PIGS

Chr 17AR

phosphatidylinositol glycan anchor biosynthesis class S

Also known as: DEE95, GPIBD18, PIG-S

NCBI Gene: 94005ENSG00000087111UniProt: Q96S52

This gene encodes a protein that is involved in GPI-anchor biosynthesis. The glycosylphosphatidylinositol (GPI) anchor is a glycolipid found on many blood cells and serves to anchor proteins to the cell surface. This gene encodes an essential component of the multisubunit enzyme, GPI transamidase. GPI transamidase mediates GPI anchoring in the endoplasmic reticulum, by catalyzing the transfer of fully assembled GPI units to proteins. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Developmental and epileptic encephalopathy 95MIM #618143
AR
UniProtGlycosylphosphatidylinositol biosynthesis defect 18
155
ClinVar variants
19
Pathogenic / LP
0.00
pLI score
4
Active trials
Clinical Summary— PIGS
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
19 Pathogenic / Likely Pathogenic· 90 VUS of 155 total submissions
💊
Clinical Trials
4 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.77LOEUF
pLI 0.000
Z-score 2.45
OE 0.47 (0.30–0.77)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.78Z-score
OE missense 0.88 (0.80–0.97)
285 obs / 324.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.47 (0.30–0.77)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.88 (0.80–0.97)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.98
0≤1.21.6
LoF obs/exp: 12 / 25.3Missense obs/exp: 285 / 324.5Syn Z: 0.17

ClinVar Variant Classifications

155 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic13
Likely Pathogenic6
VUS90
Likely Benign27
Benign6
13
Pathogenic
6
Likely Pathogenic
90
VUS
27
Likely Benign
6
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
3
8
0
13
Likely Pathogenic
1
2
3
0
6
VUS
1
83
6
0
90
Likely Benign
0
9
0
18
27
Benign
0
4
2
0
6
Total41011918142

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

PIGS · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

PIGS-related neurological syndrome fetal akinesia/epileptic encephalopathy

strong
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Developmental and epileptic encephalopathy 95

MIM #618143

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Origin and evolution of pathogenic coronaviruses.
Cui J et al.·Nat Rev Microbiol
2019Review
The Epidemiology and Variation in Pseudorabies Virus: A Continuing Challenge to Pigs and Humans.
Liu Q et al.·Viruses
2022Review
Promising strategy for developing mRNA-based universal influenza virus vaccine for human population, poultry, and pigs- focus on the bigger picture.
Rcheulishvili N et al.·Front Immunol
2022Review
Coregulation of host-adapted metabolism and virulence by pathogenic yersiniae.
Heroven AK et al.·Front Cell Infect Microbiol
2014Review
Porcine Circoviruses and Xenotransplantation.
Denner J et al.·Viruses
2017Review
A Novel Human Acute Encephalitis Caused by Pseudorabies Virus Variant Strain.
Liu Q et al.·Clin Infect Dis
2021
[Xenotransplantation of solid organs].
Schmoeckel M et al.·Chirurgie (Heidelb)
2024Review
The emergence and diversification of a zoonotic pathogen from within the microbiota of intensively farmed pigs.
Murray GGR et al.·Proc Natl Acad Sci U S A
2023
Antibiotic resistance in Chlamydiae.
Sandoz KM et al.·Future Microbiol
2010Review
Immunobiology of liver xenotransplantation.
Ekser B et al.·Expert Rev Clin Immunol
2012Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Effects of different combinations of dietary zinc and copper levels on the mitochondrial energy metabolism, oxidative balance, antioxidant system, and inflammation in weaned pigs.
Villeneuve G et al.·J Anim Sci
2026
Dietary copper-driven colonic dysbiosis mediates oxidative stress and butyrate deficiency to facilitate the spread of resistome in pigs.
Wen Y et al.·NPJ Biofilms Microbiomes
2026
First Evidence of Porcine Epidemic Diarrhoea Virus and African Swine Fever Virus Natural Co-Infection in Pigs from Karnataka, India: An Epidemiological Investigation.
Hiremath JB et al.·Curr Microbiol
2026
Retrospective evaluation of parenteral penicillin G procaine/benzathine and ceftiofur crystalline free acid use in chinchillas and guinea pigs: 124 cases (2001-2023).
Cooper A et al.·J Am Vet Med Assoc
2026Cohort
Stable expression of Interleukin-18 in a live-attenuated PRRSV backbone confers safe and potent immune protection in pigs.
Guo Z et al.·Int J Biol Macromol
2026
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
B-Cell Non-Hodgkin LymphomaHistiocytic and Dendritic Cell NeoplasmMyelodysplastic Syndrome

A Vaccine (VSV-hIFNβ-NIS) With or Without Cyclophosphamide and Combinations of Ipilimumab, Nivolumab, and Cemiplimab in Treating Relapsed or Refractory Multiple Myeloma, Acute Myeloid Leukemia or Lymphoma

RECRUITING
NCT03017820Phase PHASE1Mayo ClinicStarted 2017-04-04
Biopsy ProcedureBiospecimen CollectionBone Marrow Biopsy
Prostate Adenocarcinoma

Two Studies for Patients With Unfavorable Intermediate Risk Prostate Cancer Testing Less Intense Treatment for Patients With a Low Gene Risk Score and Testing a More Intense Treatment for Patients With a Higher Gene Risk Score, The Guidance Trial

RECRUITING
NCT05050084Phase PHASE3NRG OncologyStarted 2021-12-06
BicalutamideBuserelinDarolutamide
Burn; Multiple Body Regions, Max. Second DegreeThird-Degree BurnBurn Degree Second

Safety, Tolerability and Efficacy of Nefopam Cream in Burn Patients

RECRUITING
NCT04685577Phase PHASE2University of AlbertaStarted 2022-07-10
NefopamPlacebo (Vehicle)
Prostate AdenocarcinomaStage III Prostate Cancer AJCC v8Stage IVA Prostate Cancer AJCC v8

Two Studies for Patients With High Risk Prostate Cancer Testing Less Intense Treatment for Patients With a Low Gene Risk Score and Testing a More Intense Treatment for Patients With a High Gene Risk Score, The PREDICT-RT Trial

ACTIVE NOT RECRUITING
NCT04513717Phase PHASE3NRG OncologyStarted 2021-01-21
ApalutamideBicalutamideBiospecimen Collection

External Resources

Links to major genomics databases and tools