THEM4
thioesterase superfamily member 4, the group of Thioesterase superfamily
Basic information
Region (hg38): 1:151870866-151909637
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
- not_specified (39 variants)
- not_provided (4 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the THEM4 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000053055.5. Only rare variants are included in the table.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 2 | |||||
| missense | 40 | 43 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 40 | 3 | 2 |
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| THEM4 | protein_coding | protein_coding | ENST00000368814 | 6 | 36225 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 3.89e-7 | 0.211 | 125721 | 0 | 21 | 125742 | 0.0000835 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.0841 | 119 | 122 | 0.979 | 0.00000583 | 1554 |
| Missense in 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 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00 | 0.00 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.0000544 | 0.0000544 |
| Finnish | 0.0000463 | 0.0000462 |
| European (Non-Finnish) | 0.000151 | 0.000149 |
| Middle Eastern | 0.0000544 | 0.0000544 |
| South Asian | 0.00 | 0.00 |
| Other | 0.000327 | 0.000326 |
dbNSFP
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}.;
- Pathway
- 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;VEGFA-VEGFR2 Pathway;Metabolism of lipids;Activation of AKT2;CD28 dependent PI3K/Akt signaling;CD28 co-stimulation;PI3K Cascade;Costimulation by the CD28 family;IRS-mediated signalling;Insulin receptor signalling cascade;Signaling by Insulin receptor;Mitochondrial Fatty Acid Beta-Oxidation;Immune System;Metabolism;Adaptive Immune System;Fatty acid metabolism;PIP3 activates AKT signaling;Negative regulation of the PI3K/AKT network;Signaling by VEGF;IRS-related events triggered by IGF1R;IGF1R signaling cascade;Signaling by Receptor Tyrosine Kinases;Intracellular signaling by second messengers;Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R);VEGFR2 mediated vascular permeability
(Consensus)
Recessive Scores
- pRec
- 0.0614
Intolerance Scores
- loftool
- 0.851
- rvis_EVS
- 0.93
- rvis_percentile_EVS
- 89.66
Haploinsufficiency Scores
- pHI
- 0.0384
- hipred
- N
- hipred_score
- 0.412
- ghis
- 0.425
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- N
- gene_indispensability_score
- 0.358
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Them4
- Phenotype
- liver/biliary system phenotype;
Gene ontology
- 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
- Cellular component
- mitochondrion;mitochondrial inner membrane;mitochondrial intermembrane space;mitochondrial matrix;cytosol;plasma membrane;ruffle membrane
- Molecular function
- protein binding;palmitoyl-CoA hydrolase activity;acyl-CoA hydrolase activity;myristoyl-CoA hydrolase activity