PIGY

phosphatidylinositol glycan anchor biosynthesis class Y, the group of Phosphatidylinositol glycan anchor biosynthesis|Glycosylphosphatidylinositol-N-acetylglucosaminyltransferase complex

Basic information

Region (hg38): 4:88520998-88523776

Links

ENSG00000255072 ∙ NCBI:84992 ∙ OMIM:610662 ∙ HGNC:28213 ∙ Uniprot:Q3MUY2 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hyperphosphatasia with intellectual disability syndrome 6 (Limited), mode of inheritance: AR
• hyperphosphatasia-intellectual disability syndrome (Supportive), mode of inheritance: AR
• hyperphosphatasia with intellectual disability syndrome 6 (Limited), mode of inheritance: Unknown
• hyperphosphatasia with intellectual disability syndrome 6 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hyperphosphatasia with impaired intellectual development syndrome 6	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; Musculoskeletal; Neurologic; Ophthalmologic	26293662

ClinVar

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

• not_provided (12 variants)
• Hyperphosphatasia_with_intellectual_disability_syndrome_6 (3 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PIGY gene is commonly pathogenic or not. These statistics are base on transcript: NM_001042616.3. 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	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				2		2
missense	1		8	2		11
nonsense						0
start loss			1			1
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	1	0	9	4	0

Highest pathogenic variant AF is 6.84143e-7

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PIGY	protein_coding	protein_coding	ENST00000527353	1	217

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0972	0.594	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.321	41	35.6	1.15	0.00000159	454
Missense in Polyphen		5	4.8866	1.0232		76
Synonymous	0.518	12	14.5	0.827	7.15e-7	151
Loss of Function	0.106	1	1.12	0.892	4.59e-8	18

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	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Component of the GPI-GlcNAc transferase (GPI-GnT) complex in the endoplasmic reticulum, a complex that catalyzes transfer of GlcNAc from UDP-GlcNAc to an acceptor phosphatidylinositol, the first step in the production of GPI- anchors for cell surface proteins. May act by regulating the catalytic subunit PIGA. {ECO:0000269|PubMed:16162815}.
• Disease: DISEASE: Hyperphosphatasia with mental retardation syndrome 6 (HPMRS6) [MIM:616809]: An autosomal recessive, multisystem disorder characterized by severe developmental delay, dysmorphism, seizures, cataracts, and early death in some patients. {ECO:0000269|PubMed:26293662}. 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)

Intolerance Scores

• rvis_EVS: 0.19
• rvis_percentile_EVS: 66.57

Haploinsufficiency Scores

• hipred: N
• hipred_score: 0.170
• ghis: 0.420

Essentials

• essential_gene_CRISPR: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.169

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pigyl

Gene ontology

• Biological process: GPI anchor biosynthetic process;preassembly of GPI anchor in ER membrane
• Cellular component: glycosylphosphatidylinositol-N-acetylglucosaminyltransferase (GPI-GnT) complex;endoplasmic reticulum membrane;plasma membrane;integral component of membrane
• Molecular function: phosphatidylinositol N-acetylglucosaminyltransferase activity