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

Gene

• Entrez ID: 3158
• Gene name: 3-hydroxy-3-methylglutaryl-CoA synthase 2
• Gene symbol: HMGCS2
• Synonyms: -
• 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

SNPs

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

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT734829	hsa-miR-194-5p	qRT-PCR	31885789
MIRT734917	hsa-miR-425-5p	Western blotting, qRT-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

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0004421	Function	Hydroxymethylglutaryl-CoA synthase activity	IBA	21873635
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	IBA	21873635
GO:0005739	Component	Mitochondrion	IDA
GO:0005759	Component	Mitochondrial matrix	TAS
GO:0006084	Process	Acetyl-CoA metabolic process	IBA	21873635
GO:0006084	Process	Acetyl-CoA metabolic process	IMP	23751782
GO:0006695	Process	Cholesterol biosynthetic process	IEA
GO:0010142	Process	Farnesyl diphosphate biosynthetic process, mevalonate pathway	IBA	21873635
GO:0019216	Process	Regulation of lipid metabolic process	TAS
GO:0042802	Function	Identical protein binding	IDA	20346956
GO:0046951	Process	Ketone body biosynthetic process	IMP	23751782
GO:0046951	Process	Ketone body biosynthetic process	TAS

Other IDs

• MIM: 600234
• HGNC: 5008
• e!Ensembl: ENSG00000134240

Protein

• UniProt ID: 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

• Sequence:

  MQRLLTPVKRILQLTRAVQETSLTPARLLPVAHQRFSTASAVPLAKTDTWPKDVGILALE
  VYFPAQYVDQTDLEKYNNVEAGKYTVGLGQTRMGFCSVQEDINSLCLTVVQRLMERIQLP
  WDSVGRLEVGTETIIDKSKAVKTVLMELFQDSGNTDIEGIDTTNACYGGTASLFNAANWM
  ESSSWDGRYAMVVCGDIAVYPSGNARPTGGAGAVAMLIGPKAPLALERGLRGTHMENVYD
  FYKPNLASEYPIVDGKLSIQCYLRALDRCYTSYRKKIQNQWKQAGSDRPFTLDDLQYMIF
  HTPFCKMVQKSLARLMFNDFLSASSDTQTSLYKGLEAFGGLKLEDTYTNKDLDKALLKAS
  QDMFDKKTKASLYLSTHNGNMYTSSLYGCLASLLSHHSAQELAGSRIGAFSYGSGLAASF
  FSFRVSQDAAPGSPLDKLVSSTSDLPKRLASRKCVSPEEFTEIMNQREQFYHKVNFSPPG
  DTNSLFPGTWYLERVDEQHRRKYARRPV

• Sequence length: 508

Pathways

KEGG:

Valine, leucine and isoleucine degradation
Butanoate metabolism
Terpenoid backbone biosynthesis
Metabolic pathways
PPAR signaling pathway

Reactome:

PPARA activates gene expression
Synthesis of Ketone Bodies

Associated diseases

Causal
Disease name	Disease term	dbSNP ID	References
3-hydroxy-3-methylglutaryl-coa synthase deficiency	3-Hydroxy-3-Methylglutaryl-CoA Synthase 2 Deficiency, 3-hydroxy-3-methylglutaryl-CoA synthase deficiency	rs137852636, rs137852637, rs137852638, rs137852639, rs137852640, rs796051979, rs142637231, rs372079931, rs752626288, rs1553240165, rs1553240525, rs764706394, rs1571037298, rs776399237, rs587603096, rs1652875135, rs1653132966	12647205, 11479731, 11228257, 25511235, 27604308, 23751782, 9337379, 12072887, 21502324, 7851882, 20346956
Colonic neoplasms	Malignant tumor of colon, Colonic Neoplasms	rs267607789, rs774277300, rs781222233, rs1060502734, rs1060503333, rs1339238483	15059925, 27816970, 27816970, 15059925
Hypertension	Hypertensive disease	rs13306026, rs13333226	29523524

Unknown
Disease name	Disease term	dbSNP ID	References
Hypoglycemia	Hypoglycemia
Mouth neoplasms	Mouth Neoplasms		27816970
Malignant neoplasm of mouth	Malignant neoplasm of mouth		27816970
Myocardial ischemia	Myocardial Ischemia		16214533