PALS1

protein associated with LIN7 1, MAGUK p55 family member, the group of Crumbs complex|PDZ domain containing|Membrane associated guanylate kinases

Basic information

Region (hg38): 14:67240713-67336061

Previous symbols: [ "MPP5" ]

Links

ENSG00000072415 ∙ NCBI:64398 ∙ OMIM:606958 ∙ HGNC:18669 ∙ Uniprot:Q8N3R9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PALS1 gene.

• Cerebral palsy;Abnormal facial shape;Intellectual disability;Anxiety;Arachnoid cyst (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PALS1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous					1	1
missense	1		27	4	1	33
nonsense			1			1
start loss						0
frameshift			1			1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding					1	1
Total	1	0	29	4	3

Variants in PALS1

This is a list of pathogenic ClinVar variants found in the PALS1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
14-67279202-C-T		not specified	Uncertain significance (Aug 28, 2024)
14-67279249-G-A		not specified	Uncertain significance (Nov 09, 2021)
14-67279264-C-T		Atypical Rett syndrome	Uncertain significance (Aug 16, 2021)
14-67279268-G-A		not specified	Uncertain significance (Jun 22, 2024)
14-67279307-G-T		PALS1-related disorder	Uncertain significance (Sep 28, 2022)
14-67279348-C-T			Benign (Oct 19, 2017)
14-67279379-G-C		not specified	Uncertain significance (Dec 28, 2022)
14-67279392-GA-G		not specified	Uncertain significance (Jul 24, 2023)
14-67279516-C-T		not specified	Uncertain significance (Feb 03, 2022)
14-67292565-C-A		not specified	Likely benign (Jan 17, 2024)
14-67292565-C-T		not specified	Likely benign (Jan 17, 2024)
14-67292567-C-G		not specified	Uncertain significance (Jun 06, 2023)
14-67292655-T-C		not specified	Uncertain significance (Apr 26, 2024)
14-67292668-G-C		not specified	Uncertain significance (Jul 15, 2021)
14-67292699-G-A		not specified	Uncertain significance (Aug 11, 2024)
14-67301408-C-T		not specified	Uncertain significance (Jan 23, 2024)
14-67301432-A-C		PALS1-related disorder	Likely benign (Jan 09, 2024)
14-67302051-G-A		not specified	Uncertain significance (Aug 12, 2021)
14-67302061-G-C		not specified	Uncertain significance (Aug 15, 2023)
14-67302089-C-T		not specified	Likely benign (Dec 04, 2024)
14-67302101-G-C		not specified	Uncertain significance (Mar 16, 2022)
14-67302402-A-T			Benign (Mar 29, 2018)
14-67302419-G-A		not specified	Uncertain significance (Dec 19, 2022)
14-67302440-G-A		not specified	Uncertain significance (Jun 05, 2024)
14-67302458-G-A		not specified	Uncertain significance (Feb 28, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PALS1	protein_coding	protein_coding	ENST00000261681	13	94711

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.235	0.765	125725	0	22	125747	0.0000875

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.41	296	372	0.795	0.0000200	4481
Missense in Polyphen		98	141.33	0.69343		1707
Synonymous	-0.969	137	123	1.11	0.00000647	1213
Loss of Function	4.10	8	33.7	0.238	0.00000173	423

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000210	0.000210
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.000135	0.000132
Middle Eastern	0.00	0.00
South Asian	0.0000334	0.0000327
Other	0.000165	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May play a role in tight junctions biogenesis and in the establishment of cell polarity in epithelial cells. May modulate SC6A1/GAT1-mediated GABA uptake by stabilizing the transporter. Required for localization of EZR to the apical membrane of parietal cells and may play a role in the dynamic remodeling of the apical cytoskeleton (By similarity). {ECO:0000250}.
• Pathway: Tight junction - Homo sapiens (human);Hippo signaling pathway - Homo sapiens (human);Human papillomavirus infection - Homo sapiens (human);EMT transition in Colorectal Cancer;Tight junction interactions;Cell-cell junction organization;Cell junction organization;Cell-Cell communication (Consensus)

Recessive Scores

• pRec: 0.137

Intolerance Scores

• loftool: 0.451
• rvis_EVS: 0.47
• rvis_percentile_EVS: 78.74

Haploinsufficiency Scores

• pHI: 0.974
• hipred: Y
• hipred_score: 0.708
• ghis: 0.482

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.876

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Mpp5
• Phenotype: hematopoietic system phenotype; normal phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); immune system phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); vision/eye phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); cellular phenotype

Zebrafish Information Network

• Gene name: mpp5a
• Affected structure: cardiac muscle cell
• Phenotype tag: abnormal
• Phenotype quality: structure

Gene ontology

• Biological process: morphogenesis of an epithelial sheet;peripheral nervous system myelin maintenance;myelin assembly;protein localization to myelin sheath abaxonal region;bicellular tight junction assembly;protein localization to plasma membrane;establishment of epithelial cell polarity
• Cellular component: cytoplasm;plasma membrane;cell-cell adherens junction;bicellular tight junction;endomembrane system;protein-containing complex;myelin sheath adaxonal region;lateral loop;Schmidt-Lanterman incisure;extracellular exosome
• Molecular function: protein binding;protein domain specific binding