MAST2

protein-coding

microtubule associated serine/threonine kinase 2, the group of PDZ domain containing|AGC family kinases

Gene summary

Enables phosphatase binding activity. Predicted to be involved in several processes, including protein phosphorylation; regulation of interleukin-12 production; and spermatid differentiation. Predicted to be located in cytoplasm; cytoskeleton; and plasma membrane. Predicted to be active in microtubule cytoskeleton. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_015112.3

Inheritance

ClinVar variants

U:267B:24

Top phenotype

MAST2-related condition

gnomAD constraint

pLI —, LoF o/e 0.55

Max pathogenic AF

—

Genomic locus

chr1:45,786,987-46,036,122

External References & Databases

Ensembl (ENSG00000086015)

Transcript & Mutation Effects

hg38 • Region Span ~249.1 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

thrombotic diseaseLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0000831

Submitter: ClinGen

MAST2 is a member of the microtubule associated serine/threonine (MAST) kinase family of proteins that remains poorly studied. One variant, p.Arg89Gln, in MAST2 was reported in 4 members of a family with unknown thrombophilia (Morange et al., PMID: 33465109). The mechanism of disorder is not completely clear, however, it has been proposed that mutant MAST2 increases TFPI expression and reduces that of PAI-1. Evidence supporting this gene-disease relationship includes genetic evidences (case-level data) and experimental evidences (functional alteration in non-patient cells). Summary of Case Level Data: 0.5 POINTS Variants in this gene have been reported in 1 proband in 1 publication (PMID: 33465109). Affected patients show thrombophilia, lower plasma levels of the anticoagulant protein free-Tissue Factor Pathway Inhibitor (f-TFPI) and higher of the antifibrinolytic protein Plasminogen Activator Inhibitor-1 (PAI-1). Summary of Experimental Data: 1.5 POINTS Morange et al showed that the expression of some genes known to regulate some hemostatic properties of endothelial cells (SERPINE1, PLAU, TFPI, SERPINB8) was altered by MAST2 knockdown (PMID: 33465109). Moreover, they showed that PAI-1 accumulated in the supernatant of ECV304 cells expressing mutant MAST2 (PMID: 33465109). Finally, silencing of MAST2 significantly increased TFPI promoter activity and reduced that of SERPINE1, while overexpression of Gln89 MAST2 decreased TFPI promoter activity and increased that of SERPINE1. Moreover, phosphorylation of AKT is increased (PMID: 33465109). In summary, we obtained limited association of MAST2 with unclassified bleeding disorder. This classification was approved by the ClinGen Hemostasis Thrombosis Working Group on June 4th 2025 (SOP Version 11).

thrombotic diseaseLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0000831

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to MAST2 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 254

not providedTotal: 13

MAST2-related conditionTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_015112.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			6 clinvar	5 clinvar	2 clinvar	13
missense			253 clinvar	15 clinvar	2 clinvar	270
nonsense			2 clinvar			2
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			6 clinvar			6
Total	0	0	267	20	4	291

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 71 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_015112.3	RefSeq	NP_055927.2	29	MANE Select
ENST00000361297.7	Ensembl	ENSP00000354671.2	29	MANE Select
NM_001319245.2	RefSeq	NP_001306174.1	29	Standard
NM_001324320.2	RefSeq	NP_001311249.1	30	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

protein phosphorylation
cytoskeleton organization
peptidyl-serine phosphorylation
intracellular signal transduction
regulation of interleukin-12 biosynthetic process

Molecular Function

magnesium ion binding
protein serine/threonine kinase activity
protein binding
ATP binding
microtubule binding

Cellular Component

cytoplasm
plasma membrane
microtubule cytoskeleton

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000361297
Coding exons: 29
Length: 249138
Individuals with no LoFs: 124869
Homozygous LoFs: 1
Heterozygous LoFs: 138
Defined: 125008
p: 0.000556

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.04	845	1.03e+3	0.821	0.0000627	11557
Missense (PolyPhen)		337	455.81	0.73934		4971
Synonymous	-0.835	417	396	1.05	0.0000220	3815
Loss of Function	3.73	44	80.0	0.550	0.00000461	900

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00078	0.00077	rare
Latino/Admixed American	0.00082	0.00070	rare
Ashkenazi Jewish	0.00080	0.00079	rare
East Asian	0.00078	0.00077	rare
Finnish	0.00019	0.00019	rare
European (Non-Finnish)	0.00053	0.00051	rare
South Asian	0.00061	0.00059	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Appears to link the dystrophin/utrophin network with microtubule filaments via the syntrophins. Phosphorylation of DMD or UTRN may modulate their affinities for associated proteins. Functions in a multi-protein complex in spermatid maturation. Regulates lipopolysaccharide-induced IL-12 synthesis in macrophages by forming a complex with TRAF6, resulting in the inhibition of TRAF6 NF-kappa-B activation (By similarity). {ECO:0000250}.;

Recessive Scores

pRec: 0.106

Intolerance Scores

LoFtool: 0.843
RVIS EVS: -0.16
RVIS percentile EVS: 41.92

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.974

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High