Hmbs hydroxymethylbilane synthase [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Hmbsprovided by MGI
Official Full Name: hydroxymethylbilane synthaseprovided by MGI
Primary source: MGI:MGI:96112
See related: Ensembl:ENSMUSG00000032126 AllianceGenome:MGI:96112
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: Ups; PBGD; Uros1
Summary: Enables hydroxymethylbilane synthase activity. Involved in heme A biosynthetic process; heme B biosynthetic process; and heme O biosynthetic process. Is active in cytosol. Is expressed in several structures, including alimentary system; brain; genitourinary system; hemolymphoid system; and respiratory system. Used to study acute intermittent porphyria. Human ortholog(s) of this gene implicated in acute intermittent porphyria and sickle cell anemia. Orthologous to human HMBS (hydroxymethylbilane synthase). [provided by Alliance of Genome Resources, Dec 2024]
Expression: Biased expression in liver E14.5 (RPKM 396.9), liver E14 (RPKM 377.3) and 7 other tissues See more
Orthologs: human all
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Genomic context

Location:: 9 A5.2; 9 24.84 cM

Exon count:: 15

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	9	NC_000075.7 (44247645..44255525, complement)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	9	NC_000075.6 (44336348..44344228, complement)

Chromosome 9 - NC_000075.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Brain ventricular enlargement in human and murine acute intermittent porphyria.
Title: Brain ventricular enlargement in human and murine acute intermittent porphyria.
Severe hydroxymethylbilane synthase deficiency causes depression-like behavior and mitochondrial dysfunction in a mouse model of homozygous dominant acute intermittent porphyria.
Title: Severe hydroxymethylbilane synthase deficiency causes depression-like behavior and mitochondrial dysfunction in a mouse model of homozygous dominant acute intermittent porphyria.
To investigate the dramatically different manifestations, knock-in mice with human homozygous dominant-Acute intermittent porphyria (HD-AIP) missense mutations c.500G>A (p.Arg167Glu) or c.518_519GC>AG (p.Arg173Glu), designated R167Q or R173Q mice, respectively, were generated and compared with the previously established T1/T2 mice with ~30% residual HMBS activity and the heterozygous AIP phenotype
Title: Homozygous hydroxymethylbilane synthase knock-in mice provide pathogenic insights into the severe neurological impairments present in human homozygous dominant acute intermittent porphyria.
New bioengineered PBGD variants (for gene therapy) capable of metabolizing the toxic heme precursors produced by the liver at an increased rate were evaluated.
Title: Bioengineered PBGD variant improves the therapeutic index of gene therapy vectors for acute intermittent porphyria.
PBGD-deficient mice showed a different response to fasting as measured by altered carbohydrate metabolism in the liver and modified glucose consumption in the brain cortex. Glucose homeostasis in fasted PBGD-deficient mice was efficiently normalized after restoration of PBGD gene expression in the liver.
Title: Glucose metabolism during fasting is altered in experimental porphobilinogen deaminase deficiency.
Porphobilinogen deaminase over-expression in hepatocytes, albeit in a low proportion, reduced precursor accumulation, which is the hallmark of acute porphyric attacks.
Title: Porphobilinogen deaminase over-expression in hepatocytes, but not in erythrocytes, prevents accumulation of toxic porphyrin precursors in a mouse model of acute intermittent porphyria.
PBGD-deficient mice were characterized biochemically during phenobarbital induction of heme synthesis and enzyme replacement.
Title: Biochemical characterization of porphobilinogen deaminase-deficient mice during phenobarbital induction of heme synthesis and the effect of enzyme replacement.

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Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Chemically induced (ENU) (1)
Endonuclease-mediated (1)
Targeted (7) 1 citation

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

PMC308923P1 (e-PCR)
- UniSTS:272589

d105 (e-PCR)
- UniSTS:131818

D9Mit25.1 (e-PCR), detects polymorphism
- UniSTS:131819

D9Mit25.2 (e-PCR), detects polymorphism
- UniSTS:131820

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables amine binding	ISO Inferred from Sequence Orthology more info
enables carboxylic acid binding	ISO Inferred from Sequence Orthology more info
enables hydroxymethylbilane synthase activity	IBA Inferred from Biological aspect of Ancestor more info
enables hydroxymethylbilane synthase activity	IDA Inferred from Direct Assay more info	PubMed
enables hydroxymethylbilane synthase activity	ISO Inferred from Sequence Orthology more info
enables uroporphyrinogen-III synthase activity	ISO Inferred from Sequence Orthology more info

Process	Evidence Code	Pubs
involved_in heme A biosynthetic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in heme B biosynthetic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in heme O biosynthetic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in heme biosynthetic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in heme biosynthetic process	ISO Inferred from Sequence Orthology more info
involved_in liver development	ISO Inferred from Sequence Orthology more info
involved_in porphyrin-containing compound biosynthetic process	ISO Inferred from Sequence Orthology more info
involved_in porphyrin-containing compound metabolic process	ISO Inferred from Sequence Orthology more info
involved_in protoporphyrinogen IX biosynthetic process	IEA Inferred from Electronic Annotation more info
involved_in response to xenobiotic stimulus	ISO Inferred from Sequence Orthology more info
involved_in tetrapyrrole biosynthetic process	ISO Inferred from Sequence Orthology more info

Component	Evidence Code	Pubs
located_in axon	ISO Inferred from Sequence Orthology more info
located_in condensed chromosome	ISO Inferred from Sequence Orthology more info
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
is_active_in cytosol	IDA Inferred from Direct Assay more info	PubMed
located_in perinuclear region of cytoplasm	ISO Inferred from Sequence Orthology more info

General protein information

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Preferred Names: porphobilinogen deaminase

Names: PBG-D; pre-uroporphyrinogen synthase

NP_001103721.1

EC 2.5.1.61

NP_038579.2

EC 2.5.1.61

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_001110251.1 → NP_001103721.1 porphobilinogen deaminase isoform 2

See identical proteins and their annotated locations for NP_001103721.1

Status: VALIDATED

Description

Transcript Variant: This variant (2) contains an alternate exon in the 5' UTR, lacks a portion of the 5' coding region, and initiates translation at an alternate start codon, compared to variant 1. The encoded protein (isoform 2) has a distinct N-terminus and is shorter than isoform 1.

Source sequence(s)

AI853649, AK143558, BB844509

Consensus CDS

CCDS52779.1

UniProtKB/TrEMBL

Q3UPG1, Q99L41

Related

ENSMUSP00000095166.4, ENSMUST00000097558.5

Conserved Domains (2) summary

PRK00072
Location:1 → 327

hemC; porphobilinogen deaminase; Reviewed

cd13645
Location:3 → 282

PBP2_HuPBGD_like; Human porphobilinogen deaminase possess type 2 periplasmic binding protein fold
NM_013551.2 → NP_038579.2 porphobilinogen deaminase isoform 1

See identical proteins and their annotated locations for NP_038579.2

Status: VALIDATED

Description

Transcript Variant: This variant (1) represents the longer transcript and encodes the longer protein (isoform 1).

Source sequence(s)

AI853649, AK151020, AK166734, BY786671

Consensus CDS

CCDS23106.1

UniProtKB/Swiss-Prot

P22907, Q3TIV0

UniProtKB/TrEMBL

Q99L41

Related

ENSMUSP00000076575.8, ENSMUST00000077353.15

Conserved Domains (1) summary

cd13645
Location:20 → 299

PBP2_HuPBGD_like; Human porphobilinogen deaminase possess type 2 periplasmic binding protein fold