MELK

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

Basic information

Region (hg38): 9:36572861-36677683

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.

• Inborn genetic diseases (25 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.

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				1	2	3
missense			23	3	4	30
nonsense			1	1		2
start loss						0
frameshift			1			1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	25	5	6

Variants in MELK

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

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

Position	Type	Phenotype	Significance	ClinVar
9-36583645-A-C		not specified	Uncertain significance (Jan 07, 2022)
9-36583645-A-G			Benign (Jun 08, 2017)
9-36589541-T-G		not specified	Uncertain significance (Oct 22, 2021)
9-36589580-C-G		not specified	Uncertain significance (Mar 02, 2023)
9-36589615-T-G		not specified	Uncertain significance (Aug 12, 2021)
9-36594656-A-G		not specified	Uncertain significance (Oct 06, 2021)
9-36594660-A-G		not specified	Uncertain significance (May 17, 2023)
9-36594694-C-T		not specified	Uncertain significance (Jul 19, 2023)
9-36594704-T-C		not specified	Uncertain significance (May 17, 2023)
9-36594732-T-C			Likely benign (Oct 10, 2018)
9-36594733-G-A		not specified	Uncertain significance (Aug 28, 2023)
9-36597242-A-C		not specified	Uncertain significance (Sep 27, 2022)
9-36599460-C-A		not specified	Uncertain significance (Jun 07, 2023)
9-36599460-C-G		not specified	Uncertain significance (Feb 21, 2024)
9-36630325-G-A		Hereditary breast ovarian cancer syndrome	Uncertain significance (Aug 01, 2020)
9-36630356-C-G		not specified	Uncertain significance (Oct 12, 2022)
9-36633121-T-A		not specified	Uncertain significance (Dec 19, 2023)
9-36633155-C-G		not specified	Uncertain significance (Dec 20, 2023)
9-36633159-C-T			Likely benign (Dec 31, 2019)
9-36633169-A-G		not specified	Uncertain significance (Jan 03, 2024)
9-36643021-G-A			Likely benign (Apr 10, 2018)
9-36643028-A-C		not specified	Uncertain significance (Jan 03, 2024)
9-36651750-A-G		not specified	Uncertain significance (Jul 09, 2021)
9-36651773-T-C		not specified	Uncertain significance (Jul 14, 2022)
9-36651791-A-G		not specified	Uncertain significance (Sep 16, 2021)

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