THEM5
protein-codingthioesterase superfamily member 5, the group of Thioesterase superfamily
Gene summary
Enables long-chain fatty acyl-CoA hydrolase activity. Involved in long-chain fatty-acyl-CoA metabolic process. Located in mitochondrial matrix. [provided by Alliance of Genome Resources, Jul 2025]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~6.6 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 THEM5 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_182578.4. 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 | 0 | |||||
| missense | 27 | 4 | 31 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 28 | 4 | 0 | 32 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_872384.2 | 6 | MANE Select | |
| Ensembl | ENSP00000357807.4 | 6 | MANE Select | |
| Ensembl | ENSP00000406809.2 | 3 | Standard | |
| RefSeq | XP_011507723.1 | 5 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Fatty acid elongation - Homo sapiens (human)
- Metabolism of lipids
- Mitochondrial Fatty Acid Beta-Oxidation
- Metabolism
- Fatty acid metabolism
Biological Process
- fatty acid metabolic process
- acyl-CoA metabolic process
- long-chain fatty-acyl-CoA metabolic process
- cardiolipin acyl-chain remodeling
Molecular Function
- protein binding
- palmitoyl-CoA hydrolase activity
- acyl-CoA hydrolase activity
- myristoyl-CoA hydrolase activity
Cellular Component
- mitochondrial matrix
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000368817
- Coding exons
- 6
- Length
- 6435
- Individuals with no LoFs
- 125666
- Homozygous LoFs
- 2
- Heterozygous LoFs
- 80
- Defined
- 125748
- p
- 0.000326
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.234 | 127 | 135 | 0.943 | 0.00000694 | 1609 |
| Missense (PolyPhen) | 31 | 31.859 | 0.97303 | 404 | ||
| Synonymous | 0.935 | 46 | 54.8 | 0.839 | 0.00000309 | 483 |
| Loss of Function | -0.973 | 14 | 10.6 | 1.32 | 4.46e-7 | 134 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00062 | 0.00062 | rare |
| Latino/Admixed American | 0.00043 | 0.00040 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00016 | 0.00016 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00028 | 0.00028 | rare |
| South Asian | 0.00078 | 0.00075 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Has acyl-CoA thioesterase activity towards long-chain (C16 and C18) fatty acyl-CoA substrates, with a preference for linoleoyl-CoA and other unsaturated long-chain fatty acid-CoA esters. Plays an important role in mitochondrial fatty acid metabolism, and in remodeling of the mitochondrial lipid cardiolipin. Required for normal mitochondrial function. {ECO:0000269|PubMed:22586271}.;
Intolerance Scores
- LoFtool
- 0.799
- RVIS EVS
- 1.01
- RVIS percentile EVS
- 90.84
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.0000350
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |