AGTPBP1

Chr 9AR

ATP/GTP binding carboxypeptidase 1

Also known as: CCP1, CONDCA, NNA1

NCBI Gene: 23287 ENSG00000135049 UniProt: Q9UPW5 OMIM: 606830

AGTPBP1 encodes a metallocarboxypeptidase that removes polyglutamate side chains from tubulin and other proteins, a process called deglutamylation that regulates microtubule dynamics. Mutations cause autosomal recessive childhood-onset neurodegeneration with cerebellar atrophy. The gene is highly constrained against loss-of-function variants (LOEUF 0.351), indicating that complete loss of function is likely incompatible with normal development.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

NNA1 is a zinc carboxypeptidase that contains nuclear localization signals and an ATP/GTP-binding motif that was initially cloned from regenerating spinal cord neurons of the mouse.[supplied by OMIM, Jul 2002]

OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.351 OMIM phenotype

Clinical Summary— AGTPBP1

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Gene-Disease Validity (ClinGen)

neurodegeneration, childhood-onset, with cerebellar atrophy · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.22) despite low pLI — interpret in context.

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ClinVar Variants

24 unique Pathogenic / Likely Pathogenic· 125 VUS of 199 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

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?

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?

LoF OE?0.22 (0.15–0.35)

0≤0.351.4

Missense OE?0.77 (0.72–0.83)

0≤0.61.4

Synonymous OE?0.95

0≤1.21.6

LoF obs/exp: 14 / 62.4Missense obs/exp: 477 / 617.6Syn Z: 0.53

ClinVar Variant Classifications

199 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic13

Likely Pathogenic11

VUS125

Likely Benign12

Benign7

Conflicting3

Pathogenic

Likely Pathogenic

125

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	10	3	0	0	13
Likely Pathogenic	9	2	0	0	11
VUS	3	116	4	2	125
Likely Benign	0	6	0	6	12
Benign	0	1	3	3	7
Conflicting	—				3
Total	22	128	7	11	171

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

View in ClinVar →

27 pathogenic / likely-pathogenic (of 37) ClinVar copy-number / structural variants overlap AGTPBP1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →