HACD3
protein-coding3-hydroxyacyl-CoA dehydratase 3, the group of 3-hydroxyacyl-CoA dehydratase family
Gene summary
Enables enzyme binding activity and very-long-chain (3R)-3-hydroxyacyl-CoA dehydratase activity. Involved in fatty acid biosynthetic process; positive regulation by virus of viral protein levels in host cell; and positive regulation of viral genome replication. Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Jun 2026]
- PTPLAD1
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~47.9 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to HACD3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_016395.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 1 | ||||
| missense | 56 | 1 | 57 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 6 | 6 | ||||
| Total | 0 | 0 | 64 | 1 | 0 | 65 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_057479.2 | 11 | MANE Select | |
| Ensembl | ENSP00000261875.5 | 11 | MANE Select | |
| RefSeq | NP_001398065.1 | 8 | Standard | |
| Ensembl | ENSP00000392491.2 | 10 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Biosynthesis of unsaturated fatty acids - Homo sapiens (human)
- Fatty acid elongation - Homo sapiens (human)
- miR-targeted genes in epithelium - TarBase
- miR-targeted genes in lymphocytes - TarBase
- miR-targeted genes in muscle cell - TarBase
Biological Process
- I-kappaB kinase/NF-kappaB signaling
- activation of JUN kinase activity
- small GTPase mediated signal transduction
- Rho protein signal transduction
- Rac protein signal transduction
Molecular Function
- GTPase activator activity
- protein binding
- 3-hydroxyacyl-CoA dehydratase activity
- enzyme binding
- very-long-chain 3-hydroxyacyl-CoA dehydratase activity
Cellular Component
- mitochondrion
- endoplasmic reticulum
- endoplasmic reticulum membrane
- cytosol
- focal adhesion
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000261875
- Coding exons
- 11
- Length
- 47932
- Individuals with no LoFs
- 124620
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 33
- Defined
- 124653
- p
- 0.000132
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.03 | 153 | 193 | 0.792 | 0.0000102 | 2367 |
| Missense (PolyPhen) | 52 | 73.829 | 0.70433 | 922 | ||
| Synonymous | 1.60 | 51 | 67.7 | 0.753 | 0.00000354 | 653 |
| Loss of Function | 3.07 | 8 | 24.3 | 0.329 | 0.00000138 | 265 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00014 | 0.00013 | rare |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0.00010 | 0.000099 | rare |
| East Asian | 0.00033 | 0.00033 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00020 | 0.00019 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0.00017 | 0.00017 | rare |
dbNSFP Gene Annotations
Source:
- Function
- 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. May be involved in Rac1-signaling pathways leading to the modulation of gene expression. Promotes insulin receptor/INSR autophosphorylation and is involved in INSR internalization (PubMed:25687571). {ECO:0000269|PubMed:10747961, ECO:0000269|PubMed:18554506, ECO:0000269|PubMed:25687571}.;
Recessive Scores
- pRec
- 0.115
Intolerance Scores
- RVIS EVS
- 0.28
- RVIS percentile EVS
- 71.27
Essentials
- Essential (gene trap)
- N