AGTPBP1

Chr 9AR

ATP/GTP binding carboxypeptidase 1

ENSG00000135049UniProt: Q9UPW5

Metallocarboxypeptidase that mediates protein deglutamylation of tubulin and non-tubulin target proteins (PubMed:22170066, PubMed:24022482, PubMed:30420557). Catalyzes the removal of polyglutamate side chains present on the gamma-carboxyl group of glutamate residues within the C-terminal tail of alpha- and beta-tubulin (PubMed:22170066, PubMed:24022482, PubMed:30420557). Specifically cleaves tubulin long-side-chains, while it is not able to remove the branching point glutamate (PubMed:24022482). Also catalyzes the removal of polyglutamate residues from the carboxy-terminus of alpha-tubulin as well as non-tubulin proteins such as MYLK (PubMed:22170066). Involved in KLF4 deglutamylation which promotes KLF4 proteasome-mediated degradation, thereby negatively regulating cell pluripotency maintenance and embryogenesis (PubMed:29593216)

Primary Disease Associations & Inheritance

Neurodegeneration, childhood-onset, with cerebellar atrophyMIM #618276
AR
0
ClinVar variants
0
Pathogenic / LP
0.42
pLI score
0
Active trials
Clinical Summary— AGTPBP1
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.22) despite low pLI — interpret in context.
Some data sources returned errors (2)

ncbi: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

clinvarCount: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
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.
0.35LOEUF
pLI 0.422
Z-score 5.68
OE 0.22 (0.15–0.35)
Moderately constrained

More LoF-intolerant than ~75% of genes

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.
2.01Z-score
OE missense 0.77 (0.72–0.83)
477 obs / 617.6 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.0.22 (0.15–0.35)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.77 (0.72–0.83)
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.0.95
0≤1.21.6
LoF obs/exp: 14 / 62.4Missense obs/exp: 477 / 617.6Syn Z: 0.53

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

AGTPBP1 · protein map & ClinVar variants

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

Gene2Phenotype Curations

AGTPBP1-related neurodegeneration, childhood-onset, with cerebellar atrophy

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

Neurodegeneration, childhood-onset, with cerebellar atrophy

MIM #618276

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Human teratozoospermia-related AGTPBP1 R791H mutation is associated with sperm head and tail defects in a CRISPR-engineered murine model.
Wang YY et al.·J Assist Reprod Genet
2026🔓 Open AccessFunctional
Lacosamide Is a Novel Drug That Improves AGTPBP1 Knockout-Mediated Impairment of Neuronal and Dopaminergic Function.
Wang HP et al.·Mol Neurobiol
2025🔓 Open Access
Targeting AGTPBP1 inhibits pancreatic cancer progression via regulating microtubules and ERK signaling pathway.
Li DZ et al.·Mol Med
2024🔓 Open Access
Circ-AGTPBP1 promotes white matter injury through miR-140-3p/Pcdh17 axis role of Circ-AGTPBP1 in white matter injury.
Zhu Z et al.·J Bioenerg Biomembr
2024
Deleterious genetic changes in AGTPBP1 result in teratozoospermia with sperm head and flagella defects.
Lin YH et al.·J Cell Mol Med
2024🔓 Open Access
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