Seroatlas · Human Serome Atlas

HMGCS2

Hydroxymethylglutaryl-CoA synthase, mitochondrial

Also known as: HMCS2_HUMAN

Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene

Protein identityUniProt · HPA

UniProt accession
P54868
Gene
HMGCS2
Ensembl
ENSG00000134240
Chromosome
1
Canonical length
508 aa
Protein class
Disease related genes, Enzymes, Human disease related genes, Metabolic proteins, Plasma proteins, Potential drug targets, Predicted intracellular proteins
Subcellular location
Mitochondria
Quaternary structure
Homodimer

OverviewNCBI Gene

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 deprivation, such as fasting. Mutations in this gene are associated with HMG-CoA synthase deficiency. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Oct 2009]

Canonical amino-acid sequenceUniProt

508 residues, UniProt reviewed canonical sequence.

>P54868|HMGCS2
     1  MQRLLTPVKR ILQLTRAVQE TSLTPARLLP VAHQRFSTAS AVPLAKTDTW PKDVGILALE
    61  VYFPAQYVDQ TDLEKYNNVE AGKYTVGLGQ TRMGFCSVQE DINSLCLTVV QRLMERIQLP
   121  WDSVGRLEVG TETIIDKSKA VKTVLMELFQ DSGNTDIEGI DTTNACYGGT ASLFNAANWM
   181  ESSSWDGRYA MVVCGDIAVY PSGNARPTGG AGAVAMLIGP KAPLALERGL RGTHMENVYD
   241  FYKPNLASEY PIVDGKLSIQ CYLRALDRCY TSYRKKIQNQ WKQAGSDRPF TLDDLQYMIF
   301  HTPFCKMVQK SLARLMFNDF LSASSDTQTS LYKGLEAFGG LKLEDTYTNK DLDKALLKAS
   361  QDMFDKKTKA SLYLSTHNGN MYTSSLYGCL ASLLSHHSAQ ELAGSRIGAF SYGSGLAASF
   421  FSFRVSQDAA PGSPLDKLVS STSDLPKRLA SRKCVSPEEF TEIMNQREQF YHKVNFSPPG
   481  DTNSLFPGTW YLERVDEQHR RKYARRPV

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against HMGCS2 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability
Intracellular
Secreted
No
Transmembrane segments
0
Mean surface accessibility (rSASA)
0.26
Highest tissue expression
2,276 nTPM

Expression across tissuesHPA

Tissue

  • liver: 2,276 nTPM
  • colon: 344 nTPM
  • rectum: 214 nTPM
  • breast: 209 nTPM
  • duodenum: 156 nTPM
  • small intestine: 143 nTPM

Single-cell type

  • hepatocytes: 1,288 nCPM
  • colonocytes: 497 nCPM
  • enteric stem cells: 407 nCPM
  • enteric transient amplifying cells: 323 nCPM
  • retinal pigment epithelial cells: 286 nCPM
  • goblet cells: 276 nCPM

Immune cell

  • basophil: 0 nTPM
  • classical monocyte: 0 nTPM
  • eosinophil: 0 nTPM
  • gdT-cell: 0 nTPM
  • intermediate monocyte: 0 nTPM
  • MAIT T-cell: 0 nTPM

Brain region

  • choroid plexus: 11 nTPM
  • hypothalamus: 0.2 nTPM
  • midbrain: 0.2 nTPM
  • basal ganglia: 0.1 nTPM
  • cerebellum: 0.1 nTPM
  • medulla oblongata: 0.1 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about HMGCS2.

Disease | AllUniProt

Conditions HMGCS2 is implicated in, by any mechanism.

  • 3-hydroxy-3-methylglutaryl-CoA synthase-2 deficiency (HMGCS2D) MIM:605911

Disease | GeneticClinVar

56 pathogenic / likely-pathogenic of 347 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)
1.2
gnomAD pLI
0
gnomAD missense Z
-0.19
DepMap mean gene effect
-0.01
DepMap dependency class
none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

Molecular functions

Cellular components

Protein domainsUniProt · Pfam · InterPro

KeywordsUniProt

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads HMGCS2 as an antibody target. Whether an autoantibody or antibody against HMGCS2 could matter depends on whether native HMGCS2 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

HMGCS2 is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.

Annotation status

The present source text does not explicitly label HMGCS2 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

Canonical record: https://seroatlas.com/gene/HMGCS2. Study-independent annotations aggregated from UniProt, Human Protein Atlas, PubMed, IEDB, Pfam, InterPro, Gene Ontology, AlphaFold, gnomAD, DepMap, ClinVar, TCGA. Catalog release seroatlas-reviewed-human-uniprot-20260313.

Seroatlas is the reference for exploring autoantibody and antibody serology at the human-protein level: the autoreactome and human serome, multiplex serology (HuProt, HuScan, VirScan, PhIP-Seq).

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