MELK

maternal embryonic leucine zipper kinase, the group of MELK family kinases

Basic information

Region (hg38): 9:36572862-36677683

Links

ENSG00000165304

∙ NCBI:9833 ∙ OMIM:607025 ∙ HGNC:16870 ∙ Uniprot:Q14680 ∙ 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 MELK gene.

not_specified (77 variants)
not_provided (10 variants)
Hereditary_breast_ovarian_cancer_syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MELK gene is commonly pathogenic or not. These statistics are base on transcript: NM_000014791.4. 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				1 clinvar	2 clinvar	3
missense			73 clinvar	5 clinvar	4 clinvar	82
nonsense			1 clinvar	1 clinvar		2
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)						0
Total	0	0	75	7	6

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MELK	protein_coding	protein_coding	ENST00000298048	17	104820

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
4.51e-22	0.00250	125562	1	185	125748	0.000740

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.897	298	345	0.864	0.0000173	4264
Missense in Polyphen		105	137.58	0.76319		1668
Synonymous	-0.349	124	119	1.04	0.00000574	1184
Loss of Function	0.319	34	36.1	0.943	0.00000160	482

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000447	0.000439
Ashkenazi Jewish	0.000100	0.0000992
East Asian	0.00234	0.00223
Finnish	0.0000959	0.0000924
European (Non-Finnish)	0.000331	0.000308
Middle Eastern	0.00234	0.00223
South Asian	0.00325	0.00304
Other	0.000654	0.000652

dbNSFP

Source: dbNSFP

Function: FUNCTION: Serine/threonine-protein kinase involved in various processes such as cell cycle regulation, self-renewal of stem cells, apoptosis and splicing regulation. Has a broad substrate specificity; phosphorylates BCL2L14, CDC25B, MAP3K5/ASK1 and ZNF622. Acts as an activator of apoptosis by phosphorylating and activating MAP3K5/ASK1. Acts as a regulator of cell cycle, notably by mediating phosphorylation of CDC25B, promoting localization of CDC25B to the centrosome and the spindle poles during mitosis. Plays a key role in cell proliferation and carcinogenesis. Required for proliferation of embryonic and postnatal multipotent neural progenitors. Phosphorylates and inhibits BCL2L14, possibly leading to affect mammary carcinogenesis by mediating inhibition of the pro-apoptotic function of BCL2L14. Also involved in the inhibition of spliceosome assembly during mitosis by phosphorylating ZNF622, thereby contributing to its redirection to the nucleus. May also play a role in primitive hematopoiesis. {ECO:0000269|PubMed:11802789, ECO:0000269|PubMed:12400006, ECO:0000269|PubMed:14699119, ECO:0000269|PubMed:15908796, ECO:0000269|PubMed:16216881, ECO:0000269|PubMed:17280616}.;
Disease: DISEASE: Note=Defects in MELK are associated with some cancers, such as brain or breast cancers. Expression is dramatically increased in aggressive undifferentiated tumors, correlating with poor patient outcome in breast and brain cancers, suggesting a role in tumor-initiating cells and proliferation via its function in cell proliferation regulation.;

Recessive Scores

pRec: 0.179

Intolerance Scores

loftool: 0.916
rvis_EVS: 0.62
rvis_percentile_EVS: 83.47

Haploinsufficiency Scores

pHI: 0.444
hipred: Y
hipred_score: 0.658
ghis: 0.551

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.746

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Melk
Phenotype: endocrine/exocrine gland phenotype;

Zebrafish Information Network

Gene name: melk
Affected structure: whole organism
Phenotype tag: abnormal
Phenotype quality: has fewer parts of type

Gene ontology

Biological process: G2/M transition of mitotic cell cycle;protein phosphorylation;apoptotic process;cell population proliferation;intrinsic apoptotic signaling pathway in response to oxidative stress;peptidyl-tyrosine phosphorylation;hemopoiesis;intracellular signal transduction;positive regulation of apoptotic process;protein autophosphorylation;neural precursor cell proliferation
Cellular component: nucleus;cytoplasm;plasma membrane;cell cortex;membrane
Molecular function: protein serine/threonine kinase activity;non-membrane spanning protein tyrosine kinase activity;calcium ion binding;protein binding;ATP binding;lipid binding