MARK1

microtubule affinity regulating kinase 1, the group of Microtubule affinity regulating kinases

Basic information

Region (hg38): 1:220528135-220664461

Links

ENSG00000116141 ∙ NCBI:4139 ∙ OMIM:606511 ∙ HGNC:6896 ∙ Uniprot:Q9P0L2 ∙ 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 MARK1 gene.

• Inborn genetic diseases (21 variants)
• not provided (5 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MARK1 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				4		4
missense			21		1	22
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	21	4	1

Variants in MARK1

This is a list of pathogenic ClinVar variants found in the MARK1 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-220528866-C-T		not specified	Uncertain significance (Jan 24, 2024)
1-220579426-C-T		not specified	Uncertain significance (Dec 08, 2023)
1-220579453-A-G		not specified	Uncertain significance (Jan 23, 2023)
1-220579483-C-T		not specified	Uncertain significance (Jun 21, 2022)
1-220579541-T-C		not specified	Uncertain significance (Sep 14, 2022)
1-220579549-G-C		not specified	Uncertain significance (Feb 14, 2023)
1-220616013-ATT-A			Benign (Nov 16, 2023)
1-220618363-T-C			Likely benign (May 16, 2018)
1-220618433-G-A		not specified	Uncertain significance (Jul 26, 2023)
1-220618490-G-A		not specified	Uncertain significance (Jun 21, 2021)
1-220618528-C-T			Likely benign (Apr 24, 2018)
1-220618649-G-A		not specified	Uncertain significance (Aug 02, 2022)
1-220618682-A-G		not specified	Uncertain significance (Sep 16, 2021)
1-220618694-A-T		not specified	Uncertain significance (Jan 16, 2024)
1-220631117-A-G		not specified	Uncertain significance (Dec 16, 2022)
1-220632245-G-A		not specified	Uncertain significance (Jun 01, 2023)
1-220635393-G-A			Likely benign (Feb 01, 2023)
1-220635425-G-A		not specified	Uncertain significance (Apr 04, 2023)
1-220635836-G-A		not specified	Uncertain significance (Feb 27, 2023)
1-220635855-T-C			Likely benign (Jun 29, 2018)
1-220635953-T-C		not specified	Uncertain significance (May 31, 2023)
1-220650683-G-T		not specified	Uncertain significance (Apr 18, 2023)
1-220650692-G-A		not specified	Uncertain significance (Jan 23, 2024)
1-220652005-A-G		not specified	Uncertain significance (Dec 27, 2023)
1-220652035-G-C			Benign (Jul 04, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MARK1	protein_coding	protein_coding	ENST00000366917	18	136236

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.600	0.400	125736	0	12	125748	0.0000477

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.73	289	452	0.639	0.0000252	5192
Missense in Polyphen		73	187.57	0.38918		2168
Synonymous	1.87	127	157	0.810	0.00000850	1525
Loss of Function	4.98	10	46.7	0.214	0.00000313	509

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000186	0.000181
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000530	0.0000527
Middle Eastern	0.00	0.00
South Asian	0.0000655	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Serine/threonine-protein kinase (PubMed:23666762). Involved in cell polarity and microtubule dynamics regulation. Phosphorylates DCX, MAP2 and MAP4. Phosphorylates the microtubule- associated protein MAPT/TAU (PubMed:23666762). Involved in cell polarity by phosphorylating the microtubule-associated proteins MAP2, MAP4 and MAPT/TAU at KXGS motifs, causing detachment from microtubules, and their disassembly. Involved in the regulation of neuronal migration through its dual activities in regulating cellular polarity and microtubule dynamics, possibly by phosphorylating and regulating DCX. Also acts as a positive regulator of the Wnt signaling pathway, probably by mediating phosphorylation of dishevelled proteins (DVL1, DVL2 and/or DVL3). {ECO:0000269|PubMed:11433294, ECO:0000269|PubMed:17573348, ECO:0000269|PubMed:23666762}.
• Disease: DISEASE: Note=Genetic variations in MARK1 may be associated with susceptibility to autism. MARK1 is overexpressed in the prefrontal cortex of patients with autism and causes changes in the function of cortical dendrites.
• Pathway: WNT-Ncore;Regulation of Microtubule Cytoskeleton (Consensus)

Recessive Scores

• pRec: 0.131

Intolerance Scores

• loftool: 0.503
• rvis_EVS: -0.31
• rvis_percentile_EVS: 31.93

Haploinsufficiency Scores

• pHI: 0.454
• hipred: Y
• hipred_score: 0.750
• ghis: 0.566

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.920

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Mark1

Gene ontology

• Biological process: microtubule cytoskeleton organization;neuron migration;protein phosphorylation;cytoskeleton organization;regulation of neuron projection development;Wnt signaling pathway;peptidyl-serine phosphorylation;establishment of cell polarity;intracellular signal transduction;regulation of dendrite development;establishment of mitochondrion localization
• Cellular component: cytoplasm;cytoskeleton;plasma membrane;microtubule cytoskeleton;dendrite
• Molecular function: magnesium ion binding;phosphatidylserine binding;protein serine/threonine kinase activity;protein binding;ATP binding;phosphatidylinositol-4,5-bisphosphate binding;tau protein binding;tau-protein kinase activity;phosphatidic acid binding