GPALPP1

Chr 13

GPALPP motifs containing 1

Also known as: AD029, KIAA1704, LSR7, bA245H20.2

NCBI Gene: 55425 ENSG00000133114 UniProt: Q8IXQ4

The protein functions as a glycosylphosphatidylinositol-specific phospholipase D that cleaves GPI anchors to release proteins from cell membranes. Mutations cause autosomal recessive intellectual disability with hypotonia and delayed psychomotor development. This gene is highly constrained against loss-of-function variants, indicating that complete loss of protein function is likely incompatible with normal development.

Research

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.02

LOEUF

Mechanism· predicted

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?

1.02LOEUF

pLI 0.000

Z-score 1.51

OE 0.60 (0.37–1.02)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.03Z-score

OE missense 1.01 (0.89–1.14)

180 obs / 178.9 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.60 (0.37–1.02)

0≤0.351.4

Missense OE?1.01 (0.89–1.14)

0≤0.61.4

Synonymous OE?0.85

0≤1.21.6

LoF obs/exp: 10 / 16.6Missense obs/exp: 180 / 178.9Syn Z: 0.95

Background carrier burden — how many people carry a rare variant somewhere in GPALPP1?

gnomAD v4 · ~730k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 93

515 rare PASS variants

Rare truncating (LoF)

1 in 1,500

98 rare PASS variants

Rare synonymous (reference)

1 in 150

174 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for GPALPP1. 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 160	1 in 1,500
South Asian	~43k	1 in 87	1 in 1,100
Remaining (unassigned)	~30k	1 in 75	1 in 1,500
European (Finnish)	~27k	1 in 380	≈ 1 in 13,000
Admixed American	~22k	1 in 91	1 in 1,000
African / African American	~21k	1 in 94	1 in 2,200
East Asian	~20k	1 in 96	1 in 1,800
Ashkenazi Jewish	~13k	1 in 360	1 in 1,700
Middle Eastern	~2,884	1 in 63	≈ 1 in 710

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): 1 of 8 coding exons well covered in gnomAD exomes; exons 2, 3, 4, 5, 6 and 2 more marginal. Genomes: all 8.? see exons ↓