PIGC

Chr 1AR

phosphatidylinositol glycan anchor biosynthesis class C

Also known as: GPI2, GPIBD16, MRT62

NCBI Gene: 5279 ENSG00000135845 UniProt: Q92535 OMIM: 601730

This protein is a subunit of the GPI-N-acetylglucosaminyltransferase complex that catalyzes the first step of glycosylphosphatidylinositol (GPI) anchor biosynthesis, which is essential for anchoring many proteins to cell surfaces. Biallelic mutations cause glycosylphosphatidylinositol biosynthesis defect 16, inherited in an autosomal recessive pattern. The gene shows tolerance to loss-of-function variants (LOEUF 1.056), suggesting that complete loss of function may be required for disease manifestation.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes an endoplasmic reticulum associated protein that is involved in glycosylphosphatidylinositol (GPI) lipid anchor biosynthesis. The GPI lipid anchor is a glycolipid found on many blood cells and serves to anchor proteins to the cell surface. The encoded protein is one subunit of the GPI N-acetylglucosaminyl (GlcNAc) transferase that transfers GlcNAc to phosphatidylinositol (PI) on the cytoplasmic side of the endoplasmic reticulum. Two alternatively spliced transcripts that encode the same protein have been found for this gene. A pseudogene on chromosome 11 has also been characterized. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

DNmechanismARLOEUF 1.061 OMIM phenotype

Clinical Summary— PIGC

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Gene-Disease Validity (ClinGen)

glycosylphosphatidylinositol biosynthesis defect 16 · ARLimited

Limited evidence — not for standalone diagnostic reporting

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Population Constraint (gnomAD)

Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

7 unique Pathogenic / Likely Pathogenic· 59 VUS of 87 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?

1.06LOEUF

pLI 0.006

Z-score 1.46

OE 0.50 (0.26–1.06)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.79Z-score

OE missense 0.83 (0.72–0.95)

137 obs / 165.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.50 (0.26–1.06)

0≤0.351.4

Missense OE?0.83 (0.72–0.95)

0≤0.61.4

Synonymous OE?0.63

0≤1.21.6

LoF obs/exp: 5 / 10.0Missense obs/exp: 137 / 165.5Syn Z: 2.34

This gene — mechanism propensity

0.6840th %ile

GOF

0.5857th %ile

LOF

0.2970th %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

87 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic4

Likely Pathogenic3

VUS59

Likely Benign13

Benign5

Conflicting2

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	2	2	0	0	4
Likely Pathogenic	1	2	0	0	3
VUS	2	56	1	0	59
Likely Benign	0	1	1	11	13
Benign	0	2	0	3	5
Conflicting	—				2
Total	5	63	2	14	86

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

View in ClinVar →

27 pathogenic / likely-pathogenic (of 32) ClinVar copy-number / structural variants overlap PIGC — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →