MPP1

protein-coding

MAGUK p55 scaffold protein 1, the group of PDZ domain containing|Membrane associated guanylate kinases

Gene summary

This gene encodes the prototype of the membrane-associated guanylate kinase (MAGUK) family proteins. MAGUKs interact with the cytoskeleton and regulate cell proliferation, signaling pathways, and intercellular junctions. The encoded protein is an extensively palmitoylated membrane phosphoprotein containing a PDZ domain, a Src homology 3 (SH3) motif, and a guanylate kinase domain. This gene product interacts with various cytoskeletal proteins and cell junctional proteins in different tissue and cell types, and may be involved in the regulation of cell shape, hair cell development, neural patterning of the retina, and apico-basal polarity and tumor suppression pathways in non-erythroid cells. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2009]

Previous symbols:

DXS552E

MANE transcript

NM_002436.4

Inheritance

—

ClinVar variants

U:156B:3

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.06

Max pathogenic AF

—

Genomic locus

chrX:154,778,684-154,821,007

External References & Databases

Ensembl (ENSG00000130830)

Transcript & Mutation Effects

hg38 • Region Span ~42.3 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to MPP1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 42

not providedTotal: 7

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002436.4. 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			12 clinvar	1 clinvar		13
missense			101 clinvar	1 clinvar	1 clinvar	103
nonsense			14 clinvar			14
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			29 clinvar			29
Total	0	0	156	2	1	159

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 39 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_002436.4	RefSeq	NP_002427.1	12	MANE Select
ENST00000369534.8	Ensembl	ENSP00000358547.3	12	MANE Select
NM_001166460.2	RefSeq	NP_001159932.1	12	Standard
NM_001166461.2	RefSeq	NP_001159933.1	12	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

MECP2 and Associated Rett Syndrome

Biological Process

signal transduction
GMP metabolic process
GDP metabolic process
regulation of neutrophil chemotaxis

Molecular Function

guanylate kinase activity
protein binding

Cellular Component

cytosol
plasma membrane
membrane
nuclear speck
cortical cytoskeleton

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000369534
Coding exons: 12
Length: 42324
Individuals with no LoFs: 125685
Homozygous LoFs: 0
Heterozygous LoFs: 2
Defined: 125687
p: 0.00000796

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.67	119	183	0.652	0.0000142	3075
Missense (PolyPhen)		35	64.451	0.54305		1252
Synonymous	0.512	69	74.6	0.925	0.00000612	877
Loss of Function	3.68	1	17.7	0.0565	0.00000125	302

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000076	0.000062	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000015	0.0000088	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Essential regulator of neutrophil polarity. Regulates neutrophil polarization by regulating AKT1 phosphorylation through a mechanism that is independent of PIK3CG activity (By similarity). {ECO:0000250}.;

Recessive Scores

pRec: 0.105

Intolerance Scores

LoFtool: 0.0774
RVIS EVS: -0.18
RVIS percentile EVS: 40.16

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.968

Gene Damage Prediction

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