PIGS

Chr 17AR

phosphatidylinositol glycan anchor biosynthesis class S

Also known as: DEE95, GPIBD18, PIG-S

NCBI Gene: 94005 ENSG00000087111 UniProt: Q96S52 OMIM: 610271

This gene encodes a component of the GPI-anchor transamidase complex that catalyzes the attachment of GPI anchors to proteins in the endoplasmic reticulum, enabling these proteins to be anchored to cell surfaces. Biallelic mutations cause developmental and epileptic encephalopathy 95, inherited in an autosomal recessive pattern. The gene is highly constrained against loss-of-function variants (LOEUF 0.769), reflecting its essential role in cellular function.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Developmental and epileptic encephalopathy 95MIM #618143

UniProtGlycosylphosphatidylinositol biosynthesis defect 18

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · glycosylphosphatidylinositol biosynthesis defect 18 · AR · ClinGen 2025

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

7167

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.77

LOEUF

LOF

Mechanism· G2P

📖

GeneReview available — PIGS

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.77LOEUF

pLI 0.000

Z-score 2.45

OE 0.47 (0.30–0.77)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.78Z-score

OE missense 0.88 (0.80–0.97)

285 obs / 324.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.47 (0.30–0.77)

0≤0.351.4

Missense OE?0.88 (0.80–0.97)

0≤0.61.4

Synonymous OE?0.98

0≤1.21.6

LoF obs/exp: 12 / 25.3Missense obs/exp: 285 / 324.5Syn Z: 0.17

Background carrier burden — how many people carry a rare variant somewhere in PIGS?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 99

675 rare PASS variants

Rare truncating (LoF)

1 in 1,100

93 rare PASS variants

Rare synonymous (reference)

1 in 180

287 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for PIGS. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 100	1 in 1,000
South Asian	~43k	1 in 110	1 in 2,700
Remaining (unassigned)	~30k	1 in 86	1 in 3,000
European (Finnish)	~27k	1 in 220	1 in 3,800
Admixed American	~22k	1 in 85	1 in 1,600
African / African American	~21k	1 in 65	1 in 2,300
East Asian	~20k	1 in 91	1 in 750
Ashkenazi Jewish	~13k	1 in 200	1 in 930
Middle Eastern	~2,884	1 in 63	≈ 1 in 2,900

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 12 coding exons well covered in gnomAD exomes and genomes.? see exons ↓