ACLY

ATP citrate lyase

Basic information

Region (hg38): 17:41866916-41930542

Links

ENSG00000131473 ∙ NCBI:47 ∙ OMIM:108728 ∙ HGNC:115 ∙ Uniprot:P53396 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

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

• Inborn genetic diseases (33 variants)
• not provided (7 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ACLY 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				1	4	5
missense			33	1		34
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding						0
Total	0	0	33	2	4

Variants in ACLY

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

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

Position	Type	Phenotype	Significance	ClinVar
17-41868765-A-G		not specified	Uncertain significance (Jan 10, 2023)
17-41869512-C-T		not specified	Uncertain significance (Dec 28, 2023)
17-41871731-C-T			Uncertain significance (-)
17-41871757-T-C		not specified	Uncertain significance (Feb 10, 2022)
17-41872039-A-G		not specified	Uncertain significance (Jan 06, 2023)
17-41872078-G-A			Uncertain significance (-)
17-41873894-G-C		not specified	Uncertain significance (Apr 20, 2023)
17-41878170-T-C		not specified	Uncertain significance (Aug 30, 2022)
17-41878178-G-A			Benign (May 14, 2018)
17-41878185-T-C		not specified	Uncertain significance (Nov 19, 2022)
17-41878893-T-C		not specified	Uncertain significance (Aug 08, 2023)
17-41883166-C-T		not specified	Uncertain significance (Mar 01, 2024)
17-41883201-C-T		not specified	Uncertain significance (Apr 25, 2022)
17-41884203-A-G		not specified	Uncertain significance (Jan 19, 2024)
17-41884264-A-G		not specified	Uncertain significance (Feb 17, 2024)
17-41884269-G-A		not specified	Uncertain significance (Oct 17, 2023)
17-41886139-T-C			Likely benign (Aug 16, 2018)
17-41886236-T-G		not specified	Uncertain significance (Apr 06, 2022)
17-41886297-G-C		not specified	Uncertain significance (May 04, 2023)
17-41887615-A-C		not specified	Uncertain significance (Nov 15, 2021)
17-41887630-T-A		not specified	Uncertain significance (Mar 17, 2023)
17-41887649-G-T		not specified	Uncertain significance (Dec 20, 2022)
17-41887691-C-T		not specified	Uncertain significance (Jan 03, 2022)
17-41892284-C-T			Uncertain significance (-)
17-41892379-G-A		not specified	Uncertain significance (Apr 12, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ACLY	protein_coding	protein_coding	ENST00000352035	28	63635

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0836	0.916	125686	0	62	125748	0.000247

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.28	437	678	0.645	0.0000401	7214
Missense in Polyphen		117	264.89	0.4417		2799
Synonymous	1.45	241	271	0.888	0.0000181	2183
Loss of Function	5.48	15	61.3	0.245	0.00000353	668

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000242	0.000242
Ashkenazi Jewish	0.000200	0.000198
East Asian	0.00416	0.00185
Finnish	0.00	0.00
European (Non-Finnish)	0.000177	0.000176
Middle Eastern	0.00416	0.00185
South Asian	0.00	0.00
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: ATP-citrate synthase is the primary enzyme responsible for the synthesis of cytosolic acetyl-CoA in many tissues. Has a central role in de novo lipid synthesis. In nervous tissue it may be involved in the biosynthesis of acetylcholine. {ECO:0000269|PubMed:23932781}.
• Pathway: Citrate cycle (TCA cycle) - Homo sapiens (human);Transfer of Acetyl Groups into Mitochondria;Glutaminolysis and Cancer;Sterol Regulatory Element-Binding Proteins (SREBP) signalling;TCA Cycle and Deficiency of Pyruvate Dehydrogenase complex (PDHc);Fatty Acid Biosynthesis;Amino Acid metabolism;Lipid Metabolism Pathway;Liver steatosis AOP;Pathways in clear cell renal cell carcinoma;Neutrophil degranulation;Metabolism of lipids;Fatty acyl-CoA biosynthesis;Citrate cycle;TCR;Innate Immune System;Immune System;Metabolism;Lysine degradation;Fatty acid metabolism;acetyl-CoA biosynthesis from citrate (Consensus)

Recessive Scores

• pRec: 0.543

Intolerance Scores

• loftool: 0.211
• rvis_EVS: -0.77
• rvis_percentile_EVS: 13.1

Haploinsufficiency Scores

• pHI: 0.720
• hipred: Y
• hipred_score: 0.704
• ghis: 0.586

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: K
• gene_indispensability_pred: E
• gene_indispensability_score: 0.958

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Acly
• 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)

Zebrafish Information Network

• Gene name: aclya
• Affected structure: motor neuron
• Phenotype tag: abnormal
• Phenotype quality: decreased length

Gene ontology

• Biological process: acetyl-CoA biosynthetic process;citrate metabolic process;oxaloacetate metabolic process;fatty acid biosynthetic process;cholesterol biosynthetic process;lipid biosynthetic process;coenzyme A metabolic process;positive regulation of cellular metabolic process;neutrophil degranulation;fatty-acyl-CoA biosynthetic process
• Cellular component: extracellular region;nucleoplasm;cytosol;plasma membrane;citrate lyase complex;membrane;azurophil granule lumen;extracellular exosome;ficolin-1-rich granule lumen
• Molecular function: ATP citrate synthase activity;protein binding;ATP binding;metal ion binding;cofactor binding