PALS2

protein-coding

protein associated with LIN7 2, MAGUK p55 family member, the group of PDZ domain containing|Membrane associated guanylate kinases

Gene summary

Members of the peripheral membrane-associated guanylate kinase (MAGUK) family function in tumor suppression and receptor clustering by forming multiprotein complexes containing distinct sets of transmembrane, cytoskeletal, and cytoplasmic signaling proteins. All MAGUKs contain a PDZ-SH3-GUK core and are divided into 4 subfamilies, DLG-like (see DLG1; MIM 601014), ZO1-like (see TJP1; MIM 601009), p55-like (see MPP1; MIM 305360), and LIN2-like (see CASK; MIM 300172), based on their size and the presence of additional domains. MPP6 is a member of the p55-like MAGUK subfamily (Tseng et al., 2001 [PubMed 11311936]).[supplied by OMIM, Mar 2008]

Previous symbols:

MPP6

MANE transcript

NM_001303037.2

Inheritance

—

ClinVar variants

U:63B:3

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.18

Max pathogenic AF

—

Genomic locus

chr7:24,573,268-24,694,193

External References & Databases

Ensembl (ENSG00000105926)

Transcript & Mutation Effects

hg38 • Region Span ~120.9 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 PALS2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 56

not providedTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001303037.2. 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			2 clinvar	1 clinvar	2 clinvar	5
missense			57 clinvar			57
nonsense			1 clinvar			1
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	63	1	2	66

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 49 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001303037.2	RefSeq	NP_001289966.1	11	MANE Select
ENST00000222644.10	Ensembl	ENSP00000222644.4	11	MANE Select
NM_016447.4	RefSeq	NP_057531.2	11	Standard
ENST00000396475.6	Ensembl	ENSP00000379737.2	11	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

protein-containing complex assembly

Molecular Function

protein binding
PDZ domain binding

Cellular Component

plasma membrane
membrane
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000222644
Coding exons: 11
Length: 120926
Individuals with no LoFs: 125730
Homozygous LoFs: 0
Heterozygous LoFs: 14
Defined: 125744
p: 0.0000557

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.12	184	285	0.646	0.0000141	3552
Missense (PolyPhen)		52	101.29	0.51339		1249
Synonymous	-0.125	100	98.4	1.02	0.00000475	1000
Loss of Function	3.98	5	27.6	0.181	0.00000159	343

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0.00030	0.00030	rare
East Asian	0.00011	0.00011	rare
Finnish	0.00014	0.00014	rare
European (Non-Finnish)	0.000026	0.000026	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.118

Intolerance Scores

RVIS EVS: -0.09
RVIS percentile EVS: 46.74

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.826

Gene Damage Prediction

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