AGTPBP1

ATP/GTP binding carboxypeptidase 1, the group of M14 carboxypeptidases|Armadillo like helical domain containing

Basic information

Region (hg38): 9:85546539-85742029

Links

ENSG00000135049 ∙ NCBI:23287 ∙ OMIM:606830 ∙ HGNC:17258 ∙ Uniprot:Q9UPW5 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• neurodegeneration, childhood-onset, with cerebellar atrophy (Definitive), mode of inheritance: AR
• neurodegeneration, childhood-onset, with cerebellar atrophy (Strong), mode of inheritance: AR
• neurodegeneration, childhood-onset, with cerebellar atrophy (Strong), mode of inheritance: AR
• pontocerebellar hypoplasia type 1 (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neurodegeneration, childhood-onset, with cerebellar atrophy	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic	30420557

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the AGTPBP1 gene.

• Neurodegeneration, childhood-onset, with cerebellar atrophy (7 variants)
• AGTPBP1-related disorder (2 variants)
• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the AGTPBP1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				4	2	6
missense	2	1	52	3		58
nonsense	1	4				5
start loss						0
frameshift	3					3
inframe indel			1			1
splice donor/acceptor (+/-2bp)	2	2				4
splice region			1		1	2
non coding			4		3	7
Total	8	7	57	7	5

Highest pathogenic variant AF is 0.00000658

Variants in AGTPBP1

This is a list of pathogenic ClinVar variants found in the AGTPBP1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
9-85547120-A-C		Inborn genetic diseases	Uncertain significance (Dec 01, 2022)
9-85547131-A-G		Inborn genetic diseases	Uncertain significance (May 14, 2024)
9-85547150-C-T		Inborn genetic diseases	Uncertain significance (Feb 06, 2023)
9-85547151-T-G		AGTPBP1-related disorder	Likely benign (Oct 01, 2024)
9-85547200-A-G		Inborn genetic diseases	Uncertain significance (Jun 26, 2024)
9-85547201-T-C		Inborn genetic diseases	Uncertain significance (Jan 02, 2024)
9-85547263-T-C		Inborn genetic diseases	Uncertain significance (Mar 06, 2023)
9-85575417-A-T		Inborn genetic diseases	Uncertain significance (Nov 09, 2024)
9-85575433-T-C		AGTPBP1-related disorder • Inborn genetic diseases	Likely benign (Nov 13, 2024)
9-85575443-C-G		Inborn genetic diseases	Uncertain significance (Jun 17, 2022)
9-85575463-C-T		Inborn genetic diseases	Uncertain significance (Dec 12, 2023)
9-85578925-A-C		Inborn genetic diseases	Uncertain significance (Aug 17, 2022)
9-85579006-G-A		Inborn genetic diseases	Uncertain significance (Nov 10, 2022)
9-85579010-T-C		AGTPBP1-related disorder	Likely benign (Feb 21, 2023)
9-85579026-T-C		Inborn genetic diseases	Uncertain significance (May 17, 2021)
9-85579056-C-A		Neurodegeneration, childhood-onset, with cerebellar atrophy	Uncertain significance (Sep 15, 2024)
9-85579086-T-C		Inborn genetic diseases	Uncertain significance (Dec 07, 2021)
9-85585473-G-A		Inborn genetic diseases	Likely benign (Dec 03, 2024)
9-85586851-C-T		Neurodegeneration, childhood-onset, with cerebellar atrophy	Uncertain significance (Mar 29, 2024)
9-85586895-T-A		Neurodegeneration, childhood-onset, with cerebellar atrophy	Pathogenic (Jan 11, 2019)
9-85586956-G-A		Inborn genetic diseases	Uncertain significance (Oct 16, 2023)
9-85586961-C-CTACATG		Neurodegeneration, childhood-onset, with cerebellar atrophy	Uncertain significance (Oct 07, 2024)
9-85588358-C-T		Neurodegeneration, childhood-onset, with cerebellar atrophy	Uncertain significance (Jun 03, 2020)
9-85588359-G-A		Aplasia/Hypoplasia of the cerebellum;Global developmental delay	Pathogenic (Sep 09, 2023)
9-85588368-G-A		Neurodegeneration, childhood-onset, with cerebellar atrophy	Likely pathogenic (Mar 16, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
AGTPBP1	protein_coding	protein_coding	ENST00000376083	25	195490

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.422	0.578	125709	0	37	125746	0.000147

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.01	477	618	0.772	0.0000314	7799
Missense in Polyphen		98	184.6	0.53089		2308
Synonymous	0.527	208	218	0.955	0.0000113	2200
Loss of Function	5.68	14	62.4	0.224	0.00000348	811

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000213	0.000211
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.000329	0.000326
Finnish	0.00	0.00
European (Non-Finnish)	0.000151	0.000149
Middle Eastern	0.000329	0.000326
South Asian	0.000237	0.000229
Other	0.000164	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Metallocarboxypeptidase that mediates deglutamylation of target proteins. Catalyzes the deglutamylation of polyglutamate side chains generated by post-translational polyglutamylation in proteins such as tubulins. Also removes gene-encoded polyglutamates from the carboxy-terminus of target proteins such as MYLK. Acts as a long-chain deglutamylase and specifically shortens long polyglutamate chains, while it is not able to remove the branching point glutamate, a process catalyzed by AGBL5/CCP5. {ECO:0000250|UniProtKB:Q641K1}.
• Pathway: Olfactory bulb development and olfactory learning;Post-translational protein modification;Metabolism of proteins;Carboxyterminal post-translational modifications of tubulin (Consensus)

Recessive Scores

• pRec: 0.143

Intolerance Scores

• loftool: 0.604
• rvis_EVS: -1.08
• rvis_percentile_EVS: 7.2

Haploinsufficiency Scores

• pHI: 0.721
• hipred: Y
• hipred_score: 0.563
• ghis: 0.579

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.172

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Agtpbp1
• Phenotype: endocrine/exocrine gland phenotype; growth/size/body region phenotype; muscle phenotype; cellular phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); reproductive system phenotype; vision/eye phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); hearing/vestibular/ear phenotype

Zebrafish Information Network

• Gene name: agtpbp1
• Affected structure: ventricular system
• Phenotype tag: abnormal
• Phenotype quality: edematous

Gene ontology

• Biological process: eye photoreceptor cell differentiation;proteolysis;mitochondrion organization;cerebellar Purkinje cell differentiation;olfactory bulb development;C-terminal protein deglutamylation;protein side chain deglutamylation;neuromuscular process
• Cellular component: nucleus;nucleolus;cytoplasm;mitochondrion;cytosol;intracellular membrane-bounded organelle
• Molecular function: metallocarboxypeptidase activity;zinc ion binding;tubulin binding