PIGO

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

Basic information

Region (hg38): 9:35087236-35096619

Links

ENSG00000165282 ∙ NCBI:84720 ∙ OMIM:614730 ∙ HGNC:23215 ∙ Uniprot:Q8TEQ8 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hyperphosphatasia with intellectual disability syndrome 2 (Strong), mode of inheritance: AR
• hyperphosphatasia with intellectual disability syndrome 2 (Definitive), mode of inheritance: AR
• hyperphosphatasia with intellectual disability syndrome 2 (Strong), mode of inheritance: AR
• hyperphosphatasia-intellectual disability syndrome (Supportive), mode of inheritance: AR
• hyperphosphatasia with intellectual disability syndrome 2 (Strong), mode of inheritance: AR
• complex neurodevelopmental disorder (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hyperphosphatasia with impaired intellectual development syndrome 2	AR	Cardiovascular	The condition can involve congenital cardiac anomalies, and awareness may allow early management	Cardiovascular; Craniofacial; Musculoskeletal; Neurologic; Renal	22683086

ClinVar

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

• Hyperphosphatasia with intellectual disability syndrome 2 (800 variants)
• not provided (168 variants)
• not specified (48 variants)
• Inborn genetic diseases (41 variants)
• PIGO-related condition (5 variants)
• Hyperphosphatasia-intellectual disability syndrome (3 variants)
• Hyperphosphatasia with intellectual disability syndrome 2;Aganglionic megacolon (1 variants)
• Intellectual disability (1 variants)
• Hyperphosphatasia with intellectual disability syndrome 1 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PIGO 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	199	5	217
missense	1	4	446	6	3	460
nonsense	16	4	2			22
start loss						0
frameshift	25	7	2			34
inframe indel			8			8
splice donor/acceptor (+/-2bp)		5				5
splice region			5	18	1	24
non coding			10	53	13	76
Total	42	20	481	258	21

Highest pathogenic variant AF is 0.0000263

Variants in PIGO

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

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

Position	Type	Phenotype	Significance	ClinVar
9-35088710-C-T		Hyperphosphatasia with intellectual disability syndrome 2	Uncertain significance (Jan 12, 2018)
9-35088720-T-A		Hyperphosphatasia with intellectual disability syndrome 2	Uncertain significance (Jan 12, 2018)
9-35088825-G-C		Hyperphosphatasia with intellectual disability syndrome 2	Benign/Likely benign (Jun 29, 2018)
9-35088841-G-A		Hyperphosphatasia with intellectual disability syndrome 2	Uncertain significance (Jan 13, 2018)
9-35088871-C-T		Hyperphosphatasia with intellectual disability syndrome 2	Uncertain significance (Jan 12, 2018)
9-35088872-C-G		Hyperphosphatasia with intellectual disability syndrome 2	Uncertain significance (Jan 12, 2018)
9-35088873-C-T		Hyperphosphatasia with intellectual disability syndrome 2	Uncertain significance (Jan 13, 2018)
9-35089031-G-A		Hyperphosphatasia with intellectual disability syndrome 2	Uncertain significance (Jan 13, 2018)
9-35089051-A-C		Hyperphosphatasia with intellectual disability syndrome 2	Benign (Sep 05, 2021)
9-35089080-TCA-T		PIGO-related disorder	Likely benign (Jul 07, 2023)
9-35089095-C-T		Hyperphosphatasia with intellectual disability syndrome 2	Likely benign (Jan 28, 2020)
9-35089100-G-C		Hyperphosphatasia with intellectual disability syndrome 2	Uncertain significance (Jun 04, 2022)
9-35089100-GC-CT		Hyperphosphatasia with intellectual disability syndrome 2	Uncertain significance (Apr 20, 2022)
9-35089103-G-A		Hyperphosphatasia with intellectual disability syndrome 2	Uncertain significance (Jun 15, 2020)
9-35089109-G-T		Hyperphosphatasia with intellectual disability syndrome 2	Uncertain significance (Oct 08, 2020)
9-35089118-G-A			Uncertain significance (Jan 05, 2021)
9-35089129-G-A		Hyperphosphatasia with intellectual disability syndrome 2	Uncertain significance (Jun 28, 2018)
9-35089129-G-C		Hyperphosphatasia with intellectual disability syndrome 2	Uncertain significance (Mar 15, 2022)
9-35089131-G-A		Hyperphosphatasia with intellectual disability syndrome 2	Likely benign (Sep 12, 2017)
9-35089132-C-G		Hyperphosphatasia with intellectual disability syndrome 2	Uncertain significance (Jul 26, 2022)
9-35089143-A-G		Hyperphosphatasia with intellectual disability syndrome 2	Likely benign (Aug 06, 2022)
9-35089146-C-A		Hyperphosphatasia with intellectual disability syndrome 2	Likely benign (Dec 31, 2022)
9-35089147-ACT-A			Uncertain significance (Sep 21, 2017)
9-35089150-C-T		Hyperphosphatasia with intellectual disability syndrome 2	Uncertain significance (Jan 06, 2020)
9-35089155-C-T		Hyperphosphatasia with intellectual disability syndrome 2	Likely benign (Jan 27, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PIGO	protein_coding	protein_coding	ENST00000378617	10	7907

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
6.14e-11	0.991	125620	0	128	125748	0.000509

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.957	549	616	0.892	0.0000343	6925
Missense in Polyphen		154	192.89	0.79838		2338
Synonymous	-0.943	275	256	1.07	0.0000137	2454
Loss of Function	2.50	23	40.1	0.573	0.00000222	406

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00107	0.00106
Ashkenazi Jewish	0.000199	0.0000992
East Asian	0.000382	0.000381
Finnish	0.000142	0.000139
European (Non-Finnish)	0.000750	0.000747
Middle Eastern	0.000382	0.000381
South Asian	0.000131	0.000131
Other	0.000327	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Ethanolamine phosphate transferase involved in glycosylphosphatidylinositol-anchor biosynthesis. Transfers ethanolamine phosphate to the GPI third mannose which links the GPI-anchor to the C-terminus of the proteins by an amide bond. {ECO:0000269|PubMed:24049131, ECO:0000269|PubMed:28337824}.
• Disease: DISEASE: Hyperphosphatasia with mental retardation syndrome 2 (HPMRS2) [MIM:614749]: An autosomal recessive form of intellectual disability characterized by facial dysmorphism, brachytelephalangy, and persistent elevated serum alkaline phosphatase (hyperphosphatasia). Some patients may have additional features, such as cardiac septal defects or seizures. {ECO:0000269|PubMed:22683086, ECO:0000269|PubMed:24049131, ECO:0000269|PubMed:28337824, ECO:0000269|PubMed:28545593}. 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: 0.0915

Intolerance Scores

• loftool: 0.653
• rvis_EVS: -1.35
• rvis_percentile_EVS: 4.61

Haploinsufficiency Scores

• pHI: 0.337
• hipred: N
• hipred_score: 0.426
• ghis: 0.639

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.416

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pigo

Gene ontology

• Biological process: GPI anchor biosynthetic process
• Cellular component: endoplasmic reticulum membrane;membrane;integral component of membrane
• Molecular function: mannose-ethanolamine phosphotransferase activity