PIGQ

Chr 16AR

phosphatidylinositol glycan anchor biosynthesis class Q

Also known as: DEE77, EIEE77, GPI1, GPIBD19, MCAHS4, c407A10.1

NCBI Gene: 9091ENSG00000007541UniProt: Q9BRB3OMIM: 605754

The PIGQ protein is a N-acetylglucosaminyl transferase component that catalyzes the first step in glycosylphosphatidylinositol (GPI)-anchor biosynthesis, transferring N-acetylglucosamine from UDP-GlcNAc to phosphatidylinositol to create anchors that attach proteins to cell surfaces. Mutations cause multiple congenital anomalies-hypotonia-seizures syndrome 4 through an autosomal recessive inheritance pattern. The pathogenic mechanism involves gain-of-function mutations.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismARLOEUF 0.901 OMIM phenotype
Clinical Summary— PIGQ
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Gene-Disease Validity (ClinGen)
developmental and epileptic encephalopathy, 77 · 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
75 unique Pathogenic / Likely Pathogenic· 234 VUS of 588 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.90LOEUF
pLI 0.000
Z-score 1.91
OE 0.57 (0.37–0.90)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-0.09Z-score
OE missense 1.01 (0.94–1.09)
488 obs / 482.1 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.57 (0.37–0.90)
0≤0.351.4
Missense OE1.01 (0.94–1.09)
0≤0.61.4
Synonymous OE1.16
0≤1.21.6
LoF obs/exp: 13 / 22.9Missense obs/exp: 488 / 482.1Syn Z: -1.91
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
limitedPIGQ-related severe early-onset epilepsyLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.6649th %ile
GOF
0.73top 25%
LOF
0.3259th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

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

ClinVar Variant Classifications

588 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic67
Likely Pathogenic8
VUS234
Likely Benign193
Benign54
Conflicting17
67
Pathogenic
8
Likely Pathogenic
234
VUS
193
Likely Benign
54
Benign
17
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
21
0
46
0
67
Likely Pathogenic
6
2
0
0
8
VUS
9
194
24
7
234
Likely Benign
1
25
51
116
193
Benign
0
8
39
7
54
Conflicting
—17
Total37229160130573

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

View in ClinVar →

Protein Context — Lollipop Plot

PIGQ · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
ARV1 is a component of the enzyme initiating glycosylphosphatidylinositol biosynthesis.
Lu T et al.·J Biol Chem
2025
Neuronal RBM5 modulates cell signaling responses to traumatic and hypoxic-ischemic injury in a sex-dependent manner
Snyder K et al.·Cell Death Discov
2023
Genome-Wide Analysis of DNA Methylation Signatures Linking Prenatal Exposure to the Chinese Great Famine and Blood Lipids in Late Adulthood: The Genomic Research of the Chinese Famine (GRECF) Study.
Wang H et al.·Nutrients
2025
Enriched phenotypes in rare variant carriers suggest pathogenic mechanisms in rare disease patients
Fitzsimmons L et al.·BioData Min
2025Cohort
First insights into the honey bee (Apis mellifera) brain lipidome and its neonicotinoid-induced alterations associated with reduced self-grooming behavior
Morfin N et al.·J Adv Res
2021
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Early infantile epileptic encephalopathy due to biallelic pathogenic variants in PIGQ: Report of seven new subjects and review of the literature.
Johnstone DL et al.·J Inherit Metab Dis
2020Review
Expanding the phenotype of PIGP deficiency to multiple congenital anomalies-hypotonia-seizures syndrome.
Martín-Grau C et al.·Clin Genet
2023
PIGQ glycosylphosphatidylinositol-anchored protein deficiency: Characterizing the phenotype.
Starr LJ et al.·Am J Med Genet A
2019Case report
Identifying novel risk conferring genes involved in glycosylation processes with familial schizophrenia in an Indian cohort: Prediction of ADAMTS9 gene variant for structural stability.
Shekhar BR et al.·Gene
2023Cohort
A defect in GPI synthesis as a suggested mechanism for the role of ARV1 in intellectual disability and seizures.
Segel R et al.·Neurogenetics
2020Case report
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