AGBL1

protein-coding

AGBL carboxypeptidase 1, the group of M14 carboxypeptidases|Armadillo like helical domain containing

Gene summary

Polyglutamylation is a reversible posttranslational modification catalyzed by polyglutamylases that results in the addition of glutamate side chains on the modified protein. This gene encodes a glutamate decarboxylase that catalyzes the deglutamylation of polyglutamylated proteins. Mutations in this gene result in dominant late-onset Fuchs corneal dystrophy. [provided by RefSeq, Nov 2013]

MANE transcript

NM_001386094.1

Inheritance

ClinVar variants

U:185B:47

Top phenotype

Corneal dystrophy, Fuchs endothelial, 8

Max pathogenic AF

—

Genomic locus

chr15:86,079,871-87,049,169

External References & Databases

Ensembl (ENSG00000273540)

Transcript & Mutation Effects

hg38 • Region Span ~969.3 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

corneal dystrophy, Fuchs endothelial, 8LIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0014228

Submitter: PanelApp Australia

corneal dystrophy, Fuchs endothelial, 8LIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0014228

Submitter: G2P

Fuchs' endothelial dystrophySUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0005321

Submitter: Orphanet

Clinical Genomic Database (CGD)

Corneal dystrophy, Fuchs endothelial, 8AD

Manifestation: Ophthalmologic

Intervention: General

Rationale: 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

Refs: 24094747

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to AGBL1 variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 212

AGBL1-related disorderTotal: 24

not providedTotal: 12

Corneal dystrophy, Fuchs endothelial, 8Total: 6

Fuchs' endothelial dystrophyTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001386094.1. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			4 clinvar	17 clinvar		21
missense			179 clinvar	25 clinvar	5 clinvar	209
nonsense			1 clinvar			1
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)						0
Total	0	0	185	42	5	232

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 11 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001386094.1	RefSeq	NP_001373023.1	23	MANE Select
ENST00000614907.3	Ensembl	ENSP00000490608.2	23	MANE Select
NM_152336.4	RefSeq	NP_689549.3	25	Standard
ENST00000441037.7	Ensembl	ENSP00000413001.3	25	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Post-translational protein modification
Metabolism of proteins
Carboxyterminal post-translational modifications of tubulin

Biological Process

proteolysis
C-terminal protein deglutamylation
protein side chain deglutamylation

Molecular Function

metallocarboxypeptidase activity
zinc ion binding
tubulin binding

Cellular Component

cytosol

dbNSFP Gene Annotations

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:Q09M05}.;

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Indispensability pred.: N
Indispensability score: 0.0741

Gene Damage Prediction

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