Acute intermittent porphyria
Gene: HMBSEnsemblGeneIds (GRCh38): ENSG00000256269
EnsemblGeneIds (GRCh37): ENSG00000256269
OMIM: 609806, Gene2Phenotype
HMBS is in 13 panels
4 reviews
Achchuthan Shanmugasundram (Genomics England Curator)
The mode of inheritance of this gene has been updated to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.Created: 10 Dec 2025, 1:56 p.m. | Last Modified: 10 Dec 2025, 1:56 p.m.
Panel Version: 1.5
Sarah Leigh (Genomics England Curator)
Based on review by Sharon Whatley (International Porphyria Network), should the mode of inheritance for this gene on this panel be changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal?Created: 24 Apr 2025, 11:52 a.m. | Last Modified: 24 Apr 2025, 11:52 a.m.
Panel Version: 1.3
Mode of inheritance
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Sharon Whatley (International Porphyria Network)
Relevant metabolic investigation: urine porphobilinogen (to be completed before genetic testing for diagnosis of an acute porphyric attack)
PMID: 27539938 Chen reports that pathogenic HMBS allele frequency is high in the general population (1/1,782) and that the HMBS gene has very low penetrance (<1%) so that genetic testing alone may be misleading and cause misdiagnosis
PMID: 38940544 Aarsand IPNET advises that an acute attack of acute intermittent porphyria is diagnosed using a biochemical test for urine porphobilinogen as the penetrance of acute intermittent porphyria is so low. Genetic testing of the HMBS gene should only be used for family testing where penetrance is higher (10-20%) so that the patients can be advised against precipitating factors such as alcohol and certain drugs.
Careful consideration should be given to the reporting of a single pathogenic variant as an incidental finding in the HMBS gene, due to its low clinical penetrance.
PMID: 14262853 De Villeneuve, 1577472 Llewellyn, 15534187 Solis, 14970743 Hessels, 27558376 Kevelam, 31153822 Dixon and 34089223 Stutterd, reported the very rare finding of biallelic variants in the HMBS gene in six children (5 families) five children with severe progressive neurological disease and in six adults (3 families) with leukoencephalopathy but without confirmed attacks of porphyria.Created: 4 Apr 2025, 11:40 a.m. | Last Modified: 4 Apr 2025, 11:40 a.m.
Panel Version: 1.1
Mode of inheritance
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Phenotypes
176000
Publications
Eleanor Williams (Genomics England Curator)
HMBS has been added to the panel for R169 Acute intermittent porphyria with a green rating as agreed with the NHS Genomic Medicine Service.Created: 14 Jan 2023, 5:58 p.m. | Last Modified: 14 Jan 2023, 6:30 p.m.
Panel Version: 0.4
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Details
- Mode of Inheritance
- BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
- Sources
-
- NHS GMS
- Expert Review Green
- Phenotypes
-
- Porphyria, acute intermittent, nonerythroid variant, OMIM:176000
- Porphyria, acute intermittent, OMIM:176000
- acute intermittent porphyria, MONDO:0008294
- Encephalopathy, porphyria-related, OMIM:620704
- encephalopathy, porphyria-related, MONDO:0958224
- Leukoencephalopathy, porphyria-related, OMIM: 620711
- OMIM
- 609806
- Clinvar variants
- Variants in HMBS
- Penetrance
- None
- Publications
- Panels with this gene
-
- Inherited white matter disorders
- Hereditary neuropathy or pain disorder
- Undiagnosed metabolic disorders
- Bilateral congenital or childhood onset cataracts
- Childhood onset hereditary spastic paraplegia
- Cutaneous photosensitivity with a likely genetic cause
- Childhood onset dystonia, chorea or related movement disorder
- Likely inborn error of metabolism
- White matter disorders and cerebral calcification - narrow panel
- Hereditary neuropathy
- Acute intermittent porphyria
- Ataxia and cerebellar anomalies - narrow panel
- Non-acute porphyrias
History Filter Activity
Removed Tag
Achchuthan Shanmugasundram (Genomics England Curator)Tag Q2_25_ MOI was removed from gene: HMBS.
Set mode of inheritance
Achchuthan Shanmugasundram (Genomics England Curator)Mode of inheritance for gene HMBS was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Removed Tag
Arina Puzriakova (Genomics England Curator)Tag Q2_25_expert_review was removed from gene: HMBS.
Added Tag, Added Tag
Sarah Leigh (Genomics England Curator)Tag Q2_25_ MOI tag was added to gene: HMBS. Tag Q2_25_expert_review tag was added to gene: HMBS.
Set Phenotypes
Sarah Leigh (Genomics England Curator)Phenotypes for gene: HMBS were changed from to Porphyria, acute intermittent, nonerythroid variant, OMIM:176000; Porphyria, acute intermittent, OMIM:176000; acute intermittent porphyria, MONDO:0008294; Encephalopathy, porphyria-related, OMIM:620704; encephalopathy, porphyria-related, MONDO:0958224; Leukoencephalopathy, porphyria-related, OMIM: 620711
Set publications
Sarah Leigh (Genomics England Curator)Publications for gene: HMBS were set to
Created, Added New Source, Set mode of inheritance
Eleanor Williams (Genomics England Curator)gene: HMBS was added gene: HMBS was added to Acute intermittent porphyria. Sources: Expert Review Green,NHS GMS Mode of inheritance for gene: HMBS was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown