TRIB1

protein-coding

tribbles pseudokinase 1

Gene summary

Enables several functions, including mitogen-activated protein kinase kinase binding activity; protein kinase inhibitor activity; and transcription regulator inhibitor activity. Involved in several processes, including negative regulation of signal transduction; negative regulation of smooth muscle cell proliferation; and regulation of MAP kinase activity. Located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_025195.4

Inheritance

—

ClinVar variants

U:50B:4

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.1

Max pathogenic AF

—

Genomic locus

chr8:125,430,358-125,438,403

External References & Databases

Ensembl (ENSG00000173334)

Transcript & Mutation Effects

hg38 • Region Span ~8.0 kb

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GenCC 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 TRIB1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 49

not providedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_025195.4. 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			2 clinvar	2 clinvar	1 clinvar	5
missense			48 clinvar		1 clinvar	49
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	50	2	2	54

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 8 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_025195.4	RefSeq	NP_079471.1	3	MANE Select
ENST00000311922.4	Ensembl	ENSP00000312150.3	3	MANE Select
NM_001282985.2	RefSeq	NP_001269914.1	2	Standard
ENST00000519576.1	Ensembl	ENSP00000428879.1	1	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

protein phosphorylation
negative regulation of protein kinase activity
JNK cascade
negative regulation of smooth muscle cell migration
negative regulation of lipopolysaccharide-mediated signaling pathway

Molecular Function

protein kinase activity
protein kinase inhibitor activity
protein binding
ATP binding
transcription factor binding

Cellular Component

nucleus
cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000311922
Coding exons: 3
Length: 8085
Individuals with no LoFs: 125743
Homozygous LoFs: 0
Heterozygous LoFs: 3
Defined: 125746
p: 0.0000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.21	119	162	0.733	0.0000100	2367
Missense (PolyPhen)		19	40.421	0.47005		529
Synonymous	-1.05	81	69.8	1.16	0.00000459	796
Loss of Function	2.68	1	10.3	0.0973	6.26e-7	136

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000018	0.000018	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Adapter protein involved in protein degradation by interacting with COP1 ubiquitin ligase (PubMed:27041596). The COP1-binding motif is masked by autoinhibitory interactions with the protein kinase domain (PubMed:26455797). Serves to alter COP1 substrate specificity by directing the activity of COP1 toward CEBPA (PubMed:27041596). Binds selectively the recognition sequence of CEBPA (PubMed:26455797). Regulates myeloid cell differentiation by altering the expression of CEBPA in a COP1- dependent manner (By similarity). Controls macrophage, eosinophil and neutrophil differentiation via the COP1-binding domain (By similarity). Interacts with MAPK kinases and regulates activation of MAP kinases, but has no kinase activity (PubMed:15299019, PubMed:26455797). {ECO:0000250|UniProtKB:Q8K4K4, ECO:0000269|PubMed:15299019, ECO:0000269|PubMed:26455797, ECO:0000305|PubMed:27041596}.;

Recessive Scores

pRec: 0.166

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.993

Gene Damage Prediction

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