MAST4

protein-coding

microtubule associated serine/threonine kinase family member 4, the group of PDZ domain containing|AGC family kinases

Gene summary

This gene encodes a member of the microtubule-associated serine/threonine protein kinases. The proteins in this family contain a domain that gives the kinase the ability to determine its own scaffold to control the effects of their kinase activities. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Mar 2014]

MANE transcript

NM_001164664.2

Inheritance

ClinVar variants

P:3U:331B:49

Top phenotype

neurodevelopmental disorder

gnomAD constraint

pLI —, LoF o/e 0.28

Max pathogenic AF

—

Genomic locus

chr5:66,596,380-67,169,593

External References & Databases

Ensembl (ENSG00000069020)

Transcript & Mutation Effects

hg38 • Region Span ~573.2 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

neurodevelopmental disorderSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0700092

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to MAST4 variants in ClinVar

9 Conditions Cataloged

not specifiedTotal: 337

not providedTotal: 33

Infantile spasmsTotal: 3

Neurodevelopmental disorderTotal: 1

MAST-associated epilepsy syndromeTotal: 1

Moyamoya angiopathyTotal: 1

MAST4-related disorderTotal: 1

MAST4-related conditionTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001164664.2. 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			4 clinvar	15 clinvar	3 clinvar	22
missense		3 clinvar	322 clinvar	28 clinvar	3 clinvar	356
nonsense			1 clinvar			1
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	3	331	43	6	383

Highest pathogenic variant AF is 0.0000027365359

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 61 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001164664.2	RefSeq	NP_001158136.1	29	MANE Select
ENST00000403625.7	Ensembl	ENSP00000385727.1	29	MANE Select
NM_001290226.2	RefSeq	NP_001277155.1	27	Standard
NM_001290227.2	RefSeq	NP_001277156.1	25	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

cytoskeleton organization
peptidyl-serine phosphorylation
intracellular signal transduction

Molecular Function

magnesium ion binding
protein serine/threonine kinase activity
ATP binding

Cellular Component

cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000403625
Coding exons: 29
Length: 573248
Individuals with no LoFs: 124453
Homozygous LoFs: 0
Heterozygous LoFs: 208
Defined: 124661
p: 0.000835

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.93	1257	1.46e+3	0.858	0.0000853	16865
Missense (PolyPhen)		316	520.95	0.60658		6053
Synonymous	0.814	576	601	0.958	0.0000371	5416
Loss of Function	6.72	28	101	0.278	0.00000606	1190

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00032	0.00032	rare
Latino/Admixed American	0.00061	0.00061	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.0049	0.0043	notable
Finnish	0.00023	0.00023	rare
European (Non-Finnish)	0.00046	0.00044	rare
South Asian	0.0015	0.0014	notable
Other	0.0012	0.0012	notable

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.0819

Intolerance Scores

LoFtool: 0.913
RVIS EVS: -0.22
RVIS percentile EVS: 37.7

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.834

Gene Damage Prediction

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