MARK3

microtubule affinity regulating kinase 3, the group of Microtubule affinity regulating kinases

Basic information

Region (hg38): 14:103385376-103503831

Links

ENSG00000075413 ∙ NCBI:4140 ∙ OMIM:602678 ∙ HGNC:6897 ∙ Uniprot:P27448 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• visual impairment and progressive phthisis bulbi (Limited), mode of inheritance: AR
• visual impairment and progressive phthisis bulbi (Limited), mode of inheritance: AR
• visual impairment and progressive phthisis bulbi (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Visual impairment and progressive phthisis bulbi	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	29771303

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MARK3 gene.

• Inborn genetic diseases (18 variants)
• not specified (1 variants)
• Visual impairment and progressive phthisis bulbi (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MARK3 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						0
missense			18			18
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding			1			1
Total	0	0	19	0	0

Variants in MARK3

This is a list of pathogenic ClinVar variants found in the MARK3 region.

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

Position	Type	Phenotype	Significance	ClinVar
14-103386072-A-G		not specified	Uncertain significance (Dec 19, 2023)
14-103405137-G-A		not specified	Uncertain significance (Jul 09, 2021)
14-103405149-C-T			Uncertain significance (-)
14-103405170-A-C		not specified	Uncertain significance (Dec 18, 2023)
14-103405174-A-G		MARK3-related disorder	Likely benign (Sep 20, 2019)
14-103405175-C-T		not specified	Uncertain significance (Oct 17, 2023)
14-103428439-A-G		not specified	Uncertain significance (Mar 20, 2023)
14-103451987-A-T		MARK3-related disorder	Likely benign (Jul 01, 2019)
14-103457138-A-G		Visual impairment and progressive phthisis bulbi • MARK3-related disorder	Benign (Sep 05, 2021)
14-103465979-G-A		not specified	Uncertain significance (Oct 25, 2023)
14-103466080-G-A		not specified	Uncertain significance (Dec 12, 2023)
14-103466080-G-C		MARK3-related disorder	Likely benign (Sep 17, 2019)
14-103466359-G-A		not specified	Uncertain significance (Dec 21, 2023)
14-103466413-A-G		not specified	Uncertain significance (Dec 08, 2023)
14-103467084-A-G		not specified	Uncertain significance (Dec 19, 2022)
14-103468039-G-T		not specified	Uncertain significance (Jan 10, 2022)
14-103468064-A-G		not specified	Uncertain significance (Aug 30, 2022)
14-103468090-A-C		not specified	Uncertain significance (Aug 23, 2021)
14-103475021-G-A		MARK3-related disorder	Benign (Jun 18, 2019)
14-103475025-C-G		not specified	Uncertain significance (Jun 21, 2023)
14-103475026-C-T		not specified	Uncertain significance (Nov 30, 2022)
14-103475042-C-A		MARK3-related disorder	Benign (Sep 30, 2019)
14-103475055-A-G		MARK3-related disorder	Benign (Sep 30, 2019)
14-103475113-G-A		not specified	Uncertain significance (Jun 27, 2023)
14-103475117-G-A		MARK3-related disorder	Benign (Jun 25, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MARK3	protein_coding	protein_coding	ENST00000429436	18	118440

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000143	1.00	124765	0	32	124797	0.000128

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.51	344	432	0.796	0.0000249	4941
Missense in Polyphen		133	216.55	0.61419		2411
Synonymous	-0.386	164	158	1.04	0.00000938	1441
Loss of Function	3.42	17	40.5	0.420	0.00000236	481

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000434	0.000433
Ashkenazi Jewish	0.0000993	0.0000993
East Asian	0.000111	0.000111
Finnish	0.00	0.00
European (Non-Finnish)	0.000133	0.000132
Middle Eastern	0.000111	0.000111
South Asian	0.000140	0.000131
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Serine/threonine-protein kinase (PubMed:23666762). Involved in the specific phosphorylation of microtubule-associated proteins for MAP2 and MAP4. Phosphorylates the microtubule- associated protein MAPT/TAU (PubMed:23666762). Phosphorylates CDC25C on 'Ser-216'. Regulates localization and activity of some histone deacetylases by mediating phosphorylation of HDAC7, promoting subsequent interaction between HDAC7 and 14-3-3 and export from the nucleus (PubMed:16980613). Negatively regulates the Hippo signaling pathway and antagonizes the phosphorylation of LATS1. Cooperates with DLG5 to inhibit the kinase activity of STK3/MST2 toward LATS1 (PubMed:28087714). {ECO:0000269|PubMed:16980613, ECO:0000269|PubMed:23666762, ECO:0000269|PubMed:28087714}.
• Disease: DISEASE: Note=Defects in MARK3 may be involved in an autosomal recessive ocular disease characterized by visual impairment manifested at birth, and progressive eye degeneration. {ECO:0000269|PubMed:29771303}.
• Pathway: MAP2K and MAPK activation;RAF activation;Disease;Signal Transduction;Negative regulation of MAPK pathway;RAF/MAP kinase cascade;MAPK1/MAPK3 signaling;MAPK family signaling cascades;Signaling by RAS mutants;Signaling by high-kinase activity BRAF mutants;Signaling by moderate kinase activity BRAF mutants;Paradoxical activation of RAF signaling by kinase inactive BRAF;Signaling by BRAF and RAF fusions;Oncogenic MAPK signaling;Diseases of signal transduction (Consensus)

Recessive Scores

• pRec: 0.163

Intolerance Scores

• loftool: 0.894
• rvis_EVS: -0.69
• rvis_percentile_EVS: 15.27

Haploinsufficiency Scores

• pHI: 0.398
• hipred: Y
• hipred_score: 0.648
• ghis: 0.571

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.974

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Mark3
• Phenotype: homeostasis/metabolism phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); 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); growth/size/body region phenotype; liver/biliary system phenotype

Gene ontology

• Biological process: MAPK cascade;microtubule cytoskeleton organization;protein phosphorylation;peptidyl-serine phosphorylation;establishment of cell polarity;positive regulation of protein binding;negative regulation of hippo signaling;intracellular signal transduction;peptidyl-serine autophosphorylation
• Cellular component: cytoplasm;cytosol;plasma membrane;dendrite;extracellular exosome
• Molecular function: protein serine/threonine kinase activity;protein binding;ATP binding;tau protein binding;tau-protein kinase activity