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

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.

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.

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			5	249	18	272
missense		2	263	69	41	375
nonsense			3			3
start loss					1	1
frameshift			3			3
inframe indel			12	4		16
splice donor/acceptor (+/-2bp)			3	2		5
splice region			21	53	14	88
non coding			6	156	56	218
Total	0	2	295	480	116

Variants in PACS2

This is a list of pathogenic ClinVar variants found in the PACS2 region.

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

Position	Type	Phenotype	Significance	ClinVar
14-105314177-G-A			Benign (May 14, 2021)
14-105314207-C-A			Benign (May 26, 2021)
14-105314227-G-A			Benign (May 13, 2021)
14-105314317-A-G			Benign (May 22, 2021)
14-105314544-T-C			Benign (May 22, 2021)
14-105314925-G-C		Developmental and epileptic encephalopathy, 66	Uncertain significance (Jan 08, 2023)
14-105314930-A-G			Likely benign (Aug 18, 2020)
14-105314935-G-C			Uncertain significance (May 27, 2023)
14-105314935-G-T			Uncertain significance (Nov 08, 2022)
14-105314938-T-G			Uncertain significance (Sep 12, 2022)
14-105314938-TCGGCCTCCC-T			Uncertain significance (Aug 24, 2023)
14-105314939-C-A			Likely benign (Feb 05, 2021)
14-105314939-C-T			Likely benign (Nov 08, 2022)
14-105314938-T-TCGGCCTCCC			Uncertain significance (May 25, 2022)
14-105314943-C-T			Uncertain significance (Jan 06, 2024)
14-105314945-CCCCGGCGCG-C			Uncertain significance (Oct 23, 2023)
14-105314946-C-G		Inborn genetic diseases	Uncertain significance (Apr 07, 2023)
14-105314945-C-CCCCGGCGCG			Likely benign (Jan 11, 2024)
14-105314947-C-T			Uncertain significance (Jan 15, 2023)
14-105314949-G-A			Uncertain significance (Nov 27, 2023)
14-105314951-C-A			Likely benign (Jun 23, 2022)
14-105314951-C-T			Benign/Likely benign (Jan 30, 2024)
14-105314952-G-GCGCCCGGCGCGCTCAACA			Uncertain significance (Jan 17, 2022)
14-105314954-G-A			Likely benign (Feb 14, 2023)
14-105314954-G-T			Likely benign (Aug 18, 2020)

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