MCID: FML117
MIFTS: 34

Familial Cold Autoinflammatory Syndrome 2

Categories: Genetic diseases, Bone diseases, Skin diseases, Rare diseases, Immune diseases, Blood diseases

Aliases & Classifications for Familial Cold Autoinflammatory Syndrome 2

MalaCards integrated aliases for Familial Cold Autoinflammatory Syndrome 2:

Name: Familial Cold Autoinflammatory Syndrome 2 57 12 75 29 13 6 15 73
Fcas2 57 59 75
Nlrp12-Associated Hereditary Periodic Fever Syndrome 12 59
Familial Cold Autoinflammatory Syndrome 2, Susceptibility to 6
Autoinflammatory Syndrome, Cold, Familial, Type 2 40
Familial Cold Autoinflammatory Syndrome Type 2 59
Naps12 59

Characteristics:

Orphanet epidemiological data:

59
nlrp12-associated hereditary periodic fever syndrome
Inheritance: Autosomal dominant; Age of onset: Infancy,Neonatal;

OMIM:

57
Inheritance:
autosomal dominant

Miscellaneous:
incomplete penetrance
phenotypic variability
variable age at onset, range infancy to adult
episodes are triggered by cold exposure
episodes can last hours, days, or weeks
responsive to steroid treatment


HPO:

32
familial cold autoinflammatory syndrome 2:
Onset and clinical course phenotypic variability infantile onset
Inheritance autosomal dominant inheritance


Classifications:



External Ids:

OMIM 57 611762
Disease Ontology 12 DOID:0090063
ICD10 33 E85.0
Orphanet 59 ORPHA247868
UMLS via Orphanet 74 C2673198
ICD10 via Orphanet 34 E85.0
MedGen 42 C2673198
MeSH 44 D056587
UMLS 73 C2673198

Summaries for Familial Cold Autoinflammatory Syndrome 2

OMIM : 57 Familial cold autoinflammatory syndrome-2 (FCAS2) is an autosomal dominant autoinflammatory disorder characterized by episodic and recurrent rash, urticaria, arthralgia, myalgia, and headache. In most patients, these episodes are accompanied by fever and serologic evidence of inflammation. Most, but not all, patients report exposure to cold as a trigger for the episodes. Additional features may include abdominal pain, thoracic pain, and sensorineural deafness. The age at onset is variable, ranging from the first year of life to middle age, and the severity and clinical manifestations are heterogeneous (summary by Shen et al., 2017). For a phenotypic description and a discussion of genetic heterogeneity of familial cold autoinflammatory syndrome, see FCAS1 (120100). (611762)

MalaCards based summary : Familial Cold Autoinflammatory Syndrome 2, also known as fcas2, is related to cryopyrin-associated periodic syndrome and chronic meningitis. An important gene associated with Familial Cold Autoinflammatory Syndrome 2 is NLRP12 (NLR Family Pyrin Domain Containing 12), and among its related pathways/superpathways is Nucleotide-binding Oligomerization Domain (NOD) pathway. Affiliated tissues include skin and bone, and related phenotypes are sensorineural hearing impairment and skin rash

Disease Ontology : 12 A familial cold autoinflammatory syndrome characterized by autosomal dominant inheritance that has material basis in heterozygous mutation in the NLRP12 gene on chromosome 19q13.

UniProtKB/Swiss-Prot : 75 Familial cold autoinflammatory syndrome 2: A rare autosomal dominant systemic inflammatory disease characterized by recurrent episodes of maculopapular rash associated with arthralgias, myalgias, fever and chills, swelling of the extremities, and conjunctivitis after generalized exposure to cold.

Related Diseases for Familial Cold Autoinflammatory Syndrome 2

Diseases in the Familial Cold Autoinflammatory Syndrome family:

Familial Cold Autoinflammatory Syndrome 1 Familial Cold Autoinflammatory Syndrome 2
Familial Cold Autoinflammatory Syndrome 3 Familial Cold Autoinflammatory Syndrome 4

Diseases related to Familial Cold Autoinflammatory Syndrome 2 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 12)
# Related Disease Score Top Affiliating Genes
1 cryopyrin-associated periodic syndrome 9.7 CRP NLRP3
2 chronic meningitis 9.6 CRP NLRP3
3 muckle-wells syndrome 9.6 CRP NLRP3
4 wells syndrome 9.6 CRP NLRP3
5 skeletal tuberculosis 9.6 CRP NLRP3
6 exanthem 9.5 CRP NLRP3
7 pericardial effusion 9.5 CRP NLRP3
8 familial cold autoinflammatory syndrome 9.5 NLRP12 NLRP3
9 familial mediterranean fever 9.4 CRP NLRP3
10 bone inflammation disease 9.3 CRP NLRP3
11 meningitis 9.2 CRP NLRP3
12 arthropathy 9.0 CRP NLRP3

Graphical network of the top 20 diseases related to Familial Cold Autoinflammatory Syndrome 2:



Diseases related to Familial Cold Autoinflammatory Syndrome 2

Symptoms & Phenotypes for Familial Cold Autoinflammatory Syndrome 2

Symptoms via clinical synopsis from OMIM:

57
Neurologic Central Nervous System:
headache, episodic

AbdomenSpleen:
splenomegaly (in some patients)

Head And Neck Ears:
sensorineural deafness (in some patients)

Skeletal:
arthralgias, episodic
arthritis, episodic

Muscle Soft Tissue:
myalgias, episodic

Laboratory Abnormalities:
serum c-reactive protein may be increased
erythrocyte sedimentation rate may be increased
increased acute phase reactants

Metabolic Features:
fever, episodic

Abdomen:
abdominal pain, episodic

Head And Neck Mouth:
aphthous ulcers, episodic

Skin Nails Hair Skin:
rash, episodic
urticaria, episodic

Immunology:
lymphadenopathy (in some patients)
lymphocytosis, episodic (in some patients)


Clinical features from OMIM:

611762

Human phenotypes related to Familial Cold Autoinflammatory Syndrome 2:

32 (show all 10)
# Description HPO Frequency HPO Source Accession
1 sensorineural hearing impairment 32 HP:0000407
2 skin rash 32 HP:0000988
3 urticaria 32 HP:0001025
4 episodic fever 32 HP:0001954
5 abdominal pain 32 HP:0002027
6 headache 32 HP:0002315
7 arthralgia 32 HP:0002829
8 myalgia 32 HP:0003326
9 recurrent aphthous stomatitis 32 HP:0011107
10 elevated c-reactive protein level 32 HP:0011227

GenomeRNAi Phenotypes related to Familial Cold Autoinflammatory Syndrome 2 according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased shRNA abundance (Z-score < -2) GR00366-A-134 9.17 NLRP3
2 Decreased shRNA abundance (Z-score < -2) GR00366-A-148 9.17 CRP
3 Decreased shRNA abundance (Z-score < -2) GR00366-A-173 9.17 NLRP3
4 Decreased shRNA abundance (Z-score < -2) GR00366-A-180 9.17 CRP
5 Decreased shRNA abundance (Z-score < -2) GR00366-A-68 9.17 CRP
6 Decreased shRNA abundance (Z-score < -2) GR00366-A-89 9.17 CRP NLRP3

Drugs & Therapeutics for Familial Cold Autoinflammatory Syndrome 2

Search Clinical Trials , NIH Clinical Center for Familial Cold Autoinflammatory Syndrome 2

Genetic Tests for Familial Cold Autoinflammatory Syndrome 2

Genetic tests related to Familial Cold Autoinflammatory Syndrome 2:

# Genetic test Affiliating Genes
1 Familial Cold Autoinflammatory Syndrome 2 29 NLRP12

Anatomical Context for Familial Cold Autoinflammatory Syndrome 2

MalaCards organs/tissues related to Familial Cold Autoinflammatory Syndrome 2:

41
Skin, Bone

Publications for Familial Cold Autoinflammatory Syndrome 2

Variations for Familial Cold Autoinflammatory Syndrome 2

ClinVar genetic disease variations for Familial Cold Autoinflammatory Syndrome 2:

6
(show top 50) (show all 124)
# Gene Variation Type Significance SNP ID Assembly Location
1 NLRP12 NM_144687.3(NLRP12): c.850C> T (p.Arg284Ter) single nucleotide variant Pathogenic rs104895564 GRCh37 Chromosome 19, 54314063: 54314063
2 NLRP12 NM_144687.3(NLRP12): c.850C> T (p.Arg284Ter) single nucleotide variant Pathogenic rs104895564 GRCh38 Chromosome 19, 53810809: 53810809
3 NLRP12 NM_144687.3(NLRP12): c.2072+2dupT duplication Pathogenic rs104895565 GRCh38 Chromosome 19, 53809585: 53809585
4 NLRP12 NM_144687.3(NLRP12): c.2072+2dupT duplication Pathogenic rs104895565 GRCh37 Chromosome 19, 54312839: 54312839
5 NLRP12 NM_144687.3(NLRP12): c.1206C> G (p.Phe402Leu) single nucleotide variant Benign rs34971363 GRCh38 Chromosome 19, 53810453: 53810453
6 NLRP12 NM_144687.3(NLRP12): c.1206C> G (p.Phe402Leu) single nucleotide variant Benign rs34971363 GRCh37 Chromosome 19, 54313707: 54313707
7 NLRP12 NM_144687.3(NLRP12): c.969T> G (p.Leu323=) single nucleotide variant Benign/Likely benign rs142063194 GRCh37 Chromosome 19, 54313944: 54313944
8 NLRP12 NM_144687.3(NLRP12): c.969T> G (p.Leu323=) single nucleotide variant Benign/Likely benign rs142063194 GRCh38 Chromosome 19, 53810690: 53810690
9 NLRP12 NM_144687.3(NLRP12): c.910C> T (p.His304Tyr) single nucleotide variant Benign/Likely benign rs141245482 GRCh38 Chromosome 19, 53810749: 53810749
10 NLRP12 NM_144687.3(NLRP12): c.910C> T (p.His304Tyr) single nucleotide variant Benign/Likely benign rs141245482 GRCh37 Chromosome 19, 54314003: 54314003
11 NLRP12 NM_144687.3(NLRP12): c.-12C> T single nucleotide variant Benign rs4539722 GRCh38 Chromosome 19, 53824186: 53824186
12 NLRP12 NM_144687.3(NLRP12): c.-12C> T single nucleotide variant Benign rs4539722 GRCh37 Chromosome 19, 54327440: 54327440
13 NLRP12 NM_144687.3(NLRP12): c.3024C> T (p.Asn1008=) single nucleotide variant Benign/Likely benign rs140769141 GRCh38 Chromosome 19, 53795933: 53795933
14 NLRP12 NM_144687.3(NLRP12): c.3024C> T (p.Asn1008=) single nucleotide variant Benign/Likely benign rs140769141 GRCh37 Chromosome 19, 54299187: 54299187
15 NLRP12 NM_144687.3(NLRP12): c.609C> T (p.Asp203=) single nucleotide variant Benign/Likely benign rs34854934 GRCh38 Chromosome 19, 53811050: 53811050
16 NLRP12 NM_144687.3(NLRP12): c.609C> T (p.Asp203=) single nucleotide variant Benign/Likely benign rs34854934 GRCh37 Chromosome 19, 54314304: 54314304
17 NLRP12 NM_144687.3(NLRP12): c.3046C> T (p.Arg1016Ter) single nucleotide variant Likely benign rs35064500 GRCh38 Chromosome 19, 53795911: 53795911
18 NLRP12 NM_144687.3(NLRP12): c.3046C> T (p.Arg1016Ter) single nucleotide variant Likely benign rs35064500 GRCh37 Chromosome 19, 54299165: 54299165
19 NLRP12 NM_144687.3(NLRP12): c.2755C> T (p.Arg919Trp) single nucleotide variant Benign/Likely benign rs61741349 GRCh38 Chromosome 19, 53801228: 53801228
20 NLRP12 NM_144687.3(NLRP12): c.2755C> T (p.Arg919Trp) single nucleotide variant Benign/Likely benign rs61741349 GRCh37 Chromosome 19, 54304482: 54304482
21 NLRP12 NM_144687.3(NLRP12): c.2141A> G (p.Asn714Ser) single nucleotide variant Benign/Likely benign rs150848917 GRCh37 Chromosome 19, 54310851: 54310851
22 NLRP12 NM_144687.3(NLRP12): c.2141A> G (p.Asn714Ser) single nucleotide variant Benign/Likely benign rs150848917 GRCh38 Chromosome 19, 53807597: 53807597
23 NLRP12 NM_144687.3(NLRP12): c.960G> A (p.Thr320=) single nucleotide variant Benign/Likely benign rs77625808 GRCh37 Chromosome 19, 54313953: 54313953
24 NLRP12 NM_144687.3(NLRP12): c.960G> A (p.Thr320=) single nucleotide variant Benign/Likely benign rs77625808 GRCh38 Chromosome 19, 53810699: 53810699
25 NLRP12 NM_144687.3(NLRP12): c.1996T> C (p.Tyr666His) single nucleotide variant Uncertain significance rs766112183 GRCh37 Chromosome 19, 54312917: 54312917
26 NLRP12 NM_144687.3(NLRP12): c.1996T> C (p.Tyr666His) single nucleotide variant Uncertain significance rs766112183 GRCh38 Chromosome 19, 53809663: 53809663
27 NLRP12 NM_144687.3(NLRP12): c.1349C> T (p.Pro450Leu) single nucleotide variant Conflicting interpretations of pathogenicity rs143640165 GRCh37 Chromosome 19, 54313564: 54313564
28 NLRP12 NM_144687.3(NLRP12): c.1349C> T (p.Pro450Leu) single nucleotide variant Conflicting interpretations of pathogenicity rs143640165 GRCh38 Chromosome 19, 53810310: 53810310
29 NLRP12 NM_144687.3(NLRP12): c.1347C> G (p.Ala449=) single nucleotide variant Benign rs111234757 GRCh37 Chromosome 19, 54313566: 54313566
30 NLRP12 NM_144687.3(NLRP12): c.1347C> G (p.Ala449=) single nucleotide variant Benign rs111234757 GRCh38 Chromosome 19, 53810312: 53810312
31 NLRP12 NM_144687.3(NLRP12): c.2754G> C (p.Leu918=) single nucleotide variant Benign/Likely benign rs61741347 GRCh38 Chromosome 19, 53801229: 53801229
32 NLRP12 NM_144687.3(NLRP12): c.2754G> C (p.Leu918=) single nucleotide variant Benign/Likely benign rs61741347 GRCh37 Chromosome 19, 54304483: 54304483
33 NLRP12 NM_144687.3(NLRP12): c.2748G> A (p.Gln916=) single nucleotide variant Likely benign rs368633277 GRCh38 Chromosome 19, 53801235: 53801235
34 NLRP12 NM_144687.3(NLRP12): c.2748G> A (p.Gln916=) single nucleotide variant Likely benign rs368633277 GRCh37 Chromosome 19, 54304489: 54304489
35 NLRP12 NM_144687.3(NLRP12): c.2576G> A (p.Arg859Gln) single nucleotide variant Benign/Likely benign rs79884502 GRCh38 Chromosome 19, 53803961: 53803961
36 NLRP12 NM_144687.3(NLRP12): c.2576G> A (p.Arg859Gln) single nucleotide variant Benign/Likely benign rs79884502 GRCh37 Chromosome 19, 54307215: 54307215
37 NLRP12 NM_144687.3(NLRP12): c.779C> T (p.Thr260Met) single nucleotide variant Conflicting interpretations of pathogenicity rs150280940 GRCh37 Chromosome 19, 54314134: 54314134
38 NLRP12 NM_144687.3(NLRP12): c.779C> T (p.Thr260Met) single nucleotide variant Conflicting interpretations of pathogenicity rs150280940 GRCh38 Chromosome 19, 53810880: 53810880
39 NLRP12 NM_144687.3(NLRP12): c.291T> C (p.Asp97=) single nucleotide variant Likely benign rs201046901 GRCh38 Chromosome 19, 53814987: 53814987
40 NLRP12 NM_144687.3(NLRP12): c.291T> C (p.Asp97=) single nucleotide variant Likely benign rs201046901 GRCh37 Chromosome 19, 54318241: 54318241
41 NLRP12 NC_000019.10: g.(?_53807475)_(53807688_?)del deletion Uncertain significance GRCh38 Chromosome 19, 53807475: 53807688
42 NLRP12 NC_000019.10: g.(?_53807475)_(53807688_?)del deletion Uncertain significance GRCh37 Chromosome 19, 54310729: 54310942
43 NLRP12 NM_144687.3(NLRP12): c.2394A> G (p.Gln798=) single nucleotide variant Benign rs4806773 GRCh37 Chromosome 19, 54308554: 54308554
44 NLRP12 NM_144687.3(NLRP12): c.2394A> G (p.Gln798=) single nucleotide variant Benign rs4806773 GRCh38 Chromosome 19, 53805300: 53805300
45 NLRP12 NM_144687.3(NLRP12): c.154G> A (p.Gly52Ser) single nucleotide variant Uncertain significance rs369053968 GRCh37 Chromosome 19, 54327275: 54327275
46 NLRP12 NM_144687.3(NLRP12): c.154G> A (p.Gly52Ser) single nucleotide variant Uncertain significance rs369053968 GRCh38 Chromosome 19, 53824021: 53824021
47 NLRP12 NM_144687.3(NLRP12): c.1886C> A (p.Ala629Asp) single nucleotide variant Uncertain significance rs146250162 GRCh38 Chromosome 19, 53809773: 53809773
48 NLRP12 NM_144687.3(NLRP12): c.1886C> A (p.Ala629Asp) single nucleotide variant Uncertain significance rs146250162 GRCh37 Chromosome 19, 54313027: 54313027
49 NLRP12 NM_144687.3(NLRP12): c.3038C> A (p.Thr1013Lys) single nucleotide variant Uncertain significance rs538392013 GRCh37 Chromosome 19, 54299173: 54299173
50 NLRP12 NM_144687.3(NLRP12): c.3038C> A (p.Thr1013Lys) single nucleotide variant Uncertain significance rs538392013 GRCh38 Chromosome 19, 53795919: 53795919

Expression for Familial Cold Autoinflammatory Syndrome 2

Search GEO for disease gene expression data for Familial Cold Autoinflammatory Syndrome 2.

Pathways for Familial Cold Autoinflammatory Syndrome 2

Pathways related to Familial Cold Autoinflammatory Syndrome 2 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 10.24 NLRP12 NLRP3

GO Terms for Familial Cold Autoinflammatory Syndrome 2

Biological processes related to Familial Cold Autoinflammatory Syndrome 2 according to GeneCards Suite gene sharing:

(show all 14)
# Name GO ID Score Top Affiliating Genes
1 innate immune response GO:0045087 9.58 CRP NLRP12 NLRP3
2 regulation of gene expression GO:0010468 9.54 NLRP12 NLRP3
3 negative regulation of inflammatory response GO:0050728 9.52 NLRP12 NLRP3
4 defense response to Gram-positive bacterium GO:0050830 9.51 CRP NLRP3
5 activation of cysteine-type endopeptidase activity involved in apoptotic process GO:0006919 9.49 NLRP12 NLRP3
6 negative regulation of NF-kappaB transcription factor activity GO:0032088 9.48 NLRP12 NLRP3
7 regulation of inflammatory response GO:0050727 9.46 NLRP12 NLRP3
8 regulation of cytokine production GO:0001817 9.43 NLRP12 NLRP3
9 inflammatory response GO:0006954 9.43 CRP NLRP12 NLRP3
10 signaling GO:0023052 9.37 NLRP12 NLRP3
11 regulation of I-kappaB kinase/NF-kappaB signaling GO:0043122 9.32 NLRP12 NLRP3
12 negative regulation of immune response GO:0050777 9.16 NLRP12 NLRP3
13 positive regulation of interleukin-1 beta secretion GO:0050718 8.96 NLRP12 NLRP3
14 negative regulation of NIK/NF-kappaB signaling GO:1901223 8.62 NLRP12 NLRP3

Sources for Familial Cold Autoinflammatory Syndrome 2

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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