PACS1

phosphofurin acidic cluster sorting protein 1

Basic information

Region (hg38): 11:66070271-66244744

Links

ENSG00000175115 ∙ NCBI:55690 ∙ OMIM:607492 ∙ HGNC:30032 ∙ Uniprot:Q6VY07 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• intellectual disability, autosomal dominant 40 (Definitive), mode of inheritance: AD
• Schuurs-Hoeijmakers syndrome (Strong), mode of inheritance: AD
• Schuurs-Hoeijmakers syndrome (Supportive), mode of inheritance: AD
• Schuurs-Hoeijmakers syndrome (Definitive), mode of inheritance: AD
• Schuurs-Hoeijmakers syndrome (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Schuss-Hoeijmakers syndrome	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Musculoskeletal; Neurologic	23159249

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PACS1 gene.

• Schuurs-Hoeijmakers syndrome (444 variants)
• not provided (213 variants)
• Inborn genetic diseases (86 variants)
• not specified (39 variants)
• PACS1-related condition (5 variants)
• Intellectual disability (3 variants)
• See cases (2 variants)
• Multiple congenital anomalies (1 variants)
• Global developmental delay (1 variants)
• Hypospadias (1 variants)
• Neurodevelopmental disorder (1 variants)
• Aganglionic megacolon (1 variants)
• PACS1-related syndrome (1 variants)
• Optic disc pallor;Mitral valve prolapse;Aortic root aneurysm;Horseshoe kidney;Hypotelorism (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PACS1 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			2	130	8	140
missense	1	2	167	28	12	210
nonsense		1	3			4
start loss						0
frameshift			4			4
inframe indel			7	3	2	12
splice donor/acceptor (+/-2bp)		1	1			2
splice region			18	35	6	59
non coding			3	101	53	157
Total	1	4	187	262	75

Variants in PACS1

This is a list of pathogenic ClinVar variants found in the PACS1 region.

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

Position	Type	Phenotype	Significance	ClinVar
11-66070485-C-T		PACS1-related disorder	Likely benign (Mar 16, 2022)
11-66070507-G-A		Inborn genetic diseases	Likely benign (Apr 11, 2017)
11-66070513-T-C			Likely benign (Jul 01, 2022)
11-66070530-G-C		Inborn genetic diseases	Likely benign (Dec 15, 2023)
11-66070532-G-T		Inborn genetic diseases	Uncertain significance (Nov 18, 2022)
11-66070534-C-T			Likely benign (Dec 18, 2018)
11-66070551-G-A		Schuurs-Hoeijmakers syndrome	Uncertain significance (Jan 22, 2021)
11-66070560-T-G			Likely benign (Jun 11, 2021)
11-66070563-C-T		Inborn genetic diseases	Likely benign (Jan 10, 2023)
11-66070569-C-G		not specified • Inborn genetic diseases • PACS1-related disorder	Conflicting classifications of pathogenicity (Sep 26, 2019)
11-66070573-TCAGCAGCCGCCGCCGCAGCAGCAGCAG-T		PACS1-related disorder	Uncertain significance (Feb 22, 2024)
11-66070575-A-C		Inborn genetic diseases	Uncertain significance (Apr 07, 2023)
11-66070578-A-AGCC		not specified	Conflicting classifications of pathogenicity (Dec 04, 2018)
11-66070581-C-A		Inborn genetic diseases	Uncertain significance (Apr 07, 2023)
11-66070581-CGCCGCCGCAGCAGCAGCAGCAGCA-C		Inborn genetic diseases	Likely benign (May 05, 2021)
11-66070581-C-CGCCGCCGCAGCAGCAGCAGCAGCA		not specified • Inborn genetic diseases • Schuurs-Hoeijmakers syndrome • PACS1-related disorder	Benign/Likely benign (Sep 15, 2023)
11-66070587-CGCA-C		PACS1-related disorder	Likely benign (Mar 14, 2019)
11-66070587-CGCAGCAGCA-C		Schuurs-Hoeijmakers syndrome	Uncertain significance (Feb 09, 2023)
11-66070588-G-A		not specified • Schuurs-Hoeijmakers syndrome • Inborn genetic diseases	Benign (Aug 04, 2023)
11-66070587-C-CGCA		Inborn genetic diseases	Benign (Dec 12, 2019)
11-66070587-C-CGCAGCAGCA		Schuurs-Hoeijmakers syndrome	Conflicting classifications of pathogenicity (Apr 07, 2021)
11-66070590-A-C		not specified • PACS1-related disorder	Conflicting classifications of pathogenicity (Sep 02, 2021)
11-66070592-C-G			Uncertain significance (Nov 24, 2020)
11-66070599-A-C			Likely benign (Jan 19, 2021)
11-66070599-AGCAGCAGCCGCC-A		Inborn genetic diseases	Likely benign (Feb 28, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PACS1	protein_coding	protein_coding	ENST00000320580	24	174385

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.0000124	125741	0	6	125747	0.0000239

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.71	302	546	0.553	0.0000315	6241
Missense in Polyphen		83	226.33	0.36673		2582
Synonymous	1.48	197	225	0.875	0.0000139	1919
Loss of Function	5.99	4	49.4	0.0810	0.00000237	576

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000441	0.0000439
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Coat protein that is involved in the localization of trans-Golgi network (TGN) membrane proteins that contain acidic cluster sorting motifs. Controls the endosome-to-Golgi trafficking of furin and mannose-6-phosphate receptor by connecting the acidic-cluster-containing cytoplasmic domain of these molecules with the adapter-protein complex-1 (AP-1) of endosomal clathrin- coated membrane pits. Involved in HIV-1 nef-mediated removal of MHC-I from the cell surface to the TGN. {ECO:0000269|PubMed:11331585, ECO:0000269|PubMed:15692563}.
• Disease: DISEASE: Schuurs-Hoeijmakers syndrome (SHMS) [MIM:615009]: A syndromic form of mental retardation, a disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. SHMS patients have intellectual disability in combination with distinct craniofacial features and genital abnormalities. {ECO:0000269|PubMed:23159249}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Disease;Host Interactions of HIV factors;HIV Infection;Infectious disease;Nef mediated downregulation of MHC class I complex cell surface expression;Nef-mediates down modulation of cell surface receptors by recruiting them to clathrin adapters;The role of Nef in HIV-1 replication and disease pathogenesis (Consensus)

Recessive Scores

• pRec: 0.115

Intolerance Scores

• loftool: 0.179
• rvis_EVS: -1.09
• rvis_percentile_EVS: 7.11

Haploinsufficiency Scores

• pHI: 0.263
• hipred: Y
• hipred_score: 0.775
• ghis: 0.589

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.747

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pacs1

Zebrafish Information Network

• Gene name: pacs1a
• Affected structure: whole organism
• Phenotype tag: abnormal
• Phenotype quality: semi-lethal (sensu genetics)

Gene ontology

• Biological process: protein localization to Golgi apparatus;regulation of defense response to virus by virus;protein localization to plasma membrane
• Cellular component: Golgi apparatus;cytosol;COPI-coated vesicle
• Molecular function: protein binding;ion channel binding