PIGV

phosphatidylinositol glycan anchor biosynthesis class V, the group of Dolichyl D-mannosyl phosphate dependent mannosyltransferases|Phosphatidylinositol glycan anchor biosynthesis

Basic information

Region (hg38): 1:26787054-26800659

Links

ENSG00000060642 ∙ NCBI:55650 ∙ OMIM:610274 ∙ HGNC:26031 ∙ Uniprot:Q9NUD9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hyperphosphatasia with intellectual disability syndrome 1 (Definitive), mode of inheritance: AR
• hyperphosphatasia with intellectual disability syndrome 1 (Strong), mode of inheritance: AR
• hyperphosphatasia with intellectual disability syndrome 1 (Moderate), mode of inheritance: AR
• hyperphosphatasia-intellectual disability syndrome (Supportive), mode of inheritance: AR
• hyperphosphatasia with intellectual disability syndrome 1 (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 1	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	Audiologic/Otolaryngologic; Craniofacial; Dermatologic; Gastrointestinal; Musculoskeletal; Neurologic	5465362; 1724113; 16638507; 17351347; 20080219; 20802478; 20578257; 21739589; 22315194

ClinVar

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

• not_provided (295 variants)
• Inborn_genetic_diseases (69 variants)
• Hyperphosphatasia_with_intellectual_disability_syndrome_1 (51 variants)
• not_specified (21 variants)
• PIGV-related_disorder (10 variants)
• Hyperphosphatasia-intellectual_disability_syndrome (1 variants)
• Elevated_circulating_alkaline_phosphatase_concentration (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PIGV gene is commonly pathogenic or not. These statistics are base on transcript: NM_000017837.4. 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			3	119		122
missense	3	8	168	13		192
nonsense		3	4			7
start loss						0
frameshift		1	10			11
splice donor/acceptor (+/-2bp)		1	1			2
Total	3	13	186	132	0

Highest pathogenic variant AF is 0.000124529

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PIGV	protein_coding	protein_coding	ENST00000374145	3	10927

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.51e-8	0.386	125690	0	58	125748	0.000231

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.398	240	258	0.930	0.0000139	3169
Missense in Polyphen		78	93.661	0.83279		1231
Synonymous	0.202	106	109	0.975	0.00000582	1074
Loss of Function	0.811	14	17.7	0.792	9.52e-7	190

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000148	0.000148
Ashkenazi Jewish	0.000299	0.000298
East Asian	0.000163	0.000163
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000343	0.000343
Middle Eastern	0.000163	0.000163
South Asian	0.000261	0.000261
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Alpha-1,6-mannosyltransferase involved in glycosylphosphatidylinositol-anchor biosynthesis. Transfers the second mannose to the glycosylphosphatidylinositol during GPI precursor assembly. {ECO:0000269|PubMed:15623507, ECO:0000269|PubMed:15720390}.
• Disease: DISEASE: Hyperphosphatasia with mental retardation syndrome 1 (HPMRS1) [MIM:239300]: A severe syndrome characterized by elevated serum alkaline phosphatase, severe mental retardation, seizures, hypotonia, facial dysmorphism, and hypoplastic terminal phalanges. {ECO:0000269|PubMed:20802478}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Glycosylphosphatidylinositol (GPI)-anchor biosynthesis - Homo sapiens (human);Vitamin B6-dependent and responsive disorders;Synthesis of glycosylphosphatidylinositol (GPI);Post-translational modification: synthesis of GPI-anchored proteins;Post-translational protein modification;Metabolism of proteins (Consensus)

Intolerance Scores

• loftool: 0.258
• rvis_EVS: -0.4
• rvis_percentile_EVS: 26.73

Haploinsufficiency Scores

• pHI: 0.355
• hipred: N
• hipred_score: 0.167
• ghis: 0.560

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.465

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pigv
• Phenotype: growth/size/body region phenotype; endocrine/exocrine gland phenotype; craniofacial phenotype; renal/urinary system phenotype; skeleton phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; digestive/alimentary phenotype; vision/eye phenotype; immune system phenotype

Gene ontology

• Biological process: GPI anchor biosynthetic process;preassembly of GPI anchor in ER membrane;mannosylation
• Cellular component: endoplasmic reticulum membrane;integral component of membrane;mannosyltransferase complex
• Molecular function: mannosyltransferase activity;glycolipid mannosyltransferase activity;dolichyl-phosphate-mannose-glycolipid alpha-mannosyltransferase activity