HACD1	RNF170	psi-mi:“MI:0915”(physical association)	0.560
HACD1	CPLX4	psi-mi:“MI:0915”(physical association)	0.560
SLC15A1	METTL15	psi-mi:“MI:0914”(association)	0.530
HACD1	SEMG1	psi-mi:“MI:0914”(association)	0.530
HACD1	XPO1	psi-mi:“MI:0914”(association)	0.350
EDEM2	HACD1	psi-mi:“MI:0914”(association)	0.350
SLC22A4	RTL8C	psi-mi:“MI:0914”(association)	0.350
SSMEM1		psi-mi:“MI:0914”(association)	0.350
TECR	ELOVL7	psi-mi:“MI:0914”(association)	0.350
HACD1	TMEM106C	psi-mi:“MI:0915”(physical association)	0.000
HACD1	CPLX4	psi-mi:“MI:0915”(physical association)	0.000
HACD1	RNF170	psi-mi:“MI:0915”(physical association)	0.000
TECR	HACD1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (34): SEMG2 (Affinity Capture-MS), SEMG1 (Affinity Capture-MS), SEMG1 (Affinity Capture-MS), SEMG2 (Affinity Capture-MS), PTPLA (Affinity Capture-MS), PTPLA (Affinity Capture-MS), PTPLA (Reconstituted Complex), PTPLA (Two-hybrid), RPN1 (Affinity Capture-MS), ATP2A2 (Affinity Capture-MS), ATP2B1 (Affinity Capture-MS), CSE1L (Affinity Capture-MS), CORO1C (Affinity Capture-MS), RPN2 (Affinity Capture-MS), PHB (Affinity Capture-MS)

ESM2 similar proteins: A0A0P0WY03, A0A161IUT7, A6ZSP9, B0YJ81, F1QYC4, G5ED45, I1MSF2, K7LC65, O14346, O60353, P38703, P39540, P40857, P78970, Q0JJZ6, Q10255, Q28C60, Q28GF5, Q2KIP8, Q3TUD9, Q4Q5G6, Q4V7N7, Q4W1W1, Q5F410, Q5GKZ7, Q5I396, Q5RBK3, Q5RCN4, Q5XXA6, Q61089, Q651J5, Q6DGF8, Q6K991, Q6Y1H2, Q7RTM1, Q7Z139, Q8BGQ4, Q8BHY3, Q8CFW1, Q8J2Q2

Diamond homologs: B0YJ81, O14346, O17040, P40857, Q2KIP8, Q4W1W1, Q5RBK3, Q5ZEJ0, Q6Y1H2, Q7XSZ4, Q8VZB2, Q9D3B1, Q9N1R5, Q9QY80, Q5ZM57, Q7SY06, A7YY55, Q5NVQ2, Q8K2C9, Q9P035

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
HACD1	“up-regulates activity”	FASN	“chemical activation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	15
Likely pathogenic	3
Uncertain significance	83
Likely benign	65
Benign	20

Top pathogenic / likely-pathogenic (18)

Variant ID	HGVS	Classification
1421427	NC_000010.10:g.(?17632363)(17659338_?)del	Pathogenic
1452988	NM_014241.4(HACD1):c.743_747del (p.Tyr248fs)	Pathogenic
1515844	NM_014241.4(HACD1):c.373_375+2del	Pathogenic
157511	NM_014241.4(HACD1):c.744C>A (p.Tyr248Ter)	Pathogenic
1698406	NM_014241.4:c.739_740delinsN[1250]	Pathogenic
1698409	NM_014241.4(HACD1):c.785-1G>T	Pathogenic
1929981	NM_014241.4(HACD1):c.599G>A (p.Trp200Ter)	Pathogenic
1952319	NM_014241.4(HACD1):c.503_504del (p.Val168fs)	Pathogenic
2425917	NC_000010.10:g.(?17632363)(17646066_?)del	Pathogenic
2741747	NM_014241.4(HACD1):c.706del (p.Ser235_Ile236insTer)	Pathogenic
2978369	NM_014241.4(HACD1):c.103del (p.Arg35fs)	Pathogenic
3244989	NC_000010.10:g.(?17645539)(17646066_?)del	Pathogenic
3252063	NM_014241.4(HACD1):c.355C>T (p.Gln119Ter)	Pathogenic
3605210	NM_014241.4(HACD1):c.133G>T (p.Glu45Ter)	Pathogenic
3631030	NM_014241.4(HACD1):c.312_313del (p.His104fs)	Pathogenic
1490608	NM_014241.4(HACD1):c.484-15_533del	Likely pathogenic
1698408	NM_014241.4(HACD1):c.458G>A (p.Trp153Ter)	Likely pathogenic
1943492	NM_014241.4(HACD1):c.483+2T>A	Likely pathogenic

SpliceAI

1041 predictions. Top by Δscore:

Variant	Effect	Δscore
10:17590452:T:TC	acceptor_gain	1.0000
10:17594293:T:A	donor_gain	1.0000
10:17599272:A:C	donor_gain	1.0000
10:17603558:A:AC	donor_gain	1.0000
10:17603559:C:CC	donor_gain	1.0000
10:17617078:CGTA:C	donor_loss	1.0000
10:17617079:GTAC:G	donor_loss	1.0000
10:17617080:TA:T	donor_loss	1.0000
10:17617081:A:AC	donor_gain	1.0000
10:17617081:AC:A	donor_gain	1.0000
10:17617081:ACC:A	donor_gain	1.0000
10:17617082:C:CC	donor_gain	1.0000
10:17617082:CC:C	donor_gain	1.0000
10:17617082:CCC:C	donor_gain	1.0000
10:17617082:CCCCG:C	donor_gain	1.0000
10:17590450:CAT:C	acceptor_gain	0.9900
10:17590452:T:C	acceptor_gain	0.9900
10:17603923:AACTT:A	donor_loss	0.9900
10:17603924:ACTT:A	donor_loss	0.9900
10:17603925:CTTA:C	donor_loss	0.9900
10:17603926:TTA:T	donor_loss	0.9900
10:17603927:TA:T	donor_loss	0.9900
10:17603928:A:AC	donor_gain	0.9900
10:17603928:ACC:A	donor_loss	0.9900
10:17603929:C:CC	donor_gain	0.9900
10:17603929:CCT:C	donor_gain	0.9900
10:17604044:CCAC:C	acceptor_gain	0.9900
10:17604045:CACC:C	acceptor_gain	0.9900
10:17604046:ACC:A	acceptor_loss	0.9900
10:17604048:C:CG	acceptor_loss	0.9900

AlphaMissense

1870 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:17594210:A:T	I260K	0.983
10:17594371:A:C	F206L	0.980
10:17594371:A:T	F206L	0.980
10:17594373:A:G	F206L	0.980
10:17603605:A:C	S146R	0.980
10:17603605:A:T	S146R	0.980
10:17603607:T:G	S146R	0.980
10:17594319:C:G	A224P	0.979
10:17594318:G:T	A224D	0.978
10:17599372:A:G	W175R	0.976
10:17599372:A:T	W175R	0.976
10:17590409:T:A	R274S	0.975
10:17590409:T:G	R274S	0.975
10:17603586:A:G	W153R	0.975
10:17603586:A:T	W153R	0.975
10:17594258:A:T	V244D	0.973
10:17599340:G:C	F185L	0.973
10:17599340:G:T	F185L	0.973
10:17599342:A:G	F185L	0.973
10:17594210:A:C	I260R	0.972
10:17599394:A:C	S167R	0.972
10:17599394:A:T	S167R	0.972
10:17599396:T:G	S167R	0.972
10:17590410:C:G	R274T	0.971
10:17599293:G:T	A201D	0.967
10:17594251:A:C	F246L	0.966
10:17594251:A:T	F246L	0.966
10:17594253:A:G	F246L	0.966
10:17599297:A:G	W200R	0.966
10:17599297:A:T	W200R	0.966

dbSNP variants (sampled 300 via entrez): RS1000146070 (10:17612042 G>A), RS1000357983 (10:17606875 C>G), RS1000523938 (10:17591541 G>A), RS1000616602 (10:17617461 T>C,G), RS1000737602 (10:17596943 A>G,T), RS1000961672 (10:17608074 C>A,T), RS1001096263 (10:17597296 G>A), RS1001100909 (10:17613543 C>T), RS1001151639 (10:17613162 G>A,C), RS1001216323 (10:17618717 T>C), RS1001942540 (10:17592477 G>A), RS1002164162 (10:17614657 G>C), RS1002214109 (10:17604213 C>T), RS1002546829 (10:17593590 T>C), RS1002945886 (10:17593839 C>A,G)

Disease associations

OMIM: gene MIM:610467 | disease phenotypes: MIM:619967

GenCC curated gene-disease

Disease	Classification	Inheritance
congenital myopathy 11	Definitive	Autosomal recessive
congenital myopathy	Strong	Autosomal recessive
congenital fiber-type disproportion myopathy	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
congenital myopathy	Definitive	AR

Mondo (3): congenital myopathy 11 (MONDO:0859264), congenital fiber-type disproportion myopathy (MONDO:0009711), congenital myopathy (MONDO:0019952)

Orphanet (0):

HPO phenotypes

73 total (30 of 73 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000218	High palate
HP:0000276	Long face
HP:0000347	Micrognathia
HP:0000602	Ophthalmoplegia
HP:0000678	Dental crowding
HP:0000767	Pectus excavatum
HP:0001252	Hypotonia
HP:0001270	Motor delay
HP:0001284	Areflexia
HP:0001315	Reduced tendon reflexes
HP:0001371	Flexion contracture
HP:0001374	Congenital hip dislocation
HP:0001508	Failure to thrive
HP:0001558	Decreased fetal movement
HP:0001561	Polyhydramnios
HP:0001609	Hoarse voice
HP:0001612	Weak cry
HP:0001623	Breech presentation
HP:0001627	Abnormal heart morphology
HP:0001631	Atrial septal defect
HP:0001643	Patent ductus arteriosus
HP:0001648	Cor pulmonale
HP:0001655	Patent foramen ovale
HP:0001761	Pes cavus
HP:0001762	Talipes equinovarus
HP:0001824	Weight loss
HP:0002015	Dysphagia
HP:0002058	Myopathic facies
HP:0002086	Abnormality of the respiratory system

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST007732_14	Allergic disease (asthma, hay fever or eczema)	7.000000e-07

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

35 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, decreases expression	7
methylmercuric chloride	increases expression, affects cotreatment	3
trichostatin A	increases expression, affects cotreatment	3
mercuric bromide	increases expression, affects cotreatment	2
entinostat	affects cotreatment, increases expression	2
Vorinostat	affects cotreatment, increases expression	2
Panobinostat	affects cotreatment, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Cyclosporine	decreases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, increases expression	2
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cobaltous chloride	decreases expression	1
potassium chromate(VI)	decreases expression	1
periodate-oxidized adenosine	affects expression	1
beta-methylcholine	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
ICG 001	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
Temozolomide	decreases expression	1
Atrazine	increases expression	1
Carbamazepine	affects expression	1
Dexamethasone	increases expression	1
Diazinon	increases methylation	1
Doxorubicin	affects expression, increases expression	1
Estradiol	affects cotreatment, increases expression	1
Fluorouracil	affects response to substance	1
Phthalic Acids	increases methylation	1
Progesterone	affects cotreatment, increases expression	1
Tetrachlorodibenzodioxin	decreases expression, increases expression	1
Tobacco Smoke Pollution	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00272883	Not specified	RECRUITING	Molecular and Genetic Studies of Congenital Myopathies
NCT06791369	Not specified	NOT_YET_RECRUITING	The Prevalence of RYR1-related Disease
NCT02020187	Not specified	COMPLETED	Aerobic Training in Patients With Congenital Myopathies
NCT03018184	Not specified	COMPLETED	Contractile Cross Sectional Areas and Muscle Strength in Patients With Congenital Myopathies
NCT04733976	Not specified	COMPLETED	Bullying in Youth With Muscular Dystrophy and Congenital Myopathies
NCT05099107	Not specified	COMPLETED	Changes of Motor Function Tests in Congenital Myopathy Subjects Treated With Oral Salbutamol as Compared to no Treatment
NCT05199246	Not specified	COMPLETED	Assessment of Safety and Acute Effects of a Lower-limb Powered Dermoskeleton in Patients With Neuromuscular Disorders
NCT05200702	Not specified	COMPLETED	Assessment of Safety and Acute Effects of a Knee-hip Powered Soft Exoskeleton in Patients With Neuromuscular Disorders
NCT05692349	Not specified	UNKNOWN	Magnetic Resonance Imaging and Ultrasonography in Evaluation of Muscle Diseases
NCT06833489	Not specified	RECRUITING	Transcriptomic Analysis to Put an End to Misdiagnosis in Patients With Rare Muscle Diseases
NCT07138963	Not specified	RECRUITING	Phenotype - Genotype Correlation in a Sample of Egyptian Patients With Congenital Myopathies and Congenital Muscular Dystrophies
NCT07415837	Not specified	RECRUITING	Evaluation of the Role of miR-1 in the Pathogenesis and as a Biomarker in Muscular Dystrophies and Congenital Myopathies
NCT07502989	Not specified	RECRUITING	Muscle Health Measurements Using Electrical Impedance Myography
NCT07580365	Not specified	NOT_YET_RECRUITING	VirtualPark_Pediatric