AIP
MCID: PRP083
MIFTS: 62

Porphyria, Acute Intermittent (AIP)

Categories: Gastrointestinal diseases, Genetic diseases, Liver diseases, Metabolic diseases, Nephrological diseases, Neuronal diseases, Rare diseases, Skin diseases

Aliases & Classifications for Porphyria, Acute Intermittent

MalaCards integrated aliases for Porphyria, Acute Intermittent:

Name: Porphyria, Acute Intermittent 57 75 13 44 40
Acute Intermittent Porphyria 12 75 24 53 59 74 29 6 15 72
Porphobilinogen Deaminase Deficiency 57 24 53 74
Pbgd Deficiency 57 24 53 74
Porphyria, Acute Intermittent, Nonerythroid Variant 57 29 6
Uroporphyrinogen Synthase Deficiency 57 53 74
Porphyria, Swedish Type 57 53 74
Ups Deficiency 57 53 74
Aip 57 53 74
Hydroxymethylbilane Synthase Deficiency 53 72
Aip - Acute Intermittent Porphyria 12
Porphyria Intermittent Acute 12
Porphyria Acute Intermittent 55
Pyrroloporphyria 12
Hmbs Deficiency 53

Characteristics:

Orphanet epidemiological data:

59
acute intermittent porphyria
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Europe),1-9/1000000 (Europe),<1/1000000 (France),1-9/1000000 (France),<1/1000000 (Italy),1-9/1000000 (Italy),<1/1000000 (Finland),1-9/1000000 (Finland),<1/1000000 (Netherlands),1-9/1000000 (Netherlands),<1/1000000 (Norway),1-9/1000000 (Norway),<1/1000000 (Poland),1-9/1000000 (Poland),<1/1000000 (Spain),1-9/1000000 (Spain),<1/1000000 (Sweden),1-5/10000 (Sweden),<1/1000000 (Switzerland),1-9/1000000 (Switzerland),<1/1000000 (United Kingdom),1-9/1000000 (United Kingdom); Age of onset: Adolescent,Adult;

OMIM:

57
Inheritance:
autosomal dominant

Miscellaneous:
acute attacks rarely occur before puberty
attacks precipitated by drugs (e.g. barbiturates, sulfonamides), alcohol, infection, starvation, and hormonal changes
attacks more common in women
ninety percent of patients with pbg deaminase deficiency are clinically unaffected


HPO:

32
porphyria, acute intermittent:
Inheritance autosomal dominant inheritance


GeneReviews:

24
Penetrance The penetrance for clinical manifestations of an hmbs pathogenic variant is not accurately known....

Classifications:



External Ids:

Disease Ontology 12 DOID:3890
OMIM 57 176000
MeSH 44 D017118
NCIt 50 C84536
SNOMED-CT 68 90842001
MESH via Orphanet 45 D017118
ICD10 via Orphanet 34 E80.2
UMLS via Orphanet 73 C0162565
Orphanet 59 ORPHA79276
UMLS 72 C0162565 C2936779

Summaries for Porphyria, Acute Intermittent

OMIM : 57 Porphyrias are inherited defects in the biosynthesis of heme. Acute intermittent porphyria, the most common form of porphyria, is an autosomal dominant disorder characterized by recurrent attacks of abdominal pain, gastrointestinal dysfunction, and neurologic disturbances. In the classic form of AIP, both the ubiquitous 'nonerythroid' housekeeping HMBS isoform and the 'erythroid' HMBS isoform are deficient. However, about 5% of families have the 'nonerythroid variant' of AIP, with a defect only in the ubiquitous nonerythroid HMBS isoform and normal levels of the erythroid HMBS isoform. Clinical characteristics in the 2 forms are identical; diagnostic methods based on the level of enzyme in erythrocytes is ineffective (Puy et al., 1998; Petrides, 1998; Whatley et al., 2000). There are several other forms of porphyria: see porphyria cutanea tarda (176100), variegata porphyria (176200), coproporphyria (121300), acute hepatic porphyria (125270), and congenital erythropoietic porphyria (263700). (176000)

MalaCards based summary : Porphyria, Acute Intermittent, also known as acute intermittent porphyria, is related to porphyria and acute porphyria, and has symptoms including seizures, constipation and vomiting. An important gene associated with Porphyria, Acute Intermittent is HMBS (Hydroxymethylbilane Synthase), and among its related pathways/superpathways are Metabolism and Porphyrin and chlorophyll metabolism. The drugs Tin mesoporphyrin and Tin have been mentioned in the context of this disorder. Affiliated tissues include liver, testes and skin, and related phenotypes are depressivity and seizures

NIH Rare Diseases : 53 Acute intermittent porphyria (AIP) is one of the liver (hepatic) porphyrias. AIP is caused by low levels of porphobilinogen deaminase (PBGD), an enzyme also often called hydroxymethylbilane synthase. The low levels of PBGD are generally not sufficient to cause symptoms; however, activating factors such as hormones, drugs, and dietary changes may trigger symptoms. Although most individuals with AIP never develop symptoms, symptomatic individuals typically present with abdominal pain with nausea. Treatment is dependent on the symptoms.

UniProtKB/Swiss-Prot : 74 Acute intermittent porphyria: A form of porphyria. Porphyrias are inherited defects in the biosynthesis of heme, resulting in the accumulation and increased excretion of porphyrins or porphyrin precursors. They are classified as erythropoietic or hepatic, depending on whether the enzyme deficiency occurs in red blood cells or in the liver. AIP is an autosomal dominant form of hepatic porphyria characterized by attacks of gastrointestinal disturbances, abdominal colic, with neurological dysfunctions, hypertension, tachycardia and peripheral neuropathy. Most attacks are precipitated by drugs, alcohol, caloric deprivation, infections, or endocrine factors.

Wikipedia : 75 Acute intermittent porphyria (AIP) is a rare autosomal dominant metabolic disorder affecting the... more...

GeneReviews: NBK1193

Related Diseases for Porphyria, Acute Intermittent

Diseases related to Porphyria, Acute Intermittent via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 310)
# Related Disease Score Top Affiliating Genes
1 porphyria 28.8 UROS UROD PPOX HMBS FECH CPOX
2 acute porphyria 28.6 UROS UROD PPOX HMBS FECH CPOX
3 protoporphyria, erythropoietic, 1 27.2 UROS PPOX HMBS FECH CPOX ALAD
4 porphyria, congenital erythropoietic 27.1 UROS UROD HMBS FECH CPOX ALAD
5 porphyria cutanea tarda 26.5 FECH CPOX ALAS1 ALAD UROS UROD
6 coproporphyria, hereditary 25.7 UROS UROD PPOX HMBS FECH CPOX
7 aip-related familial isolated pituitary adenomas 12.6
8 acromegaly 12.3
9 pituitary adenoma 1, multiple types 12.2
10 acute interstitial pneumonia 12.1
11 pituitary adenoma, prolactin-secreting 12.1
12 autoimmune pancreatitis 12.0
13 adenoma 11.9
14 pituitary adenoma 11.9
15 familial isolated pituitary adenoma 11.7
16 gigantism 11.7
17 acroleukopathy, symmetric 11.7
18 pituitary tumors 11.7
19 pituitary apoplexy 11.7
20 idiopathic interstitial pneumonia 11.7
21 hormone producing pituitary cancer 11.6
22 carney complex variant 11.6
23 multiple endocrine neoplasia, type iv 11.6
24 functioning pituitary adenoma 11.6
25 autoimmune pancreatitis type 1 11.6
26 acth-secreting pituitary adenoma 11.5
27 hepatitis b 11.5
28 aminolevulinic acid dehydratase deficiency porphyria 11.5
29 chester porphyria 11.3
30 endocrine organ benign neoplasm 11.3
31 pituitary infarct 11.3
32 hyperpituitarism 11.3
33 pituitary gland disease 11.3
34 cancer-associated retinopathy 11.3
35 autoimmune pancreatitis type 2 11.2
36 silent pituitary adenoma 11.1
37 null pituitary adenoma 11.1
38 multiple endocrine neoplasia 10.5
39 syndrome of inappropriate antidiuretic hormone 10.5
40 multiple endocrine neoplasia, type i 10.5
41 kidney disease 10.4
42 systemic lupus erythematosus 10.3
43 abdominal obesity-metabolic syndrome 1 10.3
44 encephalopathy, progressive, early-onset, with episodic rhabdomyolysis 10.3
45 guillain-barre syndrome 10.3
46 inherited metabolic disorder 10.3
47 lupus erythematosus 10.3
48 hepatocellular carcinoma 10.3
49 cortical blindness 10.2
50 status epilepticus 10.2

Graphical network of the top 20 diseases related to Porphyria, Acute Intermittent:



Diseases related to Porphyria, Acute Intermittent

Symptoms & Phenotypes for Porphyria, Acute Intermittent

Human phenotypes related to Porphyria, Acute Intermittent:

59 32 (show all 40)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 depressivity 59 32 hallmark (90%) Very frequent (99-80%) HP:0000716
2 seizures 59 32 hallmark (90%) Very frequent (99-80%) HP:0001250
3 nausea and vomiting 59 32 hallmark (90%) Very frequent (99-80%) HP:0002017
4 abdominal pain 59 32 hallmark (90%) Very frequent (99-80%) HP:0002027
5 myalgia 59 32 hallmark (90%) Very frequent (99-80%) HP:0003326
6 anxiety 59 32 hallmark (90%) Very frequent (99-80%) HP:0000739
7 anorexia 59 32 hallmark (90%) Very frequent (99-80%) HP:0002039
8 insomnia 59 32 hallmark (90%) Very frequent (99-80%) HP:0100785
9 abnormal urinary color 59 32 hallmark (90%) Very frequent (99-80%) HP:0012086
10 urinary retention 59 32 hallmark (90%) Very frequent (99-80%) HP:0000016
11 hyperhidrosis 59 32 frequent (33%) Frequent (79-30%) HP:0000975
12 constipation 59 32 frequent (33%) Frequent (79-30%) HP:0002019
13 arrhythmia 59 32 frequent (33%) Frequent (79-30%) HP:0011675
14 paresthesia 59 32 frequent (33%) Frequent (79-30%) HP:0003401
15 hypertensive crisis 59 32 frequent (33%) Frequent (79-30%) HP:0100735
16 hallucinations 59 32 occasional (7.5%) Occasional (29-5%) HP:0000738
17 renal insufficiency 59 32 occasional (7.5%) Occasional (29-5%) HP:0000083
18 cranial nerve paralysis 59 32 occasional (7.5%) Occasional (29-5%) HP:0006824
19 arthralgia 59 32 occasional (7.5%) Occasional (29-5%) HP:0002829
20 weight loss 59 32 occasional (7.5%) Occasional (29-5%) HP:0001824
21 hyperlipidemia 59 32 occasional (7.5%) Occasional (29-5%) HP:0003077
22 hyponatremia 59 32 occasional (7.5%) Occasional (29-5%) HP:0002902
23 lethargy 59 32 occasional (7.5%) Occasional (29-5%) HP:0001254
24 diaphragmatic paralysis 59 32 occasional (7.5%) Occasional (29-5%) HP:0006597
25 paraparesis 59 32 occasional (7.5%) Occasional (29-5%) HP:0002385
26 hepatocellular carcinoma 59 32 occasional (7.5%) Occasional (29-5%) HP:0001402
27 hypertension 59 32 Frequent (79-30%) HP:0000822
28 muscle weakness 59 32 Very frequent (99-80%) HP:0001324
29 behavioral abnormality 59 Very frequent (99-80%)
30 vomiting 32 HP:0002013
31 psychotic episodes 32 HP:0000725
32 diarrhea 32 HP:0002014
33 respiratory paralysis 32 HP:0002203
34 urinary incontinence 32 HP:0000020
35 dysuria 32 HP:0100518
36 tachycardia 32 HP:0001649
37 nausea 32 HP:0002018
38 acute episodes of neuropathic symptoms 32 HP:0003489
39 paralytic ileus 32 HP:0002590
40 elevated urinary delta-aminolevulinic acid 32 HP:0003163

Symptoms via clinical synopsis from OMIM:

57
Cardiovascular Vascular:
hypertension

Abdomen Gastrointestinal:
constipation
vomiting
abdominal pain
diarrhea
nausea
more
Respiratory Lung:
respiratory paralysis

Cardiovascular Heart:
tachycardia

Neoplasia:
increased incidence of hepatocellular carcinoma

Neurologic Central Nervous System:
seizures
anxiety
psychotic episodes
acute episodes of neuropathic symptoms
depression
more
Neurologic Peripheral Nervous System:
paralysis
acute episodes of neuropathic symptoms
weakness
motor, sensory, or autonomic neuropathy

Genitourinary Bladder:
urinary incontinence
dysuria
urinary retention

Endocrine Features:
syndrome of inappropriate antidiuretic hormone (siadh)

Laboratory Abnormalities:
erythrocyte porphobilinogen (pbg) deaminase deficiency (exception: type ii aip)
increased urinary delta-aminolevulinic acid (ala) and porphobilinogen (pbg) during acute attacks
urine occasionally port-wine in color secondary to porphobilinogen

Clinical features from OMIM:

176000

UMLS symptoms related to Porphyria, Acute Intermittent:


seizures, constipation, vomiting, abdominal pain, diarrhea, dysuria, nausea, weakness

MGI Mouse Phenotypes related to Porphyria, Acute Intermittent:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 homeostasis/metabolism MP:0005376 9.5 AVP CPOX FECH HMBS PPOX UROD
2 mortality/aging MP:0010768 9.23 ALAS1 AVP CPOX FECH HMBS PPOX

Drugs & Therapeutics for Porphyria, Acute Intermittent

Drugs for Porphyria, Acute Intermittent (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 42)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1 Tin mesoporphyrin Phase 2
2
Tin Phase 2 7440-31-5
3
Guaifenesin Approved, Investigational, Vet_approved Phase 1 93-14-1 3516
4
Omeprazole Approved, Investigational, Vet_approved Phase 1 73590-58-6 4594
5
Midazolam Approved, Illicit Phase 1 59467-70-8 4192
6
Dextromethorphan Approved Phase 1 125-71-3 5360696 5362449
7
Losartan Approved Phase 1 114798-26-4 3961
8
Caffeine Approved Phase 1 58-08-2 2519
9
Dopamine Approved Phase 1 51-61-6, 62-31-7 681
10
Chlorpromazine Approved, Investigational, Vet_approved Phase 1 50-53-3 2726
11 Gastrointestinal Agents Phase 1
12 Antacids Phase 1
13 Respiratory System Agents Phase 1
14 Chlorpheniramine, phenylpropanolamine drug combination Phase 1
15 Neurotransmitter Agents Phase 1
16 Excitatory Amino Acid Antagonists Phase 1
17 Proton Pump Inhibitors Phase 1
18 Anti-Ulcer Agents Phase 1
19 Excitatory Amino Acids Phase 1
20 Antitussive Agents Phase 1
21 Liver Extracts Phase 1
22 Tranquilizing Agents Phase 1
23 Antiemetics Phase 1
24 Dopamine Agents Phase 1
25 Central Nervous System Depressants Phase 1
26 Antipsychotic Agents Phase 1
27 Dopamine Antagonists Phase 1
28 Autonomic Agents Phase 1
29 Psychotropic Drugs Phase 1
30 Peripheral Nervous System Agents Phase 1
31
Iron Approved, Experimental 15438-31-0, 7439-89-6 23925 27284
32
Aminolevulinic acid Approved 106-60-5 137
33
Isoniazid Approved, Investigational 54-85-3 3767
34
Protoporphyrin IX Experimental 553-12-8
35 Lipid Regulating Agents
36 Anti-Infective Agents
37 Anti-Bacterial Agents
38 Hypolipidemic Agents
39 Dermatologic Agents
40 Photosensitizing Agents
41 Antitubercular Agents
42 Antimetabolites

Interventional clinical trials:

(show all 24)
# Name Status NCT ID Phase Drugs
1 A Multi-centre, Double-blind, Randomized, Placebo-controlled, Parallel Group Trial, Investigating the Efficacy and Safety of Porphozym (Recombinant Human Porphobilinogen Deaminase) in the Treatment of Acute Attacks in AIP Completed NCT00418795 Phase 2, Phase 3 recombinant human porphobilinogen deaminase (Porphozym)
2 ENVISION: A Phase 3 Randomized, Double-blind, Placebo-Controlled Multicenter Study With an Open-label Extension to Evaluate the Efficacy and Safety of Givosiran in Patients With Acute Hepatic Porphyrias Active, not recruiting NCT03338816 Phase 3 Givosiran;Placebo
3 Studies in Porphyria III: Heme and Tin Mesoporphyrin in Acute Porphyrias Completed NCT00004396 Phase 2 heme arginate;tin mesoporphyrin
4 Phase I/II Study of Heme Arginate and Tin Mesoporphyrin for Acute Porphyria Completed NCT00004789 Phase 1, Phase 2 heme arginate;tin mesoporphyrin
5 Safety and Efficacy of Panhematin™ for Prevention of Acute Attacks of Porphyria Recruiting NCT02922413 Phase 2
6 A Multicenter, Open-label Extension Study to Evaluate the Long-term Safety and Clinical Activity of Subcutaneously Administered ALN-AS1 in Patients With Acute Intermittent Porphyria Who Have Completed a Previous Clinical Study With ALN-AS1 Active, not recruiting NCT02949830 Phase 1, Phase 2 givosiran (ALN-AS1)
7 A Double-blind, Randomized, Placebo-controlled, Parallel Group Trial on the Efficacy and Safety of PanhematinTM in the Treatment of Acute Attacks of Porphyria Active, not recruiting NCT02180412 Phase 2
8 A Phase 2, Open-Label, Multiple-Dose Study Investigating the Efficacy and Safety of Panhematin in Patients With Low or Intermediate-1 Risk Myelodysplastic Syndrome Terminated NCT00467610 Phase 2 Panhematin
9 A Phase 1, Single-ascending Dose, Multiple-ascending Dose, and Multi-dose Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics Study of Subcutaneously Administered ALN AS1 in Patients With Acute Intermittent Porphyria (AIP) Completed NCT02452372 Phase 1 givosiran (ALN-AS1);Sterile Normal Saline (0.9% NaCl)
10 A Drug-Drug Interaction Study to Investigate the Effect of Givosiran on the Pharmacokinetics (PK) of Midazolam, Caffeine, Losartan, Omeprazole, and Dextromethorphan in Patients With Acute Intermittent Porphyria (AIP) Who Are Asymptomatic High Excreters (ASHE) Completed NCT03505853 Phase 1 Givosiran;5-probe cocktail
11 Phase I, Multicentre, Open Label, Single Dose, Dose-ranging Clinical Trial to Investigate the Safety and Tolerability of a Gene Therapy rAAV2/5-PBGD for the Treatment of Acute Intermittent Porphyria Completed NCT02082860 Phase 1
12 A Single Center, Single Dose, Open-Label, Two-Period Replicate Pilot Study to Investigate Intra-subject Variability in the Bioavailability of a Formulation Containing Chlorpromazine Hydrochloride (25 mg Sugar Coated Tablets) in at Least 16 Healthy Males and Females Under Fasting Conditions Completed NCT02943213 Phase 1 Chlorpromazine Hydrochloride
13 Effect of Hemin on Heme-Oxygenase-1 Activity in Healthy Subjects Completed NCT00882804 Phase 1 Hemin infusion;placebo infusion
14 Clinical Diagnosis of Acute Porphyria Completed NCT01568554
15 Observational Study of Acute Intermittent Porphyria Patients Completed NCT02076763
16 Study of Nutritional Factors in Porphyria Completed NCT00004788
17 Longitudinal Study of the Porphyrias Recruiting NCT01561157
18 Evidence-based Assessment of Medication Sensitivity in Acute Hepatic Porphyria Recruiting NCT03906214
19 BioTyrosin - Biomarker for the Early Diagnosis and Monitoring in Tyrosinemia Type 1 - An International, Multicenter, Epidemiological Protocol Recruiting NCT03284658
20 Acute Porphyrias: Biomarkers for Disease Activity and Response to Treatment Active, not recruiting NCT02935400 Hemin
21 Dental Health, Diet, Inflammation and Biomarkers in Patients With Acute Intermittent Porphyria(AIP) Active, not recruiting NCT01617642
22 Expanded Access Protocol of Givosiran for Patients With Acute Hepatic Porphyria (AHP) Available NCT04056481 Givosiran
23 INSIGHT-AHP: A Study to Characterize the Prevalence of Acute Hepatic Porphyria (AHP) in Patients With Clinical Presentation and History Consistent With AHP Terminated NCT03547297
24 Quantification of the Effects of Isoniazid Treatment on Erythrocyte and Plasma Protoporphyrin IX Concentration and Plasma Aminolevulinic Acid in Patients With Erythropoietic Protoporphyria Terminated NCT01550705 Isoniazid

Search NIH Clinical Center for Porphyria, Acute Intermittent

Inferred drug relations via UMLS 72 / NDF-RT 51 :


Chlorpromazine
Chlorpromazine
Chlorpromazine hydrochloride
Hemin
Hemin

Cochrane evidence based reviews: porphyria, acute intermittent

Genetic Tests for Porphyria, Acute Intermittent

Genetic tests related to Porphyria, Acute Intermittent:

# Genetic test Affiliating Genes
1 Acute Intermittent Porphyria 29 HMBS
2 Porphyria, Acute Intermittent, Nonerythroid Variant 29

Anatomical Context for Porphyria, Acute Intermittent

MalaCards organs/tissues related to Porphyria, Acute Intermittent:

41
Liver, Testes, Skin, Kidney, Brain, Thyroid, Cerebellum

Publications for Porphyria, Acute Intermittent

Articles related to Porphyria, Acute Intermittent:

(show top 50) (show all 1686)
# Title Authors PMID Year
1
Exon 1 donor splice site mutations in the porphobilinogen deaminase gene in the non-erythroid variant form of acute intermittent porphyria. 9 38 4 8 71
9860299 1998
2
Acute intermittent porphyria: studies of the severe homozygous dominant disease provides insights into the neurologic attacks in acute porphyrias. 38 4 8 71
15534187 2004
3
Homozygous acute intermittent porphyria in a 7-year-old boy with massive excretions of porphyrins and porphyrin precursors. 38 4 8 71
14970743 2004
4
A point mutation G----A in exon 12 of the porphobilinogen deaminase gene results in exon skipping and is responsible for acute intermittent porphyria. 38 4 8 71
2789372 1989
5
Non-erythroid form of acute intermittent porphyria caused by promoter and frameshift mutations distant from the coding sequence of exon 1 of the HMBS gene. 9 38 8 71
11071386 2000
6
Acute intermittent porphyria in Finland: 19 mutations in the porphobilinogen deaminase gene. 9 38 8 71
7757070 1995
7
Identification of the most common mutation within the porphobilinogen deaminase gene in Swedish patients with acute intermittent porphyria. 9 38 8 71
1961762 1991
8
Demystification of Chester porphyria: a nonsense mutation in the Porphobilinogen Deaminase gene. 38 8 71
17298217 2006
9
Acute intermittent porphyria in Sweden. Molecular, functional and clinical consequences of some new mutations found in the porphobilinogen deaminase gene. 9 38 4 8
12372055 2002
10
Acute intermittent porphyria: mutation analysis and identification of gene carriers in a German kindred by PCR-DGGE analysis. 38 8 71
10343207 1998
11
Molecular epidemiology and diagnosis of PBG deaminase gene defects in acute intermittent porphyria. 38 8 71
9199558 1997
12
Homozygous acute intermittent porphyria: compound heterozygosity for adjacent base transitions in the same codon of the porphobilinogen deaminase gene. 38 8 71
1577472 1992
13
Tissue-specific splicing mutation in acute intermittent porphyria. 38 8 71
2563167 1989
14
Chester porphyria: biochemical studies of a new form of acute porphyria. 38 8 71
2864531 1985
15
Liver transplantation as a cure for acute intermittent porphyria. 38 4 8
15001330 2004
16
Feline acute intermittent porphyria: a phenocopy masquerading as an erythropoietic porphyria due to dominant and recessive hydroxymethylbilane synthase mutations. 9 38 8
19934113 2010
17
Ancestral founder of mutation W283X in the porphobilinogen deaminase gene among acute intermittent porphyria patients. 9 38 71
12566739 2002
18
Identification and characterization of hydroxymethylbilane synthase mutations causing acute intermittent porphyria: evidence for an ancestral founder of the common G111R mutation. 9 38 71
10494093 1999
19
Comparison of complementary and genomic DNA sequencing for the detection of mutations in the HMBS gene in British patients with acute intermittent porphyria: identification of 25 novel mutations. 9 38 8
10453740 1999
20
Insertion of Alu element responsible for acute intermittent porphyria. 9 38 71
10408772 1999
21
Porphobilinogen deaminase deficiency in mice causes a neuropathy resembling that of human hepatic porphyria. 9 38 8
8563760 1996
22
Acute intermittent porphyria: identification and expression of exonic mutations in the hydroxymethylbilane synthase gene. An initiation codon missense mutation in the housekeeping transcript causes "variant acute intermittent porphyria" with normal expression of the erythroid-specific enzyme. 9 38 71
7962538 1994
23
Molecular basis of acute intermittent porphyria: mutations and polymorphisms in the human hydroxymethylbilane synthase gene. 9 38 8
7866402 1994
24
Detection of eleven mutations causing acute intermittent porphyria using denaturing gradient gel electrophoresis. 9 38 71
8270254 1994
25
Two new mutations in the porphobilinogen deaminase gene and a screening method using PCR amplification of specific alleles. 9 38 71
8270256 1994
26
Detection of a high mutation frequency in exon 12 of the porphobilinogen deaminase gene in patients with acute intermittent porphyria. 9 38 71
8262523 1993
27
Acute intermittent porphyria caused by an arginine to histidine substitution (R26H) in the cofactor-binding cleft of porphobilinogen deaminase. 9 38 71
8401516 1993
28
High prevalence of a point mutation in the porphobilinogen deaminase gene in Dutch patients with acute intermittent porphyria. 9 38 71
8096492 1993
29
CRIM-positive mutations of acute intermittent porphyria in Finland. 9 38 71
1301948 1992
30
Linkage disequilibrium between DNA polymorphisms within the porphobilinogen deaminase gene. 9 38 8
1973402 1990
31
Haplotyping of the human porphobilinogen deaminase gene in acute intermittent porphyria by polymerase chain reaction. 9 38 8
2303246 1990
32
Phase 1 Trial of an RNA Interference Therapy for Acute Intermittent Porphyria. 38 8
30726693 2019
33
Recurrent attacks of acute hepatic porphyria: major role of the chronic inflammatory response in the liver. 38 8
29498764 2018
34
An update of clinical management of acute intermittent porphyria. 38 8
26366103 2015
35
Urinary excretion of porphyrins, porphobilinogen and δ-aminolaevulinic acid following an attack of acute intermittent porphyria. 38 8
23908454 2014
36
Diagnostic strategies for autosomal dominant acute porphyrias: retrospective analysis of 467 unrelated patients referred for mutational analysis of the HMBS, CPOX, or PPOX gene. 9 38 4
19460837 2009
37
Structure of human porphobilinogen deaminase at 2.8 A: the molecular basis of acute intermittent porphyria. 9 38 4
19207107 2009
38
Neurological manifestations of acute intermittent porphyria. 9 38 4
19268005 2009
39
Acute Intermittent Porphyria 38 71
20301372 2005
40
Clinical and biochemical characteristics and genotype-phenotype correlation in 143 Finnish and Russian patients with acute intermittent porphyria. 9 38 4
15643298 2005
41
Acute intermittent porphyria: prevalence of mutations in the porphobilinogen deaminase gene in blood donors in France. 9 38 4
9350165 1997
42
Genetic investigation of the porphobilinogen deaminase gene in Swedish acute intermittent porphyria families. 38 71
9225970 1997
43
Increased delta aminolevulinic acid and decreased pineal melatonin production. A common event in acute porphyria studies in the rat. 38 8
8550820 1996
44
Acute intermittent porphyria caused by a G to C mutation in exon 12 of the porphobilinogen deaminase gene that results in exon skipping. 38 71
8262514 1993
45
Evidence for involvement of a second genetic locus on chromosome 11q in porphyrin metabolism. 9 8
8340112 1993
46
High frequency of mutations in exon 10 of the porphobilinogen deaminase gene in patients with a CRIM-positive subtype of acute intermittent porphyria. 38 71
1496994 1992
47
Detection of seven point mutations in the porphobilinogen deaminase gene in patients with acute intermittent porphyria, by direct sequencing of in vitro amplified cDNA. 38 71
1427766 1992
48
Vincent van Gogh's illness: acute intermittent porphyria? 38 8
1773180 1991
49
Genetic heterogeneity of the porphobilinogen deaminase gene in Swedish families with acute intermittent porphyria. 38 8
1679034 1991
50
Molecular heterogeneity of acute intermittent porphyria: identification of four additional mutations resulting in the CRIM-negative subtype of the disease. 38 71
1714233 1991

Variations for Porphyria, Acute Intermittent

ClinVar genetic disease variations for Porphyria, Acute Intermittent:

6 (show top 50) (show all 83)
# Gene Variation Type Significance SNP ID GRCh37 Pos GRCh38 Pos
1 HMBS NM_000190.4(HMBS): c.518G> A (p.Arg173Gln) single nucleotide variant Pathogenic rs118204096 11:118962142-118962142 11:119091432-119091432
2 HMBS NM_000190.4(HMBS): c.463C> T (p.Gln155Ter) single nucleotide variant Pathogenic rs118204097 11:118960940-118960940 11:119090230-119090230
3 HMBS NM_000190.4(HMBS): c.446G> A (p.Arg149Gln) single nucleotide variant Pathogenic rs118204098 11:118960923-118960923 11:119090213-119090213
4 HMBS NM_000190.4(HMBS): c.734T> G (p.Leu245Arg) single nucleotide variant Pathogenic rs118204099 11:118963196-118963196 11:119092486-119092486
5 HMBS NM_000190.4(HMBS): c.900del (p.His300fs) deletion Pathogenic 11:118963719-118963719 11:119093009-119093009
6 HMBS HMBS, 9-BP DEL, EX10 deletion Pathogenic
7 HMBS NM_000190.4(HMBS): c.593G> A (p.Trp198Ter) single nucleotide variant Pathogenic rs118204100 11:118962217-118962217 11:119091507-119091507
8 HMBS NM_000190.4(HMBS): c.91G> A (p.Ala31Thr) single nucleotide variant Pathogenic rs118204104 11:118959348-118959348 11:119088638-119088638
9 HMBS NM_000190.4(HMBS): c.100C> A (p.Gln34Lys) single nucleotide variant Pathogenic rs118204105 11:118959357-118959357 11:119088647-119088647
10 HMBS NM_000190.4(HMBS): c.499C> T (p.Arg167Trp) single nucleotide variant Pathogenic rs118204101 11:118962123-118962123 11:119091413-119091413
11 HMBS NM_000190.4(HMBS): c.500G> T (p.Arg167Leu) single nucleotide variant Pathogenic rs118204095 11:118962124-118962124 11:119091414-119091414
12 HMBS NM_000190.4(HMBS): c.163G> T (p.Ala55Ser) single nucleotide variant Pathogenic rs118204106 11:118959794-118959794 11:119089084-119089084
13 HMBS NM_000190.4(HMBS): c.174del (p.Thr59fs) deletion Pathogenic 11:118959805-118959805 11:119089095-119089095
14 HMBS NM_000190.4(HMBS): c.181dup (p.Asp61fs) duplication Pathogenic 11:118959812-118959812 11:119089102-119089102
15 HMBS NM_000190.4(HMBS): c.211-1G> A single nucleotide variant Pathogenic 11:118959926-118959926 11:119089216-119089216
16 HMBS NM_000190.4(HMBS): c.728_729CT[1] (p.Leu244fs) short repeat Pathogenic 11:118963192-118963193 11:119092482-119092483
17 HMBS NM_000190.4(HMBS): c.739T> C (p.Cys247Arg) single nucleotide variant Pathogenic rs118204111 11:118963201-118963201 11:119092491-119092491
18 HMBS NM_000190.4(HMBS): c.734_741dup (p.Ile248fs) duplication Pathogenic 11:118963196-118963203 11:119092486-119092493
19 HMBS NM_000190.4(HMBS): c.748G> A (p.Glu250Lys) single nucleotide variant Pathogenic rs118204112 11:118963210-118963210 11:119092500-119092500
20 HMBS NM_000190.4(HMBS): c.754G> A (p.Ala252Thr) single nucleotide variant Pathogenic rs118204113 11:118963216-118963216 11:119092506-119092506
21 HMBS NM_000190.4(HMBS): c.755C> T (p.Ala252Val) single nucleotide variant Pathogenic rs118204114 11:118963217-118963217 11:119092507-119092507
22 HMBS NM_000190.4(HMBS): c.766C> A (p.His256Asn) single nucleotide variant Pathogenic rs118204115 11:118963228-118963228 11:119092518-119092518
23 HMBS NM_000190.4(HMBS): c.771+1G> C single nucleotide variant Pathogenic 11:118963234-118963234 11:119092524-119092524
24 HMBS HMBS, IVS14DS, G-A, +1 single nucleotide variant Pathogenic
25 HMBS NM_000190.4(HMBS): c.266+1G> C single nucleotide variant Pathogenic 11:118959983-118959983 11:119089273-119089273
26 HMBS NM_000190.4(HMBS): c.647G> A (p.Gly216Asp) single nucleotide variant Pathogenic rs118204116 11:118962869-118962869 11:119092159-119092159
27 HMBS HMBS, 2-BP DEL, 847TG deletion Pathogenic
28 HMBS HMBS, ALU INS insertion Pathogenic
29 HMBS HMBS, 1-BP DEL, -154G deletion Pathogenic
30 HMBS HMBS, 1-BP DEL, 41A deletion Pathogenic
31 HMBS NM_000190.4(HMBS): c.849G> A (p.Trp283Ter) single nucleotide variant Pathogenic rs118204117 11:118963668-118963668 11:119092958-119092958
32 HMBS NM_000190.4(HMBS): c.1A> G (p.Met1Val) single nucleotide variant Pathogenic rs118204118 11:118955744-118955744 11:119085034-119085034
33 HMBS NM_000190.4(HMBS): c.242T> C (p.Leu81Pro) single nucleotide variant Pathogenic rs118204119 11:118959958-118959958 11:119089248-119089248
34 HMBS NM_000190.4(HMBS): c.445C> T (p.Arg149Ter) single nucleotide variant Pathogenic rs118204120 11:118960922-118960922 11:119090212-119090212
35 HMBS NM_000190.4(HMBS): c.669_698del (p.Glu223_Leu232del) deletion Pathogenic rs1555206128 11:118963131-118963160 11:119092421-119092450
36 HMBS NM_000190.3 deletion Pathogenic rs1555206402 11:118963985-118964039 11:119093275-119093329
37 HMBS NM_000190.4(HMBS): c.33+1G> A single nucleotide variant Pathogenic 11:118955777-118955777 11:119085067-119085067
38 HMBS HMBS, EX12DEL deletion Pathogenic
39 HMBS NM_000190.4(HMBS): c.77G> A (p.Arg26His) single nucleotide variant Pathogenic rs118204103 11:118959008-118959008 11:119088298-119088298
40 HMBS NM_000190.4(HMBS): c.33+1G> T single nucleotide variant Pathogenic 11:118955777-118955777 11:119085067-119085067
41 HMBS NM_000190.4(HMBS): c.346C> T (p.Arg116Trp) single nucleotide variant Pathogenic rs118204094 11:118960701-118960701 11:119089991-119089991
42 HMBS HMBS, 2-BP DEL, 218AG deletion Pathogenic
43 HMBS NM_000190.4(HMBS): c.331G> A (p.Gly111Arg) single nucleotide variant Pathogenic rs118204107 11:118960457-118960457 11:119089747-119089747
44 HMBS NM_000190.4(HMBS): c.499-1G> A single nucleotide variant Pathogenic 11:118962122-118962122 11:119091412-119091412
45 HMBS NM_000190.4(HMBS): c.530T> G (p.Leu177Arg) single nucleotide variant Pathogenic rs118204108 11:118962154-118962154 11:119091444-119091444
46 HMBS NM_000190.4(HMBS): c.601C> T (p.Arg201Trp) single nucleotide variant Pathogenic/Likely pathogenic rs118204109 11:118962225-118962225 11:119091515-119091515
47 HMBS NM_000190.4(HMBS): c.667G> A (p.Glu223Lys) single nucleotide variant Likely pathogenic rs118204110 11:118963129-118963129 11:119092419-119092419
48 HMBS NM_000190.4(HMBS): c.500G> A (p.Arg167Gln) single nucleotide variant Likely pathogenic rs118204095 11:118962124-118962124 11:119091414-119091414
49 HMBS NM_000190.4(HMBS): c.583C> T (p.Arg195Cys) single nucleotide variant Likely pathogenic rs34413634 11:118962207-118962207 11:119091497-119091497
50 HMBS NM_000190.4(HMBS): c.891dup (p.Thr298fs) duplication Likely pathogenic 11:118963710-118963710 11:119093000-119093000

UniProtKB/Swiss-Prot genetic disease variations for Porphyria, Acute Intermittent:

74 (show top 50) (show all 89)
# Symbol AA change Variation ID SNP ID
1 HMBS p.Arg22Cys VAR_003638 rs189159450
2 HMBS p.Arg26His VAR_003639 rs118204103
3 HMBS p.Ala31Thr VAR_003640 rs118204104
4 HMBS p.Gln34Lys VAR_003641 rs118204105
5 HMBS p.Ala55Ser VAR_003642 rs118204106
6 HMBS p.Val93Phe VAR_003643
7 HMBS p.Lys98Arg VAR_003644
8 HMBS p.Gly111Arg VAR_003645 rs118204107
9 HMBS p.Arg116Gln VAR_003646 rs116504627
10 HMBS p.Arg116Trp VAR_003647 rs118204094
11 HMBS p.Pro119Leu VAR_003648
12 HMBS p.Arg149Leu VAR_003649
13 HMBS p.Arg149Gln VAR_003650 rs118204098
14 HMBS p.Arg167Gln VAR_003651 rs118204095
15 HMBS p.Arg167Trp VAR_003652 rs118204101
16 HMBS p.Arg173Gln VAR_003653 rs118204096
17 HMBS p.Arg173Trp VAR_003654 rs575222284
18 HMBS p.Leu177Arg VAR_003655 rs118204108
19 HMBS p.Arg195Cys VAR_003656 rs34413634
20 HMBS p.Arg201Trp VAR_003657 rs118204109
21 HMBS p.Val222Met VAR_003658 rs126194787
22 HMBS p.Glu223Lys VAR_003659 rs118204110
23 HMBS p.Arg225Gly VAR_003660
24 HMBS p.Leu238Arg VAR_003661
25 HMBS p.Leu245Arg VAR_003662 rs118204099
26 HMBS p.Cys247Phe VAR_003663
27 HMBS p.Cys247Arg VAR_003664 rs118204111
28 HMBS p.Glu250Ala VAR_003665
29 HMBS p.Glu250Lys VAR_003666 rs118204112
30 HMBS p.Ala252Thr VAR_003667 rs118204113
31 HMBS p.Ala252Val VAR_003668 rs118204114
32 HMBS p.His256Asn VAR_003669 rs118204115
33 HMBS p.Thr269Ile VAR_003670
34 HMBS p.Gly274Arg VAR_003671
35 HMBS p.Leu278Pro VAR_003672
36 HMBS p.Gly280Arg VAR_003673
37 HMBS p.Gly24Ser VAR_011001
38 HMBS p.Arg26Cys VAR_011002 rs998842815
39 HMBS p.Ser28Asn VAR_011003
40 HMBS p.Ala31Pro VAR_011004
41 HMBS p.Gln34Pro VAR_011005
42 HMBS p.Thr35Met VAR_011006 rs974712040
43 HMBS p.Leu42Ser VAR_011007
44 HMBS p.Asp61Asn VAR_011008
45 HMBS p.Leu85Arg VAR_011009
46 HMBS p.Val90Gly VAR_011010
47 HMBS p.Val124Asp VAR_011011
48 HMBS p.Val202Leu VAR_011013 rs914335144
49 HMBS p.Glu209Lys VAR_011014 rs100785987
50 HMBS p.Gly216Asp VAR_011015 rs118204116

Expression for Porphyria, Acute Intermittent

Search GEO for disease gene expression data for Porphyria, Acute Intermittent.

Pathways for Porphyria, Acute Intermittent

GO Terms for Porphyria, Acute Intermittent

Cellular components related to Porphyria, Acute Intermittent according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cytosol GO:0005829 9.5 UROS UROD HMBS CPOX AVP ALAS1
2 mitochondrial intermembrane space GO:0005758 9.16 PPOX CPOX
3 mitochondrion GO:0005739 9.02 UROS PPOX FECH CPOX ALAS1

Biological processes related to Porphyria, Acute Intermittent according to GeneCards Suite gene sharing:

(show all 13)
# Name GO ID Score Top Affiliating Genes
1 response to drug GO:0042493 9.7 PPOX FECH ALAD
2 protoporphyrinogen IX biosynthetic process GO:0006782 9.7 UROS UROD PPOX HMBS CPOX ALAS1
3 response to ethanol GO:0045471 9.61 FECH AVP ALAD
4 tetrapyrrole biosynthetic process GO:0033014 9.56 UROS HMBS ALAS1 ALAD
5 generation of precursor metabolites and energy GO:0006091 9.51 FECH AVP
6 response to platinum ion GO:0070541 9.5 UROS FECH ALAD
7 porphyrin-containing compound biosynthetic process GO:0006779 9.5 UROS UROD PPOX HMBS FECH CPOX
8 response to lead ion GO:0010288 9.49 FECH ALAD
9 response to metal ion GO:0010038 9.48 FECH ALAD
10 response to arsenic-containing substance GO:0046685 9.46 FECH ALAD
11 response to methylmercury GO:0051597 9.4 FECH ALAD
12 protoporphyrinogen IX metabolic process GO:0046501 9.37 PPOX FECH
13 heme biosynthetic process GO:0006783 9.23 UROS UROD PPOX HMBS FECH CPOX

Molecular functions related to Porphyria, Acute Intermittent according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 lyase activity GO:0016829 8.92 UROS UROD FECH ALAD

Sources for Porphyria, Acute Intermittent

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