HMBS

Protein identityUniProt · HPA

UniProt accession

P08397

Gene

HMBS

Ensembl

ENSG00000256269

Chromosome

11

Canonical length

361 aa

Protein class

Disease related genes, Enzymes, Human disease related genes, Metabolic proteins, Plasma proteins, Potential drug targets, Predicted intracellular proteins

Subcellular location

Lipid droplets

OverviewNCBI Gene

This gene encodes a member of the hydroxymethylbilane synthase superfamily. The encoded protein is the third enzyme of the heme biosynthetic pathway and catalyzes the head to tail condensation of four porphobilinogen molecules into the linear hydroxymethylbilane. Mutations in this gene are associated with the autosomal dominant disease acute intermittent porphyria. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

361 residues, UniProt reviewed canonical sequence.

>P08397|HMBS
     1  MSGNGNAAAT AEENSPKMRV IRVGTRKSQL ARIQTDSVVA TLKASYPGLQ FEIIAMSTTG
    61  DKILDTALSK IGEKSLFTKE LEHALEKNEV DLVVHSLKDL PTVLPPGFTI GAICKRENPH
   121  DAVVFHPKFV GKTLETLPEK SVVGTSSLRR AAQLQRKFPH LEFRSIRGNL NTRLRKLDEQ
   181  QEFSAIILAT AGLQRMGWHN RVGQILHPEE CMYAVGQGAL GVEVRAKDQD ILDLVGVLHD
   241  PETLLRCIAE RAFLRHLEGG CSVPVAVHTA MKDGQLYLTG GVWSLDGSDS IQETMQATIH
   301  VPAQHEDGPE DDPQLVGITA RNIPRGPQLA AQNLGISLAN LLLSKGAKNI LDVARQLNDA
   361  H

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against HMBS 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

160 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about HMBS.

Disease | AllUniProt

Conditions HMBS is implicated in, by any mechanism.

• Acute intermittent porphyria (AIP) MIM:176000
• Encephalopathy, porphyria-related (ENCEP) MIM:620704
• Leukoencephalopathy, porphyria-related (LENCEP) MIM:620711

Disease | GeneticClinVar

176 pathogenic / likely-pathogenic of 751 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Acute intermittent porphyria
• Encephalopathy, porphyria-related
• Porphyria, acute intermittent, nonerythroid variant
• HMBS-related disorder
• Leukoencephalopathy, porphyria-related

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)

0.34

gnomAD pLI

0.95

gnomAD missense Z

0.64

DepMap mean gene effect

-0.13

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• heme A biosynthetic process
• heme B biosynthetic process
• heme biosynthetic process
• protoporphyrinogen IX biosynthetic process

Molecular functions

• hydroxymethylbilane synthase activity

Cellular components

• cytoplasm
• cytosol

Protein domainsUniProt · Pfam · InterPro

• Porphobilinogen deaminase
• Porphobilinogen deaminase, N-terminal
• Porphobilinogen deaminase, C-terminal
• Porphobilinogen deaminase, dipyrromethane cofactor binding site
• Porphobilinogen deaminase, C-terminal domain superfamily
• Porphobilinogen deaminase, dipyromethane cofactor binding domain
• Porphobilinogen deaminase, C-terminal domain

KeywordsUniProt

• Acetylation
• Cytoplasm
• Heme biosynthesis
• Phosphoprotein
• Porphyrin biosynthesis
• Transferase