PIGP

Chr 21AR

phosphatidylinositol glycan anchor biosynthesis class P

Also known as: DCRC, DCRC-S, DEE55, DSCR5, DSRC, EIEE55, PIG-P

NCBI Gene: 51227 ENSG00000185808 UniProt: P57054 OMIM: 605938

The PIGP gene encodes an enzyme that catalyzes the transfer of N-acetylglucosamine to phosphatidylinositol in the first step of glycosylphosphatidylinositol (GPI)-anchor biosynthesis, which anchors proteins to cell surfaces. Mutations cause developmental and epileptic encephalopathy 55 through autosomal recessive inheritance. The pathogenic mechanism involves gain-of-function effects that disrupt normal GPI-anchor biosynthesis.

OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

This gene encodes an enzyme involved in the first step of glycosylphosphatidylinositol (GPI)-anchor biosynthesis. The GPI-anchor is a glycolipid found on many blood cells that serves to anchor proteins to the cell surface. The encoded protein is a component of the GPI-N-acetylglucosaminyltransferase complex that catalyzes the transfer of N-acetylglucosamine (GlcNAc) from UDP-GlcNAc to phosphatidylinositol (PI). This gene is located in the Down Syndrome critical region on chromosome 21 and is a candidate for the pathogenesis of Down syndrome. This gene has multiple pseudogenes and is a member of the phosphatidylinositol glycan anchor biosynthesis gene family. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Feb 2016]

OMIM ResearchGenerating clinical summary…

MultiplemechanismARLOEUF 1.371 OMIM phenotype

Clinical Summary— PIGP

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Gene-Disease Validity (ClinGen)

developmental and epileptic encephalopathy, 55 · ARModerate

Moderate evidence — consider for supplementary testing

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Population Constraint (gnomAD)

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

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ClinVar Variants

2 unique Pathogenic / Likely Pathogenic· 83 VUS of 168 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?

1.37LOEUF

pLI 0.002

Z-score 0.88

OE 0.66 (0.34–1.37)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.56Z-score

OE missense 1.18 (0.99–1.40)

92 obs / 78.1 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.66 (0.34–1.37)

0≤0.351.4

Missense OE?1.18 (0.99–1.40)

0≤0.61.4

Synonymous OE?1.24

0≤1.21.6

LoF obs/exp: 5 / 7.6Missense obs/exp: 92 / 78.1Syn Z: -1.03

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

moderatePIGP-related multiple congenital anomalies-hypotonia-seizures syndromeOTHERAR

This gene — mechanism propensity

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

0.7230th %ile

GOF

0.72top 25%

LOF

0.2873th %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

168 submitted variants in ClinVar

ClinVar

Classification Summary

Likely Pathogenic2

VUS83

Likely Benign66

Benign9

Conflicting2

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	0	0	0	0	0
Likely Pathogenic	1	1	0	0	2
VUS	12	68	3	0	83
Likely Benign	0	0	28	38	66
Benign	0	5	3	1	9
Conflicting	—				2
Total	13	74	34	39	162

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

View in ClinVar →

66 pathogenic / likely-pathogenic (of 78) ClinVar copy-number / structural variants overlap PIGP — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →