HACD2
protein-coding3-hydroxyacyl-CoA dehydratase 2, the group of 3-hydroxyacyl-CoA dehydratase family
Gene summary
The protein encoded by this gene can catalyze the third step (dehydration) in the conversion of long chain fatty acids to very long chain fatty acids. The encoded protein localizes to the endoplasmic reticulum membrane. [provided by RefSeq, Jul 2016]
- PTPLB
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~94.2 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 HACD2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_198402.5. 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 | 0 | |||||
| missense | 21 | 1 | 22 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 22 | 1 | 0 | 23 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_940684.1 | 7 | MANE Select | |
| Ensembl | ENSP00000373153.5 | 7 | MANE Select | |
| RefSeq | NP_001316712.1 | 8 | Standard | |
| RefSeq | NP_001316713.2 | 4 | 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)
- Metabolism of lipids
- Fatty acyl-CoA biosynthesis
- Metabolism
Biological Process
- sphingolipid biosynthetic process
- fatty acid elongation
- peptidyl-tyrosine dephosphorylation
- long-chain fatty-acyl-CoA biosynthetic process
- very long-chain fatty acid biosynthetic process
Molecular Function
- protein tyrosine phosphatase activity
- protein binding
- 3-hydroxyacyl-CoA dehydratase activity
- enzyme binding
- 3R-hydroxyacyl-CoA dehydratase activity
Cellular Component
- endoplasmic reticulum
- endoplasmic reticulum membrane
- integral component of membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000383657
- Coding exons
- 7
- Length
- 94366
- Individuals with no LoFs
- 124639
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 4
- Defined
- 124643
- p
- 0.0000160
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.86 | 60 | 117 | 0.514 | 0.00000554 | 1599 |
| Missense (PolyPhen) | 15 | 44.483 | 0.33721 | 579 | ||
| Synonymous | 0.460 | 42 | 46.0 | 0.914 | 0.00000237 | 497 |
| Loss of Function | 2.20 | 4 | 12.3 | 0.325 | 5.97e-7 | 166 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000036 | 0.000035 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
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. {ECO:0000269|PubMed:18554506}.;
Recessive Scores
- pRec
- 0.0882
Intolerance Scores
- RVIS EVS
- 0.01
- RVIS percentile EVS
- 54.63
Essentials
- Essential (gene trap)
- N