MPPE1

Chr 18

metallophosphoesterase 1

Also known as: Cdc1, PGAP5

NCBI Gene: 65258 ENSG00000154889 UniProt: Q53F39 OMIM: 611900

The protein is a metallophosphoesterase that removes ethanolamine-phosphate from GPI-anchor protein intermediates during glycan remodeling, enabling efficient transport of GPI-anchored proteins from the endoplasmic reticulum to the Golgi apparatus. Mutations in MPPE1 cause congenital disorder of glycosylation type Iq, which presents with intellectual disability, seizures, and hypotonia with autosomal recessive inheritance. The gene shows relaxed evolutionary constraint with a high LOEUF score of 1.207, indicating tolerance to loss-of-function variants in the general population.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to enable GPI-mannose ethanolamine phosphate phosphodiesterase activity and manganese ion binding activity. Involved in GPI anchor biosynthetic process. Located in Golgi apparatus. [provided by Alliance of Genome Resources, Jun 2026]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.21

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.21LOEUF

pLI 0.000

Z-score 0.85

OE 0.79 (0.54–1.21)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.35Z-score

OE missense 0.93 (0.83–1.05)

210 obs / 224.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.79 (0.54–1.21)

0≤0.351.4

Missense OE?0.93 (0.83–1.05)

0≤0.61.4

Synonymous OE?1.01

0≤1.21.6

LoF obs/exp: 16 / 20.1Missense obs/exp: 210 / 224.9Syn Z: -0.05

Background carrier burden — how many people carry a rare variant somewhere in MPPE1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 90

474 rare PASS variants

Rare truncating (LoF)

1 in 320

110 rare PASS variants

Rare synonymous (reference)

1 in 190

176 rare PASS variants

Rare missense and truncating variants are carried at similar rates in MPPE1; 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 99	1 in 1,200
South Asian	~43k	1 in 97	1 in 290
Remaining (unassigned)	~30k	1 in 69	1 in 210
European (Finnish)	~27k	1 in 250	1 in 3,300
Admixed American	~22k	1 in 82	1 in 140
African / African American	~21k	1 in 95	1 in 360
East Asian	~20k	1 in 130	1 in 770
Ashkenazi Jewish	~13k	1 in 440	1 in 430
Middle Eastern	~2,884	1 in 120	1 in 480

Each group is summed over the variants that are rare in that group. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 7 of 9 coding exons well covered in gnomAD exomes; exons 3, 6 marginal. Genomes: all 9.? see exons ↓