Seroatlas · Human Serome Atlas

HMGCS1

Hydroxymethylglutaryl-CoA synthase, cytoplasmic

Also known as: HMCS1_HUMAN, HMGCS

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

Protein identityUniProt · HPA

UniProt accession: Q01581
Gene: HMGCS1
Ensembl: ENSG00000112972
Chromosome: 5
Canonical length: 520 aa
Protein class: Enzymes, Metabolic proteins, Plasma proteins, Predicted intracellular proteins
Subcellular location: Nucleoplasm,Plasma membrane,Cytosol
Quaternary structure: Homodimer

OverviewNCBI Gene

Enables protein homodimerization activity. Predicted to be involved in acetyl-CoA metabolic process and farnesyl diphosphate biosynthetic process, mevalonate pathway. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Jul 2025]

Canonical amino-acid sequenceUniProt

520 residues, UniProt reviewed canonical sequence.

>Q01581|HMGCS1
     1  MPGSLPLNAE ACWPKDVGIV ALEIYFPSQY VDQAELEKYD GVDAGKYTIG LGQAKMGFCT
    61  DREDINSLCM TVVQNLMERN NLSYDCIGRL EVGTETIIDK SKSVKTNLMQ LFEESGNTDI
   121  EGIDTTNACY GGTAAVFNAV NWIESSSWDG RYALVVAGDI AVYATGNARP TGGVGAVALL
   181  IGPNAPLIFE RGLRGTHMQH AYDFYKPDML SEYPIVDGKL SIQCYLSALD RCYSVYCKKI
   241  HAQWQKEGND KDFTLNDFGF MIFHSPYCKL VQKSLARMLL NDFLNDQNRD KNSIYSGLEA
   301  FGDVKLEDTY FDRDVEKAFM KASSELFSQK TKASLLVSNQ NGNMYTSSVY GSLASVLAQY
   361  SPQQLAGKRI GVFSYGSGLA ATLYSLKVTQ DATPGSALDK ITASLCDLKS RLDSRTGVAP
   421  DVFAENMKLR EDTHHLVNYI PQGSIDSLFE GTWYLVRVDE KHRRTYARRP TPNDDTLDEG
   481  VGLVHSNIAT EHIPSPAKKV PRLPATAAEP EAAVISNGEH

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against HMGCS1 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): 0.27
Highest tissue expression: 365 nTPM

Expression across tissuesHPA

Tissue

liver: 365 nTPM
esophagus: 128 nTPM
cerebral cortex: 110 nTPM
duodenum: 88 nTPM
skin: 82 nTPM
vagina: 65 nTPM

Single-cell type

epididymal principal cells: 1,140 nCPM
urothelial cells: 659 nCPM
esophageal suprabasal cells: 633 nCPM
alveolar cells type 2: 590 nCPM
colonocytes: 539 nCPM
esophageal apical cells: 526 nCPM

Immune cell

memory B-cell: 3.8 nTPM
non-classical monocyte: 3.6 nTPM
myeloid DC: 3.5 nTPM
memory CD8 T-cell: 3.4 nTPM
basophil: 3.3 nTPM
intermediate monocyte: 3.3 nTPM

Brain region

pons: 101 nTPM
medulla oblongata: 100 nTPM
hypothalamus: 96 nTPM
cerebral cortex: 80 nTPM
hippocampal formation: 76 nTPM
thalamus: 74 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about HMGCS1.

Disease | GeneticClinVar

5 pathogenic / likely-pathogenic of 43 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

Rigid spine syndrome
Congenital myopathy 28 with rigid spine

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): 0.21
gnomAD pLI: 1
gnomAD missense Z: 3.04
DepMap mean gene effect: -1.76
DepMap dependency class: pan

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 7% 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 HMGCS1 as an antibody target. Whether an autoantibody or antibody against HMGCS1 could matter depends on whether native HMGCS1 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

HMGCS1 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 HMGCS1 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

Loading the interactive Seroatlas protein explorer...