Gene Details | GeDiPNet - Complete Gene Info, Disease Associations & Pathways

Gene Gene SNPs miRNA Gene ontology Other IDs Protein Pathways Associated diseases
Entrez ID Entrez Gene ID - the GENE ID in NCBI Gene database.	3155
Gene name Gene Name - the full gene name approved by the HGNC.	3-hydroxy-3-methylglutaryl-CoA lyase
Gene symbol Gene Symbol - the official gene symbol approved by the HGNC.	HMGCL
Synonyms (NCBI Gene) Gene synonyms aliases	HL, HMGCL1
Chromosome Chromosome number	1
Chromosome location Chromosomal Location - indicates the cytogenetic location of the gene or region on the chromosome.	1p36.11
Summary Summary of gene provided in NCBI Entrez Gene.	The protein encoded by this gene belongs to the HMG-CoA lyase family. It is a mitochondrial enzyme that catalyzes the final step of leucine degradation and plays a key role in ketone body formation. Mutations in this gene are associated with HMG-CoA lyase

Show/Hide all(19)

SNP ID	Visualize variation	Clinical significance	Consequence
rs112508527	A>C,G,T	Likely-benign, likely-pathogenic	Synonymous variant, stop gained, coding sequence variant, intron variant
rs121964997	C>T	Pathogenic	Missense variant, coding sequence variant
rs121964998	C>T	Pathogenic	Missense variant, coding sequence variant
rs200189529	G>A,C	Likely-pathogenic, likely-benign	Stop gained, intron variant, coding sequence variant, synonymous variant
rs568718845	T>C	Likely-pathogenic, uncertain-significance	Intron variant
rs727503963	T>C,G	Pathogenic-likely-pathogenic, pathogenic	Coding sequence variant, missense variant
rs752137615	AG>-	Pathogenic, likely-pathogenic	Frameshift variant, coding sequence variant
rs760106433	G>T	Pathogenic, uncertain-significance	Coding sequence variant, missense variant
rs763494292	C>A	Pathogenic	Stop gained, coding sequence variant
rs764264834	GA>-	Pathogenic	Frameshift variant, intron variant, coding sequence variant
rs765198174	G>A,T	Likely-pathogenic, likely-benign	Stop gained, synonymous variant, coding sequence variant
rs770225915	G>A	Likely-pathogenic	Stop gained, coding sequence variant
rs890995574	G>A	Likely-pathogenic	Coding sequence variant, stop gained
rs1184002840	G>-	Likely-pathogenic	Frameshift variant, coding sequence variant
rs1425615804	A>T	Likely-pathogenic	Stop gained, coding sequence variant
rs1553131955	T>C	Likely-pathogenic	Splice acceptor variant
rs1553132209	A>T	Pathogenic	Intron variant, coding sequence variant, missense variant
rs1553132520	T>-	Likely-pathogenic	Intron variant, frameshift variant, coding sequence variant
rs1553133042	->G	Likely-pathogenic	Frameshift variant, coding sequence variant

Show/Hide all(9)

miRTarBase ID	miRNA	Experiments	Reference
MIRT044352	hsa-miR-106b-5p	CLASH	23622248
MIRT2011329	hsa-miR-1976	CLIP-seq
MIRT2011330	hsa-miR-3160-5p	CLIP-seq
MIRT2011331	hsa-miR-4268	CLIP-seq
MIRT2011332	hsa-miR-4722-3p	CLIP-seq
MIRT2011333	hsa-miR-938	CLIP-seq
MIRT2243541	hsa-miR-4716-5p	CLIP-seq
MIRT2243542	hsa-miR-4749-3p	CLIP-seq
MIRT2243543	hsa-miR-587	CLIP-seq

Show/Hide all(32)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000287	Function	Magnesium ion binding	IDA	9200711
GO:0003824	Function	Catalytic activity	IEA
GO:0004419	Function	Hydroxymethylglutaryl-CoA lyase activity	IBA
GO:0004419	Function	Hydroxymethylglutaryl-CoA lyase activity	IDA	8027038, 8670134, 9200711, 9869651, 12464283, 22847177, 22865860
GO:0004419	Function	Hydroxymethylglutaryl-CoA lyase activity	IEA
GO:0005198	Function	Structural molecule activity	IDA	12464283
GO:0005739	Component	Mitochondrion	HTP	34800366
GO:0005739	Component	Mitochondrion	IBA
GO:0005739	Component	Mitochondrion	IDA	9869651
GO:0005739	Component	Mitochondrion	IEA
GO:0005759	Component	Mitochondrial matrix	IEA
GO:0005759	Component	Mitochondrial matrix	NAS	8102917
GO:0005759	Component	Mitochondrial matrix	TAS
GO:0005777	Component	Peroxisome	IDA	9869651, 12464283
GO:0005777	Component	Peroxisome	IEA
GO:0005782	Component	Peroxisomal matrix	TAS
GO:0005829	Component	Cytosol	TAS
GO:0006552	Process	L-leucine catabolic process	IBA
GO:0006552	Process	L-leucine catabolic process	NAS	9200711
GO:0006552	Process	L-leucine catabolic process	TAS	8027038
GO:0006629	Process	Lipid metabolic process	IDA	8027038
GO:0006629	Process	Lipid metabolic process	IEA
GO:0007005	Process	Mitochondrion organization	IEA
GO:0016829	Function	Lyase activity	IEA
GO:0016833	Function	Oxo-acid-lyase activity	IEA
GO:0030145	Function	Manganese ion binding	IDA	9200711
GO:0032991	Component	Protein-containing complex	IDA	12464283
GO:0046872	Function	Metal ion binding	IDA	16330550
GO:0046872	Function	Metal ion binding	IEA
GO:0046951	Process	Ketone body biosynthetic process	IBA
GO:0046951	Process	Ketone body biosynthetic process	IDA	9200711, 22847177, 22865860
GO:0046951	Process	Ketone body biosynthetic process	IEA

MIM	HGNC	e!Ensembl
613898	5005	ENSG00000117305

Protein

UniProt ID

P35914

Protein name

Hydroxymethylglutaryl-CoA lyase, mitochondrial (HL) (HMG-CoA lyase) (EC 4.1.3.4) (3-hydroxy-3-methylglutarate-CoA lyase)

Protein function

Mitochondrial 3-hydroxy-3-methylglutaryl-CoA lyase that catalyzes a cation-dependent cleavage of (S)-3-hydroxy-3-methylglutaryl-CoA into acetyl-CoA and acetoacetate, a key step in ketogenesis. Terminal step in leucine catabolism. Ketone bodies (

PDB

2CW6 , 3MP3 , 3MP4 , 3MP5

Family and domains

Pfam

Accession	ID	Position in sequence	Description	Type
PF00682	HMGL-like	32 → 306	HMGL-like	Domain

Tissue specificity

TISSUE SPECIFICITY: Highest expression in liver. Expressed in pancreas, kidney, intestine, testis, fibroblasts and lymphoblasts. Very low expression in brain and skeletal muscle. The relative expression of isoform 2 (at mRNA level) is highest in heart (30

Sequence

MAAMRKALPRRLVGLASLRAVSTSSMGTLPKRVKIVEVGPRDGLQNEKNIVSTPVKIKLI
DMLSEAGLSVIETTSFVSPKWVPQMGDHTEVLKGIQKFPGINYPVLTPNLKGFEAAVAAG
AKEVVIFGAASELFTKKNINCSIEESFQRFDAILKAAQSANISVRGYVSCALGCPYEGKI
SPAKVAEVTKKFYSMGCYEISLGDTIGVGTPGIMKDMLSAVMQEVPLAALAVHCHDTYGQ
ALANTLMALQMGVSVVDSSVAGLGGCPYAQGASGNLATEDLVYMLEGLGIHTGVNLQKLL
EAGNFICQALNRKTSSKVAQATCKL

Sequence length

325

Interactions

View interactions

	KEGG		Reactome
	Valine, leucine and isoleucine degradation Butanoate metabolism Metabolic pathways Peroxisome		Synthesis of Ketone Bodies Peroxisomal protein import

Show/Hide Causal Diseases (2)

Disease merge term	Disease name	dbSNP ID	References
Causal Diseases caused by PATHOGENIC or LIKELY PATHOGENIC variants from ClinVar only
deficiency of hydroxymethylglutaryl-coa lyase	Deficiency of hydroxymethylglutaryl-CoA lyase	rs112508527, rs121964998, rs200189529, rs786205431, rs890995574, rs1553132520, rs727503963, rs1553133042, rs770225915, rs1302190999, rs763494292, rs1425615804, rs1324641233, rs760106433, rs1184002840 View all (10 more)	N/A
Long Chain 3-Hydroxyacyl-CoA Dehydrogenase Deficiency	long chain 3-hydroxyacyl-coa dehydrogenase deficiency	rs727503963, rs770225915, rs764264834, rs1409716731, rs1212444447, rs121964997	N/A

Show/Hide Unknown Diseases (1)

Disease merge term	Disease name	Evidence	References	Source
Unknown Includes: (1) ClinVar NON-pathogenic variants (Uncertain, Benign, Conflicting, VUS), (2) GenCC associations, (3) GWAS associations, (4) CBGDA evidence-based associations. NOTE: Diseases with pathogenic evidence are excluded to avoid conflicts.
Anxiety Disorder	Anxiety	N/A	N/A	GWAS

Show/Hide Text Mining Associations (14)

Disease Name	Relationship Type	References
Associations from Text Mining Disease associations identified through Pubtator
3 Hydroxy 3 Methylglutaryl CoA Lyase Deficiency	Associate	12874287, 17173698, 20532825, 32059735, 8798725
3 Hydroxy 3 Methylglutaryl CoA Lyase Deficiency	Inhibit	17173698
Colonic Neoplasms	Associate	34564978
Genetic Diseases Inborn	Associate	16330546
Glioblastoma	Stimulate	38069906
Glioma	Associate	38069906
Hypoglycemia	Associate	16330546
Leukemia Hairy Cell	Stimulate	26145173
Melanoma	Stimulate	26145173
Metabolic Diseases	Associate	16330546
Nasopharyngeal Carcinoma	Associate	28931870
Neoplasm Metastasis	Associate	26537687, 28931870
Neoplasms	Associate	23082721, 26145173, 26537687, 38069906
Prostatic Neoplasms	Associate	23443136

HMGCL (3-hydroxy-3-methylglutaryl-CoA lyase)