MARK4

microtubule affinity regulating kinase 4, the group of Microtubule affinity regulating kinases

Basic information

Region (hg38): 19:45079288-45305284

Previous symbols: [ "MARKL1" ]

Links

ENSG00000007047

∙ NCBI:57787 ∙ OMIM:606495 ∙ HGNC:13538 ∙ Uniprot:Q96L34 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

neurodevelopmental disorder (Limited), mode of inheritance: AD

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MARK4 gene.

not_specified (78 variants)
not_provided (5 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MARK4 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001199867.2. 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	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	3 clinvar	2 clinvar	7
missense			75 clinvar			75
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	77	3	2

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MARK4	protein_coding	protein_coding	ENST00000262891	17	225996

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.998	0.00223	125737	0	11	125748	0.0000437

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.92	312	495	0.630	0.0000343	4776
Missense in Polyphen		95	165.01	0.57571		1584
Synonymous	0.315	205	211	0.972	0.0000146	1612
Loss of Function	4.90	4	35.5	0.113	0.00000192	397

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000178	0.000178
Ashkenazi Jewish	0.0000998	0.0000992
East Asian	0.00	0.00
Finnish	0.0000503	0.0000462
European (Non-Finnish)	0.0000264	0.0000264
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.000164	0.000163

dbNSFP

Source: dbNSFP

Function: FUNCTION: Serine/threonine-protein kinase (PubMed:15009667, PubMed:14594945, PubMed:23666762, PubMed:23184942). Phosphorylates the microtubule-associated protein MAPT/TAU (PubMed:14594945, PubMed:23666762). Also phosphorylates the microtubule-associated proteins MAP2 and MAP4 (PubMed:14594945). Involved in regulation of the microtubule network, causing reorganization of microtubules into bundles (PubMed:14594945, PubMed:25123532). Required for the initiation of axoneme extension during cilium assembly (PubMed:23400999). Regulates the centrosomal location of ODF2 and phosphorylates ODF2 in vitro (PubMed:23400999). Plays a role in cell cycle progression, specifically in the G1/S checkpoint (PubMed:25123532). Reduces neuronal cell survival (PubMed:15009667). Plays a role in energy homeostasis by regulating satiety and metabolic rate (By similarity). Promotes adipogenesis by activating JNK1 and inhibiting the p38MAPK pathway, and triggers apoptosis by activating the JNK1 pathway (By similarity). Phosphorylates mTORC1 complex member RPTOR and acts as a negative regulator of the mTORC1 complex, probably due to disruption of the interaction between phosphorylated RPTOR and the RRAGA/RRAGC heterodimer which is required for mTORC1 activation (PubMed:23184942). {ECO:0000250|UniProtKB:Q8CIP4, ECO:0000269|PubMed:14594945, ECO:0000269|PubMed:15009667, ECO:0000269|PubMed:23184942, ECO:0000269|PubMed:23400999, ECO:0000269|PubMed:23666762, ECO:0000269|PubMed:25123532}.;
Pathway: Anchoring of the basal body to the plasma membrane;LKB1 signaling events;Cilium Assembly;Organelle biogenesis and maintenance (Consensus)

Recessive Scores

pRec: 0.140

Intolerance Scores

loftool: 0.0914
rvis_EVS: -0.98
rvis_percentile_EVS: 8.75

Haploinsufficiency Scores

pHI: 0.540
hipred: Y
hipred_score: 0.806
ghis: 0.567

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.930

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Mark4
Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); homeostasis/metabolism phenotype; growth/size/body region phenotype;

Gene ontology

Biological process: microtubule cytoskeleton organization;microtubule bundle formation;protein phosphorylation;cell cycle;nervous system development;establishment of cell polarity;intracellular signal transduction;positive regulation of programmed cell death;cilium organization;positive regulation of cilium assembly;regulation of centrosome cycle;cell division;ciliary basal body-plasma membrane docking;positive regulation of protein localization to centrosome
Cellular component: gamma-tubulin complex;cytoplasm;centrosome;microtubule organizing center;cytosol;microtubule cytoskeleton;dendrite;midbody;ciliary basal body;neuron projection
Molecular function: protein serine/threonine kinase activity;protein binding;ATP binding;microtubule binding;gamma-tubulin binding;ubiquitin binding;tau protein binding;tau-protein kinase activity