MERTK

MER proto-oncogene, tyrosine kinase, the group of Receptor tyrosine kinases|Fibronectin type III domain containing|I-set domain containing

Basic information

Region (hg38): 2:111898606-112029561

Links

ENSG00000153208 ∙ NCBI:10461 ∙ OMIM:604705 ∙ HGNC:7027 ∙ Uniprot:Q12866 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• retinitis pigmentosa (Supportive), mode of inheritance: AD
• retinitis pigmentosa 38 (Definitive), mode of inheritance: AR
• retinitis pigmentosa 38 (Strong), mode of inheritance: AR
• MERTK-related retinopathy (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Retinitis pigmentosa 38	AD/AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Ophthalmologic	11062461; 11727200; 17301963; 22180149

ClinVar

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

• not provided (633 variants)
• Retinitis pigmentosa (84 variants)
• Retinitis pigmentosa 38 (56 variants)
• Retinal dystrophy (34 variants)
• Inborn genetic diseases (29 variants)
• not specified (12 variants)
• Autosomal recessive retinitis pigmentosa (9 variants)
• Retinitis Pigmentosa, Recessive (3 variants)
• MERTK-related condition (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MERTK 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			10	127	5	142
missense	3	8	295	11	7	324
nonsense	13	6				19
start loss						0
frameshift	22	7	4			33
inframe indel			7			7
splice donor/acceptor (+/-2bp)	10	9				19
splice region	2	5	21	17	2	47
non coding			11	49	9	69
Total	48	30	327	187	21

Highest pathogenic variant AF is 0.0000394

Variants in MERTK

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

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

Position	Type	Phenotype	Significance	ClinVar
2-111898617-C-T		Retinitis pigmentosa	Uncertain significance (Jan 13, 2018)
2-111898702-G-A		Retinitis pigmentosa	Likely benign (Jan 13, 2018)
2-111898740-G-T			Uncertain significance (Aug 01, 2022)
2-111898745-G-A			Uncertain significance (Jul 17, 2023)
2-111898745-GC-G			Pathogenic (Mar 28, 2022)
2-111898749-C-G			Uncertain significance (Jun 06, 2022)
2-111898749-C-T			Uncertain significance (Aug 30, 2021)
2-111898750-G-A			Likely benign (Aug 09, 2022)
2-111898756-G-T		Retinitis pigmentosa	Conflicting classifications of pathogenicity (Jun 27, 2022)
2-111898755-C-CGCTGCT			Uncertain significance (May 06, 2021)
2-111898762-G-A		Retinitis pigmentosa	Uncertain significance (Jan 12, 2018)
2-111898769-C-T			Uncertain significance (Nov 06, 2021)
2-111898780-C-A			Uncertain significance (May 13, 2021)
2-111898780-C-T			Likely benign (Feb 11, 2023)
2-111898787-TGGCGTAGAGGTGAGTGCGCCC-T		Retinitis pigmentosa 38	Likely pathogenic (Jan 03, 2022)
2-111898791-G-T			Uncertain significance (Sep 27, 2022)
2-111898794-G-C			Uncertain significance (Sep 07, 2022)
2-111898795-A-T		not specified • Retinitis pigmentosa • Retinitis pigmentosa 38	Conflicting classifications of pathogenicity (Jan 31, 2024)
2-111898797-G-A		Retinitis pigmentosa 38	Pathogenic (Mar 09, 2010)
2-111898799-G-C		Retinal dystrophy • Retinitis pigmentosa	Uncertain significance (Aug 22, 2022)
2-111898802-T-C			Uncertain significance (Jun 01, 2022)
2-111898803-G-A			Likely benign (Jul 03, 2023)
2-111898815-G-A		not specified • Retinitis pigmentosa 38	Benign (Jan 30, 2024)
2-111898815-G-T			Likely benign (Dec 27, 2023)
2-111929100-T-G			Likely benign (Oct 05, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MERTK	protein_coding	protein_coding	ENST00000295408	19	131083

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.66e-11	0.999	125642	0	106	125748	0.000422

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.588	509	548	0.929	0.0000316	6535
Missense in Polyphen		187	197.16	0.94848		2387
Synonymous	0.494	207	216	0.957	0.0000136	1977
Loss of Function	2.94	25	46.7	0.536	0.00000272	526

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000666	0.000666
Ashkenazi Jewish	0.00	0.00
East Asian	0.000598	0.000598
Finnish	0.000970	0.000971
European (Non-Finnish)	0.000352	0.000352
Middle Eastern	0.000598	0.000598
South Asian	0.000555	0.000555
Other	0.000489	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to several ligands including LGALS3, TUB, TULP1 or GAS6. Regulates many physiological processes including cell survival, migration, differentiation, and phagocytosis of apoptotic cells (efferocytosis). Ligand binding at the cell surface induces autophosphorylation of MERTK on its intracellular domain that provides docking sites for downstream signaling molecules. Following activation by ligand, interacts with GRB2 or PLCG2 and induces phosphorylation of MAPK1, MAPK2, FAK/PTK2 or RAC1. MERTK signaling plays a role in various processes such as macrophage clearance of apoptotic cells, platelet aggregation, cytoskeleton reorganization and engulfment. Functions in the retinal pigment epithelium (RPE) as a regulator of rod outer segments fragments phagocytosis. 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:17005688}.
• Disease: DISEASE: Retinitis pigmentosa 38 (RP38) [MIM:613862]: A retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well. {ECO:0000269|PubMed:11062461}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Ebola Virus Pathway on Host;Ebola Virus Pathway on Host;Cell surface interactions at the vascular wall;Hemostasis (Consensus)

Recessive Scores

• pRec: 0.244

Intolerance Scores

• loftool: 0.785
• rvis_EVS: 0.87
• rvis_percentile_EVS: 88.89

Haploinsufficiency Scores

• pHI: 0.102
• hipred: N
• hipred_score: 0.491
• ghis: 0.449

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: H
• gene_indispensability_pred: E
• gene_indispensability_score: 0.603

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Mertk
• Phenotype: liver/biliary system phenotype; 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; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); reproductive system phenotype; pigmentation phenotype; digestive/alimentary 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); vision/eye phenotype; immune system phenotype; cellular phenotype; skeleton 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); endocrine/exocrine gland phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: natural killer cell differentiation;negative regulation of cytokine production;protein phosphorylation;phagocytosis;cell surface receptor signaling pathway;transmembrane receptor protein tyrosine kinase signaling pathway;cell-cell signaling;spermatogenesis;nervous system development;Wnt signaling pathway;cell migration;peptidyl-tyrosine phosphorylation;platelet activation;secretion by cell;substrate adhesion-dependent cell spreading;apoptotic cell clearance;protein kinase B signaling;positive regulation of phagocytosis;leukocyte migration;negative regulation of lymphocyte activation;retina development in camera-type eye;vagina development;neutrophil clearance;negative regulation of leukocyte apoptotic process
• Cellular component: photoreceptor outer segment;extracellular space;cytoplasm;plasma membrane;integral component of plasma membrane;rhabdomere;receptor complex
• Molecular function: transmembrane receptor protein tyrosine kinase activity;protein binding;ATP binding;Wnt-protein binding