AMPD2

Chr 1AR

adenosine monophosphate deaminase 2

Also known as: AMPD, PCH9, SPG63

NCBI Gene: 271ENSG00000116337UniProt: Q01433

The protein encoded by this gene is important in purine metabolism by converting AMP to IMP. The encoded protein, which acts as a homotetramer, is one of three AMP deaminases found in mammals. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2012]

Primary Disease Associations & Inheritance

?Spastic paraplegia 63, autosomal recessiveMIM #615686
AR
Pontocerebellar hypoplasia, type 9MIM #615809
AR
574
ClinVar variants
65
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— AMPD2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
65 Pathogenic / Likely Pathogenic· 222 VUS of 574 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.64LOEUF
pLI 0.000
Z-score 3.42
OE 0.43 (0.30–0.64)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
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?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.43 (0.30–0.64)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.67 (0.61–0.72)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.96
0≤1.21.6
LoF obs/exp: 18 / 41.8Missense obs/exp: 379 / 568.9Syn Z: 0.46

ClinVar Variant Classifications

574 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic36
Likely Pathogenic29
VUS222
Likely Benign233
Benign43
Conflicting11
36
Pathogenic
29
Likely Pathogenic
222
VUS
233
Likely Benign
43
Benign
11
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
12
3
21
0
36
Likely Pathogenic
14
8
7
0
29
VUS
1
192
26
3
222
Likely Benign
0
12
98
123
233
Benign
0
0
36
7
43
Conflicting
—11
Total27215188133574

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

AMPD2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

AMPD2-related pontocerebellar hypoplasia

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

?Spastic paraplegia 63, autosomal recessive

MIM #615686

Molecular basis of disorder known

Autosomal recessive

Pontocerebellar hypoplasia, type 9

MIM #615809

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Delineating the phenotype and genetic basis of AMPD2-related pontocerebellar hypoplasia.
Gilboa T et al.·Neurogenetics
2023
Clinical and genetic spectrum of AMPD2-related pontocerebellar hypoplasia type 9.
Kortüm F et al.·Eur J Hum Genet
2018
Broadening the phenotype and genotype spectrum of novel mutations in pontocerebellar hypoplasia with a comprehensive molecular literature review.
Ghasemi MR et al.·BMC Med Genomics
2024Review
MIF Facilitates Resistance to Androgen Deprivation Therapy by Regulating AMPD2 Expression in Prostate Cancer Cells.
Li C et al.·Prostate
2026
Homozygous variants in AMPD2 and COL11A1 lead to a complex phenotype of pontocerebellar hypoplasia type 9 and Stickler syndrome type 2.
Abreu NJ et al.·Am J Med Genet A
2020Case report
NovelmiRNA-25 inhibits AMPD2 in peripheral blood mononuclear cells of patients with systemic lupus erythematosus and represents a promising novel biomarker.
Guo G et al.·J Transl Med
2018Cohort
Adenylate deaminase. A multigene family in humans and rats.
Morisaki T et al.·J Biol Chem
1990
APOBEC3B Promotes SARS-CoV-2 Through Activation of PKR/eIF2⍺ and AMPD2 Dysregulation.
Fixman B et al.·Viruses
2025
Pontocerebellar hypoplasia type-9 due to a novel p.Arg503Ter truncating variant in AMPD2: a report from India.
Holla VV et al.·Acta Neurol Belg
2023
First-line exome sequencing in Palestinian and Israeli Arabs with neurological disorders is efficient and facilitates disease gene discovery.
Hengel H et al.·Eur J Hum Genet
2020
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools