TYRO3

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

Basic information

Region (hg38): 15:41557675-41583589

Previous symbols: [ "RSE" ]

Links

ENSG00000092445 ∙ NCBI:7301 ∙ OMIM:600341 ∙ HGNC:12446 ∙ Uniprot:Q06418 ∙ 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 TYRO3 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TYRO3 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					3	3
missense			37		3	40
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	37	0	6

Variants in TYRO3

This is a list of pathogenic ClinVar variants found in the TYRO3 region.

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

Position	Type	Phenotype	Significance	ClinVar
15-41561192-T-A		not specified	Uncertain significance (Jun 04, 2024)
15-41561204-G-C		not specified	Uncertain significance (Sep 01, 2021)
15-41561231-G-T		not specified	Uncertain significance (Sep 17, 2021)
15-41561286-A-G		not specified	Uncertain significance (Dec 19, 2022)
15-41561539-C-A		not specified	Uncertain significance (Feb 13, 2024)
15-41562687-C-T			Benign (Apr 24, 2018)
15-41564203-G-A		not specified	Uncertain significance (Oct 03, 2022)
15-41564241-C-T		not specified	Uncertain significance (Jan 03, 2024)
15-41564269-A-ACACTGCCTGCAGCCCCCTTCAACATCACC		46,XX disorder of sex development	Uncertain significance (Jan 01, 2023)
15-41565084-T-G		not specified	Uncertain significance (Jan 03, 2022)
15-41567406-C-T		not specified	Uncertain significance (Sep 01, 2021)
15-41567517-C-T		not specified	Uncertain significance (Jun 05, 2024)
15-41568347-A-T		not specified	Uncertain significance (Dec 21, 2023)
15-41568948-G-A		not specified	Uncertain significance (Jun 05, 2024)
15-41568965-G-A		not specified	Uncertain significance (Jan 10, 2022)
15-41569016-C-T		not specified	Uncertain significance (Dec 26, 2023)
15-41570036-G-T		not specified	Uncertain significance (Feb 26, 2024)
15-41570063-T-C		not specified	Uncertain significance (Mar 28, 2023)
15-41570080-G-A		not specified	Uncertain significance (Apr 20, 2024)
15-41570104-G-A		not specified	Uncertain significance (Jan 09, 2024)
15-41570148-G-A			Benign (Dec 31, 2019)
15-41570326-G-A		not specified	Uncertain significance (Mar 20, 2023)
15-41570624-G-A		not specified	Uncertain significance (Sep 16, 2021)
15-41570625-A-G		not specified	Uncertain significance (Jul 06, 2021)
15-41570654-C-T		not specified	Uncertain significance (Jan 26, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TYRO3	protein_coding	protein_coding	ENST00000263798	19	21664

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
8.33e-10	0.999	124392	0	1356	125748	0.00541

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.57	413	513	0.805	0.0000306	5690
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00642	0.00640
Ashkenazi Jewish	0.0193	0.0153
East Asian	0.000327	0.000326
Finnish	0.00416	0.00366
European (Non-Finnish)	0.00767	0.00665
Middle Eastern	0.000327	0.000326
South Asian	0.00479	0.00442
Other	0.00937	0.00768

dbNSFP

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}.
• Pathway: Ebola Virus Pathway on Host;Ebola Virus Pathway on Host (Consensus)

Recessive Scores

• pRec: 0.240

Intolerance Scores

• loftool: 0.249
• rvis_EVS: -0.82
• rvis_percentile_EVS: 11.98

Haploinsufficiency Scores

• pHI: 0.266
• hipred: Y
• hipred_score: 0.625
• ghis: 0.556

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.959

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tyro3
• Phenotype: skeleton phenotype; immune system phenotype; vision/eye phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; reproductive system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); liver/biliary system phenotype; homeostasis/metabolism phenotype; cellular phenotype; endocrine/exocrine gland phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan)

Gene ontology

• Biological process: natural killer cell differentiation;cell adhesion;signal transduction;transmembrane receptor protein tyrosine kinase signaling pathway;neuropeptide signaling pathway;spermatogenesis;phosphatidylinositol 3-kinase signaling;Wnt signaling pathway;peptidyl-tyrosine phosphorylation;forebrain cell migration;platelet activation;secretion by cell;negative regulation of toll-like receptor signaling pathway;substrate adhesion-dependent cell spreading;ovulation cycle;apoptotic cell clearance;protein kinase B signaling;negative regulation of neuron apoptotic process;negative regulation of innate immune response;viral entry into host cell;protein autophosphorylation;negative regulation of inflammatory response;negative regulation of lymphocyte activation;vagina development;neuron cellular homeostasis;platelet aggregation
• Cellular component: nucleus;nuclear envelope;endoplasmic reticulum membrane;integral component of plasma membrane;cell surface;receptor complex
• Molecular function: virus receptor activity;protein tyrosine kinase activity;transmembrane receptor protein tyrosine kinase activity;protein binding;ATP binding;Wnt-protein binding;phosphatidylinositol 3-kinase binding;protein heterodimerization activity