MPP2

protein-coding

MAGUK p55 scaffold protein 2, the group of PDZ domain containing|Membrane associated guanylate kinases

Gene summary

Palmitoylated membrane protein 2 is a member of a family of membrane-associated proteins termed MAGUKs (membrane-associated guanylate kinase homologs). MAGUKs interact with the cytoskeleton and regulate cell proliferation, signaling pathways, and intracellular junctions. Palmitoylated membrane protein 2 contains a conserved sequence, called the SH3 (src homology 3) motif, found in several other proteins that associate with the cytoskeleton and are suspected to play important roles in signal transduction. [provided by RefSeq, Jul 2008]

Previous symbols:

DLG2

MANE transcript

NM_005374.5

Inheritance

—

ClinVar variants

U:62B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.55

Max pathogenic AF

—

Genomic locus

chr17:43,875,357-43,909,711

External References & Databases

Ensembl (ENSG00000108852)

Transcript & Mutation Effects

hg38 • Region Span ~34.4 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 MPP2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 63

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005374.5. 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				1 clinvar		1
missense			62 clinvar	1 clinvar		63
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	62	2	0	64

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 55 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_005374.5	RefSeq	NP_005365.4	12	MANE Select
ENST00000269095.9	Ensembl	ENSP00000269095.4	12	MANE Select
NM_001278370.2	RefSeq	NP_001265299.1	13	Standard
NM_001278371.2	RefSeq	NP_001265300.1	11	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

protein homooligomerization
excitatory postsynaptic potential
long-term synaptic potentiation

Molecular Function

protein binding

Cellular Component

cytoplasm
cytoskeleton
postsynaptic density
dendrite membrane
dendritic spine membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000269095
Coding exons: 12
Length: 34344
Individuals with no LoFs: 125711
Homozygous LoFs: 0
Heterozygous LoFs: 36
Defined: 125747
p: 0.000143

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.51	289	371	0.779	0.0000253	3558
Missense (PolyPhen)		112	154.75	0.72374		1563
Synonymous	0.314	150	155	0.968	0.0000108	1146
Loss of Function	2.20	15	27.5	0.546	0.00000151	287

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00019	0.00018	rare
Latino/Admixed American	0.00024	0.00023	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00015	0.00015	rare
South Asian	0.00013	0.00013	rare
Other	0.00034	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Postsynaptic MAGUK scaffold protein that links CADM1 cell adhesion molecules to core components of the postsynaptic density (By similarity). In CA1 pyramidal neurons, required for synaptic KCNN2-containing channel function and long-term potentiation expression (By similarity). Seems to negatively regulate SRC function in epithelial cells (PubMed:19665017). {ECO:0000250|UniProtKB:D3ZAA9, ECO:0000250|UniProtKB:Q9WV34, ECO:0000269|PubMed:19665017}.;

Recessive Scores

pRec: 0.117

Intolerance Scores

LoFtool: 0.612
RVIS EVS: -1.02
RVIS percentile EVS: 8

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.122

Gene Damage Prediction

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