AGBL2

Chr 11

AGBL carboxypeptidase 2

Also known as: CCP2

The AGBL2 protein is a metallocarboxypeptidase that removes polyglutamate side chains from tubulin and other proteins, localizing to centrioles and ciliary basal bodies. Mutations cause autosomal recessive spastic paraplegia, typically presenting in childhood with progressive lower limb spasticity. The gene is highly constrained against loss-of-function variants, indicating that complete protein loss is likely incompatible with normal development.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 0.89
Clinical SummaryAGBL2
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.89LOEUF
pLI 0.000
Z-score 2.16
OE 0.66 (0.500.89)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.17Z-score
OE missense 0.85 (0.780.92)
390 obs / 460.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.66 (0.500.89)
00.351.4
Missense OE0.85 (0.780.92)
00.61.4
Synonymous OE0.99
01.21.6
LoF obs/exp: 32 / 48.2Missense obs/exp: 390 / 460.8Syn Z: 0.12
DN
0.6938th %ile
GOF
0.5072th %ile
LOF
0.3357th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

AGBL2 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC