ACLY

ATP citrate lyase

Basic information

Region (hg38): 17:41866917-41930542

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.

not_specified (103 variants)
not_provided (17 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. These statistics are base on transcript: NM_000001096.3. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			5 clinvar	1 clinvar	4 clinvar	10
missense			107 clinvar	1 clinvar		108
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	112	2	4

Loading clinvar variants...

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