PIGH

Chr 14

phosphatidylinositol glycan anchor biosynthesis class H

Also known as: GPI-H

NCBI Gene: 5283 ENSG00000100564 UniProt: Q14442

This gene encodes an endoplasmic reticulum associated protein that is involved in glycosylphosphatidylinositol (GPI)-anchor biosynthesis. The GPI anchor is a glycolipid found on many blood cells and which serves to anchor proteins to the cell surface. The protein encoded by this gene is a subunit of the GPI N-acetylglucosaminyl (GlcNAc) transferase that transfers GlcNAc to phosphatidylinositol (PI) on the cytoplasmic side of the endoplasmic reticulum. [provided by RefSeq, Jul 2008]

Research

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtGlycosylphosphatidylinositol biosynthesis defect 17

Clinical highlights

Gene–disease validity (ClinGen)

Limited · glycosylphosphatidylinositol biosynthesis defect 17 · AR · ClinGen 2025

not for standalone diagnostic reporting

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.87

LOEUF

LOF

Mechanism· G2P

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.87LOEUF

pLI 0.231

Z-score 1.81

OE 0.28 (0.11–0.87)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.95Z-score

OE missense 0.73 (0.60–0.89)

69 obs / 95.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.28 (0.11–0.87)

0≤0.351.4

Missense OE?0.73 (0.60–0.89)

0≤0.61.4

Synonymous OE?0.65

0≤1.21.6

LoF obs/exp: 2 / 7.3Missense obs/exp: 69 / 95.0Syn Z: 1.73

Background carrier burden — how many people carry a rare variant somewhere in PIGH?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 230

314 rare PASS variants

Rare truncating (LoF)

1 in 520

63 rare PASS variants

Rare synonymous (reference)

1 in 410

102 rare PASS variants

Rare missense and truncating variants are carried at similar rates in PIGH; this gene does not show strong loss-of-function constraint by this measure. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 290	1 in 550
South Asian	~43k	1 in 180	1 in 570
Remaining (unassigned)	~30k	1 in 150	1 in 330
European (Finnish)	~27k	1 in 1,600	1 in 800
Admixed American	~22k	1 in 170	1 in 470
African / African American	~21k	1 in 150	1 in 430
East Asian	~20k	1 in 180	1 in 360
Ashkenazi Jewish	~13k	1 in 240	1 in 1,100
Middle Eastern	~2,884	1 in 530	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 3 of 4 coding exons well covered in gnomAD exomes; exon 3 marginal. Genomes: all 4.? see exons ↓