AMPD2

Chr 1AR

adenosine monophosphate deaminase 2

ENSG00000116337 UniProt: Q01433 OMIM: 102771

The protein converts AMP to IMP as part of the purine nucleotide cycle, functioning as a homotetramer that plays a critical role in cellular energy metabolism. Mutations cause autosomal recessive spastic paraplegia 63 and pontocerebellar hypoplasia type 9, affecting the central nervous system with early-onset developmental abnormalities. The gene is highly constrained against loss-of-function variants, indicating intolerance to protein-disrupting mutations.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

AMP deaminase plays a critical role in energy metabolism. Catalyzes the deamination of AMP to IMP and plays an important role in the purine nucleotide cycle

OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.642 OMIM phenotypes

Clinical Summary— AMPD2

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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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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.64LOEUF

pLI 0.000

Z-score 3.42

OE 0.43 (0.30–0.64)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

2.83Z-score

OE missense 0.67 (0.61–0.72)

379 obs / 568.9 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.43 (0.30–0.64)

0≤0.351.4

Missense OE?0.67 (0.61–0.72)

0≤0.61.4

Synonymous OE?0.96

0≤1.21.6

LoF obs/exp: 18 / 41.8Missense obs/exp: 379 / 568.9Syn Z: 0.46

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveAMPD2-related pontocerebellar hypoplasiaLOFAR

This gene — mechanism propensity

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

0.6358th %ile

GOF

0.6051th %ile

LOF

0.3843th %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.