THEM4
protein-codingthioesterase superfamily member 4, the group of Thioesterase superfamily
Gene summary
Protein kinase B (PKB) is a major downstream target of receptor tyrosine kinases that signal via phosphatidylinositol 3-kinase. Upon cell stimulation, PKB is translocated to the plasma membrane, where it is phosphorylated in the C-terminal regulatory domain. The protein encoded by this gene negatively regulates PKB activity by inhibiting phosphorylation. Transcription of this gene is commonly downregulated in glioblastomas. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~38.8 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 THEM4 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_053055.5. 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 | 2 | 2 | ||||
| missense | 44 | 1 | 2 | 47 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 44 | 3 | 2 | 49 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_444283.2 | 6 | MANE Select | |
| Ensembl | ENSP00000357804.3 | 6 | MANE Select | |
| Ensembl | ENSP00000431288.1 | 3 | Standard | |
| Ensembl | ENSP00000433304.1 | 2 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- PI3K-Akt signaling pathway - Homo sapiens (human)
- Fatty acid elongation - Homo sapiens (human)
- miR-targeted genes in lymphocytes - TarBase
- PI3K-Akt Signaling Pathway
- Signal Transduction
Biological Process
- fatty acid metabolic process
- acyl-CoA metabolic process
- protein kinase B signaling
- negative regulation of protein kinase B signaling
- regulation of mitochondrial membrane permeability involved in apoptotic process
Molecular Function
- protein binding
- palmitoyl-CoA hydrolase activity
- acyl-CoA hydrolase activity
- myristoyl-CoA hydrolase activity
Cellular Component
- mitochondrion
- mitochondrial inner membrane
- mitochondrial intermembrane space
- mitochondrial matrix
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000368814
- Coding exons
- 6
- Length
- 36225
- Individuals with no LoFs
- 125721
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 21
- Defined
- 125742
- p
- 0.0000835
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.0841 | 119 | 122 | 0.979 | 0.00000583 | 1554 |
| Missense (PolyPhen) | 41 | 35.808 | 1.145 | 449 | ||
| Synonymous | -0.884 | 49 | 41.7 | 1.17 | 0.00000204 | 438 |
| Loss of Function | 0.0996 | 10 | 10.3 | 0.967 | 4.36e-7 | 134 |
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 | 0.000054 | 0.000054 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.00015 | 0.00015 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0.00033 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Has acyl-CoA thioesterase activity towards medium and long-chain (C14 to C18) fatty acyl-CoA substrates, and probably plays an role in mitochondrial fatty acid metabolism. Plays a role in the apoptotic process, possibly via its regulation of AKT1 activity. According to PubMed:11598301, inhibits AKT1 phosphorylation and activity. According to PubMed:17615157, enhances AKT1 activity by favoring its phosphorylation and translocation to plasma membrane. {ECO:0000269|PubMed:11598301, ECO:0000269|PubMed:17615157, ECO:0000269|PubMed:19168129, ECO:0000269|PubMed:19421406, ECO:0000269|PubMed:19453107, ECO:0000269|PubMed:22871024}.;
Recessive Scores
- pRec
- 0.0614
Intolerance Scores
- LoFtool
- 0.851
- RVIS EVS
- 0.93
- RVIS percentile EVS
- 89.66
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.358
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |