• 3
    Haplo
    Score
  • 0
    Triplo
    Score

Gene Facts External Data Attribution

HGNC Symbol
HMBS (HGNC:4982) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
HGNC Name
hydroxymethylbilane synthase
Gene type
protein-coding gene
Locus type
gene with protein product
Previous symbols
PBGD, UPS, PORC
Alias symbols
No aliases found
%HI
5.34(Read more about the DECIPHER Haploinsufficiency Index)
pLI
0.95(Read more about gnomAD pLI score)
LOEUF
0.34(Read more about gnomAD LOEUF score)
Cytoband
11q23.3
Genomic Coordinates
GRCh37/hg19: chr11:118955591-118964259 NCBI Ensembl UCSC
GRCh38/hg38: chr11:119084881-119093549 NCBI Ensembl UCSC
MANE Select Transcript
NM_000190.4 ENST00000652429.1 (Read more about MANE Select)
Function
As part of the heme biosynthetic pathway, catalyzes the sequential polymerization of four molecules of porphobilinogen to form hydroxymethylbilane, also known as preuroporphyrinogen (PubMed:18936296, PubMed:19138865, PubMed:23815679, PubMed:18004775). Catalysis begins with the assembly of the dipyrromethane cofactor by the apoenzyme from two molecules of porphobilinogen or from preuroporphyrinogen. The covalently linked cofactor acts as a primer, around which the tetrapyrrole product is assemble... (Source: Uniprot)

Dosage Sensitivity Summary (Gene)

Dosage ID:
ISCA-7024
Curation Status:
Complete
Issue Type:
Dosage Curation - Gene
Haploinsufficiency:
Sufficient Evidence for Haploinsufficiency (3)
Triplosensitivity:
No Evidence for Triplosensitivity (0)
Last Evaluated:
01/08/2020

Haploinsufficiency (HI) Score Details

HI Score:
3
HI Evidence Strength:
Sufficient Evidence for Haploinsufficiency (Disclaimer)
HI Disease:
HI Evidence:
  • PUBMED: 19460837
    Whatley et al. studied 467 unrelated patients with proven or putative porphyria. Amongst 123 different HMBS mutations detected by sequencing or qPCR were four multi-exon deletions: exons 3-15, 3-4, 9-15, and 3-11. Article associated with porphyria and hepatocellular carcinoma PMID: 23344888 Sardh et al. studied the incidence of primary liver cancer and clinical characteristics in a cohort of 179 acute porphyria patients above the age of 50 years. Out of 20 acute intermittent porphyria patients with hepatocellular carcinoma (HCC), 18 patients had nonsense, frameshift or splice variants. W198X was the most common variant in this cohort. It was found in 9 patients. The other reported variants were: c.826-2A>G, c.499-1G>A, c.345-2A>G, c.88-2A>G, c.207delT.
  • PUBMED: 12372055
    Floderus et al. studied patients with acute intermittent porphyria (AIP). HMBS mutations were detected by DGGE and confirmed by sequencing. A wide mutation spectrum was reported, including: an M1 variant, nonsense variants (in exons 4, 10, and 12), several canonical splice site variants, and several frameshift variants. Article associated with porphyria and hepatocellular carcinoma PMID: 25445397 Xiaoye Schneider-Yin et al. studied 1 patient with two variants in HMBS gene. A 68-year old Swiss female was diagnosed as an asymptomatic carrier of germline mutation p.G111R variant in the HMBS gene was known in her family with AIP. She had never experienced an acute porphyric attack and her urinary PBG concentrations were only slightly above the normal range. She had two solid lesions of 1.7 cm and 2.7 cm, highly suspicious of HCC, in liver. Authors detected a second somatic variant, only in the cancerous tissue i.e. p.L220X in the HMBS gene of this patient, located in trans to the respective germline mutation.
  • PUBMED: 10790212
    di Montemuros et al. report seven mutations in eight patients with AIP (biochemically confirmed) detected by DGGE and sequencing: two splicing variants, three frameshift variants, and two nonsense variants.
HI Evidence Comments:
Haploinsufficiency of the HMBS gene causes acute intermittent porphyria. Haploinsufficiency of the HMBS gene also causes HCC in patients above age 50 with incidence rates range from 0.16 to 0.35% according to the populations studied.

Triplosensitivity (TS) Score Details

TS Score:
0
TS Evidence Strength:
No Evidence for Triplosensitivity (Disclaimer)
TS Evidence Comments:
No duplications involving only the entire HMBS gene reported

Genomic View

Select assembly: (NC_000011.9) (NC_000011.10)