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

Gene Gene information from NCBI Gene database. Gene SNPs miRNA Gene ontology Other IDs Protein Pathways Associated diseases
Entrez ID	3158
Gene name	3-hydroxy-3-methylglutaryl-CoA synthase 2
Gene symbol	HMGCS2
Synonyms (NCBI Gene)	-
Chromosome	1
Chromosome location	1p12
Summary	The protein encoded by this gene belongs to the HMG-CoA synthase family. It is a mitochondrial enzyme that catalyzes the first reaction of ketogenesis, a metabolic pathway that provides lipid-derived energy for various organs during times of carbohydrate

Show/Hide all (16)

SNP ID	Visualize variation	Clinical significance	Consequence
rs28937320	C>T	Pathogenic	Coding sequence variant, missense variant
rs76773981	C>G,T	Uncertain-significance, conflicting-interpretations-of-pathogenicity	Missense variant, coding sequence variant
rs137852636	A>G	Pathogenic	Missense variant, coding sequence variant
rs137852638	C>T	Likely-pathogenic, pathogenic	Missense variant, intron variant, coding sequence variant
rs137852639	C>T	Conflicting-interpretations-of-pathogenicity	Missense variant, coding sequence variant
rs137852640	T>C	Pathogenic	Missense variant, coding sequence variant
rs138739620	G>A	Conflicting-interpretations-of-pathogenicity, uncertain-significance, likely-benign	Synonymous variant, coding sequence variant
rs142637231	G>A,T	Pathogenic, likely-benign, uncertain-significance, benign	Coding sequence variant, synonymous variant, stop gained
rs200607527	G>A	Uncertain-significance, likely-pathogenic	Missense variant, coding sequence variant
rs752626288	C>T	Pathogenic	Coding sequence variant, missense variant
rs764706394	C>G	Likely-pathogenic	Splice donor variant
rs796051979	A>T	Likely-pathogenic	Splice donor variant, intron variant
rs886045207	G>A	Conflicting-interpretations-of-pathogenicity	Synonymous variant, intron variant, coding sequence variant
rs1553240165	T>-	Pathogenic	Splice acceptor variant
rs1553240525	A>-	Pathogenic	Intron variant, frameshift variant, coding sequence variant
rs1571037298	A>G	Pathogenic	Splice donor variant, intron variant

Show/Hide all (13)

miRTarBase ID	miRNA	Experiments	Reference
MIRT734829	hsa-miR-194-5p	qRT-PCR	31885789
MIRT734917	hsa-miR-425-5p	Western blottingqRT-PCR	32742270
MIRT2243607	hsa-miR-1289	CLIP-seq
MIRT2243608	hsa-miR-1825	CLIP-seq
MIRT2243609	hsa-miR-199a-5p	CLIP-seq
MIRT2243610	hsa-miR-199b-5p	CLIP-seq
MIRT2243611	hsa-miR-3198	CLIP-seq
MIRT2243612	hsa-miR-4294	CLIP-seq
MIRT2243613	hsa-miR-4309	CLIP-seq
MIRT2243614	hsa-miR-873	CLIP-seq
MIRT2546791	hsa-miR-4314	CLIP-seq
MIRT2546792	hsa-miR-4778-5p	CLIP-seq
MIRT2546793	hsa-miR-630	CLIP-seq

Show/Hide all (61)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001822	Process	Kidney development	IEA
GO:0001889	Process	Liver development	IEA
GO:0004421	Function	Hydroxymethylglutaryl-CoA synthase activity	IBA
GO:0004421	Function	Hydroxymethylglutaryl-CoA synthase activity	IEA
GO:0004421	Function	Hydroxymethylglutaryl-CoA synthase activity	IMP	23751782
GO:0004421	Function	Hydroxymethylglutaryl-CoA synthase activity	ISS
GO:0004421	Function	Hydroxymethylglutaryl-CoA synthase activity	TAS
GO:0005739	Component	Mitochondrion	HTP	34800366
GO:0005739	Component	Mitochondrion	IBA
GO:0005739	Component	Mitochondrion	IDA
GO:0005739	Component	Mitochondrion	IEA
GO:0005739	Component	Mitochondrion	TAS	7851882
GO:0005759	Component	Mitochondrial matrix	IEA
GO:0005759	Component	Mitochondrial matrix	TAS
GO:0006084	Process	Acetyl-CoA metabolic process	IBA
GO:0006084	Process	Acetyl-CoA metabolic process	IEA
GO:0006084	Process	Acetyl-CoA metabolic process	IMP	23751782
GO:0006629	Process	Lipid metabolic process	IEA
GO:0006694	Process	Steroid biosynthetic process	IEA
GO:0006695	Process	Cholesterol biosynthetic process	IEA
GO:0007494	Process	Midgut development	IEA
GO:0007584	Process	Response to nutrient	IEA
GO:0008202	Process	Steroid metabolic process	IEA
GO:0008203	Process	Cholesterol metabolic process	IEA
GO:0008299	Process	Isoprenoid biosynthetic process	IEA
GO:0009266	Process	Response to temperature stimulus	IEA
GO:0009410	Process	Response to xenobiotic stimulus	IEA
GO:0009617	Process	Response to bacterium	IEA
GO:0010038	Process	Response to metal ion	IEA
GO:0010142	Process	Farnesyl diphosphate biosynthetic process, mevalonate pathway	IBA
GO:0010142	Process	Farnesyl diphosphate biosynthetic process, mevalonate pathway	IEA
GO:0016126	Process	Sterol biosynthetic process	IEA
GO:0016740	Function	Transferase activity	IEA
GO:0016746	Function	Acyltransferase activity	IEA
GO:0030324	Process	Lung development	IEA
GO:0032868	Process	Response to insulin	IEA
GO:0032869	Process	Cellular response to insulin stimulus	IEA
GO:0032870	Process	Cellular response to hormone stimulus	IEA
GO:0033555	Process	Multicellular organismal response to stress	IEA
GO:0033574	Process	Response to testosterone	IEA
GO:0033762	Process	Response to glucagon	IEA
GO:0034014	Process	Response to triglyceride	IEA
GO:0034284	Process	Response to monosaccharide	IEA
GO:0034696	Process	Response to prostaglandin F	IEA
GO:0042594	Process	Response to starvation	IEA
GO:0042802	Function	Identical protein binding	IDA	20346956
GO:0043434	Process	Response to peptide hormone	IEA
GO:0045471	Process	Response to ethanol	IEA
GO:0046951	Process	Ketone body biosynthetic process	IEA
GO:0046951	Process	Ketone body biosynthetic process	IMP	23751782
GO:0046951	Process	Ketone body biosynthetic process	TAS
GO:0051384	Process	Response to glucocorticoid	IEA
GO:0051591	Process	Response to cAMP	IEA
GO:0060416	Process	Response to growth hormone	IEA
GO:0060612	Process	Adipose tissue development	IEA
GO:0070542	Process	Response to fatty acid	IEA
GO:0070543	Process	Response to linoleic acid	IEA
GO:0071222	Process	Cellular response to lipopolysaccharide	IEA
GO:0071230	Process	Cellular response to amino acid stimulus	IEA
GO:0071385	Process	Cellular response to glucocorticoid stimulus	IEA
GO:0071398	Process	Cellular response to fatty acid	IEA

MIM	HGNC	e!Ensembl
600234	5008	ENSG00000134240

P54868

Protein name

Hydroxymethylglutaryl-CoA synthase, mitochondrial (HMG-CoA synthase) (EC 2.3.3.10) (3-hydroxy-3-methylglutaryl coenzyme A synthase)

Protein function

Catalyzes the first irreversible step in ketogenesis, condensing acetyl-CoA to acetoacetyl-CoA to form HMG-CoA, which is converted by HMG-CoA reductase (HMGCR) into mevalonate. {ECO:0000269|PubMed:11228257, ECO:0000269|PubMed:23751782, ECO:00002

PDB

2WYA

Family and domains

Pfam

Accession	ID	Position in sequence	Description	Type
PF01154	HMG_CoA_synt_N	50 → 223	Hydroxymethylglutaryl-coenzyme A synthase N terminal	Domain
PF08540	HMG_CoA_synt_C	224 → 506	Hydroxymethylglutaryl-coenzyme A synthase C terminal	Domain

Tissue specificity

TISSUE SPECIFICITY: Expression in liver is 200-fold higher than in any other tissue. Low expression in colon, kidney, testis, and pancreas. Very low expression in heart and skeletal muscle (PubMed:16940161, PubMed:21952825, PubMed:7893153). Not detected i

Sequence

MQRLLTPVKRILQLTRAVQETSLTPARLLPVAHQRFSTASAVPLAKTDTWPKDVGILALE
VYFPAQYVDQTDLEKYNNVEAGKYTVGLGQTRMGFCSVQEDINSLCLTVVQRLMERIQLP
WDSVGRLEVGTETIIDKSKAVKTVLMELFQDSGNTDIEGIDTTNACYGGTASLFNAANWM
ESSSWDGRYAMVVCGDIAVYPSGNARPTGGAGAVAMLIGPKAPLALERGLRGTHMENVYD
FYKPNLASEYPIVDGKLSIQCYLRALDRCYTSYRKKIQNQWKQAGSDRPFTLDDLQYMIF
HTPFCKMVQKSLARLMFNDFLSASSDTQTSLYKGLEAFGGLKLEDTYTNKDLDKALLKAS
QDMFDKKTKASLYLSTHNGNMYTSSLYGCLASLLSHHSAQELAGSRIGAFSYGSGLAASF
FSFRVSQDAAPGSPLDKLVSSTSDLPKRLASRKCVSPEEFTEIMNQREQFYHKVNFSPPG
DTNSLFPGTWYLERVDEQHRRKYARRPV

Sequence length

508

Interactions

View interactions

	KEGG		Reactome
	Valine, leucine and isoleucine degradation Butanoate metabolism Terpenoid backbone biosynthesis Metabolic pathways PPAR signaling pathway		PPARA activates gene expression Synthesis of Ketone Bodies

Evidence Score: ★☆☆☆☆ Gene-disease association found in Text Mining only ★★☆☆☆ Found in Text Mining and Unknown/Other Associations ★★★☆☆ Reported in Unknown/Other Associations across ≥2 Sources ★★★★☆ ClinVar: Pathogenic/Likely Pathogenic (<5 Variants) ★★★★★ ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Show/Hide Causal Diseases (3)

Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Causal Diseases associated with Pathogenic or Likely Pathogenic variants in ClinVar
3-hydroxy-3-methylglutaryl-CoA synthase deficiency	Likely pathogenic; Pathogenic	rs145838142, rs763531478, rs751009381, rs2101283564, rs2101248147, rs1454719802, rs1652885850, rs2101283660, rs1652955748, rs587688416, rs1406920400, rs779321975, rs762211049, rs111313628, rs2101273359 View all (26 more)	RCV002647318 RCV003002049 RCV005206526 RCV001449675 RCV001530187 View all (36 more)	★★★★★ ★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Colon adenocarcinoma	Pathogenic	rs587603096	RCV005913576	★★★★★ ★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
HMGCS2-related disorder	Pathogenic	rs137852637	RCV003407311	★★★★★ ★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Show/Hide Unknown Diseases (9)

Phenotype Name	Clinical Significance	Source	Evidence Score
Unknown / Other Associations ClinVar entries with uncertain/conflicting evidence, and associations from other databases (OMIM, Orphanet, GWAS, etc.) where the gene is not established as causal.
COLONIC NEOPLASMS	—	CTD	★★★★★ ★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Colorectal cancer	Uncertain significance	ClinVar	★★★★★ ★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CONGESTIVE HEART FAILURE	—	Disgenet	★★★★★ ★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEART FAILURE	—	CTD, Disgenet CTD, Disgenet	★★★★★ ★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hepatocellular carcinoma	Benign	ClinVar	★★★★★ ★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MOUTH NEOPLASMS	—	CTD	★★★★★ ★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MYOCARDIAL ISCHEMIA	—	CTD, Disgenet CTD, Disgenet	★★★★★ ★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ovarian serous cystadenocarcinoma	Likely benign	ClinVar	★★★★★ ★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Sarcoma	Benign	ClinVar	★★★★★ ★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Show/Hide Text Mining Associations (59)

Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Associations from Text Mining Disease associations identified through text mining
3-Hydroxy-3-Methylglutaryl-CoA Synthase 2 Deficiency	3-hydroxy-3-methylglutaryl-CoA synthase deficiency	CLINGEN_DG	11228257, 11479731, 12072887, 12647205, 21502324, 23751782, 25511235, 7851882		★★★★★ ★☆☆☆☆ Found in Text Mining only
3-Hydroxy-3-Methylglutaryl-CoA Synthase 2 Deficiency	3-hydroxy-3-methylglutaryl-CoA synthase deficiency	UNIPROT_DG	11228257, 11479731, 12647205		★★★★★ ★☆☆☆☆ Found in Text Mining only
3-Hydroxy-3-Methylglutaryl-CoA Synthase 2 Deficiency	3-hydroxy-3-methylglutaryl-CoA synthase deficiency	ORPHANET_DG	11479731, 23751782		★★★★★ ★☆☆☆☆ Found in Text Mining only
3-Hydroxy-3-Methylglutaryl-CoA Synthase 2 Deficiency	3-hydroxy-3-methylglutaryl-CoA synthase deficiency	CLINVAR_DG	11479731, 12072887, 20346956, 23751782, 25511235		★★★★★ ★☆☆☆☆ Found in Text Mining only
3-Hydroxy-3-Methylglutaryl-CoA Synthase 2 Deficiency	3-hydroxy-3-methylglutaryl-CoA synthase deficiency	BEFREE	25111118		★★★★★ ★☆☆☆☆ Found in Text Mining only
3-Hydroxy-3-Methylglutaryl-CoA Synthase 2 Deficiency	3-hydroxy-3-methylglutaryl-CoA synthase deficiency	GENOMICS_ENGLAND_DG	27604308, 9337379		★★★★★ ★☆☆☆☆ Found in Text Mining only
3-Hydroxy-3-Methylglutaryl-CoA Synthase 2 Deficiency	3-hydroxy-3-methylglutaryl-CoA synthase deficiency	CTD_human_DG			★★★★★ ★☆☆☆☆ Found in Text Mining only
3-hydroxy-3-methylglutaryl-CoA synthase deficiency	3-hydroxy-3-methylglutaryl-CoA synthase deficiency	Orphanet			★★★★★ ★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Alzheimer Disease	Alzheimer disease	Pubtator	17387528	Associate	★★★★★ ★☆☆☆☆ Found in Text Mining only
Aortic Valve Disease	Aortic valve disease	Pubtator	27250500	Associate	★★★★★ ★☆☆☆☆ Found in Text Mining only
Breast Carcinoma	Breast Carcinoma	BEFREE	23082721		★★★★★ ★☆☆☆☆ Found in Text Mining only
Breast Neoplasms	Breast neoplasm	Pubtator	25389781	Associate	★★★★★ ★☆☆☆☆ Found in Text Mining only
Carcinoma	Carcinoma	BEFREE	16940161		★★★★★ ★☆☆☆☆ Found in Text Mining only
Carcinoma Hepatocellular	Hepatocellular carcinoma	Pubtator	32298312, 36432116, 36936948, 37567069	Associate	★★★★★ ★☆☆☆☆ Found in Text Mining only
Carcinoma Renal Cell	Renal cell carcinoma	Pubtator	31886185	Associate	★★★★★ ★☆☆☆☆ Found in Text Mining only
Carcinoma Renal Cell	Renal cell carcinoma	Pubtator	37670031	Inhibit	★★★★★ ★☆☆☆☆ Found in Text Mining only
Carcinoma, Ovarian Epithelial	Ovarian Epithelial carcinoma	BEFREE	29997262		★★★★★ ★☆☆☆☆ Found in Text Mining only
Cardiomegaly	Cardiomegaly	Pubtator	30567295	Associate	★★★★★ ★☆☆☆☆ Found in Text Mining only
Celiac Disease	Celiac disease	Pubtator	20454521	Associate	★★★★★ ★☆☆☆☆ Found in Text Mining only
Cirrhosis	Cirrhosis	BEFREE	31779269		★★★★★ ★☆☆☆☆ Found in Text Mining only
Colitis Ulcerative	Ulcerative colitis	Pubtator	36419192, 37457727	Associate	★★★★★ ★☆☆☆☆ Found in Text Mining only
Colon Carcinoma	Colon Carcinoma	BEFREE	16940161		★★★★★ ★☆☆☆☆ Found in Text Mining only
Colonic Neoplasms	Colonic Neoplasms	CTD_human_DG	15059925, 27816970		★★★★★ ★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Colonic Neoplasms	Colonic neoplasm	Pubtator	16940161	Inhibit	★★★★★ ★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Colorectal Carcinoma	Colorectal Cancer	BEFREE	27816970, 28546759, 31355161		★★★★★ ★☆☆☆☆ Found in Text Mining only
Colorectal Neoplasms	Colorectal neoplasm	Pubtator	16940161, 31949199	Associate	★★★★★ ★☆☆☆☆ Found in Text Mining only
Colorectal Neoplasms	Colorectal neoplasm	Pubtator	31355161	Inhibit	★★★★★ ★☆☆☆☆ Found in Text Mining only
Colorectal Neoplasms	Colorectal neoplasm	Pubtator	32155177	Stimulate	★★★★★ ★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus	Diabetes Mellitus	BEFREE	30460485		★★★★★ ★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus, Insulin-Dependent	Diabetes Mellitus	BEFREE	28676675		★★★★★ ★☆☆☆☆ Found in Text Mining only
Diabetic Cardiomyopathies	Diabetic cardiomyopathy	Pubtator	35506308, 38160540	Associate	★★★★★ ★☆☆☆☆ Found in Text Mining only
Dysautonomia, Familial	Dysautonomia	BEFREE	31785270		★★★★★ ★☆☆☆☆ Found in Text Mining only
Erectile dysfunction	Erectile Dysfunction	BEFREE	30460485		★★★★★ ★☆☆☆☆ Found in Text Mining only
Esophageal Squamous Cell Carcinoma	Esophageal squamous cell carcinoma	Pubtator	24551190	Associate	★★★★★ ★☆☆☆☆ Found in Text Mining only
Hereditary Breast and Ovarian Cancer Syndrome	Hereditary breast and ovarian cancer syndrome	Pubtator	25389781	Associate	★★★★★ ★☆☆☆☆ Found in Text Mining only
Hypertensive disease	Hypertension	GWASCAT_DG	29523524		★★★★★ ★☆☆☆☆ Found in Text Mining only
Hypoglycemia	Hypoglycemia	HPO_DG			★★★★★ ★☆☆☆☆ Found in Text Mining only
Inflammatory Bowel Diseases	Inflammatory bowel disease	Pubtator	37457727	Inhibit	★★★★★ ★☆☆☆☆ Found in Text Mining only
Lip and Oral Cavity Carcinoma	Lip and Oral Cavity Carcinoma	BEFREE	27816970		★★★★★ ★☆☆☆☆ Found in Text Mining only
Liver carcinoma	Liver carcinoma	BEFREE	28867541, 31779269		★★★★★ ★☆☆☆☆ Found in Text Mining only
Liver Cirrhosis	Liver Cirrhosis	BEFREE	31779269		★★★★★ ★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of breast	Breast Cancer	BEFREE	23082721		★★★★★ ★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of liver	Liver Cancer	BEFREE	31779269		★★★★★ ★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of mouth	Malignant neoplasm of mouth	BEFREE	27816970		★★★★★ ★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of mouth	Malignant neoplasm of mouth	CTD_human_DG	27816970		★★★★★ ★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of prostate	Prostate cancer	BEFREE	28546759, 31176575		★★★★★ ★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	27816970, 31176575		★★★★★ ★☆☆☆☆ Found in Text Mining only
Malignant tumor of colon	Colonic Neoplasms	CTD_human_DG	15059925, 27816970		★★★★★ ★☆☆☆☆ Found in Text Mining only
Malignant tumor of colon	Colonic Neoplasms	BEFREE	16940161		★★★★★ ★☆☆☆☆ Found in Text Mining only
Mouth Neoplasms	Mouth Neoplasms	CTD_human_DG	27816970		★★★★★ ★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Myocardial Ischemia	Myocardial Ischemia	CTD_human_DG	16214533		★★★★★ ★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Neoplasms	Neoplasms	BEFREE	23082721, 25929810, 28867541, 31176575		★★★★★ ★☆☆☆☆ Found in Text Mining only
Prostate carcinoma	Prostate cancer	BEFREE	28546759, 31176575		★★★★★ ★☆☆☆☆ Found in Text Mining only
Prostatic Neoplasms	Prostatic neoplasm	Pubtator	23443136, 31980029, 33780364	Associate	★★★★★ ★☆☆☆☆ Found in Text Mining only
Rectal Carcinoma	Rectal Carcinoma	BEFREE	25929810		★★★★★ ★☆☆☆☆ Found in Text Mining only
Rectal Neoplasms	Rectal Neoplasms	BEFREE	16940161		★★★★★ ★☆☆☆☆ Found in Text Mining only
Sjogren's Syndrome	Sjogren syndrome	Pubtator	29504848	Associate	★★★★★ ★☆☆☆☆ Found in Text Mining only
Squamous cell carcinoma of esophagus	Esophagus Neoplasm	BEFREE	24551190, 28546759		★★★★★ ★☆☆☆☆ Found in Text Mining only
Urinary Bladder Neoplasms	Urinary bladder neoplasms	Pubtator	33753712	Associate	★★★★★ ★☆☆☆☆ Found in Text Mining only

HMGCS2 (3-hydroxy-3-methylglutaryl-CoA synthase 2)