PIGS

phosphatidylinositol glycan anchor biosynthesis class S, the group of Glycosylphosphatidylinositol transamidase complex|Phosphatidylinositol glycan anchor biosynthesis

Basic information

Region (hg38): 17:28553383-28571794

Links

ENSG00000087111 ∙ NCBI:94005 ∙ OMIM:610271 ∙ HGNC:14937 ∙ Uniprot:Q96S52 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• glycosylphosphatidylinositol biosynthesis defect 18 (Strong), mode of inheritance: AR
• glycosylphosphatidylinositol biosynthesis defect 18 (Moderate), mode of inheritance: AR
• glycosylphosphatidylinositol biosynthesis defect 18 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Developmental and epileptic encephalopathy 95	AR	Neurologic	Among other manifestations, individuals may have difficult-to-control seizures, and management with oral pyridoxine has been described as beneficial	Audiologic/Otolaryngologic; Craniofacial; Musculoskeletal; Neurologic	30269814; 33410539

ClinVar

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

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PIGS 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				13		13
missense		2	45	6	2	55
nonsense		2	1			3
start loss						0
frameshift		1				1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			1			1
non coding						0
Total	0	5	46	19	2

Variants in PIGS

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

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

Position	Type	Phenotype	Significance	ClinVar
17-28554221-C-T		PIGS-related disorder	Likely benign (Nov 07, 2019)
17-28554254-C-T		PIGS-related disorder	Likely benign (Oct 01, 2024)
17-28554257-G-A		Inborn genetic diseases	Uncertain significance (Dec 07, 2021)
17-28554292-G-C			Likely benign (May 01, 2023)
17-28554323-T-C			Uncertain significance (Feb 05, 2022)
17-28554373-C-T		PIGS-related disorder	Likely benign (Jun 01, 2023)
17-28554378-C-T		Inborn genetic diseases	Uncertain significance (May 15, 2024)
17-28554401-G-A			Uncertain significance (Jul 01, 2024)
17-28554407-G-C		PIGS-related disorder	Likely benign (Jun 07, 2019)
17-28554408-C-A		Inborn genetic diseases	Uncertain significance (Mar 18, 2024)
17-28554420-C-T		PIGS-related disorder	Likely benign (Oct 01, 2024)
17-28554421-G-A			Likely benign (May 01, 2023)
17-28554452-A-T		Glycosylphosphatidylinositol biosynthesis defect 18	Likely pathogenic (Aug 16, 2024)
17-28554474-C-T		PIGS-related disorder	Likely benign (Nov 01, 2024)
17-28554481-T-C			Likely benign (Jun 01, 2022)
17-28554859-C-T			Uncertain significance (Jun 01, 2024)
17-28554891-TTGCCCAGAAGCTGCGCCAGGGAGGTAAGGGTGGTGG-AGCAACC		Glycosylphosphatidylinositol biosynthesis defect 18	Pathogenic (May 21, 2021)
17-28554895-C-A		Inborn genetic diseases	Uncertain significance (Mar 30, 2024)
17-28554905-C-T			Likely benign (Oct 01, 2024)
17-28554942-T-C		Inborn genetic diseases	Uncertain significance (Dec 10, 2024)
17-28554969-C-T		Glycosylphosphatidylinositol biosynthesis defect 18	Uncertain significance (Oct 12, 2019)
17-28555039-G-A		Glycosylphosphatidylinositol biosynthesis defect 18	Uncertain significance (Dec 10, 2019)
17-28555042-G-A		not specified	Uncertain significance (Dec 21, 2015)
17-28555044-G-A		Inborn genetic diseases	Uncertain significance (Jan 08, 2024)
17-28556167-G-A		Inborn genetic diseases	Uncertain significance (Jun 21, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PIGS	protein_coding	protein_coding	ENST00000308360	12	18490

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000181	0.994	125693	0	55	125748	0.000219

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.780	285	325	0.878	0.0000178	3564
Missense in Polyphen		65	91.769	0.7083		1036
Synonymous	0.172	133	136	0.981	0.00000762	1172
Loss of Function	2.45	12	25.3	0.475	0.00000116	303

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000397	0.000391
Ashkenazi Jewish	0.000497	0.000496
East Asian	0.000275	0.000272
Finnish	0.000139	0.000139
European (Non-Finnish)	0.000283	0.000281
Middle Eastern	0.000275	0.000272
South Asian	0.0000653	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Component of the GPI transamidase complex. Essential for transfer of GPI to proteins, particularly for formation of carbonyl intermediates. {ECO:0000269|PubMed:11483512}.
• Pathway: Glycosylphosphatidylinositol (GPI)-anchor biosynthesis - Homo sapiens (human);Attachment of GPI anchor to uPAR;Post-translational modification: synthesis of GPI-anchored proteins;Post-translational protein modification;Metabolism of proteins (Consensus)

Recessive Scores

• pRec: 0.122

Intolerance Scores

• loftool: 0.708
• rvis_EVS: 0.09
• rvis_percentile_EVS: 60.57

Haploinsufficiency Scores

• pHI: 0.205
• hipred: N
• hipred_score: 0.426
• ghis: 0.533

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: H
• gene_indispensability_pred: N
• gene_indispensability_score: 0.421

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pigs

Gene ontology

• Biological process: attachment of GPI anchor to protein
• Cellular component: endoplasmic reticulum membrane;membrane;GPI-anchor transamidase complex
• Molecular function: GPI-anchor transamidase activity;protein binding