Acute intermittent porphyria: genes and variants
Acute intermittent porphyria is linked to 1 analyzed protein (HMBS). 21 DNA variants are known to cause it; 31 more are uncertain, and 2 of those already look disease-causing on computable evidence.
Last updated 2026-09-30. Research information, not medical advice.
Genes linked to Acute intermittent porphyria
HMBS: Porphobilinogen deaminase
An enzyme in heme biosynthesis that joins four porphobilinogen molecules to form hydroxymethylbilane. This step is required to build the tetrapyrrole framework of heme, and HMBS dysfunction causes acute intermittent porphyria.
21 disease-causing and 31 uncertain variants in HMBS are linked to Acute intermittent porphyria.
Known disease-causing variants in Acute intermittent porphyria
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| HMBS R167Q | 167 | Disease-causing (★★) | |
| HMBS R167W | 167 | Disease-causing (★★) | |
| HMBS T35M | 35 | Disease-causing (★★) | |
| HMBS G111R | 111 | Disease-causing (★★) | |
| HMBS R116W | 116 | Disease-causing (★★) | |
| HMBS R173W | 173 | Disease-causing (★★) | |
| HMBS R26C | 26 | Disease-causing (★★) | |
| HMBS Q204H | 204 | Disease-causing (★★) | |
| HMBS V215M | 215 | Disease-causing (★★) | |
| HMBS R173P | 173 | Disease-causing (★) | |
| HMBS D61Y | 61 | Disease-causing (★) | |
| HMBS L92P | 92 | Disease-causing (★) | |
| HMBS A122P | 122 | Disease-causing (★) | |
| HMBS R167L | 167 | Disease-causing | |
| HMBS A31T | 31 | Disease-causing | |
| HMBS Q34K | 34 | Disease-causing | |
| HMBS A252V | 252 | Disease-causing | |
| HMBS R149Q | 149 | Disease-causing | |
| HMBS E250K | 250 | Disease-causing | |
| HMBS L245R | 245 | Disease-causing | |
| HMBS H256N | 256 | Disease-causing |
Uncertain variants in Acute intermittent porphyria that look disease-causing
| Variant | Position | Protein part | Clinical label | Evidence |
|---|---|---|---|---|
| HMBS R116Q | 116 | Conflicting reports (★) | +6: R116W at the same position is pathogenic; REVEL 0.953 | |
| HMBS A252T | 252 | Uncertain (★★) | +6: 2 other pathogenic changes within 3 positions; A252V at the same position is pathogenic; REVEL 0.793 |
Diseases related to Acute intermittent porphyria
- Encephalopathy, porphyria-related, also linked to HMBS
- Leukoencephalopathy, porphyria-related, also linked to HMBS
Frequently asked questions
Which genes are linked to Acute intermittent porphyria?
In CATVariant, Acute intermittent porphyria is linked to 1 analyzed protein: HMBS (Porphobilinogen deaminase).
How many genetic variants are linked to Acute intermittent porphyria?
85 variants: 21 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 31 are of uncertain significance or have conflicting reports.
Which uncertain variants in Acute intermittent porphyria look disease-causing?
2 uncertain variants reach the likely-pathogenic range of the ACMG/AMP points scale on computable evidence, for example HMBS R116Q and HMBS A252T. These are leads for expert review, not diagnoses.
About this data
Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from the latest public CATVariant analysis of each human protein. Evidence scores use the ACMG/AMP Bayesian points scale with computable criteria only (position among known disease variants, rarity in gnomAD, calibrated predictors, deep mutational scanning); there is no family or patient data, so they prioritise variants for expert review and never classify them.
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