MARK3

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

Basic information

Region (hg38): 14:103385377-103503831

Links

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

Transcripts

Transcript IDs starting with ENST are treated as Ensembl, all others as RefSeq. Showing 4 of 136.

Transcript ID	Protein ID	Coding exons	MANE Select	MANE Plus Clinical
NM_001128918.3	NP_001122390.2	18	yes	-
ENST00000429436.7	ENSP00000411397.2	18	yes	-
NM_002376.7	NP_002367.5	16	-	-
NM_001128919.3	NP_001122391.2	17	-	-

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

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.

• not_specified (79 variants)
• MARK3-related_disorder (11 variants)
• not_provided (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. These statistics are base on transcript: NM_001128918.3. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	3	3	7
missense	1		83	2	1	87
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			3			3
Total	1	0	87	5	4

Highest pathogenic variant AF is 0.000031597534

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
		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

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

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