PACS2

phosphofurin acidic cluster sorting protein 2

Basic information

Region (hg38): 14:105300563-105398147

Previous symbols: [ "PACS1L" ]

Links

ENSG00000179364

∙ NCBI:23241 ∙ OMIM:610423 ∙ HGNC:23794 ∙ Uniprot:Q86VP3 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

developmental and epileptic encephalopathy, 66 (Moderate), mode of inheritance: AD
developmental and epileptic encephalopathy, 66 (Strong), mode of inheritance: AD
developmental and epileptic encephalopathy, 66 (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Developmental and epileptic encephalopathy 66	AD	Cardiovascular	The condition can involve congenital cardiac anomalies, and awareness may allow early management	Cardiovascular; Craniofacial; Genitourinary; Hematologic; Musculoskeletal; Neurologic	29656858

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PACS2 gene.

not_provided (1114 variants)
Inborn_genetic_diseases (88 variants)
PACS2-related_disorder (43 variants)
Developmental_and_epileptic_encephalopathy,_66 (42 variants)
Intellectual_disability (8 variants)
not_specified (5 variants)
See_cases (2 variants)
Developmental_and_epileptic_encephalopathy,_1 (2 variants)
Cleft_palate (1 variants)
Seizure (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PACS2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001100913.3. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			12 clinvar	298 clinvar	21 clinvar	331
missense		5 clinvar	333 clinvar	122 clinvar	44 clinvar	504
nonsense			4 clinvar			4
start loss						0
frameshift			7 clinvar			7
splice donor/acceptor (+/-2bp)			5 clinvar	2 clinvar		7
Total	0	5	361	422	65

Highest pathogenic variant AF is 0.0000020641794

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PACS2	protein_coding	protein_coding	ENST00000458164	25	97585

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.996	0.00417	125337	0	16	125353	0.0000638

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.24	414	563	0.735	0.0000371	5881
Missense in Polyphen		175	274.74	0.63698		2848
Synonymous	-1.41	298	269	1.11	0.0000217	1765
Loss of Function	5.41	7	47.1	0.149	0.00000219	540

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000355	0.000216
Ashkenazi Jewish	0.000426	0.000398
East Asian	0.00	0.00
Finnish	0.000104	0.0000924
European (Non-Finnish)	0.0000361	0.0000354
Middle Eastern	0.00	0.00
South Asian	0.0000358	0.0000327
Other	0.000169	0.000164

dbNSFP

Source: dbNSFP

Function: FUNCTION: Multifunctional sorting protein that controls the endoplasmic reticulum (ER)-mitochondria communication, including the apposition of mitochondria with the ER and ER homeostasis. In addition, in response to apoptotic inducer, translocates BIB to mitochondria, which initiates a sequence of events including the formation of mitochondrial truncated BID, the release of cytochrome c, the activation of caspase-3 thereby causing cell death. May also be involved in ion channel trafficking, directing acidic cluster-containing ion channels to distinct subcellular compartments. {ECO:0000269|PubMed:15692563, ECO:0000269|PubMed:15692567}.;

Recessive Scores

pRec: 0.133

Intolerance Scores

loftool: 0.444
rvis_EVS: -0.73
rvis_percentile_EVS: 14.24

Haploinsufficiency Scores

pHI: 0.220
hipred: Y
hipred_score: 0.783
ghis: 0.535

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: N
gene_indispensability_score: 0.253

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Pacs2
Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); limbs/digits/tail phenotype; skeleton phenotype; homeostasis/metabolism phenotype; cellular phenotype;

Zebrafish Information Network

Gene name: pacs2
Affected structure: whole organism
Phenotype tag: abnormal
Phenotype quality: semi-lethal (sensu genetics)

Gene ontology

Biological process: autophagosome assembly;apoptotic process;viral process;protein localization to phagophore assembly site;protein localization to plasma membrane
Cellular component: mitochondrion;endoplasmic reticulum
Molecular function: protein binding;ion channel binding