TRIP6

protein-coding

thyroid hormone receptor interactor 6, the group of MicroRNA protein coding host genes|Zyxin family

Gene summary

This gene is a member of the zyxin family and encodes a protein with three LIM zinc-binding domains. This protein localizes to focal adhesion sites and along actin stress fibers. Recruitment of this protein to the plasma membrane occurs in a lysophosphatidic acid (LPA)-dependent manner and it regulates LPA-induced cell migration. Alternatively spliced variants which encode different protein isoforms have been described; however, not all variants have been fully characterized. [provided by RefSeq, Jul 2008]

MANE transcript

NM_003302.3

Inheritance

—

ClinVar variants

U:89B:3

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.37

Max pathogenic AF

—

Genomic locus

chr7:100,867,387-100,873,454

External References & Databases

Ensembl (ENSG00000087077)

Transcript & Mutation Effects

hg38 • Region Span ~6.1 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 TRIP6 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 85

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_003302.3. 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	1 clinvar		3
missense			84 clinvar	1 clinvar	1 clinvar	86
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	89	2	1	92

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 45 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_003302.3	RefSeq	NP_003293.2	9	MANE Select
ENST00000200457.9	Ensembl	ENSP00000200457.4	9	MANE Select
ENST00000417475.5	Ensembl	ENSP00000413817.1	4	Standard
ENST00000429658.1	Ensembl	ENSP00000389194.1	6	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
trip6	Danio rerio	Structure: muscle cell Quality: structure abnormal

Gene / Model

Organism

Observed Phenotype

trip6

Danio rerio

Structure: muscle cell

Quality: structure

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

NOD-like receptor signaling pathway - Homo sapiens (human)
EGFR1
LPA receptor mediated events
AP-1 transcription factor network

Biological Process

positive regulation of cell migration
focal adhesion assembly
positive regulation of NIK/NF-kappaB signaling

Molecular Function

RNA binding
interleukin-1 receptor binding
protein binding
kinase binding
metal ion binding

Cellular Component

nucleus
cytosol
cytoskeleton
plasma membrane
focal adhesion

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000200457
Coding exons: 9
Length: 6317
Individuals with no LoFs: 125717
Homozygous LoFs: 0
Heterozygous LoFs: 31
Defined: 125748
p: 0.000123

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.0768	281	285	0.987	0.0000170	2990
Missense (PolyPhen)		105	117.32	0.89501		1187
Synonymous	-0.136	129	127	1.02	0.00000847	1027
Loss of Function	2.70	8	21.5	0.372	0.00000108	236

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000063	0.000062	rare
Latino/Admixed American	0.000087	0.000087	rare
Ashkenazi Jewish	0.00020	0.00020	rare
East Asian	0.00017	0.00011	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00015	0.00015	rare
South Asian	0.00016	0.00016	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Relays signals from the cell surface to the nucleus to weaken adherens junction and promote actin cytoskeleton reorganization and cell invasiveness. Involved in lysophosphatidic acid-induced cell adhesion and migration. Acts as a transcriptional coactivator for NF-kappa-B and JUN, and mediates the transrepression of these transcription factors induced by glucocorticoid receptor. {ECO:0000269|PubMed:14688263, ECO:0000269|PubMed:15489293, ECO:0000269|PubMed:16624523, ECO:0000269|PubMed:19017743}.;

Recessive Scores

pRec: 0.149

Intolerance Scores

LoFtool: 0.294
RVIS EVS: 0.2
RVIS percentile EVS: 67.36

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.952

Gene Damage Prediction

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