PIGU

Chr 20AR

phosphatidylinositol glycan anchor biosynthesis class U

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

NCBI Gene: 128869ENSG00000101464UniProt: Q9H490

The protein encoded by this gene shares similarity with Saccharomyces cerevisiae Cdc91, a predicted integral membrane protein that may function in cell division control. The protein encoded by this gene is the fifth subunit of GPI transamidase that attaches GPI-anchors to proteins. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Neurodevelopmental disorder with brain anomalies, seizures, and scoliosisMIM #618590
AR
145
ClinVar variants
17
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— PIGU
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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.
📋
ClinVar Variants
17 Pathogenic / Likely Pathogenic· 51 VUS of 145 total submissions

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.
0.86LOEUF
pLI 0.000
Z-score 2.03
OE 0.52 (0.33–0.86)
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.
0.72Z-score
OE missense 0.87 (0.78–0.97)
208 obs / 239.4 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.0.52 (0.33–0.86)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.87 (0.78–0.97)
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.1.07
0≤1.21.6
LoF obs/exp: 11 / 21.1Missense obs/exp: 208 / 239.4Syn Z: -0.55

ClinVar Variant Classifications

145 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic13
Likely Pathogenic4
VUS51
Likely Benign67
Benign10
13
Pathogenic
4
Likely Pathogenic
51
VUS
67
Likely Benign
10
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
2
11
0
13
Likely Pathogenic
1
0
3
0
4
VUS
0
39
9
3
51
Likely Benign
0
3
29
35
67
Benign
0
1
7
2
10
Total1455940145

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

View 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.

Gene2Phenotype Curations

PIGU-related intellectual disability, central nervous system anomalies and scoliosis

strong
ARUndeterminedAltered Gene Product Structure
Dev. Disorders
G2P ↗
missense variantinframe deletioninframe insertion

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Neurodevelopmental disorder with brain anomalies, seizures, and scoliosis

MIM #618590

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Silencing of PIGU inhibits the progression of esophageal squamous cell carcinoma through the PI3K/AKT signaling pathway.
Zuo J et al.·Sci Rep
2025
Mutations in PIGU Impair the Function of the GPI Transamidase Complex, Causing Severe Intellectual Disability, Epilepsy, and Brain Anomalies.
Knaus A et al.·Am J Hum Genet
2019
Replication and predictive value of SNPs associated with melanoma and pigmentation traits in a Southern European case-control study.
Stefanaki I et al.·PLoS One
2013
Novel significant stage-specific differentially expressed genes in hepatocellular carcinoma.
Sarathi A et al.·BMC Cancer
2019
Glycosylphosphatidylinositol anchor biosynthesis pathway-based biomarker identification with machine learning for prognosis and T cell exhaustion status prediction in breast cancer.
Wu H et al.·Front Immunol
2024
Discovery of non-ETS gene fusions in human prostate cancer using next-generation RNA sequencing.
Pflueger D et al.·Genome Res
2011
A novel homozygous variant of the PIGK gene caused by paternal disomy in a patient with neurodevelopmental disorder, cerebellar atrophy, and seizures.
Sadamitsu K et al.·J Hum Genet
2024Case report
Overexpression of CDC91L1 (PIG-U) in bladder urothelial cell carcinoma: correlation with clinical variables and prognostic significance.
Shen YJ et al.·BJU Int
2008
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools