PIGW

phosphatidylinositol glycan anchor biosynthesis class W, the group of Phosphatidylinositol glycan anchor biosynthesis

Basic information

Region (hg38): 17:36534986-36539310

Links

ENSG00000277161 ∙ NCBI:284098 ∙ OMIM:610275 ∙ HGNC:23213 ∙ Uniprot:Q7Z7B1 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hyperphosphatasia with intellectual disability syndrome 5 (Limited), mode of inheritance: AR
• hyperphosphatasia with intellectual disability syndrome 5 (Strong), mode of inheritance: AR
• hyperphosphatasia with intellectual disability syndrome 5 (Moderate), mode of inheritance: AR
• hypercoagulability syndrome due to glycosylphosphatidylinositol deficiency (Supportive), mode of inheritance: AR
• hyperphosphatasia-intellectual disability syndrome (Supportive), mode of inheritance: AR
• hyperphosphatasia with intellectual disability syndrome 5 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Glycosylphosphatidylinositol biosynthesis defect 11	AR	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; Gastrointestinal; Neurologic	24367057

ClinVar

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

• Hyperphosphatasia with intellectual disability syndrome 5 (235 variants)
• Inborn genetic diseases (26 variants)
• not provided (21 variants)
• not specified (4 variants)
• Abnormal skeletal morphology;Cleft palate;Global developmental delay (1 variants)
• Hypercoagulability syndrome due to glycosylphosphatidylinositol deficiency (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PIGW 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				63	2	65
missense	1		151	4	3	159
nonsense			7			7
start loss						0
frameshift		1	15			16
inframe indel			6			6
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	1	1	179	67	5

Highest pathogenic variant AF is 0.0000197

Variants in PIGW

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

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

Position	Type	Phenotype	Significance	ClinVar
17-36536882-A-A			Benign (Jul 27, 2018)
17-36537106-C-A		Hyperphosphatasia with intellectual disability syndrome 5	Uncertain significance (Nov 03, 2022)
17-36537108-G-A		Inborn genetic diseases	Uncertain significance (Mar 20, 2023)
17-36537113-G-A		Hyperphosphatasia with intellectual disability syndrome 5	Likely benign (Oct 16, 2023)
17-36537116-G-C		Hyperphosphatasia with intellectual disability syndrome 5	Uncertain significance (Jul 21, 2023)
17-36537116-G-T		Hyperphosphatasia with intellectual disability syndrome 5	Uncertain significance (Aug 04, 2023)
17-36537122-G-A		Hyperphosphatasia with intellectual disability syndrome 5	Benign (Jul 31, 2023)
17-36537135-A-G		Hyperphosphatasia with intellectual disability syndrome 5	Uncertain significance (May 22, 2022)
17-36537155-C-G		Hyperphosphatasia with intellectual disability syndrome 5	Likely benign (Jun 13, 2022)
17-36537155-C-T		Hyperphosphatasia with intellectual disability syndrome 5	Likely benign (Jun 23, 2023)
17-36537156-G-A		Hyperphosphatasia with intellectual disability syndrome 5 • Inborn genetic diseases	Uncertain significance (Dec 18, 2023)
17-36537159-C-T		Hyperphosphatasia with intellectual disability syndrome 5	Likely benign (Sep 03, 2021)
17-36537170-C-T		Hyperphosphatasia with intellectual disability syndrome 5	Likely benign (Feb 24, 2022)
17-36537175-G-A		Hyperphosphatasia with intellectual disability syndrome 5	Uncertain significance (Oct 07, 2021)
17-36537178-T-C		Hyperphosphatasia with intellectual disability syndrome 5	Pathogenic (Sep 08, 2022)
17-36537201-C-T		Hyperphosphatasia with intellectual disability syndrome 5	Likely benign (May 31, 2022)
17-36537203-G-A		Hyperphosphatasia with intellectual disability syndrome 5	Likely benign (Jun 11, 2022)
17-36537206-C-CA		Hyperphosphatasia with intellectual disability syndrome 5	Uncertain significance (Apr 13, 2022)
17-36537207-A-G		Hyperphosphatasia with intellectual disability syndrome 5 • Inborn genetic diseases	Conflicting classifications of pathogenicity (Apr 01, 2023)
17-36537217-T-C		Hyperphosphatasia with intellectual disability syndrome 5	Uncertain significance (Jul 05, 2022)
17-36537226-T-G		Inborn genetic diseases	Uncertain significance (May 03, 2023)
17-36537233-G-A		Hyperphosphatasia with intellectual disability syndrome 5	Likely benign (Jun 25, 2023)
17-36537234-TAC-T		Hyperphosphatasia with intellectual disability syndrome 5	Uncertain significance (Oct 25, 2022)
17-36537245-T-C		Hyperphosphatasia with intellectual disability syndrome 5	Likely benign (Apr 09, 2023)
17-36537248-T-C		Hyperphosphatasia with intellectual disability syndrome 5	Likely benign (Feb 19, 2022)

GnomAD

Source: gnomAD

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Required for the transport of GPI-anchored proteins to the plasma membrane (PubMed:24367057). Probable acetyltransferase, which acetylates the inositol ring of phosphatidylinositol during biosynthesis of GPI-anchor. Acetylation during GPI-anchor biosynthesis is not essential for the subsequent mannosylation and is usually removed soon after the attachment of GPIs to proteins (By similarity). {ECO:0000250|UniProtKB:Q7TSN4, ECO:0000269|PubMed:24367057}.
• Disease: DISEASE: Glycosylphosphatidylinositol biosynthesis defect 11 (GPIBD11) [MIM:616025]: An autosomal recessive neurologic disorder characterized by developmental delay, mental retardation, tonic seizures associated with hypsarrhythmia, dysmorphic facial features, and elevated serum alkaline phosphatase. {ECO:0000269|PubMed:24367057}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Glycosylphosphatidylinositol (GPI)-anchor biosynthesis - Homo sapiens (human);Synthesis of glycosylphosphatidylinositol (GPI);Post-translational modification: synthesis of GPI-anchored proteins;Post-translational protein modification;Metabolism of proteins (Consensus)

Recessive Scores

• pRec: 0.0819

Intolerance Scores

• loftool: 0.297
• rvis_EVS: -0.03
• rvis_percentile_EVS: 51.92

Haploinsufficiency Scores

• pHI: 0.344
• hipred: N
• hipred_score: 0.144

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.442

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pigw

Gene ontology

• Biological process: GPI anchor metabolic process;GPI anchor biosynthetic process;preassembly of GPI anchor in ER membrane;protein localization to plasma membrane
• Cellular component: endoplasmic reticulum membrane;integral component of membrane
• Molecular function: O-acyltransferase activity;glucosaminyl-phosphotidylinositol O-acyltransferase activity