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

ENSG00000060642NCBI:55650OMIM:610274HGNC:26031Uniprot:Q9NUD9AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

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

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Hyperphosphatasia with impaired intellectual development syndrome 1ARGeneralGenetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testingAudiologic/Otolaryngologic; Craniofacial; Dermatologic; Gastrointestinal; Musculoskeletal; Neurologic5465362; 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.

EffectPLPVUSLBBSum
synonymous
3
clinvar
119
clinvar
122
missense
3
clinvar
8
clinvar
168
clinvar
13
clinvar
192
nonsense
3
clinvar
4
clinvar
7
start loss
0
frameshift
1
clinvar
10
clinvar
11
splice donor/acceptor (+/-2bp)
1
clinvar
1
clinvar
2
Total 3 13 186 132 0

Highest pathogenic variant AF is 0.000124529

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
PIGVprotein_codingprotein_codingENST00000374145 310927
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
1.51e-80.3861256900581257480.000231
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense0.3982402580.9300.00001393169
Missense in Polyphen7893.6610.832791231
Synonymous0.2021061090.9750.000005821074
Loss of Function0.8111417.70.7929.52e-7190

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0001480.000148
Ashkenazi Jewish0.0002990.000298
East Asian0.0001630.000163
Finnish0.00004620.0000462
European (Non-Finnish)0.0003430.000343
Middle Eastern0.0001630.000163
South Asian0.0002610.000261
Other0.000.00

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

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

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