AIP
MCID: PRP083
MIFTS: 64

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 73 13 44 39
Acute Intermittent Porphyria 12 73 25 20 58 72 29 6 15 70
Porphobilinogen Deaminase Deficiency 57 25 20 72
Pbgd Deficiency 57 25 20 72
Porphyria, Acute Intermittent, Nonerythroid Variant 57 29 6
Uroporphyrinogen Synthase Deficiency 57 20 72
Porphyria, Swedish Type 57 20 72
Ups Deficiency 57 20 72
Aip 57 20 72
Hydroxymethylbilane Synthase Deficiency 20 70
Aip - Acute Intermittent Porphyria 12
Porphyria Intermittent Acute 12
Porphyria Acute Intermittent 54
Pyrroloporphyria 12
Hmbs Deficiency 20

Characteristics:

Orphanet epidemiological data:

58
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 (Updated 05-Apr-2021)
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:

31
porphyria, acute intermittent:
Inheritance autosomal dominant inheritance


GeneReviews:

25
Penetrance Families from the french reference center for porphyria were evaluated for penetrance of aip. the cohort consisted of 496 symptomatic individuals and 1672 asymptomatic relatives with an hmbs pathogenic variant. the estimated penetrance of aip in affected families was 22.9% and 12.7% in the relatives of aip index cases....

Classifications:

Orphanet: 58  
Rare neurological diseases
Rare hepatic diseases
Rare renal diseases
Rare skin diseases
Inborn errors of metabolism


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 are 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) (Updated 05-Apr-2021)

MalaCards based summary : Porphyria, Acute Intermittent, also known as acute intermittent porphyria, is related to siderosis and 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 Biosynthesis of cofactors. The drugs Midazolam and Omeprazole have been mentioned in the context of this disorder. Affiliated tissues include liver, brain and kidney, and related phenotypes are abdominal pain and abnormal enzyme/coenzyme activity

GARD : 20 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 : 72 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 : 73 Acute intermittent porphyria (AIP) is a rare metabolic disorder affecting the production of heme... 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 331)
# Related Disease Score Top Affiliating Genes
1 siderosis 30.0 UROD HMOX1
2 porphyria 30.0 UROS UROD PPOX HPX HMOX1 HMBS
3 porphyria, congenital erythropoietic 29.8 UROS UROD HMBS FECH CPOX ALAD
4 variegate porphyria 28.7 UROS UROD SLC15A2 PPOX HMBS FLVCR2
5 porphyria cutanea tarda 28.5 UROS UROD SLC15A2 PPOX HPX HMBS
6 protoporphyria, erythropoietic, 1 28.1 UROS UROD PPOX HMOX1 HMBS FECH
7 acute porphyria 28.1 UROS UROD PPOX PC HMOX1 HMBS
8 coproporphyria, hereditary 28.0 UROS UROD PPOX HMBS FLVCR2 FECH
9 deficiency anemia 27.7 UROS PPOX HPX HMOX1 FLVCR2 FLVCR1
10 acromegaly 11.4
11 pituitary adenoma 1, multiple types 11.4
12 autoimmune pancreatitis 11.4
13 acute interstitial pneumonia 11.4
14 adenoma 11.3
15 pituitary adenoma 11.3
16 pituitary adenoma, prolactin-secreting 11.3
17 aip familial isolated pituitary adenomas 11.2
18 hepatitis b 11.2
19 acth-secreting pituitary adenoma 11.2
20 hepatitis 11.1
21 familial isolated pituitary adenoma 11.1
22 gigantism 11.1
23 pituitary tumors 11.1
24 multiple endocrine neoplasia 11.1
25 growth hormone secreting pituitary adenoma 11.0
26 idiopathic interstitial pneumonia 11.0
27 chester porphyria 11.0
28 pituitary apoplexy 11.0
29 primary hyperparathyroidism 11.0
30 autoimmune pancreatitis type 1 11.0
31 acroleukopathy, symmetric 11.0
32 hormone producing pituitary cancer 10.9
33 tumor predisposition syndrome 10.9
34 cutaneous telangiectasia and cancer syndrome, familial 10.9
35 inherited cancer-predisposing syndrome 10.9
36 multiple endocrine neoplasia, type i 10.9
37 autoimmune pancreatitis type 2 10.9
38 carney complex variant 10.9
39 multiple endocrine neoplasia, type iv 10.9
40 functioning pituitary adenoma 10.9
41 cell type benign neoplasm 10.8
42 endocrine organ benign neoplasm 10.8
43 pituitary infarct 10.8
44 hyperpituitarism 10.8
45 pituitary gland disease 10.8
46 cancer-associated retinopathy 10.8
47 encephalopathy 10.7
48 polyneuropathy 10.7
49 peripheral nervous system disease 10.6
50 kidney disease 10.4

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:

58 31 (show top 50) (show all 59)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 abdominal pain 58 31 hallmark (90%) Very frequent (99-80%) HP:0002027
2 abnormal enzyme/coenzyme activity 58 31 hallmark (90%) Very frequent (99-80%) HP:0012379
3 elevated urinary delta-aminolevulinic acid 58 31 hallmark (90%) Very frequent (99-80%) HP:0003163
4 porphyrinuria 58 31 hallmark (90%) Very frequent (99-80%) HP:0010473
5 increased urinary porphobilinogen 58 31 hallmark (90%) Very frequent (99-80%) HP:0012217
6 nausea and vomiting 58 31 frequent (33%) Frequent (79-30%) HP:0002017
7 constipation 58 31 frequent (33%) Frequent (79-30%) HP:0002019
8 hypertension 58 31 frequent (33%) Frequent (79-30%) HP:0000822
9 renal insufficiency 58 31 frequent (33%) Frequent (79-30%) HP:0000083
10 cranial nerve paralysis 58 31 frequent (33%) Frequent (79-30%) HP:0006824
11 back pain 58 31 frequent (33%) Frequent (79-30%) HP:0003418
12 mental deterioration 58 31 frequent (33%) Frequent (79-30%) HP:0001268
13 tachycardia 58 31 frequent (33%) Frequent (79-30%) HP:0001649
14 limb pain 58 31 frequent (33%) Frequent (79-30%) HP:0009763
15 neck pain 58 31 frequent (33%) Frequent (79-30%) HP:0030833
16 depressivity 58 31 occasional (7.5%) Occasional (29-5%) HP:0000716
17 respiratory insufficiency 58 31 occasional (7.5%) Occasional (29-5%) HP:0002093
18 hallucinations 58 31 occasional (7.5%) Occasional (29-5%) HP:0000738
19 fever 58 31 occasional (7.5%) Occasional (29-5%) HP:0001945
20 anxiety 58 31 occasional (7.5%) Occasional (29-5%) HP:0000739
21 proximal muscle weakness in lower limbs 58 31 occasional (7.5%) Occasional (29-5%) HP:0008994
22 proximal muscle weakness in upper limbs 58 31 occasional (7.5%) Occasional (29-5%) HP:0008997
23 hyponatremia 58 31 occasional (7.5%) Occasional (29-5%) HP:0002902
24 insomnia 58 31 occasional (7.5%) Occasional (29-5%) HP:0100785
25 memory impairment 58 31 occasional (7.5%) Occasional (29-5%) HP:0002354
26 restlessness 58 31 occasional (7.5%) Occasional (29-5%) HP:0000711
27 diarrhea 58 31 occasional (7.5%) Occasional (29-5%) HP:0002014
28 sensory impairment 58 31 occasional (7.5%) Occasional (29-5%) HP:0003474
29 brain imaging abnormality 58 31 occasional (7.5%) Occasional (29-5%) HP:0410263
30 abdominal distention 58 31 occasional (7.5%) Occasional (29-5%) HP:0003270
31 distal muscle weakness 58 31 occasional (7.5%) Occasional (29-5%) HP:0002460
32 confusion 58 31 occasional (7.5%) Occasional (29-5%) HP:0001289
33 excessive daytime somnolence 58 31 occasional (7.5%) Occasional (29-5%) HP:0001262
34 motor axonal neuropathy 58 31 occasional (7.5%) Occasional (29-5%) HP:0007002
35 hepatocellular carcinoma 58 31 occasional (7.5%) Occasional (29-5%) HP:0001402
36 ileus 58 31 occasional (7.5%) Occasional (29-5%) HP:0002595
37 respiratory paralysis 58 31 occasional (7.5%) Occasional (29-5%) HP:0002203
38 pseudobulbar paralysis 58 31 occasional (7.5%) Occasional (29-5%) HP:0007024
39 motor polyneuropathy 58 31 occasional (7.5%) Occasional (29-5%) HP:0007178
40 paranoia 58 31 occasional (7.5%) Occasional (29-5%) HP:0011999
41 dark urine 58 31 occasional (7.5%) Occasional (29-5%) HP:0040319
42 seizure 31 occasional (7.5%) HP:0001250
43 hyperhidrosis 58 31 very rare (1%) Very rare (<4-1%) HP:0000975
44 tremor 58 31 very rare (1%) Very rare (<4-1%) HP:0001337
45 dysuria 58 31 very rare (1%) Very rare (<4-1%) HP:0100518
46 coma 58 31 very rare (1%) Very rare (<4-1%) HP:0001259
47 urinary retention 58 31 very rare (1%) Very rare (<4-1%) HP:0000016
48 urinary incontinence 58 31 very rare (1%) Very rare (<4-1%) HP:0000020
49 seizures 58 Occasional (29-5%)
50 muscle weakness 31 HP:0001324

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Neurologic Central Nervous System:
seizures
anxiety
psychotic episodes
acute episodes of neuropathic symptoms
depression
more
Cardiovascular Vascular:
hypertension

Cardiovascular Heart:
tachycardia

Neurologic Peripheral Nervous System:
acute episodes of neuropathic symptoms
paralysis
weakness
motor, sensory, or autonomic neuropathy

Neoplasia:
increased incidence of hepatocellular carcinoma

Abdomen Gastrointestinal:
constipation
vomiting
abdominal pain
diarrhea
nausea
more
Genitourinary Bladder:
dysuria
urinary retention
urinary incontinence

Respiratory Lung:
respiratory paralysis

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 (Updated 05-Apr-2021)

UMLS symptoms related to Porphyria, Acute Intermittent:


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

MGI Mouse Phenotypes related to Porphyria, Acute Intermittent:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 homeostasis/metabolism MP:0005376 10.1 ALAD ALAS2 AVP CPOX FECH FLVCR1
2 hematopoietic system MP:0005397 10.06 ALAD ALAS2 AVP CPOX FECH FLVCR1
3 embryo MP:0005380 9.97 ALAS1 ALAS2 CPOX FECH FLVCR2 HMBS
4 mortality/aging MP:0010768 9.83 ALAD ALAS1 ALAS2 AVP CPOX FECH
5 liver/biliary system MP:0005370 9.63 FECH HMBS HMOX1 HPX UROD UROS
6 renal/urinary system MP:0005367 9.23 AVP FLVCR1 HMBS HMOX1 HPX PPOX

Drugs & Therapeutics for Porphyria, Acute Intermittent

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

(show all 17)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Midazolam Approved, Illicit Phase 1 59467-70-8 4192
2
Omeprazole Approved, Investigational, Vet_approved Phase 1 73590-58-6 4594
3
Dextromethorphan Approved Phase 1 125-71-3 5360696 5362449
4
Caffeine Approved Phase 1 58-08-2 2519
5
Losartan Approved Phase 1 114798-26-4 3961
6
Dopamine Approved Phase 1 62-31-7, 51-61-6 681
7
Chlorpromazine Approved, Investigational, Vet_approved Phase 1 50-53-3 2726
8 Liver Extracts Phase 1
9 Gastrointestinal Agents Phase 1
10 Psychotropic Drugs Phase 1
11 Dopamine Agents Phase 1
12 Dopamine Antagonists Phase 1
13 Antiemetics Phase 1
14 Neurotransmitter Agents Phase 1
15 Antipsychotic Agents Phase 1
16
Aminolevulinic acid Approved 106-60-5 137
17
Iron Approved 7439-89-6 23925 29936

Interventional clinical trials:

(show all 15)
# 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 Safety and Efficacy of Panhematin™ for Prevention of Acute Attacks of Porphyria Recruiting NCT02922413 Phase 2
4 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)
5 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
6 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
7 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)
8 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
9 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
10 Observational Study of Acute Intermittent Porphyria Patients Completed NCT02076763
11 Clinical Diagnosis of Acute Porphyria Completed NCT01568554
12 Longitudinal Study of the Porphyrias Recruiting NCT01561157
13 Dental Health, Diet, Inflammation and Biomarkers in Patients With Acute Intermittent Porphyria(AIP) Active, not recruiting NCT01617642
14 Acute Porphyrias: Biomarkers for Disease Activity and Response to Treatment Active, not recruiting NCT02935400 Hemin
15 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

Search NIH Clinical Center for Porphyria, Acute Intermittent

Inferred drug relations via UMLS 70 / NDF-RT 51 :


Chlorpromazine
Chlorpromazine hydrochloride
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:

40
Liver, Brain, Kidney, Skin, Thyroid, Cerebellum, Whole Blood

Publications for Porphyria, Acute Intermittent

Articles related to Porphyria, Acute Intermittent:

(show top 50) (show all 1760)
# Title Authors PMID Year
1
Acute intermittent porphyria in Sweden. Molecular, functional and clinical consequences of some new mutations found in the porphobilinogen deaminase gene. 61 25 57 54 6
12372055 2002
2
Identification of the most common mutation within the porphobilinogen deaminase gene in Swedish patients with acute intermittent porphyria. 61 6 25 57 54
1961762 1991
3
Acute intermittent porphyria: studies of the severe homozygous dominant disease provides insights into the neurologic attacks in acute porphyrias. 57 25 61 6
15534187 2004
4
Homozygous acute intermittent porphyria in a 7-year-old boy with massive excretions of porphyrins and porphyrin precursors. 61 25 6 57
14970743 2004
5
A point mutation G----A in exon 12 of the porphobilinogen deaminase gene results in exon skipping and is responsible for acute intermittent porphyria. 6 57 25 61
2789372 1989
6
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. 6 57 54 61
11071386 2000
7
Exon 1 donor splice site mutations in the porphobilinogen deaminase gene in the non-erythroid variant form of acute intermittent porphyria. 54 6 57 61
9860299 1998
8
Acute intermittent porphyria in Finland: 19 mutations in the porphobilinogen deaminase gene. 61 54 57 6
7757070 1995
9
Demystification of Chester porphyria: a nonsense mutation in the Porphobilinogen Deaminase gene. 61 6 57
17298217 2006
10
Acute intermittent porphyria: mutation analysis and identification of gene carriers in a German kindred by PCR-DGGE analysis. 57 6 61
10343207 1998
11
Molecular epidemiology and diagnosis of PBG deaminase gene defects in acute intermittent porphyria. 57 6 61
9199558 1997
12
Homozygous acute intermittent porphyria: compound heterozygosity for adjacent base transitions in the same codon of the porphobilinogen deaminase gene. 61 57 6
1577472 1992
13
Tissue-specific splicing mutation in acute intermittent porphyria. 57 6 61
2563167 1989
14
Chester porphyria: biochemical studies of a new form of acute porphyria. 6 61 57
2864531 1985
15
Phase 1 Trial of an RNA Interference Therapy for Acute Intermittent Porphyria. 61 25 57
30726693 2019
16
Acute intermittent porphyria in Argentina: an update. 6 25 61
26075277 2015
17
Feline acute intermittent porphyria: a phenocopy masquerading as an erythropoietic porphyria due to dominant and recessive hydroxymethylbilane synthase mutations. 57 61 54
19934113 2010
18
Ancestral founder of mutation W283X in the porphobilinogen deaminase gene among acute intermittent porphyria patients. 54 61 6
12566739 2002
19
Identification and characterization of hydroxymethylbilane synthase mutations causing acute intermittent porphyria: evidence for an ancestral founder of the common G111R mutation. 6 61 54
10494093 1999
20
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. 54 61 57
10453740 1999
21
Insertion of Alu element responsible for acute intermittent porphyria. 6 61 54
10408772 1999
22
Porphobilinogen deaminase deficiency in mice causes a neuropathy resembling that of human hepatic porphyria. 61 54 57
8563760 1996
23
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. 54 6 61
7962538 1994
24
Detection of eleven mutations causing acute intermittent porphyria using denaturing gradient gel electrophoresis. 54 6 61
8270254 1994
25
Two new mutations in the porphobilinogen deaminase gene and a screening method using PCR amplification of specific alleles. 54 61 6
8270256 1994
26
Molecular basis of acute intermittent porphyria: mutations and polymorphisms in the human hydroxymethylbilane synthase gene. 61 54 57
7866402 1994
27
Detection of a high mutation frequency in exon 12 of the porphobilinogen deaminase gene in patients with acute intermittent porphyria. 61 6 54
8262523 1993
28
Acute intermittent porphyria caused by an arginine to histidine substitution (R26H) in the cofactor-binding cleft of porphobilinogen deaminase. 54 61 6
8401516 1993
29
High prevalence of a point mutation in the porphobilinogen deaminase gene in Dutch patients with acute intermittent porphyria. 61 54 6
8096492 1993
30
CRIM-positive mutations of acute intermittent porphyria in Finland. 54 6 61
1301948 1992
31
Linkage disequilibrium between DNA polymorphisms within the porphobilinogen deaminase gene. 54 61 57
1973402 1990
32
Haplotyping of the human porphobilinogen deaminase gene in acute intermittent porphyria by polymerase chain reaction. 54 61 57
2303246 1990
33
Sex differences in vascular reactivity in mesenteric arteries from a mouse model of acute intermittent porphyria. 57 61
30639047 2019
34
Recurrent attacks of acute hepatic porphyria: major role of the chronic inflammatory response in the liver. 57 61
29498764 2018
35
An update of clinical management of acute intermittent porphyria. 61 57
26366103 2015
36
Urinary excretion of porphyrins, porphobilinogen and δ-aminolaevulinic acid following an attack of acute intermittent porphyria. 57 61
23908454 2014
37
Diagnostic strategies for autosomal dominant acute porphyrias: retrospective analysis of 467 unrelated patients referred for mutational analysis of the HMBS, CPOX, or PPOX gene. 54 25 61
19460837 2009
38
Neurological manifestations of acute intermittent porphyria. 25 61 54
19268005 2009
39
Liver transplantation as a cure for acute intermittent porphyria. 61 57
15001330 2004
40
Genetic investigation of the porphobilinogen deaminase gene in Swedish acute intermittent porphyria families. 6 61
9225970 1997
41
Increased delta aminolevulinic acid and decreased pineal melatonin production. A common event in acute porphyria studies in the rat. 57 61
8550820 1996
42
Acute intermittent porphyria caused by a G to C mutation in exon 12 of the porphobilinogen deaminase gene that results in exon skipping. 6 61
8262514 1993
43
Evidence for involvement of a second genetic locus on chromosome 11q in porphyrin metabolism. 54 57
8340112 1993
44
Detection of seven point mutations in the porphobilinogen deaminase gene in patients with acute intermittent porphyria, by direct sequencing of in vitro amplified cDNA. 61 6
1427766 1992
45
High frequency of mutations in exon 10 of the porphobilinogen deaminase gene in patients with a CRIM-positive subtype of acute intermittent porphyria. 61 6
1496994 1992
46
Vincent van Gogh's illness: acute intermittent porphyria? 61 57
1773180 1991
47
Genetic heterogeneity of the porphobilinogen deaminase gene in Swedish families with acute intermittent porphyria. 61 57
1679034 1991
48
Molecular heterogeneity of acute intermittent porphyria: identification of four additional mutations resulting in the CRIM-negative subtype of the disease. 6 61
1714233 1991
49
Acute intermittent porphyria caused by a C----T mutation that produces a stop codon in the porphobilinogen deaminase gene. 61 6
2227955 1990
50
RFLP analysis of three different types of acute intermittent porphyria. 61 57
1973403 1990

Variations for Porphyria, Acute Intermittent

ClinVar genetic disease variations for Porphyria, Acute Intermittent:

6 (show top 50) (show all 107)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 HMBS NM_000190.4(HMBS):c.33+1G>A SNV Pathogenic 1441 rs1565750784 GRCh37: 11:118955777-118955777
GRCh38: 11:119085067-119085067
2 HMBS NM_000190.4(HMBS):c.33+1G>T SNV Pathogenic 1444 rs1565750784 GRCh37: 11:118955777-118955777
GRCh38: 11:119085067-119085067
3 HMBS HMBS, 1-BP DEL, -154G Deletion Pathogenic 1481 GRCh37:
GRCh38:
4 HMBS NM_000190.4(HMBS):c.41del (p.Asn14fs) Deletion Pathogenic 1482 rs1592212904 GRCh37: 11:118958969-118958969
GRCh38: 11:119088259-119088259
5 HMBS NM_000190.4(HMBS):c.1A>G (p.Met1Val) SNV Pathogenic 1484 rs118204118 GRCh37: 11:118955744-118955744
GRCh38: 11:119085034-119085034
6 HMBS HMBS, EX12DEL Deletion Pathogenic 1442 GRCh37:
GRCh38:
7 HMBS NM_000190.4(HMBS):c.77G>A (p.Arg26His) SNV Pathogenic 1443 rs118204103 GRCh37: 11:118959008-118959008
GRCh38: 11:119088298-119088298
8 HMBS NM_000190.4(HMBS):c.346C>T (p.Arg116Trp) SNV Pathogenic 1445 rs118204094 GRCh37: 11:118960701-118960701
GRCh38: 11:119089991-119089991
9 HMBS NM_000190.4(HMBS):c.518G>A (p.Arg173Gln) SNV Pathogenic 1447 rs118204096 GRCh37: 11:118962142-118962142
GRCh38: 11:119091432-119091432
10 HMBS NM_000190.4(HMBS):c.463C>T (p.Gln155Ter) SNV Pathogenic 1448 rs118204097 GRCh37: 11:118960940-118960940
GRCh38: 11:119090230-119090230
11 HMBS NM_000190.4(HMBS):c.446G>A (p.Arg149Gln) SNV Pathogenic 1449 rs118204098 GRCh37: 11:118960923-118960923
GRCh38: 11:119090213-119090213
12 HMBS NM_000190.4(HMBS):c.734T>G (p.Leu245Arg) SNV Pathogenic 1450 rs118204099 GRCh37: 11:118963196-118963196
GRCh38: 11:119092486-119092486
13 HMBS NM_000190.4(HMBS):c.900del (p.His300fs) Deletion Pathogenic 1451 rs1565758825 GRCh37: 11:118963719-118963719
GRCh38: 11:119093009-119093009
14 HMBS HMBS, 9-BP DEL, EX10 Deletion Pathogenic 1452 GRCh37:
GRCh38:
15 HMBS NM_000190.4(HMBS):c.593G>A (p.Trp198Ter) SNV Pathogenic 1453 rs118204100 GRCh37: 11:118962217-118962217
GRCh38: 11:119091507-119091507
16 HMBS NM_000190.4(HMBS):c.91G>A (p.Ala31Thr) SNV Pathogenic 1454 rs118204104 GRCh37: 11:118959348-118959348
GRCh38: 11:119088638-119088638
17 HMBS NM_000190.4(HMBS):c.100C>A (p.Gln34Lys) SNV Pathogenic 1455 rs118204105 GRCh37: 11:118959357-118959357
GRCh38: 11:119088647-119088647
18 HMBS NM_000190.4(HMBS):c.500G>T (p.Arg167Leu) SNV Pathogenic 1457 rs118204095 GRCh37: 11:118962124-118962124
GRCh38: 11:119091414-119091414
19 HMBS NM_000190.4(HMBS):c.163G>T (p.Ala55Ser) SNV Pathogenic 1458 rs118204106 GRCh37: 11:118959794-118959794
GRCh38: 11:119089084-119089084
20 HMBS NM_000190.4(HMBS):c.174del (p.Thr59fs) Deletion Pathogenic 1459 rs1565754285 GRCh37: 11:118959804-118959804
GRCh38: 11:119089094-119089094
21 HMBS NM_000190.4(HMBS):c.181dup (p.Asp61fs) Duplication Pathogenic 1460 rs1565754296 GRCh37: 11:118959808-118959809
GRCh38: 11:119089098-119089099
22 HMBS NM_000190.4(HMBS):c.211-1G>A SNV Pathogenic 1461 rs1565754452 GRCh37: 11:118959926-118959926
GRCh38: 11:119089216-119089216
23 HMBS HMBS, 2-BP DEL, 218AG Deletion Pathogenic 1463 GRCh37:
GRCh38:
24 HMBS NM_000190.4(HMBS):c.331G>A (p.Gly111Arg) SNV Pathogenic 1464 rs118204107 GRCh37: 11:118960457-118960457
GRCh38: 11:119089747-119089747
25 HMBS NM_000190.4(HMBS):c.499-1G>A SNV Pathogenic 1465 rs1565756481 GRCh37: 11:118962122-118962122
GRCh38: 11:119091412-119091412
26 HMBS NM_000190.4(HMBS):c.530T>G (p.Leu177Arg) SNV Pathogenic 1466 rs118204108 GRCh37: 11:118962154-118962154
GRCh38: 11:119091444-119091444
27 HMBS NM_000190.4(HMBS):c.728_729CT[1] (p.Leu244fs) Microsatellite Pathogenic 1468 rs1565757839 GRCh37: 11:118963190-118963191
GRCh38: 11:119092480-119092481
28 HMBS NM_000190.4(HMBS):c.739T>C (p.Cys247Arg) SNV Pathogenic 1469 rs118204111 GRCh37: 11:118963201-118963201
GRCh38: 11:119092491-119092491
29 HMBS NM_000190.4(HMBS):c.734_741dup (p.Ile248fs) Duplication Pathogenic 1470 rs1565757857 GRCh37: 11:118963191-118963192
GRCh38: 11:119092481-119092482
30 HMBS NM_000190.4(HMBS):c.748G>A (p.Glu250Lys) SNV Pathogenic 1471 rs118204112 GRCh37: 11:118963210-118963210
GRCh38: 11:119092500-119092500
31 HMBS NM_000190.4(HMBS):c.755C>T (p.Ala252Val) SNV Pathogenic 1473 rs118204114 GRCh37: 11:118963217-118963217
GRCh38: 11:119092507-119092507
32 HMBS NM_000190.4(HMBS):c.766C>A (p.His256Asn) SNV Pathogenic 1474 rs118204115 GRCh37: 11:118963228-118963228
GRCh38: 11:119092518-119092518
33 HMBS NM_000190.4(HMBS):c.771+1G>C SNV Pathogenic 1475 rs1565758008 GRCh37: 11:118963234-118963234
GRCh38: 11:119092524-119092524
34 HMBS HMBS, IVS14DS, G-A, +1 SNV Pathogenic 1476 GRCh37:
GRCh38:
35 HMBS NM_000190.4(HMBS):c.266+1G>C SNV Pathogenic 1477 rs1565754565 GRCh37: 11:118959983-118959983
GRCh38: 11:119089273-119089273
36 HMBS NM_000190.4(HMBS):c.647G>A (p.Gly216Asp) SNV Pathogenic 1478 rs118204116 GRCh37: 11:118962869-118962869
GRCh38: 11:119092159-119092159
37 HMBS NM_000190.4(HMBS):c.847_848del (p.Trp283fs) Deletion Pathogenic 1479 rs1592220835 GRCh37: 11:118963666-118963667
GRCh38: 11:119092956-119092957
38 HMBS HMBS, ALU INS Insertion Pathogenic 1480 GRCh37:
GRCh38:
39 HMBS NM_000190.4(HMBS):c.242T>C (p.Leu81Pro) SNV Pathogenic 1485 rs118204119 GRCh37: 11:118959958-118959958
GRCh38: 11:119089248-119089248
40 HMBS NM_000190.4(HMBS):c.445C>T (p.Arg149Ter) SNV Pathogenic 1486 rs118204120 GRCh37: 11:118960922-118960922
GRCh38: 11:119090212-119090212
41 HMBS NM_000190.4(HMBS):c.669_698del (p.Glu223_Leu232del) Deletion Pathogenic 522578 rs1555206128 GRCh37: 11:118963127-118963156
GRCh38: 11:119092417-119092446
42 HMBS NM_000190.4(HMBS):c.1078_*46del (p.Ala360fs) Deletion Pathogenic 549662 rs1555206402 GRCh37: 11:118963984-118964038
GRCh38: 11:119093274-119093328
43 HMBS NM_000190.4(HMBS):c.160+5G>C SNV Pathogenic 694280 rs1592213590 GRCh37: 11:118959422-118959422
GRCh38: 11:119088712-119088712
44 HMBS NM_000190.4(HMBS):c.400del (p.Thr133_Leu134insTer) Deletion Pathogenic 374084 rs1057518886 GRCh37: 11:118960753-118960753
GRCh38: 11:119090043-119090043
45 HMBS NM_000190.4(HMBS):c.613-1G>A SNV Pathogenic 931455 GRCh37: 11:118962834-118962834
GRCh38: 11:119092124-119092124
46 HMBS NM_000190.4(HMBS):c.517C>T (p.Arg173Trp) SNV Pathogenic 649348 rs575222284 GRCh37: 11:118962141-118962141
GRCh38: 11:119091431-119091431
47 HMBS NM_000190.4(HMBS):c.500G>A (p.Arg167Gln) SNV Pathogenic 1446 rs118204095 GRCh37: 11:118962124-118962124
GRCh38: 11:119091414-119091414
48 HMBS NM_000190.4(HMBS):c.499C>T (p.Arg167Trp) SNV Pathogenic 1456 rs118204101 GRCh37: 11:118962123-118962123
GRCh38: 11:119091413-119091413
49 HMBS NM_000190.4(HMBS):c.601C>T (p.Arg201Trp) SNV Pathogenic 1462 rs118204109 GRCh37: 11:118962225-118962225
GRCh38: 11:119091515-119091515
50 HMBS NM_000190.4(HMBS):c.849G>A (p.Trp283Ter) SNV Pathogenic 1483 rs118204117 GRCh37: 11:118963668-118963668
GRCh38: 11:119092958-119092958

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

72 (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 mitochondrial matrix GO:0005759 9.26 PC FECH ALAS2 ALAS1
2 mitochondrion GO:0005739 9.23 UROS PPOX PC FLVCR1 FECH CPOX

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

(show all 23)
# Name GO ID Score Top Affiliating Genes
1 response to drug GO:0042493 9.87 PPOX HMOX1 FECH ALAD
2 response to hypoxia GO:0001666 9.78 HMOX1 ALAS2 ALAS1 ALAD
3 response to ethanol GO:0045471 9.75 FECH AVP ALAD
4 cellular iron ion homeostasis GO:0006879 9.71 HPX HMOX1 FLVCR1 ALAS2
5 porphyrin-containing compound biosynthetic process GO:0006779 9.7 UROS UROD PPOX HMBS FECH CPOX
6 tetrapyrrole biosynthetic process GO:0033014 9.65 UROS HMBS ALAS2 ALAS1 ALAD
7 biosynthetic process GO:0009058 9.61 ALAS2 ALAS1
8 response to nicotine GO:0035094 9.61 HMOX1 AVP
9 response to lead ion GO:0010288 9.6 FECH ALAD
10 erythrocyte development GO:0048821 9.59 ALAS2 ALAS1
11 response to metal ion GO:0010038 9.58 FECH ALAD
12 response to arsenic-containing substance GO:0046685 9.56 FECH ALAD
13 protoporphyrinogen IX biosynthetic process GO:0006782 9.56 UROS UROD PPOX HMBS CPOX ALAS2
14 cellular response to arsenic-containing substance GO:0071243 9.55 UROS HMOX1
15 heme transport GO:0015886 9.54 HPX FLVCR1
16 heme metabolic process GO:0042168 9.54 UROD HPX HMOX1
17 response to methylmercury GO:0051597 9.52 FECH ALAD
18 hemoglobin biosynthetic process GO:0042541 9.51 ALAS2 ALAS1
19 response to platinum ion GO:0070541 9.5 UROS FECH ALAD
20 porphyrin-containing compound metabolic process GO:0006778 9.49 ALAS2 ALAS1
21 heme export GO:0097037 9.46 FLVCR2 FLVCR1
22 protoporphyrinogen IX metabolic process GO:0046501 9.43 PPOX FECH
23 heme biosynthetic process GO:0006783 9.28 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 catalytic activity GO:0003824 9.62 PC ALAS2 ALAS1 ALAD
2 transmembrane transporter activity GO:0022857 9.54 SLC15A2 FLVCR2 FLVCR1
3 lyase activity GO:0016829 9.46 UROS UROD FECH ALAD
4 heme binding GO:0020037 9.43 HMOX1 FLVCR2 FLVCR1
5 5-aminolevulinate synthase activity GO:0003870 8.96 ALAS2 ALAS1
6 heme transporter activity GO:0015232 8.8 HPX FLVCR2 FLVCR1

Sources for Porphyria, Acute Intermittent

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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