AGBL5

AGBL carboxypeptidase 5, the group of M14 carboxypeptidases

Basic information

Region (hg38): 2:27042364-27070622

Links

ENSG00000084693 ∙ NCBI:60509 ∙ OMIM:615900 ∙ HGNC:26147 ∙ Uniprot:Q8NDL9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• retinitis pigmentosa 75 (Strong), mode of inheritance: AR
• retinitis pigmentosa (Supportive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Retinitis pigmentosa 75	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	Ophthalmologic	26355662; 26720455

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the AGBL5 gene.

• not provided (21 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the AGBL5 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			9	164	5	178
missense		3	335	4	4	346
nonsense	11		2			13
start loss						0
frameshift	9	1	4			14
inframe indel			5			5
splice donor/acceptor (+/-2bp)	1	6	4			11
splice region			10	15	2	27
non coding			4	45	6	55
Total	21	10	363	213	15

Highest pathogenic variant AF is 0.00000657

Variants in AGBL5

This is a list of pathogenic ClinVar variants found in the AGBL5 region.

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

Position	Type	Phenotype	Significance	ClinVar
2-27052957-C-T		AGBL5-related disorder	Likely benign (Jan 21, 2020)
2-27052968-C-T			Uncertain significance (Apr 21, 2020)
2-27052976-G-T			Likely benign (Sep 27, 2022)
2-27052977-G-A			Uncertain significance (Jul 12, 2022)
2-27052980-T-C			Likely benign (Oct 17, 2022)
2-27052985-G-A			Likely benign (Jul 19, 2022)
2-27052990-G-A		Inborn genetic diseases	Uncertain significance (Dec 27, 2023)
2-27052993-C-T			Uncertain significance (Oct 02, 2019)
2-27053006-A-G			Likely benign (Jul 19, 2022)
2-27053011-A-G			Uncertain significance (Jun 20, 2022)
2-27053019-C-T		Retinal dystrophy	Uncertain significance (Oct 01, 2023)
2-27053021-C-T			Likely benign (Nov 15, 2023)
2-27053032-T-C			Uncertain significance (Oct 28, 2022)
2-27053036-A-C		Retinal dystrophy	Uncertain significance (Aug 16, 2022)
2-27053043-T-A		Inborn genetic diseases	Uncertain significance (Dec 06, 2024)
2-27053046-A-G			Uncertain significance (Aug 10, 2022)
2-27053047-G-A		Inborn genetic diseases	Uncertain significance (May 03, 2023)
2-27053049-G-C		Retinal dystrophy	Uncertain significance (Jun 20, 2022)
2-27053051-T-A		Retinal dystrophy	Uncertain significance (Oct 01, 2023)
2-27053065-G-C			Uncertain significance (Sep 12, 2022)
2-27053069-T-C			Likely benign (Jan 01, 2024)
2-27053074-C-T			Uncertain significance (Aug 23, 2022)
2-27053075-G-A			Likely benign (Apr 21, 2022)
2-27053091-G-A			Uncertain significance (Nov 08, 2022)
2-27053100-T-TC			Pathogenic (Jul 19, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
AGBL5	protein_coding	protein_coding	ENST00000360131	14	28259

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.37e-8	1.00	125622	0	126	125748	0.000501

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.29	462	547	0.844	0.0000346	5753
Missense in Polyphen		101	157.29	0.64213		1502
Synonymous	-0.604	217	206	1.05	0.0000118	1874
Loss of Function	3.23	20	42.8	0.467	0.00000290	418

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000725	0.000719
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.000498	0.000489
Finnish	0.000139	0.000139
European (Non-Finnish)	0.000318	0.000273
Middle Eastern	0.000498	0.000489
South Asian	0.00196	0.00196
Other	0.000652	0.000652

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Metallocarboxypeptidase that mediates protein deglutamylation. Specifically catalyzes the deglutamylation of the branching point glutamate side chains generated by post- translational glutamylation in proteins such as tubulins. In contrast, it is not able to act as a long-chain deglutamylase that shortens long polyglutamate chains, a process catalyzed by AGTPBP1/CCP1, AGBL2/CCP2, AGBL3/CCP3, AGBL1/CCP4 and AGBL4/CCP6. Mediates deglutamylation of CGAS, regulating the antiviral activity of CGAS. {ECO:0000250|UniProtKB:Q09M02}.
• Pathway: Post-translational protein modification;Metabolism of proteins;Carboxyterminal post-translational modifications of tubulin (Consensus)

Intolerance Scores

• loftool: 0.737
• rvis_EVS: -0.99
• rvis_percentile_EVS: 8.6

Haploinsufficiency Scores

• pHI: 0.291
• hipred: Y
• hipred_score: 0.515
• ghis: 0.521

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.0761

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Agbl5
• Phenotype: mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); immune system phenotype

Zebrafish Information Network

• Gene name: agbl5
• Affected structure: ventricular system
• Phenotype tag: abnormal
• Phenotype quality: edematous

Gene ontology

• Biological process: proteolysis;protein deglutamylation;protein branching point deglutamylation;defense response to virus
• Cellular component: nucleus;cytoplasm;cytosol;microtubule cytoskeleton;midbody;intercellular bridge;mitotic spindle
• Molecular function: metallocarboxypeptidase activity;zinc ion binding;tubulin binding