TYRO3

protein-coding

TYRO3 protein tyrosine kinase, the group of Fibronectin type III domain containing|I-set domain containing|Receptor tyrosine kinases

Gene summary

The gene is part of a 3-member transmembrane receptor kinase receptor family with a processed pseudogene distal on chromosome 15. The encoded protein is activated by the products of the growth arrest-specific gene 6 and protein S genes and is involved in controlling cell survival and proliferation, spermatogenesis, immunoregulation and phagocytosis. The encoded protein has also been identified as a cell entry factor for Ebola and Marburg viruses. [provided by RefSeq, May 2010]

Previous symbols:

MANE transcript

NM_006293.4

Inheritance

—

ClinVar variants

U:116B:8

Top phenotype

Hereditary breast ovarian cancer syndrome

gnomAD constraint

pLI —, LoF o/e 0.52

Max pathogenic AF

—

Genomic locus

chr15:41,557,675-41,583,589

External References & Databases

Ensembl (ENSG00000092445)

Transcript & Mutation Effects

hg38 • Region Span ~25.9 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 TYRO3 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 93

not providedTotal: 8

Hereditary breast ovarian cancer syndromeTotal: 1

46,XX disorder of sex developmentTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_006293.4. 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	3 clinvar	7
missense			98 clinvar	1 clinvar	2 clinvar	101
nonsense						0
start loss						0
frameshift			2 clinvar			2
splice donor/acceptor (+/-2bp)			14 clinvar			14
Total	0	0	116	3	5	124

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 43 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_006293.4	RefSeq	NP_006284.2	19	MANE Select
ENST00000263798.8	Ensembl	ENSP00000263798.3	19	MANE Select
NM_001330264.2	RefSeq	NP_001317193.1	18	Standard
ENST00000559066.5	Ensembl	ENSP00000454050.1	18	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Ebola Virus Pathway on Host
Ebola Virus Pathway on Host

Biological Process

natural killer cell differentiation
cell adhesion
signal transduction
transmembrane receptor protein tyrosine kinase signaling pathway
neuropeptide signaling pathway

Molecular Function

virus receptor activity
protein tyrosine kinase activity
transmembrane receptor protein tyrosine kinase activity
protein binding
ATP binding

Cellular Component

nucleus
nuclear envelope
endoplasmic reticulum membrane
integral component of plasma membrane
cell surface

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000263798
Coding exons: 19
Length: 21664
Individuals with no LoFs: 124392
Homozygous LoFs: 0
Heterozygous LoFs: 1356
Defined: 125748
p: 0.00541

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.57	413	513	0.805	0.0000306	5690
Missense (PolyPhen)		114	191.14	0.59643		2227
Synonymous	0.0639	201	202	0.994	0.0000121	1864
Loss of Function	2.93	22	42.7	0.516	0.00000213	461

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0010	0.00098	notable
Latino/Admixed American	0.0054	0.0048	notable
Ashkenazi Jewish	0.019	0.015	notable
East Asian	0.00033	0.00033	rare
Finnish	0.0042	0.0037	notable
European (Non-Finnish)	0.0077	0.0066	notable
South Asian	0.0048	0.0044	notable
Other	0.0094	0.0077	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to several ligands including TULP1 or GAS6. Regulates many physiological processes including cell survival, migration and differentiation. Ligand binding at the cell surface induces dimerization and autophosphorylation of TYRO3 on its intracellular domain that provides docking sites for downstream signaling molecules. Following activation by ligand, interacts with PIK3R1 and thereby enhances PI3-kinase activity. Activates the AKT survival pathway, including nuclear translocation of NF-kappa-B and up-regulation of transcription of NF-kappa-B-regulated genes. TYRO3 signaling plays a role in various processes such as neuron protection from excitotoxic injury, platelet aggregation and cytoskeleton reorganization. Plays also an important role in inhibition of Toll-like receptors (TLRs)-mediated innate immune response by activating STAT1, which selectively induces production of suppressors of cytokine signaling SOCS1 and SOCS3. {ECO:0000269|PubMed:20546121}.; FUNCTION: (Microbial infection) Acts as a receptor for Ebolavirus, possibly through GAS6 binding to phosphatidyl-serine at the surface of virion envelope. {ECO:0000269|PubMed:17005688}.;

Recessive Scores

pRec: 0.240

Intolerance Scores

LoFtool: 0.249
RVIS EVS: -0.82
RVIS percentile EVS: 11.98

Essentials

Essential (CRISPR): E
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.959

Gene Damage Prediction

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