MPPED1

Chr 22

metallophosphoesterase domain containing 1

Also known as: 239AB, C22orf1, FAM1A

NCBI Gene: 758 ENSG00000186732 UniProt: O15442 OMIM: 602112

The protein is predicted to function as a hydrolase with possible metallophosphoesterase activity. Mutations cause autosomal recessive intellectual disability with behavioral abnormalities and seizures, typically presenting in early childhood. The gene shows minimal constraint against loss-of-function variants, consistent with its recessive inheritance pattern.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to enable cyclic-nucleotide phosphodiesterase activity. [provided by Alliance of Genome Resources, Jun 2026]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.83

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.83LOEUF

pLI 0.002

Z-score 2.06

OE 0.44 (0.25–0.83)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

2.60Z-score

OE missense 0.51 (0.44–0.59)

113 obs / 222.2 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.44 (0.25–0.83)

0≤0.351.4

Missense OE?0.51 (0.44–0.59)

0≤0.61.4

Synonymous OE?0.92

0≤1.21.6

LoF obs/exp: 7 / 15.8Missense obs/exp: 113 / 222.2Syn Z: 0.61

Background carrier burden — how many people carry a rare variant somewhere in MPPED1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 290

326 rare PASS variants

Rare truncating (LoF)

1 in 8,600

26 rare PASS variants

Rare synonymous (reference)

1 in 120

208 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for MPPED1. 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 330	1 in 8,200
South Asian	~43k	1 in 170	none seen
Remaining (unassigned)	~30k	1 in 270	≈ 1 in 15,000
European (Finnish)	~27k	1 in 740	≈ 1 in 8,600
Admixed American	~22k	1 in 530	≈ 1 in 5,700
African / African American	~21k	1 in 280	none seen
East Asian	~20k	1 in 250	≈ 1 in 20,000
Ashkenazi Jewish	~13k	1 in 420	none seen
Middle Eastern	~2,884	1 in 410	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): All 6 coding exons well covered in gnomAD exomes and genomes.? see exons ↓