PEPD
MCID: PRX015
MIFTS: 56

Paroxysmal Extreme Pain Disorder (PEPD)

Categories: Genetic diseases, Mental diseases, Neuronal diseases, Rare diseases, Skin diseases

Aliases & Classifications for Paroxysmal Extreme Pain Disorder

MalaCards integrated aliases for Paroxysmal Extreme Pain Disorder:

Name: Paroxysmal Extreme Pain Disorder 57 12 20 43 58 72 36 29 13 6 44 15 70
Familial Rectal Pain 12 20 43 58 72
Pepd 57 12 20 43 72
Pexpd 57 12 20 43
Submandibular, Ocular, and Rectal Pain with Flushing 20 43
Pain, Submandibular, Ocular, and Rectal, with Flushing 57
Submandibular, Ocular and Rectal Pain with Flushing 12
Pain Disorder, Paroxysmal, Extreme 39
Familial Rectal Syndrome 20
Rectal Pain, Familial 57
Pexpd; Pepd 57
Frp 72

Characteristics:

Orphanet epidemiological data:

58
paroxysmal extreme pain disorder
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM®:

57 (Updated 05-Apr-2021)
Inheritance:
autosomal dominant

Miscellaneous:
onset in neonatal period or infancy
presents with 4 types of painful episodes - (1) birth crisis, babies are born red and stiff (2) rectal crisis, triggered by defecation or emotional factors (3) ocular crisis (4) mandibular crisis, triggered by eating or yawning
attacks tend to decrease with age
allelic disorder to primary erythermalgia


HPO:

31
paroxysmal extreme pain disorder:
Inheritance autosomal dominant inheritance
Onset and clinical course neonatal onset


Classifications:

Orphanet: 58  
Rare neurological diseases


External Ids:

Disease Ontology 12 DOID:0111537
OMIM® 57 167400
KEGG 36 H00772
MeSH 44 C563475
NCIt 50 C125385
SNOMED-CT 67 699190008
UMLS via Orphanet 71 C1833661
Orphanet 58 ORPHA46348
MedGen 41 C1833661
UMLS 70 C1833661

Summaries for Paroxysmal Extreme Pain Disorder

MedlinePlus Genetics : 43 Paroxysmal extreme pain disorder is a condition characterized by skin redness and warmth (flushing) and attacks of severe pain in various parts of the body. The area of flushing typically corresponds to the site of the pain. The pain attacks experienced by people with paroxysmal extreme pain disorder usually last seconds to minutes, but in some cases can last hours. These attacks can start as early as infancy. Early in life, the pain is typically concentrated in the lower part of the body, especially around the rectum, and is usually triggered by a bowel movement. Some children may develop constipation, which is thought to be due to fear of triggering a pain attack. Pain attacks in these young children may also be accompanied by seizures, slow heartbeat, or short pauses in breathing (apnea).As a person with paroxysmal extreme pain disorder ages, the location of pain changes. Pain attacks switch from affecting the lower body to affecting the head and face, especially the eyes and jaw. Triggers of these pain attacks include changes in temperature (such as a cold wind) and emotional distress as well as eating spicy foods and drinking cold drinks.Paroxysmal extreme pain disorder is considered a form of peripheral neuropathy because it affects the peripheral nervous system, which connects the brain and spinal cord to muscles and to cells that detect sensations such as touch, smell, and pain.

MalaCards based summary : Paroxysmal Extreme Pain Disorder, also known as familial rectal pain, is related to mucocutaneous ulceration, chronic and brugada syndrome 1, and has symptoms including pain An important gene associated with Paroxysmal Extreme Pain Disorder is SCN9A (Sodium Voltage-Gated Channel Alpha Subunit 9), and among its related pathways/superpathways are Activation of cAMP-Dependent PKA and Developmental Biology. Affiliated tissues include spinal cord, skin and brain, and related phenotypes are seizure and constipation

Disease Ontology : 12 An autonomic nervous system disease characterized by onset in the neonatal period or infancy of paroxysms of rectal, ocular, or submandibular pain with flushing that has material basis in heterozygous mutation in SCN9A on chromosome 2q24.3.

GARD : 20 Paroxysmal extreme pain disorder is a form of peripheral neuropathy characterized by skin redness and warmth ( flushing ) and attacks of severe pain in various parts of the body. Early in life, the pain is often concentrated in the lower part of the body and may be triggered by a bowel movement. As a person ages, the location of the pain may change, with attacks affecting the head and face. Triggers of these pain attacks include changes in temperature, emotional distress or eating spicy foods and drinking cold beverages. Paroxysmal extreme pain disorder is caused by mutations in the SCN9A gene. This condition is inherited in an autosomal dominant pattern. Treatment may include medications used to manage chronic neuropathic pain (anticonvulsants) such as the sodium channel blocker carbamazepine.

OMIM® : 57 Paroxysmal extreme pain disorder, formerly known as familial rectal pain, is characterized by paroxysms of rectal, ocular, or submandibular pain with flushing. Onset is usually in the neonatal period or infancy (Fertleman et al., 2006). (167400) (Updated 05-Apr-2021)

KEGG : 36 Paroxysmal extreme pain disorder (PEPD) is a autosomal dominant pain disorder resulting from a set of gain-of-function mutations in SCN9A, the gene encoding Nav1.7, that impair inactivation of Nav1.7. Severe pain in PEPD patients along with flushing are induced by bowel movement or probing of the perianal areas, and are sometimes accompanied by tonic nonepileptic seizures and cardiac deficits. The pain attacks are most severe in the lower part of the body and are often triggered by temperature changes (such as cold winds), eating, and/or emotional upsets (such as crying).

UniProtKB/Swiss-Prot : 72 Paroxysmal extreme pain disorder: Autosomal dominant paroxysmal disorder of pain and autonomic dysfunction. The distinctive features are paroxysmal episodes of burning pain in the rectal, ocular, and mandibular areas accompanied by autonomic manifestations such as skin flushing.

Wikipedia : 73 Paroxysmal extreme pain disorder originally named familial rectal pain syndrome, is a rare disorder... more...

Related Diseases for Paroxysmal Extreme Pain Disorder

Diseases related to Paroxysmal Extreme Pain Disorder via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 172)
# Related Disease Score Top Affiliating Genes
1 mucocutaneous ulceration, chronic 31.8 PEPD NGF
2 brugada syndrome 1 31.7 SCN5A SCN10A PEPD
3 paramyotonia congenita of von eulenburg 30.9 SCN9A SCN8A SCN5A SCN4A SCN2A SCN1B
4 erythermalgia, primary 30.8 SCN9A SCN1A-AS1 SCN11A SCN10A
5 generalized epilepsy with febrile seizures plus, type 7 30.7 SCN9A SCN8A SCN1B SCN1A-AS1 SCN1A
6 paine syndrome 30.5 TRPV1 TRPA1 SCN9A SCN8A SCN4A SCN3A
7 sensory peripheral neuropathy 30.5 TRPV1 SCN9A SCN11A NGF
8 reflex epilepsy 30.4 SCN2A SCN1A
9 disease of mental health 30.2 TRPV1 TRPA1 SCN9A SCN8A SCN5A SCN3A
10 generalized epilepsy with febrile seizures plus 29.5 SCN9A SCN8A SCN5A SCN4B SCN4A SCN3A
11 erythromelalgia 29.3 TRPV1 TRPA1 SCN9A SCN8A SCN5A SCN4B
12 prolidase deficiency 11.5
13 bacterial vaginosis 11.1
14 hyper ige syndrome 11.0
15 legg-calve-perthes disease 11.0
16 brittle bone disorder 11.0
17 hypermobility syndrome 11.0
18 connective tissue disease 11.0
19 osteogenesis imperfecta, type i 10.9
20 hyperprolinemia, type i 10.9
21 corneal dystrophy, posterior amorphous 10.9
22 amino acid metabolic disorder 10.9
23 myoclonic epilepsy of infancy 10.4 SCN8A SCN1A
24 hyperhidrosis, gustatory 10.4 TRPV1 TRPA1
25 photokeratitis 10.4 TRPV1 TRPA1
26 long qt syndrome 12 10.4 SCN5A SCN4B
27 neurogenic arthropathy 10.4 SCN9A NGF
28 dentin sensitivity 10.4 TRPV1 TRPA1
29 long qt syndrome 10 10.4 SCN5A SCN4B
30 febrile seizures, familial, 6 10.4 SCN1B SCN1A
31 long qt syndrome 13 10.4 SCN5A SCN4B
32 genetic epilepsy with febrile seizures plus 10.4 SCN9A SCN2A SCN1A
33 lesion of sciatic nerve 10.4 TRPV1 NGF
34 neuropathy, hereditary sensory and autonomic, type vii 10.4 SCN4A SCN3A SCN11A
35 coffin-siris syndrome 4 10.4 SCN9A SCN8A SCN2A
36 spondyloepiphyseal dysplasia, maroteaux type 10.4 TRPA1 SCN9A
37 myofascial pain syndrome 10.4 TRPV1 NGF
38 detrusor sphincter dyssynergia 10.4 TRPV1 NGF
39 generalized epilepsy with febrile seizures plus, type 1 10.3 SCN1B SCN1A
40 cough variant asthma 10.3 TRPV1 NGF
41 partial motor epilepsy 10.3 SCN8A SCN2A SCN1A
42 lateral myocardial infarction 10.3 SCN5A SCN1B
43 facial dermatosis 10.3 TRPV1 TRPA1
44 indifference to pain, congenital, autosomal recessive 10.3 SCN9A SCN1A-AS1 SCN11A SCN10A
45 epilepsy, familial temporal lobe, 5 10.3 SCN9A SCN1B SCN1A
46 pseudopterygium 10.3 TRPV1 TRPA1
47 sodium channelopathy-related small fiber neuropathy 10.3 SCN9A SCN1A-AS1 SCN11A SCN10A
48 andersen cardiodysrhythmic periodic paralysis 10.3 SCN5A SCN4B SCN4A
49 episodic pain syndrome, familial, 2 10.3 SCN9A SCN3A SCN11A SCN10A
50 burning mouth syndrome 10.3 TRPV1 SCN9A NGF

Graphical network of the top 20 diseases related to Paroxysmal Extreme Pain Disorder:



Diseases related to Paroxysmal Extreme Pain Disorder

Symptoms & Phenotypes for Paroxysmal Extreme Pain Disorder

Human phenotypes related to Paroxysmal Extreme Pain Disorder:

31 58 (show all 12)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 seizure 31 hallmark (90%) HP:0001250
2 constipation 58 31 frequent (33%) Frequent (79-30%) HP:0002019
3 seizures 58 Very frequent (99-80%)
4 impaired pain sensation 31 HP:0007328
5 lacrimation abnormality 31 HP:0000632
6 tachycardia 31 HP:0001649
7 mandibular pain 31 HP:0200025
8 ocular pain 31 HP:0200026
9 bradycardia 31 HP:0001662
10 rhinorrhea 31 HP:0031417
11 flushing 31 HP:0031284
12 anal pain 31 HP:0500005

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Cardiovascular Heart:
tachycardia
bradycardia
autonomic reflex asystolic syncopal events

Head And Neck Eyes:
lacrimation, episodic
ocular pain, episodic

Neurologic Peripheral Nervous System:
autonomic reflex asystolic syncopal events
burning pain, episodic
nonepileptic tonic attacks (most common in infants and young children)

Genitourinary Bladder:
painful micturition (in some patients)

Head And Neck Face:
mandibular and submandibular pain, episodic, triggered by eating and yawning

Head And Neck Nose:
rhinorrhea, episodic

Abdomen Gastrointestinal:
rectal pain, episodic, triggered by defecation

Skin Nails Hair Skin:
reddish discoloration, episodic, associated with pain
skin flushing, episodic, associated with pain

Clinical features from OMIM®:

167400 (Updated 05-Apr-2021)

UMLS symptoms related to Paroxysmal Extreme Pain Disorder:


pain

MGI Mouse Phenotypes related to Paroxysmal Extreme Pain Disorder:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 10.28 CACNA1B KCNS1 NGF PEPD SCN10A SCN11A
2 growth/size/body region MP:0005378 10.07 CACNA1B NGF PEPD SCN11A SCN1A SCN1B
3 nervous system MP:0003631 9.83 CACNA1B NGF PEPD SCN10A SCN11A SCN1A
4 integument MP:0010771 9.81 CACNA1B KCNS1 NGF PEPD SCN10A SCN11A
5 respiratory system MP:0005388 9.17 SCN10A SCN1A SCN2A SCN4A SCN5A SCN8A

Drugs & Therapeutics for Paroxysmal Extreme Pain Disorder

Search Clinical Trials , NIH Clinical Center for Paroxysmal Extreme Pain Disorder

Cochrane evidence based reviews: paroxysmal extreme pain disorder

Genetic Tests for Paroxysmal Extreme Pain Disorder

Genetic tests related to Paroxysmal Extreme Pain Disorder:

# Genetic test Affiliating Genes
1 Paroxysmal Extreme Pain Disorder 29 SCN9A

Anatomical Context for Paroxysmal Extreme Pain Disorder

MalaCards organs/tissues related to Paroxysmal Extreme Pain Disorder:

40
Spinal Cord, Skin, Brain, Breast, Myeloid, Dorsal Root Ganglion

Publications for Paroxysmal Extreme Pain Disorder

Articles related to Paroxysmal Extreme Pain Disorder:

(show top 50) (show all 228)
# Title Authors PMID Year
1
Painful micturition in a small child: an unusual clinical picture of paroxysmal extreme pain disorder. 6 57 61
24817410 2014
2
SCN9A mutations in paroxysmal extreme pain disorder: allelic variants underlie distinct channel defects and phenotypes. 61 6 57
17145499 2006
3
Paroxysmal extreme pain disorder (previously familial rectal pain syndrome). 61 57
17679678 2007
4
What's in a name--familial rectal pain syndrome becomes paroxysmal extreme pain disorder. 57 61
17043302 2006
5
Functional profiles of SCN9A variants in dorsal root ganglion neurons and superior cervical ganglion neurons correlate with autonomic symptoms in small fibre neuropathy. 6
22826602 2012
6
Gain of function Naν1.7 mutations in idiopathic small fiber neuropathy. 6
21698661 2012
7
Familial rectal pain. 57
4112340 1972
8
Familial rectal pain. 57
4111621 1972
9
Whole exome sequencing identifies three novel gene mutations in patients with the triad of diabetic ketoacidosis, hypertriglyceridemia, and acute pancreatitis. 61
32734598 2021
10
Genome-wide discovery of genetic loci that uncouple excess adiposity from its comorbidities. 61
33619380 2021
11
Extracellular Prolidase (PEPD) Induces Anabolic Processes through EGFR, β1-integrin, and IGF-1R Signaling Pathways in an Experimental Model of Wounded Fibroblasts. 61
33477899 2021
12
Platelet-Rich Plasma Promotes the Proliferation of Human Keratinocytes via a Progression of the Cell Cycle. A Role of Prolidase. 61
33477820 2021
13
A fluorescence immunoassay for a rapid detection of Listeria monocytogenes on working surfaces. 61
33303771 2020
14
Prolidase Stimulates Proliferation and Migration through Activation of the PI3K/Akt/mTOR Signaling Pathway in Human Keratinocytes. 61
33287453 2020
15
Uncoupling sodium channel dimers restores the phenotype of a pain-linked Nav 1.7 channel mutation. 61
32663327 2020
16
Paroxysmal extreme pain disorder: A very rare genetic aetiology of syncope with bizarre flushing in an infant. 61
32918496 2020
17
Current Understanding of the Emerging Role of Prolidase in Cellular Metabolism. 61
32824561 2020
18
Coffee Consumption, Genetic Polymorphisms, and the Risk of Type 2 Diabetes Mellitus: A Pooled Analysis of Four Prospective Cohort Studies. 61
32722593 2020
19
Metabolic engineering of Escherichia coli for efficient production of L-alanyl-L-glutamine. 61
32527330 2020
20
Identification of key biomolecules in rheumatoid arthritis through the reconstruction of comprehensive disease-specific biological networks. 61
32013628 2020
21
Paroxysmal extreme pain disorder in family with c.3892G > T (p.Val1298Phe) in the SCN9A gene mutation - case report. 61
32404070 2020
22
Surgical results and prognostic factors following percutaneous full endoscopic posterior decompression for thoracic myelopathy caused by ossification of the ligamentum flavum. 61
31992790 2020
23
Functional Screening of Candidate Causal Genes for Insulin Resistance in Human Preadipocytes and Adipocytes. 61
31739742 2020
24
Understanding high ε-poly-L-lysine production by Streptomyces albulus using pH shock strategy in the level of transcriptomics. 61
31595454 2019
25
Enzymatic characteristics of a recombinant protease (rPepD) from Aspergillus niger expressed in Pichia pastoris. 61
31181254 2019
26
Systematically Designed Periodic Electrophoretic Deposition for Decorating 3D Carbon-Based Scaffolds with Bioactive Nanoparticles. 61
33438405 2019
27
Effect of the optimized selective enrichment medium on the expression of the p60 protein used as Listeria monocytogenes antigen in specific sandwich ELISA. 61
30953690 2019
28
A rare case of prolidase deficiency with situs inversus totalis, identified by a novel mutation in the PEPD gene. 61
31192996 2019
29
East Asian Genome-wide association study derived loci in relation to type 2 diabetes in the Han Chinese population. 61
31145772 2019
30
Epistasis between ADIPOQ rs1501299 and PON1 rs662 polymorphisms is potentially associated with the development of knee osteoarthritis. 61
30734899 2019
31
Percutaneous full endoscopic posterior decompression of thoracic myelopathy caused by ossification of the ligamentum flavum. 61
30656471 2019
32
A recombinant human protein targeting HER2 overcomes drug resistance in HER2-positive breast cancer. 61
30674653 2019
33
Structural basis for prolidase deficiency disease mechanisms. 61
30066404 2018
34
Flushing Disorders Associated with Gastrointestinal Symptoms: Part 2, Systemic Miscellaneous Conditions. 61
29650526 2018
35
Flushing Disorders Associated with Gastrointestinal Symptoms: Part 1, Neuroendocrine Tumors, Mast Cell Disorders and Hyperbasophila. 61
29650525 2018
36
Loss of Cardio-Protective Effects at the CDH13 Locus Due to Gene-Sleep Interaction: The BCAMS Study. 61
29903569 2018
37
Enhancing inactivation rather than reducing activation of Nav1.7 channels by a clinically effective analgesic CNV1014802. 61
29094728 2018
38
AcfA is an essential regulator for pathogenesis of fish pathogen Vibrio alginolyticus. 61
29292001 2018
39
PEPD is a pivotal regulator of p53 tumor suppressor. 61
29233996 2017
40
The Pediatric Ependymoma Protein Database (PEPD). 61
29124086 2017
41
Genetic risk of prediabetes and diabetes development in chronic myeloid leukemia patients treated with nilotinib. 61
28757432 2017
42
Interaction between genes and macronutrient intake on the risk of developing type 2 diabetes: systematic review and findings from European Prospective Investigation into Cancer (EPIC)-InterAct. 61
28592605 2017
43
Network topology of NaV1.7 mutations in sodium channel-related painful disorders. 61
28235406 2017
44
[Pain and analgesia : Mutations of voltage-gated sodium channels]. 61
27402262 2017
45
Evaluating phecodes, clinical classification software, and ICD-9-CM codes for phenome-wide association studies in the electronic health record. 61
28686612 2017
46
Characterisation of Nav1.7 functional expression in rat dorsal root ganglia neurons by using an electrical field stimulation assay. 61
29166836 2017
47
Kinetic Analysis of Membrane Potential Dye Response to NaV1.7 Channel Activation Identifies Antagonists with Pharmacological Selectivity against NaV1.5. 61
26861708 2016
48
Prolidase Deficiency in a Mexican-American Patient Identified by Array CGH Reveals a Novel and the Largest PEPD Gene Deletion. 61
27385964 2016
49
Sodium channel slow inactivation interferes with open channel block. 61
27174182 2016
50
Advanced Genetic Testing Comes to the Pain Clinic to Make a Diagnosis of Paroxysmal Extreme Pain Disorder. 61
27525141 2016

Variations for Paroxysmal Extreme Pain Disorder

ClinVar genetic disease variations for Paroxysmal Extreme Pain Disorder:

6 (show top 50) (show all 239)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 SCN1A-AS1 , SCN9A NM_001365536.1(SCN9A):c.3926T>A (p.Val1309Asp) SNV Pathogenic 6357 rs121908911 GRCh37: 2:167085481-167085481
GRCh38: 2:166228971-166228971
2 SCN1A-AS1 , SCN9A NM_001365536.1(SCN9A):c.3925G>T (p.Val1309Phe) SNV Pathogenic 6358 rs121908912 GRCh37: 2:167085482-167085482
GRCh38: 2:166228972-166228972
3 SCN1A-AS1 , SCN9A NM_001365536.1(SCN9A):c.4415T>C (p.Ile1472Thr) SNV Pathogenic 6360 rs121908914 GRCh37: 2:167060958-167060958
GRCh38: 2:166204448-166204448
4 SCN1A-AS1 , SCN9A NM_001365536.1(SCN9A):c.4424C>T (p.Thr1475Ile) SNV Pathogenic 6361 rs121908915 GRCh37: 2:167060949-167060949
GRCh38: 2:166204439-166204439
5 SCN1A-AS1 , SCN9A NM_001365536.1(SCN9A):c.4417T>G (p.Phe1473Val) SNV Pathogenic 446177 rs1553474394 GRCh37: 2:167060956-167060956
GRCh38: 2:166204446-166204446
6 SCN1A-AS1 , SCN9A NM_001365536.1(SCN9A):c.4415T>A (p.Ile1472Asn) SNV Pathogenic 446178 rs121908914 GRCh37: 2:167060958-167060958
GRCh38: 2:166204448-166204448
7 SCN1A-AS1 , SCN9A NM_001365536.1(SCN9A):c.3019C>T (p.Arg1007Cys) SNV Pathogenic 6356 rs121908910 GRCh37: 2:167129241-167129241
GRCh38: 2:166272731-166272731
8 SCN1A-AS1 , SCN9A NM_001365536.1(SCN9A):c.4928C>A (p.Ala1643Glu) SNV Pathogenic 245903 rs879253994 GRCh37: 2:167056221-167056221
GRCh38: 2:166199711-166199711
9 SCN1A-AS1 , SCN9A NM_001365536.1(SCN9A):c.4868T>C (p.Leu1623Pro) SNV Pathogenic 430091 rs1131691776 GRCh37: 2:167056281-167056281
GRCh38: 2:166199771-166199771
10 SCN1A-AS1 , SCN9A NM_001365536.1(SCN9A):c.3928G>T (p.Val1310Phe) SNV Pathogenic 6359 rs121908913 GRCh37: 2:167085479-167085479
GRCh38: 2:166228969-166228969
11 SCN1A-AS1 , SCN9A NM_001365536.1(SCN9A):c.1482G>T (p.Lys494Asn) SNV Uncertain significance 331990 rs777699798 GRCh37: 2:167142966-167142966
GRCh38: 2:166286456-166286456
12 SCN1A-AS1 , SCN9A NM_001365536.1(SCN9A):c.3538A>G (p.Asn1180Asp) SNV Uncertain significance 448293 rs750269576 GRCh37: 2:167099101-167099101
GRCh38: 2:166242591-166242591
13 SCN1A-AS1 , SCN9A NM_001365536.1(SCN9A):c.1238T>C (p.Ile413Thr) SNV Uncertain significance 193648 rs200689195 GRCh37: 2:167145023-167145023
GRCh38: 2:166288513-166288513
14 SCN9A NM_001365536.1(SCN9A):c.829C>A (p.Arg277=) SNV Uncertain significance 566530 rs121908916 GRCh37: 2:167159672-167159672
GRCh38: 2:166303162-166303162
15 SCN1A-AS1 , SCN9A NM_001365536.1(SCN9A):c.3388G>A (p.Val1130Ile) SNV Uncertain significance 663698 rs765384427 GRCh37: 2:167108359-167108359
GRCh38: 2:166251849-166251849
16 SCN9A NM_001365536.1(SCN9A):c.684C>G (p.Ile228Met) SNV Uncertain significance 198153 rs71428908 GRCh37: 2:167160752-167160752
GRCh38: 2:166304242-166304242
17 SCN1A-AS1 , SCN9A NM_001365536.1(SCN9A):c.3767A>G (p.Asn1256Ser) SNV Uncertain significance 130265 rs141268327 GRCh37: 2:167094638-167094638
GRCh38: 2:166238128-166238128
18 SCN1A-AS1 , SCN9A NM_001365536.1(SCN9A):c.3476G>A (p.Cys1159Tyr) SNV Uncertain significance 893487 GRCh37: 2:167099163-167099163
GRCh38: 2:166242653-166242653
19 SCN1A-AS1 , SCN9A NM_001365536.1(SCN9A):c.1207A>C (p.Met403Leu) SNV Uncertain significance 331993 rs746956041 GRCh37: 2:167145054-167145054
GRCh38: 2:166288544-166288544
20 SCN1A-AS1 , SCN9A NM_001365536.1(SCN9A):c.5948G>T (p.Ser1983Ile) SNV Uncertain significance 538464 rs770802841 GRCh37: 2:167055201-167055201
GRCh38: 2:166198691-166198691
21 SCN1A-AS1 , SCN9A NM_001365536.1(SCN9A):c.4820C>T (p.Thr1607Ile) SNV Uncertain significance 130271 rs200470541 GRCh37: 2:167056329-167056329
GRCh38: 2:166199819-166199819
22 SCN1A-AS1 , SCN9A NM_001365536.1(SCN9A):c.5543G>A (p.Arg1848His) SNV Uncertain significance 892606 GRCh37: 2:167055606-167055606
GRCh38: 2:166199096-166199096
23 SCN9A NM_001365536.1(SCN9A):c.294C>A (p.Phe98Leu) SNV Uncertain significance 245738 rs199824489 GRCh37: 2:167163549-167163549
GRCh38: 2:166307039-166307039
24 SCN1A-AS1 , SCN9A NM_001365536.1(SCN9A):c.1094A>G (p.Asn365Ser) SNV Uncertain significance 331995 rs886055055 GRCh37: 2:167149754-167149754
GRCh38: 2:166293244-166293244
25 SCN1A-AS1 , SCN9A NM_001365536.1(SCN9A):c.1604C>T (p.Ser535Leu) SNV Uncertain significance 538480 rs201354321 GRCh37: 2:167141333-167141333
GRCh38: 2:166284823-166284823
26 SCN9A NM_001365536.1(SCN9A):c.553C>T (p.Arg185Cys) SNV Uncertain significance 471146 rs202083986 GRCh37: 2:167162345-167162345
GRCh38: 2:166305835-166305835
27 SCN9A NM_001365536.1(SCN9A):c.184A>G (p.Ile62Val) SNV Uncertain significance 6368 rs121908920 GRCh37: 2:167168083-167168083
GRCh38: 2:166311573-166311573
28 SCN1A-AS1 , SCN9A NM_001365536.1(SCN9A):c.2351C>G (p.Thr784Ser) SNV Uncertain significance 245859 rs200624920 GRCh37: 2:167134816-167134816
GRCh38: 2:166278306-166278306
29 SCN1A-AS1 , SCN9A NM_001365536.1(SCN9A):c.1280T>C (p.Leu427Ser) SNV Uncertain significance 234638 rs192406412 GRCh37: 2:167144981-167144981
GRCh38: 2:166288471-166288471
30 SCN1A-AS1 , SCN9A NM_001365536.1(SCN9A):c.5820C>G (p.Asn1940Lys) SNV Uncertain significance 471155 rs371454107 GRCh37: 2:167055329-167055329
GRCh38: 2:166198819-166198819
31 SCN1A-AS1 , SCN9A NM_001365536.1(SCN9A):c.4368C>G (p.Ile1456Met) SNV Uncertain significance 471128 rs1362318488 GRCh37: 2:167083107-167083107
GRCh38: 2:166226597-166226597
32 SCN1A-AS1 , SCN9A NM_001365536.1(SCN9A):c.2006G>A (p.Arg669His) SNV Uncertain significance 471092 rs200374987 GRCh37: 2:167138287-167138287
GRCh38: 2:166281777-166281777
33 SCN1A-AS1 , SCN9A NM_001365536.1(SCN9A):c.1277T>A (p.Met426Lys) SNV Uncertain significance 415032 rs200415928 GRCh37: 2:167144984-167144984
GRCh38: 2:166288474-166288474
34 SCN1A-AS1 , SCN9A NM_001365536.1(SCN9A):c.4482A>G (p.Gln1494=) SNV Uncertain significance 626166 rs1558945594 GRCh37: 2:167060891-167060891
GRCh38: 2:166204381-166204381
35 SCN1A-AS1 , SCN9A NM_001365536.1(SCN9A):c.4143A>G (p.Arg1381=) SNV Uncertain significance 471123 rs200610689 GRCh37: 2:167085264-167085264
GRCh38: 2:166228754-166228754
36 SCN1A-AS1 , SCN9A NM_001365536.1(SCN9A):c.3497G>A (p.Cys1166Tyr) SNV Uncertain significance 331969 rs370455223 GRCh37: 2:167099142-167099142
GRCh38: 2:166242632-166242632
37 SCN1A-AS1 , SCN9A NM_001365536.1(SCN9A):c.4434_4436GAA[1] (p.Lys1480del) Microsatellite Uncertain significance 331964 rs886055050 GRCh37: 2:167060934-167060936
GRCh38: 2:166204424-166204426
38 SCN1A-AS1 , SCN9A NM_001365536.1(SCN9A):c.3125C>T (p.Thr1042Ile) SNV Uncertain significance 471106 rs757989638 GRCh37: 2:167129135-167129135
GRCh38: 2:166272625-166272625
39 SCN9A NM_001365536.1(SCN9A):c.822A>G (p.Lys274=) SNV Uncertain significance 538490 rs199784484 GRCh37: 2:167159679-167159679
GRCh38: 2:166303169-166303169
40 SCN1A-AS1 , SCN9A NM_001365536.1(SCN9A):c.1998G>C (p.Lys666Asn) SNV Uncertain significance 642002 rs369989247 GRCh37: 2:167138295-167138295
GRCh38: 2:166281785-166281785
41 SCN1A-AS1 , SCN9A NM_001365536.1(SCN9A):c.4503+8_4503+9insT Insertion Uncertain significance 331962 rs767624579 GRCh37: 2:167060861-167060862
GRCh38: 2:166204351-166204352
42 SCN1A-AS1 , SCN9A NM_001365536.1(SCN9A):c.*164G>A SNV Uncertain significance 892578 GRCh37: 2:167055018-167055018
GRCh38: 2:166198508-166198508
43 SCN1A-AS1 , SCN9A NM_001365536.1(SCN9A):c.*159T>C SNV Uncertain significance 892579 GRCh37: 2:167055023-167055023
GRCh38: 2:166198513-166198513
44 SCN1A-AS1 , SCN9A NM_001365536.1(SCN9A):c.3464T>A (p.Phe1155Tyr) SNV Uncertain significance 289499 rs750839038 GRCh37: 2:167108283-167108283
GRCh38: 2:166251773-166251773
45 SCN1A-AS1 , SCN9A NM_001365536.1(SCN9A):c.*237C>T SNV Uncertain significance 893366 GRCh37: 2:167054945-167054945
GRCh38: 2:166198435-166198435
46 SCN1A-AS1 , SCN9A NM_001365536.1(SCN9A):c.2240A>T (p.Asp747Val) SNV Uncertain significance 893844 GRCh37: 2:167136970-167136970
GRCh38: 2:166280460-166280460
47 SCN9A NM_001365536.1(SCN9A):c.73C>A (p.Gln25Lys) SNV Uncertain significance 893992 GRCh37: 2:167168194-167168194
GRCh38: 2:166311684-166311684
48 SCN1A-AS1 , SCN9A NM_001365536.1(SCN9A):c.*2945C>A SNV Uncertain significance 894028 GRCh37: 2:167052237-167052237
GRCh38: 2:166195727-166195727
49 SCN9A NM_002977.3(SCN9A):c.-324C>A SNV Uncertain significance 894029 GRCh37: 2:167232480-167232480
GRCh38: 2:166375970-166375970
50 SCN1A-AS1 , SCN9A NM_001365536.1(SCN9A):c.*1422T>C SNV Uncertain significance 894137 GRCh37: 2:167053760-167053760
GRCh38: 2:166197250-166197250

UniProtKB/Swiss-Prot genetic disease variations for Paroxysmal Extreme Pain Disorder:

72
# Symbol AA change Variation ID SNP ID
1 SCN9A p.Arg1007Cys VAR_032015 rs121908910
2 SCN9A p.Val1309Asp VAR_032016 rs121908911
3 SCN9A p.Val1309Phe VAR_032017 rs121908912
4 SCN9A p.Val1310Phe VAR_032018 rs121908913
5 SCN9A p.Ile1472Thr VAR_032020 rs121908914
6 SCN9A p.Phe1473Val VAR_032021 rs155347439
7 SCN9A p.Thr1475Ile VAR_032022 rs121908915
8 SCN9A p.Met1638Lys VAR_032023
9 SCN9A p.Leu1623Pro VAR_072279 rs113169177
10 SCN9A p.Ala1643Glu VAR_072280 rs879253994

Expression for Paroxysmal Extreme Pain Disorder

Search GEO for disease gene expression data for Paroxysmal Extreme Pain Disorder.

Pathways for Paroxysmal Extreme Pain Disorder

Pathways related to Paroxysmal Extreme Pain Disorder according to GeneCards Suite gene sharing:

(show all 11)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.53 SCN9A SCN8A SCN5A SCN4B SCN4A SCN3A
2
Show member pathways
13.45 SCN9A SCN8A SCN5A SCN4B SCN4A SCN3A
3
Show member pathways
13.05 SCN9A SCN8A SCN5A SCN4B SCN4A SCN3A
4
Show member pathways
12.91 SCN9A SCN8A SCN5A SCN4B SCN4A SCN3A
5 12.6 SCN9A SCN8A SCN5A SCN4A SCN2B SCN2A
6
Show member pathways
12.52 SCN9A SCN8A SCN5A SCN4B SCN4A SCN3A
7
Show member pathways
11.91 SCN9A SCN8A SCN5A SCN4B SCN4A SCN3A
8
Show member pathways
11.83 SCN9A SCN8A SCN5A SCN4B SCN4A SCN3A
9
Show member pathways
11.77 SCN9A SCN3A SCN2A
10 11.53 SCN5A SCN4B SCN2B SCN1B
11 10.88 SCN9A SCN8A SCN5A SCN4B SCN4A SCN3A

GO Terms for Paroxysmal Extreme Pain Disorder

Cellular components related to Paroxysmal Extreme Pain Disorder according to GeneCards Suite gene sharing:

(show all 12)
# Name GO ID Score Top Affiliating Genes
1 membrane GO:0016020 10.4 TRPV1 TRPA1 SCN9A SCN8A SCN5A SCN4B
2 plasma membrane GO:0005886 10.31 TRPV1 TRPA1 SCN9A SCN8A SCN5A SCN4B
3 integral component of membrane GO:0016021 10.27 TRPV1 TRPA1 SCN9A SCN8A SCN5A SCN4B
4 T-tubule GO:0030315 9.71 SCN5A SCN2A SCN1B SCN1A
5 Z disc GO:0030018 9.69 SCN8A SCN5A SCN1A
6 intrinsic component of plasma membrane GO:0031226 9.65 TRPV1 SCN4B SCN2A
7 axon GO:0030424 9.65 SCN9A SCN8A SCN4A SCN3A SCN2A SCN1B
8 axon initial segment GO:0043194 9.63 SCN8A SCN1A NAV1
9 node of Ranvier GO:0033268 9.56 SCN8A SCN2A SCN1B SCN1A
10 intercalated disc GO:0014704 9.55 SCN5A SCN4B SCN2A SCN1B SCN1A
11 sodium channel complex GO:0034706 9.5 SCN2A SCN1B SCN1A
12 voltage-gated sodium channel complex GO:0001518 9.4 SCN9A SCN8A SCN5A SCN4B SCN4A SCN3A

Biological processes related to Paroxysmal Extreme Pain Disorder according to GeneCards Suite gene sharing:

(show all 30)
# Name GO ID Score Top Affiliating Genes
1 transmembrane transport GO:0055085 10.22 TRPV1 TRPA1 SCN9A SCN8A SCN5A SCN4A
2 ion transmembrane transport GO:0034220 10.13 TRPV1 TRPA1 SCN9A SCN8A SCN5A SCN3A
3 sodium ion transmembrane transport GO:0035725 10.03 SCN9A SCN8A SCN5A SCN4B SCN4A SCN3A
4 membrane depolarization during action potential GO:0086010 10.02 SCN9A SCN8A SCN5A SCN4A SCN3A SCN2A
5 cation transmembrane transport GO:0098655 10 SCN9A SCN8A SCN5A SCN3A SCN2A SCN1A
6 neuronal action potential GO:0019228 9.97 SCN9A SCN8A SCN5A SCN4A SCN3A SCN2A
7 sodium ion transport GO:0006814 9.93 SCN9A SCN8A SCN5A SCN4B SCN4A SCN3A
8 cardiac muscle cell action potential involved in contraction GO:0086002 9.88 SCN5A SCN4B SCN2B SCN1B SCN1A
9 sensory perception of pain GO:0019233 9.86 TRPV1 TRPA1 SCN9A SCN10A
10 cardiac muscle contraction GO:0060048 9.85 SCN5A SCN4B SCN2B SCN1B
11 regulation of heart rate by cardiac conduction GO:0086091 9.84 SCN5A SCN4B SCN2B SCN1B
12 calcium ion transmembrane transport GO:0070588 9.82 TRPV1 TRPA1 CACNA1B
13 membrane depolarization during cardiac muscle cell action potential GO:0086012 9.81 SCN5A SCN4B SCN2B SCN1B
14 regulation of atrial cardiac muscle cell membrane depolarization GO:0060371 9.8 SCN5A SCN2B SCN1B SCN10A
15 regulation of ion transmembrane transport GO:0034765 9.8 SCN9A SCN8A SCN5A SCN4B SCN4A SCN3A
16 regulation of ventricular cardiac muscle cell membrane repolarization GO:0060307 9.77 SCN5A SCN4B SCN1B
17 membrane depolarization GO:0051899 9.76 SCN5A SCN1B CACNA1B
18 regulation of sodium ion transmembrane transporter activity GO:2000649 9.75 SCN4B SCN2B SCN1B
19 positive regulation of sodium ion transport GO:0010765 9.74 SCN5A SCN4B SCN1B
20 AV node cell action potential GO:0086016 9.7 SCN5A SCN4B SCN10A
21 response to pain GO:0048265 9.64 TRPV1 TRPA1
22 detection of mechanical stimulus involved in sensory perception of pain GO:0050966 9.64 TRPA1 SCN1A
23 behavioral response to pain GO:0048266 9.63 TRPV1 SCN9A
24 neuronal action potential propagation GO:0019227 9.63 SCN1B SCN1A
25 response to pyrethroid GO:0046684 9.62 SCN2B SCN1B
26 membrane depolarization during Purkinje myocyte cell action potential GO:0086047 9.62 SCN5A SCN1B
27 detection of chemical stimulus involved in sensory perception of pain GO:0050968 9.61 TRPV1 TRPA1
28 thermoception GO:0050955 9.61 TRPV1 TRPA1
29 bundle of His cell action potential GO:0086043 9.6 SCN5A SCN10A
30 ion transport GO:0006811 9.53 TRPV1 TRPA1 SCN9A SCN8A SCN5A SCN4B

Molecular functions related to Paroxysmal Extreme Pain Disorder according to GeneCards Suite gene sharing:

(show all 11)
# Name GO ID Score Top Affiliating Genes
1 cation channel activity GO:0005261 10.06 TRPV1 SCN9A SCN8A SCN5A SCN4A SCN3A
2 sodium channel activity GO:0005272 10.03 SCN9A SCN8A SCN5A SCN4B SCN4A SCN3A
3 voltage-gated sodium channel activity GO:0005248 9.93 SCN9A SCN8A SCN5A SCN4B SCN4A SCN3A
4 ion channel activity GO:0005216 9.77 TRPV1 TRPA1 SCN9A SCN8A SCN5A SCN4A
5 ion channel binding GO:0044325 9.76 SCN5A SCN4B SCN1B SCN10A
6 calcium channel activity GO:0005262 9.67 TRPV1 TRPA1 CACNA1B
7 voltage-gated sodium channel activity involved in cardiac muscle cell action potential GO:0086006 9.67 SCN5A SCN4B SCN2B SCN1B
8 sodium channel regulator activity GO:0017080 9.61 SCN4B SCN2B SCN1B
9 calcium-release channel activity GO:0015278 9.48 TRPV1 TRPA1
10 voltage-gated ion channel activity GO:0005244 9.47 SCN9A SCN8A SCN5A SCN4B SCN4A SCN3A
11 voltage-gated sodium channel activity involved in Purkinje myocyte action potential GO:0086062 9.4 SCN5A SCN1B

Sources for Paroxysmal Extreme Pain Disorder

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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