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

251

Show/Hide Causal Diseases (3)

Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
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 RCV001530188 RCV001543156 RCV001794520 RCV001794521 RCV001794522 RCV001794523 RCV001794525 RCV001794526 RCV001794527 RCV001794528 RCV001794529 RCV001839069 RCV001994741 RCV001921804 RCV003065375 RCV003509509 RCV000009839 RCV000009840 RCV000009841 RCV000009842 RCV000009844 RCV001543155 RCV003391156 RCV003828480 RCV000805374 RCV002525119 RCV000578418 RCV000578257 RCV000721978 RCV000797984 RCV001255221 RCV001065916 RCV001065915 RCV001090000 RCV001089999 RCV001170041
Colon adenocarcinoma	Pathogenic	rs587603096	RCV005913576
HMGCS2-related disorder	Pathogenic	rs137852637	RCV003407311

Show/Hide Unknown Diseases (4)

Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
Unknown Diseases with uncertain, conflicting, or no pathogenic evidence in ClinVar
Colorectal cancer	Uncertain significance	rs771289268	RCV005924142
Hepatocellular carcinoma	Benign	rs667246	RCV005921850
Ovarian serous cystadenocarcinoma	Likely benign	rs150029111	RCV005917853
Sarcoma	Benign	rs2241868	RCV005922177

Show/Hide Text Mining Associations (34)

Disease Name	Relationship Type	References
Associations from Text MiningDisease associations identified through Pubtator
3 Hydroxy 3 Methylglutaryl CoA Synthase 2 Deficiency	Associate	31597564, 32969201, 40004108
Alzheimer Disease	Associate	17387528
Aortic Valve Disease	Associate	27250500
Breast Neoplasms	Associate	25389781
Carcinoma Hepatocellular	Associate	32298312, 36432116, 36936948, 37567069
Carcinoma Renal Cell	Associate	31886185
Carcinoma Renal Cell	Inhibit	37670031
Cardiomegaly	Associate	30567295
Celiac Disease	Associate	20454521
Colitis Ulcerative	Associate	36419192, 37457727
Colonic Neoplasms	Inhibit	16940161
Colorectal Neoplasms	Associate	16940161, 31949199
Colorectal Neoplasms	Inhibit	31355161
Colorectal Neoplasms	Stimulate	32155177
Diabetic Cardiomyopathies	Associate	35506308, 38160540
Drug Related Side Effects and Adverse Reactions	Stimulate	36432116
Esophageal Squamous Cell Carcinoma	Associate	24551190
Hereditary Breast and Ovarian Cancer Syndrome	Associate	25389781
Infections	Stimulate	27744449
Inflammation	Inhibit	35506308
Inflammation	Associate	37457727
Inflammatory Bowel Diseases	Inhibit	37457727
Leukemic Infiltration	Associate	33753712
Microsatellite Instability	Inhibit	35909892
Mitral Valve Insufficiency	Associate	27250500, 30567295
Muscular Diseases	Associate	30567295
Neoplasm Metastasis	Associate	31355161
Neoplasms	Inhibit	16940161
Neoplasms	Associate	23082721, 25929810, 31355161, 33828141, 37670031
Poroma	Associate	25389781
Prostatic Neoplasms	Associate	23443136, 31980029, 33780364
Rectal Neoplasms	Associate	25929810
Sjogren's Syndrome	Associate	29504848
Urinary Bladder Neoplasms	Associate	33753712

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