THEM4

thioesterase superfamily member 4, the group of Thioesterase superfamily

Basic information

Region (hg38): 1:151870866-151909637

Links

ENSG00000159445 ∙ NCBI:117145 ∙ OMIM:606388 ∙ HGNC:17947 ∙ Uniprot:Q5T1C6 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the THEM4 gene.

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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				2		2
missense			13	1	2	16
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	13	3	2

Variants in THEM4

This is a list of pathogenic ClinVar variants found in the THEM4 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
1-151877005-C-T			Likely benign (Sep 01, 2022)
1-151877064-T-C		not specified	Uncertain significance (Oct 19, 2024)
1-151877075-A-G		not specified	Uncertain significance (May 31, 2023)
1-151877079-T-C		not specified	Uncertain significance (Feb 22, 2023)
1-151877111-C-G		not specified	Uncertain significance (Aug 27, 2024)
1-151877121-T-C		not specified	Uncertain significance (Aug 08, 2023)
1-151877123-G-A		not specified	Uncertain significance (May 27, 2022)
1-151888341-A-G			Likely benign (Jan 01, 2023)
1-151889249-T-G		not specified	Uncertain significance (May 30, 2024)
1-151889290-C-T		not specified	Uncertain significance (Dec 12, 2023)
1-151889366-C-G			Benign (Jul 16, 2018)
1-151895052-C-T			Benign (Apr 24, 2018)
1-151895058-T-C		not specified	Uncertain significance (Nov 08, 2024)
1-151895070-C-T		not specified	Uncertain significance (Mar 02, 2023)
1-151895082-C-T		not specified	Uncertain significance (May 18, 2023)
1-151895138-G-C		not specified	Uncertain significance (Nov 30, 2022)
1-151895155-A-C		not specified	Likely benign (Oct 22, 2021)
1-151895175-T-C		not specified	Uncertain significance (Sep 22, 2023)
1-151909364-T-A		not specified	Uncertain significance (Apr 09, 2024)
1-151909374-G-A		not specified	Uncertain significance (Jan 04, 2022)
1-151909377-C-T		not specified	Uncertain significance (Nov 07, 2022)
1-151909385-G-A		not specified	Uncertain significance (Sep 10, 2024)
1-151909400-A-T		not specified	Uncertain significance (Jul 30, 2024)
1-151909416-G-C		not specified	Uncertain significance (Nov 25, 2024)
1-151909448-C-G		not specified	Uncertain significance (Jun 03, 2022)

GnomAD

Source: gnomAD

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: dbNSFP

• 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