TRIB3

tribbles pseudokinase 3

Basic information

Region (hg38): 20:362835-397559

Previous symbols: [ "C20orf97" ]

Links

ENSG00000101255 ∙ NCBI:57761 ∙ OMIM:607898 ∙ HGNC:16228 ∙ Uniprot:Q96RU7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• cardiomyopathy (Limited), mode of inheritance: AD

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TRIB3 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TRIB3 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			34	4		38
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	34	4	2

Variants in TRIB3

This is a list of pathogenic ClinVar variants found in the TRIB3 region.

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

Position	Type	Phenotype	Significance	ClinVar
20-388057-A-G		not specified	Uncertain significance (Jan 03, 2024)
20-388066-T-C		not specified	Uncertain significance (Sep 19, 2022)
20-388091-C-T			Benign (Jul 30, 2018)
20-388096-G-A		not specified	Likely benign (Nov 17, 2023)
20-388111-G-A		not specified	Likely benign (Apr 25, 2023)
20-388125-C-T		not specified	Uncertain significance (Sep 20, 2023)
20-388144-C-T		not specified	Uncertain significance (Jul 08, 2022)
20-388246-G-C		not specified	Uncertain significance (May 04, 2023)
20-388248-G-A		not specified	Uncertain significance (Feb 13, 2024)
20-391342-C-T		not specified	Uncertain significance (Oct 04, 2022)
20-391359-C-T		not specified	Uncertain significance (Mar 07, 2024)
20-391380-G-C		not specified	Uncertain significance (Oct 29, 2021)
20-391387-A-G		not specified	Uncertain significance (Jun 30, 2022)
20-391411-G-A		not specified	Uncertain significance (May 18, 2022)
20-391414-C-T		not specified	Uncertain significance (Aug 26, 2022)
20-391432-G-A			Likely benign (Jan 01, 2024)
20-391476-G-A		not specified	Uncertain significance (Jan 23, 2024)
20-391485-C-T		not specified	Uncertain significance (Aug 17, 2022)
20-391486-G-A		not specified	Uncertain significance (Nov 17, 2023)
20-391486-G-T		not specified	Uncertain significance (May 09, 2024)
20-391507-C-T		not specified	Uncertain significance (Mar 20, 2024)
20-391555-G-A		not specified	Uncertain significance (Jul 28, 2021)
20-391572-C-T		not specified	Likely benign (May 15, 2024)
20-396317-C-T		not specified	Uncertain significance (Jan 19, 2022)
20-396326-C-T		not specified	Uncertain significance (Oct 04, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TRIB3	protein_coding	protein_coding	ENST00000217233	3	16943

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.16e-13	0.00325	125563	0	182	125745	0.000724

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.194	238	230	1.04	0.0000167	2224
Missense in Polyphen		82	90.189	0.9092		939
Synonymous	0.181	102	104	0.977	0.00000736	834
Loss of Function	-1.28	17	12.2	1.40	8.60e-7	110

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00252	0.00252
Ashkenazi Jewish	0.00	0.00
East Asian	0.00163	0.00147
Finnish	0.00	0.00
European (Non-Finnish)	0.000312	0.000308
Middle Eastern	0.00163	0.00147
South Asian	0.00242	0.00242
Other	0.000982	0.000652

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Disrupts insulin signaling by binding directly to Akt kinases and blocking their activation. May bind directly to and mask the 'Thr-308' phosphorylation site in AKT1. Binds to ATF4 and inhibits its transcriptional activation activity. Interacts with the NF-kappa-B transactivator p65 RELA and inhibits its phosphorylation and thus its transcriptional activation activity. Interacts with MAPK kinases and regulates activation of MAP kinases. May play a role in programmed neuronal cell death but does not appear to affect non-neuronal cells. Does not display kinase activity. Inhibits the transcriptional activity of DDIT3/CHOP and is involved in DDIT3/CHOP-dependent cell death during ER stress. Can inhibit APOBEC3A editing of nuclear DNA. {ECO:0000269|PubMed:12736262, ECO:0000269|PubMed:15299019, ECO:0000269|PubMed:15775988, ECO:0000269|PubMed:15781252, ECO:0000269|PubMed:22977230}.
• Pathway: Insulin resistance - Homo sapiens (human);Adipogenesis;Regulation of lipid metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha);Photodynamic therapy-induced unfolded protein response;Insulin Signaling;Signal Transduction;VEGFA-VEGFR2 Pathway;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;Immune System;Adaptive Immune System;PIP3 activates AKT signaling;Negative regulation of the PI3K/AKT network;Signaling by VEGF;IRS-related events triggered by IGF1R;IGF1R signaling cascade;TNFalpha;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: 0.0920

Intolerance Scores

• loftool: 0.956
• rvis_EVS: 0.47
• rvis_percentile_EVS: 78.8

Haploinsufficiency Scores

• pHI: 0.120
• hipred: N
• hipred_score: 0.398
• ghis: 0.383

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.979

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Trib3
• Phenotype: cellular phenotype; endocrine/exocrine gland phenotype; hematopoietic system phenotype; immune system phenotype

Zebrafish Information Network

• Gene name: trib3
• Affected structure: determination of liver left/right asymmetry
• Phenotype tag: abnormal
• Phenotype quality: disrupted

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;protein phosphorylation;negative regulation of protein kinase activity;regulation of glucose transmembrane transport;regulation of lipid metabolic process;positive regulation of protein binding;positive regulation of proteasomal ubiquitin-dependent protein catabolic process;cellular response to insulin stimulus;response to endoplasmic reticulum stress;regulation of MAP kinase activity;negative regulation of fat cell differentiation;negative regulation of fatty acid biosynthetic process;negative regulation of transcription, DNA-templated;positive regulation of ubiquitin-protein transferase activity;negative regulation of protein kinase B signaling;intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress
• Cellular component: nucleus;cytosol;plasma membrane
• Molecular function: transcription corepressor activity;protein kinase inhibitor activity;protein binding;ATP binding;kinase activity;protein kinase binding;mitogen-activated protein kinase kinase binding;ubiquitin protein ligase binding;ubiquitin-protein transferase regulator activity