MASTL

microtubule associated serine/threonine kinase like, the group of AGC family kinases

Basic information

Region (hg38): 10:27154823-27187953

Links

ENSG00000120539 ∙ NCBI:84930 ∙ OMIM:608221 ∙ HGNC:19042 ∙ Uniprot:Q96GX5 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal thrombocytopenia with normal platelets (Supportive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Thrombocytopenia 2	AD	Hematologic	Individuals may have bleeding tendency, and precautions (eg, in surgical situations) may be beneficial	Hematologic	10891439; 12890928; 22102272

ClinVar

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

• Thrombocytopenia (75 variants)
• not provided (40 variants)
• Inborn genetic diseases (28 variants)
• not specified (19 variants)
• MASTL-related condition (5 variants)
• Thrombocytopenia 2 (2 variants)
• Scimitar anomaly, multiple cardiac malformations, and craniofacial and central nervous system abnormalities (1 variants)
• Autosomal dominant thrombocytopenia (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MASTL 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			6	2	6	14
missense			41	8	13	62
nonsense			2			2
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)			1			1
splice region					3	3
non coding			13	7	29	49
Total	0	0	63	17	48

Variants in MASTL

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

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

Position	Type	Phenotype	Significance	ClinVar
10-27154826-T-A		Thrombocytopenia	Uncertain significance (Jun 14, 2016)
10-27154859-G-A		Thrombocytopenia	Uncertain significance (Jun 14, 2016)
10-27154946-C-T		Thrombocytopenia	Benign/Likely benign (Jun 19, 2021)
10-27155080-CG-C		Thrombocytopenia	Uncertain significance (Jun 14, 2016)
10-27155082-T-C		Thrombocytopenia	Uncertain significance (Jun 14, 2016)
10-27155173-T-G		Thrombocytopenia	Uncertain significance (Jun 14, 2016)
10-27155187-G-A		Thrombocytopenia	Uncertain significance (Jun 14, 2016)
10-27155201-G-A		Thrombocytopenia	Uncertain significance (Jun 14, 2016)
10-27155228-G-C		Thrombocytopenia	Benign/Likely benign (Jun 19, 2021)
10-27155257-C-T		Thrombocytopenia	Uncertain significance (Jun 14, 2016)
10-27155270-C-T		Thrombocytopenia	Uncertain significance (Jun 14, 2016)
10-27155311-C-CG		Thrombocytopenia	Likely benign (Jun 14, 2016)
10-27155321-T-C		Thrombocytopenia	Likely benign (Jun 14, 2016)
10-27155374-G-A		Thrombocytopenia	Benign (Jun 19, 2021)
10-27155399-C-A		not specified • Thrombocytopenia	Benign (Jun 19, 2021)
10-27155400-T-C		not specified • Thrombocytopenia	Benign (Jun 19, 2021)
10-27155415-T-G		not specified • Thrombocytopenia	Benign (Jun 19, 2021)
10-27155458-C-T		not specified	Uncertain significance (Jul 11, 2023)
10-27155460-G-C		not specified • Thrombocytopenia	Benign/Likely benign (Apr 10, 2018)
10-27155535-A-C		MASTL-related disorder	Uncertain significance (Jan 08, 2023)
10-27155536-T-C		Thrombocytopenia	Uncertain significance (Jan 12, 2018)
10-27155649-C-T		not specified	Benign (Jun 19, 2021)
10-27155777-A-T			Benign (Jun 19, 2021)
10-27155834-C-A			Benign (Jun 19, 2021)
10-27158276-T-C			Benign (Jun 20, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MASTL	protein_coding	protein_coding	ENST00000375940	12	32101

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
5.44e-13	0.798	125618	0	130	125748	0.000517

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.505	428	458	0.934	0.0000219	5839
Missense in Polyphen		140	165.19	0.84753		2187
Synonymous	1.37	146	169	0.866	0.00000878	1657
Loss of Function	1.81	25	36.9	0.678	0.00000180	483

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00129	0.00129
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.000272	0.000272
Finnish	0.00224	0.00222
European (Non-Finnish)	0.000238	0.000237
Middle Eastern	0.000272	0.000272
South Asian	0.00	0.00
Other	0.00163	0.00163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Serine/threonine kinase that plays a key role in M phase by acting as a regulator of mitosis entry and maintenance. Acts by promoting the inactivation of protein phosphatase 2A (PP2A) during M phase: does not directly inhibit PP2A but acts by mediating phosphorylation and subsequent activation of ARPP19 and ENSA at 'Ser-62' and 'Ser-67', respectively. ARPP19 and ENSA are phosphatase inhibitors that specifically inhibit the PPP2R2D (PR55-delta) subunit of PP2A. Inactivation of PP2A during M phase is essential to keep cyclin-B1-CDK1 activity high. Following DNA damage, it is also involved in checkpoint recovery by being inhibited. Phosphorylates histone protein in vitro; however such activity is unsure in vivo. May be involved in megakaryocyte differentiation. {ECO:0000269|PubMed:12890928, ECO:0000269|PubMed:19680222, ECO:0000269|PubMed:19793917, ECO:0000269|PubMed:20538976, ECO:0000269|PubMed:20818157}.
• Disease: DISEASE: Note=Defects in MASTL may play a role in the pathogenesis of thrombocytopenia, a disorder defined by reduced number of platelets in circulating blood, resulting in the potential for increased bleeding and decreased ability for clotting. {ECO:0000269|PubMed:12890928}.
• Pathway: MASTL Facilitates Mitotic Progression;Mitotic Prophase;M Phase;Cell Cycle;Cell Cycle, Mitotic (Consensus)

Recessive Scores

• pRec: 0.111

Intolerance Scores

• loftool: 0.984
• rvis_EVS: 1.14
• rvis_percentile_EVS: 92.33

Haploinsufficiency Scores

• pHI: 0.296
• hipred: N
• hipred_score: 0.170
• ghis: 0.548

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: N
• gene_indispensability_score: 0.0182

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Mastl
• Phenotype: embryo phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); cellular phenotype

Zebrafish Information Network

• Gene name: mastl
• Affected structure: thrombocyte
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: G2/M transition of mitotic cell cycle;mitotic cell cycle;cellular response to DNA damage stimulus;female meiosis II;peptidyl-serine phosphorylation;negative regulation of phosphoprotein phosphatase activity;intracellular signal transduction;cell division;regulation of cell cycle;positive regulation of ubiquitin protein ligase activity
• Cellular component: nucleus;nucleoplasm;cytoplasm;centrosome;cleavage furrow
• Molecular function: protein serine/threonine kinase activity;ATP binding;kinase activity;protein phosphatase 2A binding