PIGL

Chr 17AR

phosphatidylinositol glycan anchor biosynthesis class L

Also known as: CHIME

NCBI Gene: 9487ENSG00000108474UniProt: Q9Y2B2

This gene encodes an enzyme that catalyzes the second step of glycosylphosphatidylinositol (GPI) biosynthesis, which is the de-N-acetylation of N-acetylglucosaminylphosphatidylinositol (GlcNAc-PI). Study of a similar rat enzyme suggests that this protein localizes to the endoplasmic reticulum. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

CHIME syndromeMIM #280000
AR
UniProtColoboma, congenital heart disease, ichthyosiform dermatosis, impaired intellectual development, and ear anomalies syndrome
0
Active trials
45
Pathogenic / LP
204
ClinVar variants
2
Pubs (1 yr)
0.0
Missense Z
1.51
LOEUF
Clinical Summary— PIGL
🧬
Gene-Disease Validity (ClinGen)
syndromic intellectual disability · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
45 Pathogenic / Likely Pathogenic· 97 VUS of 204 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.51LOEUF
pLI 0.000
Z-score 0.17
OE 0.95 (0.62–1.51)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.05Z-score
OE missense 0.99 (0.86–1.14)
146 obs / 147.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.95 (0.62–1.51)
0≤0.351.4
Missense OE0.99 (0.86–1.14)
0≤0.61.4
Synonymous OE1.05
0≤1.21.6
LoF obs/exp: 13 / 13.7Missense obs/exp: 146 / 147.5Syn Z: -0.28
DN
DN
0.6551th %ile
GOF
0.4974th %ile
LOF
0.3552th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

204 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic35
Likely Pathogenic10
VUS97
Likely Benign41
Benign10
Conflicting11
35
Pathogenic
10
Likely Pathogenic
97
VUS
41
Likely Benign
10
Benign
11
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
6
1
28
0
35
Likely Pathogenic
6
4
0
0
10
VUS
0
59
32
6
97
Likely Benign
1
10
18
12
41
Benign
0
0
10
0
10
Conflicting
—11
Total13748818204

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

View in ClinVar →

PIGL · protein map & ClinVar variants

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

Gene2Phenotype Curations

PIGL-related coloboma, congenital heart disease, ichthyosiform dermatosis, impaired intellectual development, and ear anomalies syndrome (CHIME)

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. DisordersEyeSkin
G2P ↗

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Landmark / reviewRecent case evidence
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients