PIGU

Chr 20AR

phosphatidylinositol glycan anchor biosynthesis class U

Also known as: CDC91L1, GAB1, GPIBD21, NEDBSS, PIG-U

The protein functions as the fifth subunit of GPI transamidase complex, which catalyzes the attachment of GPI-anchors to proteins and is essential for GPI-anchored protein biosynthesis. Mutations cause autosomal recessive neurodevelopmental disorder with brain anomalies, seizures, and scoliosis. This disorder involves the central nervous system and musculoskeletal system, with neurodevelopmental impairment as a key feature.

OMIMResearchSummary from RefSeq, OMIM, UniProt
DNmechanismARLOEUF 0.861 OMIM phenotype
Clinical SummaryPIGU
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Gene-Disease Validity (ClinGen)
glycosylphosphatidylinositol biosynthesis defect 21 · ARLimited

Limited evidence — not for standalone diagnostic reporting

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.86LOEUF
pLI 0.000
Z-score 2.03
OE 0.52 (0.330.86)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.72Z-score
OE missense 0.87 (0.780.97)
208 obs / 239.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.52 (0.330.86)
00.351.4
Missense OE0.87 (0.780.97)
00.61.4
Synonymous OE1.07
01.21.6
LoF obs/exp: 11 / 21.1Missense obs/exp: 208 / 239.4Syn Z: -0.55
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongPIGU-related intellectual disability, central nervous system anomalies and scoliosisOTHERAR

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

DN
0.6550th %ile
GOF
0.5758th %ile
LOF
0.2581th %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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

PIGU · 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

No active trials found for this gene.

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Clinical Literature
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Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC