HMBS hydroxymethylbilane synthase [Homo sapiens (human)] - Gene

Summary

Official Symbol: HMBSprovided by HGNC
Official Full Name: hydroxymethylbilane synthaseprovided by HGNC
Primary source: HGNC:HGNC:4982
See related: Ensembl:ENSG00000256269 MIM:609806; AllianceGenome:HGNC:4982
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: UPS; PBGD; PORC; ENCEP; PBG-D; LENCEP
Summary: 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]
Expression: Biased expression in bone marrow (RPKM 55.8), colon (RPKM 5.0) and 13 other tissues See more
Orthologs: mouse all
NEW: Try the new Gene table
Try the new Transcript table

Genomic context

Location:: 11q23.3

Exon count:: 16

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	11	NC_000011.10 (119084881..119093549)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	11	NC_060935.1 (119105272..119113932)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	11	NC_000011.9 (118955591..118964259)

Chromosome 11 - NC_000011.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

Go to the top of the page Help

Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

Go to the top of the page Help

See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

Go to the top of the page Help

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Neurodevelopmental disorder in a patient with HMBS and SCN3A variants-A possibly blended phenotype further delineating autosomal recessive HMBS related disease.
Title: Neurodevelopmental disorder in a patient with HMBS and SCN3A variants-A possibly blended phenotype further delineating autosomal recessive HMBS related disease.
Identification and molecular analysis of 17 novel variants of hydroxymethylbilane synthase in Chinese patients with acute intermittent porphyria.
Title: Identification and molecular analysis of 17 novel variants of hydroxymethylbilane synthase in Chinese patients with acute intermittent porphyria.
Expanding the clinical and radiological phenotypes of leukoencephalopathy due to biallelic HMBS mutations.
Title: Expanding the clinical and radiological phenotypes of leukoencephalopathy due to biallelic HMBS mutations.
Two Novel Hydroxymethylbilane Synthase Splicing Mutations Predispose to Acute Intermittent Porphyria.
Title: Two Novel Hydroxymethylbilane Synthase Splicing Mutations Predispose to Acute Intermittent Porphyria.
Brain ventricular enlargement in human and murine acute intermittent porphyria.
Title: Brain ventricular enlargement in human and murine acute intermittent porphyria.
Mount Sinai Porphyrias Diagnostic Laboratory diagnosed 315 unrelated Acute Intermittent Porphyria individuals with HMBS mutations, including 46 previously unreported mutations.
Title: Acute hepatic porphyrias: Identification of 46 hydroxymethylbilane synthase, 11 coproporphyrinogen oxidase, and 20 protoporphyrinogen oxidase novel mutations.
Identified 40 novel HMBS mutations in unrelated individuals with acute intermittent porphyria (AIP); all mutants had less than 5% of expressed wildtype activity, except for c.1039G>C (p.A347P), which had 51% residual HMBS activity. Mutations near the active site or at the dimerization interface resulted in stably expressed proteins, while most that altered surface residues resulted in unstable protein.
Title: Identification and characterization of 40 novel hydroxymethylbilane synthase mutations that cause 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.
Using two bioinformatics pipelines for analysis of RNA fingerprints we identified significant effects of E. coli on the mRNAs HMBS, ATP2C1 and LRCH4. To see whether these three proteins were present in platelets and were influenced by the bacteria, we analysed HMBS, ATP2C1 and LRCH4 in platelet lysates and releasates by Western blot and ELISA.
Title: Impact of Escherichia coli K12 and O18:K1 on human platelets: Differential effects on platelet activation, RNAs and proteins.
In the present study, we identified four HMBS gene mutations affecting the ubiquitous isoform of porphobilinogen deaminase (PBGD) and established a dPCR protocol which would be able to detect the different transcripts of this gene.
Title: Molecular characterization, by digital PCR analysis of four HMBS gene mutations affecting the ubiquitous isoform of Porphobilinogen Deaminase (PBGD) in patients with Acute Intermittent Porphyria (AIP).

Submit: New GeneRIF Correction See all GeneRIFs (59)

Phenotypes

Go to the top of the page Help

Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Acute intermittent porphyria MedGen: C0162565 OMIM: 176000 GeneReviews: Acute Intermittent Porphyria	Compare labs
Encephalopathy, porphyria-related MedGen: C5935574 OMIM: 620704 GeneReviews: Not available	Compare labs
Leukoencephalopathy, porphyria-related MedGen: C5935575 OMIM: 620711 GeneReviews: Not available	Compare labs

Copy number response

Description
Copy number response Triplosensitivity No evidence available (Last evaluated 2020-01-08) ClinGen Genome Curation Page Haploinsufficency Sufficient evidence for dosage pathogenicity (Last evaluated 2020-01-08) ClinGen Genome Curation PagePubMed

Variation

Go to the top of the page Help

See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

Go to the top of the page Help

Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

Go to the top of the page Help

Markers

GDB:185078 (e-PCR)
- UniSTS:155407

GDB:197909 (e-PCR)
- UniSTS:156000

GDB:198121 (e-PCR)
- UniSTS:156020

MARC_4999-5000:996679654:1 (e-PCR)
- UniSTS:269432

G02272 (e-PCR)
- UniSTS:8100

GDB:179873 (e-PCR)
- UniSTS:155054

PMC165384P1 (e-PCR)
- UniSTS:271537

GDB:371404 (e-PCR)
- UniSTS:156849

GDB:371408 (e-PCR)
- UniSTS:156850

GDB:371412 (e-PCR)
- UniSTS:156851

GDB:371415 (e-PCR)
- UniSTS:156852

GDB:176383 (e-PCR)
- UniSTS:154805

GDB:371419 (e-PCR)
- UniSTS:156853

GDB:371425 (e-PCR)
- UniSTS:156854

GDB:371431 (e-PCR)
- UniSTS:156856

G59319 (e-PCR)
- UniSTS:136634

GDB:181636 (e-PCR)
- UniSTS:155322

GDB:371437 (e-PCR)
- UniSTS:156858

GDB:371443 (e-PCR)
- UniSTS:156860

GDB:196345 (e-PCR)
- UniSTS:155837

GDB:371447 (e-PCR)
- UniSTS:156861

GDB:371450 (e-PCR)
- UniSTS:156862

GDB:196348 (e-PCR)
- UniSTS:155839

PMC136706P1 (e-PCR)
- UniSTS:270803

HMBS (e-PCR)
- UniSTS:20449

D11S4628 (e-PCR)
- UniSTS:18917

STS-M95623 (e-PCR)
- UniSTS:2280

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
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	TAS Traceable Author Statement more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in heme A biosynthetic process	IEA Inferred from Electronic Annotation more info
involved_in heme B biosynthetic process	IEA Inferred from Electronic Annotation more info
involved_in heme O biosynthetic process	IEA Inferred from Electronic Annotation more info
involved_in heme biosynthetic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in heme biosynthetic process	IC Inferred by Curator more info	PubMed
involved_in heme biosynthetic process	IDA Inferred from Direct Assay more info	PubMed
involved_in heme biosynthetic process	TAS Traceable Author Statement more info
involved_in protoporphyrinogen IX biosynthetic process	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytosol	TAS Traceable Author Statement more info

General protein information

Go to the top of the page Help

Preferred Names: porphobilinogen deaminase

Names: porphyria, acute; Chester type; pre-uroporphyrinogen synthase; uroporphyrinogen I synthase; uroporphyrinogen I synthetase

NP_000181.2

EC 2.5.1.61

NP_001019553.1

EC 2.5.1.61

NP_001245137.1

EC 2.5.1.61

NP_001245138.1

EC 2.5.1.61

NP_001411981.1

EC 2.5.1.61

NP_001411982.1

EC 2.5.1.61

NP_001411983.1

EC 2.5.1.61

NP_001411985.1

EC 2.5.1.61

NP_001411986.1

EC 2.5.1.61

NP_001411987.1

EC 2.5.1.61

NP_001411988.1

EC 2.5.1.61

NP_001411990.1

EC 2.5.1.61

NP_001411991.1

EC 2.5.1.61

NP_001411992.1

EC 2.5.1.61

NP_001411994.1

EC 2.5.1.61

XP_011541098.1

EC 2.5.1.61

XP_016873118.1

EC 2.5.1.61

XP_054224575.1

EC 2.5.1.61

XP_054224577.1

EC 2.5.1.61

NCBI Reference Sequences (RefSeq)

Go to the top of the page Help

NEW Try the new Transcript table

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.

Genomic

NG_008093.1 RefSeqGene

Range

5005..13673

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_1076

mRNA and Protein(s)

NM_000190.4 → NP_000181.2 porphobilinogen deaminase isoform 1

See identical proteins and their annotated locations for NP_000181.2

Status: REVIEWED

Description

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

Source sequence(s)

AW139390, BC019323, CB128006

Consensus CDS

CCDS8409.1

UniProtKB/Swiss-Prot

A8K2L0, G3V1P4, G5EA58, P08396, P08397, Q16012

UniProtKB/TrEMBL

A0A3B3IRR1

Related

ENSP00000498786.1, ENST00000652429.1

Conserved Domains (1) summary

cd13645
Location:20 → 299

PBP2_HuPBGD_like; Human porphobilinogen deaminase possess type 2 periplasmic binding protein fold
NM_001024382.2 → NP_001019553.1 porphobilinogen deaminase isoform 2

See identical proteins and their annotated locations for NP_001019553.1

Status: REVIEWED

Source sequence(s)

AA724756, AP003391, BX647328, X04217

Consensus CDS

CCDS41726.1

UniProtKB/TrEMBL

A0A3B3IRR1

Related

ENSP00000376584.1, ENST00000392841.1

Conserved Domains (1) summary

cd13645
Location:3 → 282

PBP2_HuPBGD_like; Human porphobilinogen deaminase possess type 2 periplasmic binding protein fold
NM_001258208.2 → NP_001245137.1 porphobilinogen deaminase isoform 3

See identical proteins and their annotated locations for NP_001245137.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) lacks an alternate in-frame exon compared to variant 1. The resulting isoform (3) has the same N- and C-termini but is shorter compared to isoform 1.

Source sequence(s)

AK131072, AW139390, CB128006

Consensus CDS

CCDS58186.1

UniProtKB/TrEMBL

F5H345

Related

ENSP00000438424.1, ENST00000544387.5

Conserved Domains (2) summary

PRK00072
Location:18 → 304

hemC; porphobilinogen deaminase; Reviewed

cd13645
Location:20 → 259

PBP2_HuPBGD_like; Human porphobilinogen deaminase possess type 2 periplasmic binding protein fold
NM_001258209.2 → NP_001245138.1 porphobilinogen deaminase isoform 4

See identical proteins and their annotated locations for NP_001245138.1

Status: REVIEWED

Description

Transcript Variant: This variant (4) uses an alternate splice junction at the 3' end of the first exon and lacks an alternate in-frame exon compared to variant 1. The resulting isoform (4) is shorter at the N-terminus and lacks an alternate internal segment compared to isoform 1.

Source sequence(s)

AK000628, AP003392, AW139390, CB128006

Consensus CDS

CCDS58187.1

UniProtKB/TrEMBL

A0A3B3IRR1

Related

ENSP00000443058.1, ENST00000542729.5

Conserved Domains (2) summary

PRK00072
Location:1 → 287

hemC; porphobilinogen deaminase; Reviewed

cd13645
Location:3 → 242

PBP2_HuPBGD_like; Human porphobilinogen deaminase possess type 2 periplasmic binding protein fold
NM_001425052.1 → NP_001411981.1 porphobilinogen deaminase isoform 2

Status: REVIEWED

Source sequence(s)

AP003391, AP003392

UniProtKB/TrEMBL

A0A3B3IRR1

Related

ENSP00000444730.1, ENST00000537841.5
NM_001425053.1 → NP_001411982.1 porphobilinogen deaminase isoform 2

Status: REVIEWED

Source sequence(s)

AP003391, AP003392

UniProtKB/TrEMBL

A0A3B3IRR1
NM_001425054.1 → NP_001411983.1 porphobilinogen deaminase isoform 2

Status: REVIEWED

Source sequence(s)

AP003391, AP003392

UniProtKB/TrEMBL

A0A3B3IRR1

Related

ENSP00000496970.1, ENST00000650101.1
NM_001425056.1 → NP_001411985.1 porphobilinogen deaminase isoform 5

Status: REVIEWED

Source sequence(s)

AP003391, AP003392

UniProtKB/TrEMBL

A0A3B3IRR1
NM_001425057.1 → NP_001411986.1 porphobilinogen deaminase isoform 6

Status: REVIEWED

Source sequence(s)

AP003391, AP003392

UniProtKB/TrEMBL

A0A3B3IRR1, A0A3F2YNY7

Related

ENSP00000392041.3, ENST00000442944.7
NM_001425058.1 → NP_001411987.1 porphobilinogen deaminase isoform 7

Status: REVIEWED

Source sequence(s)

AP003391, AP003392

UniProtKB/TrEMBL

F5H345
NM_001425059.1 → NP_001411988.1 porphobilinogen deaminase isoform 8

Status: REVIEWED

Source sequence(s)

AP003391, AP003392

UniProtKB/TrEMBL

F5H345

Related

ENSP00000445429.1, ENST00000543090.5
NM_001425061.1 → NP_001411990.1 porphobilinogen deaminase isoform 9

Status: REVIEWED

Source sequence(s)

AP003391, AP003392

UniProtKB/TrEMBL

F5H345
NM_001425062.1 → NP_001411991.1 porphobilinogen deaminase isoform 10

Status: REVIEWED

Source sequence(s)

AP003391, AP003392

UniProtKB/TrEMBL

A0A3B3IRR1, A0A8I5KXV4
NM_001425063.1 → NP_001411992.1 porphobilinogen deaminase isoform 10

Status: REVIEWED

Source sequence(s)

AP003391, AP003392

UniProtKB/TrEMBL

A0A3B3IRR1, A0A8I5KXV4
NM_001425065.1 → NP_001411994.1 porphobilinogen deaminase isoform 11

Status: REVIEWED

Source sequence(s)

AP003391, AP003392

UniProtKB/TrEMBL

F5H345

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000011.10 Reference GRCh38.p14 Primary Assembly

Range

119084881..119093549

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_017017629.2 → XP_016873118.1 porphobilinogen deaminase isoform X1

UniProtKB/TrEMBL

A0A3B3IRR1

Related

ENSP00000497255.1, ENST00000648374.1

Conserved Domains (1) summary

cd13645
Location:3 → 282

PBP2_HuPBGD_like; Human porphobilinogen deaminase possess type 2 periplasmic binding protein fold
XM_011542796.2 → XP_011541098.1 porphobilinogen deaminase isoform X3

UniProtKB/TrEMBL

A0A3B3IRR1, A0A8I5KXV4

Related

ENSP00000509288.1, ENST00000686218.1

Conserved Domains (1) summary

cd13645
Location:1 → 244

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