HomeAboutRankingsData Sources
Β© 2026 GeneE
🧬
GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 15 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
HACD1
3-hydroxyacyl-CoA dehydratase 1
Chromosome 10 Β· 10p12.33
NCBI Gene: 9200Ensembl: ENSG00000165996.15HGNC: HGNC:9639UniProt: B0YJ81
31PubMed Papers
21Diseases
0Drugs
14Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
protein binding3-hydroxyacyl-CoA dehydratase activityfatty acid elongationsphingolipid biosynthetic processcongenital myopathy 11congenital myopathycongenital myopathy with corescongenital fiber-type disproportion myopathy
✦AI Summary

HACD1 (3-hydroxyacyl-CoA dehydratase 1) is a muscle-enriched enzyme catalyzing the third step of very long-chain fatty acid (VLCFA) elongation 1. In skeletal muscle, HACD1 regulates membrane lipid composition by modulating fatty acid chain length and saturation, particularly reducing lysophosphatidylcholine levels while increasing C18+ monounsaturated phospholipids 2. These lipid modifications decrease plasma membrane rigidity and promote myoblast fusion during muscle development and regeneration 2. HACD1 functions with partial redundancy alongside HACD2 across saturated and polyunsaturated fatty acid elongation pathways 3. Biallelic loss-of-function HACD1 variants cause congenital myopathy 11, characterized by neonatal-onset generalized muscle weakness, hypotonia, and fiber size disproportion 451. Pathogenic mutations include nonsense variants and splice-site alterations that reduce VLCFA synthesis 4. HACD1 deficiency produces progressive structural defects in muscle membrane systems, including T-tubule dilatation, sarcolemmal abnormalities, and mitochondrial mislocalization, impairing excitation-contraction coupling 6. The clinical presentation typically shows temporally progressive improvement characteristic of HACD1-related myopathy 4. Genetic diagnosis provides important prognostic value for this congenital condition 4.

Sources cited
1
HACD1 promotes myoblast fusion by modulating lysophosphatidylcholine content and fatty acid composition, reducing membrane rigidity
PMID: 26160855
2
HACD1 and HACD2 exhibit functional redundancy in fatty acid elongation across multiple pathways
PMID: 28784662
3
Biallelic loss-of-function HACD1 variants cause congenital myopathy with neonatal onset and characteristic progressive improvement
PMID: 33354762
4
HACD1 splice-site mutations cause congenital fiber-type disproportion myopathy
PMID: 36823680
5
HACD1 deficiency causes progressive membrane system defects including T-tubule abnormalities and mitochondrial mislocalization
PMID: 27939133
6
HACD1 catalyzes the third step of VLCFA elongation; mutations abolish enzymatic activity and cause congenital myopathy
PMID: 23933735
Disease Associationsβ“˜21
congenital myopathy 11Open Targets
0.63Moderate
congenital myopathyOpen Targets
0.46Moderate
congenital myopathy with coresOpen Targets
0.46Moderate
congenital fiber-type disproportion myopathyOpen Targets
0.37Weak
genetic disorderOpen Targets
0.19Weak
infectionOpen Targets
0.09Suggestive
neoplasmOpen Targets
0.09Suggestive
glioblastoma multiformeOpen Targets
0.09Suggestive
colorectal carcinomaOpen Targets
0.09Suggestive
gliomaOpen Targets
0.08Suggestive
cancerOpen Targets
0.08Suggestive
glycogen storage disease due to lactate dehydrogenase H-subunit deficiencyOpen Targets
0.07Suggestive
type 1 diabetes mellitusOpen Targets
0.07Suggestive
age-related macular degenerationOpen Targets
0.07Suggestive
X-linked retinal dysplasiaOpen Targets
0.06Suggestive
Familial exudative vitreoretinopathyOpen Targets
0.06Suggestive
retinitis pigmentosaOpen Targets
0.06Suggestive
Wilson diseaseOpen Targets
0.06Suggestive
melanomaOpen Targets
0.05Suggestive
alcohol sensitivity, acuteOpen Targets
0.05Suggestive
Congenital myopathy 11UniProt
Pathogenic Variants14
NM_014241.4(HACD1):c.373_375+2delPathogenic
not provided|Congenital myopathy 11
β˜…β˜†β˜†β˜†2025
NM_014241.4(HACD1):c.133G>T (p.Glu45Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 45
NM_014241.4(HACD1):c.458G>A (p.Trp153Ter)Likely pathogenic
Congenital myopathy 11
β˜…β˜†β˜†β˜†2024β†’ Residue 153
NM_014241.4(HACD1):c.355C>T (p.Gln119Ter)Pathogenic
Congenital myopathy 11
β˜…β˜†β˜†β˜†2024β†’ Residue 119
NM_014241.4(HACD1):c.599G>A (p.Trp200Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 200
NM_014241.4(HACD1):c.312_313del (p.His104fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 104
NM_014241.4(HACD1):c.706del (p.Ser235_Ile236insTer)Pathogenic
not provided
β˜…β˜†β˜†β˜†2023β†’ Residue 235
NM_014241.4(HACD1):c.103del (p.Arg35fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2023β†’ Residue 35
NM_014241.4(HACD1):c.483+2T>ALikely pathogenic
not provided
β˜…β˜†β˜†β˜†2022
NM_014241.4(HACD1):c.484-15_533delLikely pathogenic
not provided
β˜…β˜†β˜†β˜†2022
NM_014241.4(HACD1):c.743_747del (p.Tyr248fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2022β†’ Residue 248
NM_014241.4(HACD1):c.503_504del (p.Val168fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2021β†’ Residue 168
NM_014241.4(HACD1):c.785-1G>TPathogenic
Congenital myopathy 11
β˜†β˜†β˜†β˜†2024
NM_014241.4(HACD1):c.744C>A (p.Tyr248Ter)Pathogenic
Congenital myopathy 11
β˜†β˜†β˜†β˜†2013β†’ Residue 248
View on ClinVar β†—
Related Genes
HACD2Protein interaction100%FADS1Protein interaction98%SCDProtein interaction98%SCD5Protein interaction92%HACD4Protein interaction92%MTM1Protein interaction86%
Tissue Expression6 tissues
Heart
100%
Lung
14%
Brain
5%
Ovary
4%
Bone Marrow
4%
Liver
1%
Gene Interaction Network
Click a node to explore
HACD1HACD2FADS1SCDSCD5HACD4MTM1
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt B0YJ81
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
1.85LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF1.44 [1.09–1.85]
RankingsWhere HACD1 stands among ~20K protein-coding genes
  • #11,724of 20,598
    Most Researched31
  • #2,540of 5,498
    Most Pathogenic Variants14
  • #16,868of 17,882
    Most Constrained (LOEUF)1.85
Genes detectedHACD1
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
A 20-year Clinical and Genetic Neuromuscular Cohort Analysis in Lebanon: An International Effort.
PMID: 34602496
J Neuromuscul Dis Β· 2022
1.00
2
HACD1, a regulator of membrane composition and fluidity, promotes myoblast fusion and skeletal muscle growth.
PMID: 26160855
J Mol Cell Biol Β· 2015
0.90
3
The 3-hydroxyacyl-CoA dehydratases HACD1 and HACD2 exhibit functional redundancy and are active in a wide range of fatty acid elongation pathways.
PMID: 28784662
J Biol Chem Β· 2017
0.80
4
Identification of differentially expressed genes and functional annotations associated with metastases of the uveal melanoma.
PMID: 31270856
J Cell Biochem Β· 2019
0.70
5
Progressive Structural Defects in Canine Centronuclear Myopathy Indicate a Role for HACD1 in Maintaining Skeletal Muscle Membrane Systems.
PMID: 27939133
Am J Pathol Β· 2017
0.60