ACY1

aminoacylase 1, the group of M20 metallopeptidases

Basic information

Region (hg38): 3:51983339-51989197

Links

ENSG00000243989 ∙ NCBI:95 ∙ OMIM:104620 ∙ HGNC:177 ∙ Uniprot:Q03154 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• aminoacylase 1 deficiency (Definitive), mode of inheritance: AR
• aminoacylase 1 deficiency (Strong), mode of inheritance: AR
• aminoacylase 1 deficiency (Supportive), mode of inheritance: AR
• aminoacylase 1 deficiency (Strong), mode of inheritance: AR
• aminoacylase 1 deficiency (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Aminoacylase 1 deficiency	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	Biochemical; Neurologic	16274666; 16465618; 17562838; 20480396; 24117009

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ACY1 gene.

• not provided (105 variants)
• Inborn genetic diseases (24 variants)
• Aminoacylase 1 deficiency (20 variants)
• not specified (7 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ACY1 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			3	25	1	29
missense		1	53	3		57
nonsense			1			1
start loss						0
frameshift	1	2	1			4
inframe indel			1			1
splice donor/acceptor (+/-2bp)		1	1			2
splice region			3	6	1	10
non coding			2	7	7	16
Total	1	4	62	35	8

Highest pathogenic variant AF is 0.00000659

Variants in ACY1

This is a list of pathogenic ClinVar variants found in the ACY1 region.

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

Position	Type	Phenotype	Significance	ClinVar
3-51984083-G-A		Aminoacylase 1 deficiency	Uncertain significance (-)
3-51984083-G-C		Aminoacylase 1 deficiency	Uncertain significance (Aug 27, 2019)
3-51984100-G-C			Likely benign (Oct 13, 2022)
3-51984112-C-T			Likely benign (Jan 07, 2023)
3-51984113-C-T			Uncertain significance (Dec 02, 2021)
3-51984114-G-T			Uncertain significance (Feb 24, 2022)
3-51984122-C-G		Inborn genetic diseases	Uncertain significance (Aug 04, 2023)
3-51984133-C-G			Benign/Likely benign (Jan 18, 2024)
3-51984134-A-G		Inborn genetic diseases	Uncertain significance (Jun 07, 2023)
3-51984145-C-G		ACY1-related disorder	Benign/Likely benign (Jan 18, 2024)
3-51984168-C-T			Benign (Jan 08, 2024)
3-51984169-G-A		Aminoacylase 1 deficiency	Uncertain significance (Jul 01, 2021)
3-51985195-CTG-C			Likely benign (Apr 30, 2022)
3-51985196-T-G			Uncertain significance (Oct 17, 2022)
3-51985218-G-T			Uncertain significance (Jul 01, 2022)
3-51985239-C-T			Uncertain significance (Dec 30, 2022)
3-51985247-G-C			Benign (Jul 23, 2023)
3-51985360-G-A		Aminoacylase 1 deficiency	Likely pathogenic (Nov 03, 2023)
3-51985384-C-T			Likely benign (Sep 05, 2018)
3-51985385-G-C		Intellectual disability	Likely benign (Jan 01, 2019)
3-51985388-T-C			Likely benign (May 19, 2021)
3-51985443-C-T		ACY1-related disorder	Likely benign (Sep 25, 2019)
3-51985463-A-C			Uncertain significance (Dec 19, 2022)
3-51985845-C-T		ABHD14A-ACY1-related disorder	Benign/Likely benign (Dec 22, 2023)
3-51985867-G-A			Uncertain significance (Dec 11, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ACY1	protein_coding	protein_coding	ENST00000404366	14	14148

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
6.92e-9	0.686	125612	0	136	125748	0.000541

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.0951	237	241	0.983	0.0000158	2668
Missense in Polyphen		71	88.442	0.80278		1030
Synonymous	-0.441	98	92.6	1.06	0.00000597	812
Loss of Function	1.33	16	22.9	0.700	0.00000101	268

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00156	0.00155
Ashkenazi Jewish	0.00	0.00
East Asian	0.00229	0.00229
Finnish	0.0000960	0.0000924
European (Non-Finnish)	0.000459	0.000457
Middle Eastern	0.00229	0.00229
South Asian	0.000264	0.000261
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in the hydrolysis of N-acylated or N-acetylated amino acids (except L-aspartate). {ECO:0000269|PubMed:12933810}.
• Pathway: Arginine biosynthesis - Homo sapiens (human);Urea cycle and metabolism of amino groups;Biological oxidations;Metabolism;Methionine and cysteine metabolism;Urea cycle and metabolism of arginine, proline, glutamate, aspartate and asparagine;Aflatoxin activation and detoxification (Consensus)

Recessive Scores

• pRec: 0.277

Intolerance Scores

• rvis_EVS: 0.33
• rvis_percentile_EVS: 73.54

Haploinsufficiency Scores

• pHI: 0.0814
• hipred: N
• hipred_score: 0.132
• ghis: 0.456

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.984

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Acy1

Gene ontology

• Biological process: proteolysis;cellular amino acid metabolic process;xenobiotic metabolic process
• Cellular component: cytosol;extracellular exosome
• Molecular function: aminoacylase activity;protein binding;metallopeptidase activity;identical protein binding;metal ion binding