FCAS2
MCID: FML117
MIFTS: 37

Familial Cold Autoinflammatory Syndrome 2 (FCAS2)

Categories: Blood diseases, Bone diseases, Genetic diseases, Immune diseases, Nephrological diseases, Rare diseases, Skin 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 44 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 incomplete penetrance phenotypic variability infantile onset
Inheritance autosomal dominant inheritance


Classifications:



External Ids:

OMIM 57 611762
Disease Ontology 12 DOID:0090063
Orphanet 59 ORPHA247868
UMLS via Orphanet 74 C2673198
ICD10 via Orphanet 34 E85.0
MedGen 42 C2673198
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 familial cold autoinflammatory syndrome and tinea favosa. An important gene associated with Familial Cold Autoinflammatory Syndrome 2 is NLRP12 (NLR Family Pyrin Domain Containing 12), and among its related pathways/superpathways are Metabolism of water-soluble vitamins and cofactors and Nucleotide-binding Oligomerization Domain (NOD) pathway. Affiliated tissues include skin and bone, and related phenotypes are arthritis and sensorineural hearing impairment

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:

# Related Disease Score Top Affiliating Genes
1 familial cold autoinflammatory syndrome 10.0 NLRP12 NLRP3
2 tinea favosa 9.9 CHD7 NLRP3
3 pseudoxanthoma elasticum 9.9 ENPP1 VKORC1
4 aortic atherosclerosis 9.8 LDLR PON1
5 familial hyperlipidemia 9.8 LDLR PON1
6 arteries, anomalies of 9.7 LDLR PON1

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

Abdomen Spleen:
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 13)
# Description HPO Frequency HPO Source Accession
1 arthritis 32 HP:0001369
2 sensorineural hearing impairment 32 HP:0000407
3 arthralgia 32 HP:0002829
4 abdominal pain 32 HP:0002027
5 myalgia 32 HP:0003326
6 skin rash 32 HP:0000988
7 urticaria 32 HP:0001025
8 headache 32 HP:0002315
9 elevated c-reactive protein level 32 HP:0011227
10 lymphadenopathy 32 very rare (1%) HP:0002716
11 recurrent aphthous stomatitis 32 HP:0011107
12 episodic fever 32 very rare (1%) HP:0001954
13 lymphocytosis 32 very rare (1%) HP:0100827

MGI Mouse Phenotypes related to Familial Cold Autoinflammatory Syndrome 2:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 cellular MP:0005384 9.87 CHD7 ENPP1 GOLGB1 LDLR NLRP12 NLRP3
2 homeostasis/metabolism MP:0005376 9.7 CHD7 ENPP1 LDLR NLRP12 NLRP3 PON1
3 digestive/alimentary MP:0005381 9.65 CHD7 GOLGB1 LDLR NLRP12 NLRP3
4 limbs/digits/tail MP:0005371 9.26 CHD7 ENPP1 NLRP3 VKORC1
5 skeleton MP:0005390 9.02 CHD7 ENPP1 GOLGB1 NLRP3 VKORC1

Drugs & Therapeutics for Familial Cold Autoinflammatory Syndrome 2

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

Cochrane evidence based reviews: 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 184)
# 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.1343G> C (p.Gly448Ala) single nucleotide variant Uncertain significance rs104895566 GRCh37 Chromosome 19, 54313570: 54313570
6 NLRP12 NM_144687.3(NLRP12): c.1343G> C (p.Gly448Ala) single nucleotide variant Uncertain significance rs104895566 GRCh38 Chromosome 19, 53810316: 53810316
7 NLRP12 NM_144687.3(NLRP12): c.2784C> T (p.Ala928=) single nucleotide variant Benign/Likely benign rs104895569 GRCh37 Chromosome 19, 54301640: 54301640
8 NLRP12 NM_144687.3(NLRP12): c.2784C> T (p.Ala928=) single nucleotide variant Benign/Likely benign rs104895569 GRCh38 Chromosome 19, 53798386: 53798386
9 NLRP12 NM_144687.3(NLRP12): c.2830C> A (p.Arg944=) single nucleotide variant Benign/Likely benign rs104895570 GRCh37 Chromosome 19, 54301594: 54301594
10 NLRP12 NM_144687.3(NLRP12): c.2830C> A (p.Arg944=) single nucleotide variant Benign/Likely benign rs104895570 GRCh38 Chromosome 19, 53798340: 53798340
11 NLRP12 NM_144687.3(NLRP12): c.1206C> G (p.Phe402Leu) single nucleotide variant Benign rs34971363 GRCh38 Chromosome 19, 53810453: 53810453
12 NLRP12 NM_144687.3(NLRP12): c.1206C> G (p.Phe402Leu) single nucleotide variant Benign rs34971363 GRCh37 Chromosome 19, 54313707: 54313707
13 NLRP12 NM_144687.3(NLRP12): c.969T> G (p.Leu323=) single nucleotide variant Benign/Likely benign rs142063194 GRCh38 Chromosome 19, 53810690: 53810690
14 NLRP12 NM_144687.3(NLRP12): c.969T> G (p.Leu323=) single nucleotide variant Benign/Likely benign rs142063194 GRCh37 Chromosome 19, 54313944: 54313944
15 NLRP12 NM_144687.3(NLRP12): c.910C> T (p.His304Tyr) single nucleotide variant Conflicting interpretations of pathogenicity rs141245482 GRCh38 Chromosome 19, 53810749: 53810749
16 NLRP12 NM_144687.3(NLRP12): c.910C> T (p.His304Tyr) single nucleotide variant Conflicting interpretations of pathogenicity rs141245482 GRCh37 Chromosome 19, 54314003: 54314003
17 NLRP12 NM_144687.3(NLRP12): c.-12C> T single nucleotide variant Benign rs4539722 GRCh38 Chromosome 19, 53824186: 53824186
18 NLRP12 NM_144687.3(NLRP12): c.-12C> T single nucleotide variant Benign rs4539722 GRCh37 Chromosome 19, 54327440: 54327440
19 NLRP12 NM_144687.3(NLRP12): c.3024C> T (p.Asn1008=) single nucleotide variant Benign/Likely benign rs140769141 GRCh38 Chromosome 19, 53795933: 53795933
20 NLRP12 NM_144687.3(NLRP12): c.3024C> T (p.Asn1008=) single nucleotide variant Benign/Likely benign rs140769141 GRCh37 Chromosome 19, 54299187: 54299187
21 NLRP12 NM_144687.3(NLRP12): c.609C> T (p.Asp203=) single nucleotide variant Benign/Likely benign rs34854934 GRCh38 Chromosome 19, 53811050: 53811050
22 NLRP12 NM_144687.3(NLRP12): c.609C> T (p.Asp203=) single nucleotide variant Benign/Likely benign rs34854934 GRCh37 Chromosome 19, 54314304: 54314304
23 NLRP12 NM_144687.3(NLRP12): c.3046C> T (p.Arg1016Ter) single nucleotide variant Likely benign rs35064500 GRCh38 Chromosome 19, 53795911: 53795911
24 NLRP12 NM_144687.3(NLRP12): c.3046C> T (p.Arg1016Ter) single nucleotide variant Likely benign rs35064500 GRCh37 Chromosome 19, 54299165: 54299165
25 NLRP12 NM_144687.3(NLRP12): c.2755C> T (p.Arg919Trp) single nucleotide variant Benign/Likely benign rs61741349 GRCh38 Chromosome 19, 53801228: 53801228
26 NLRP12 NM_144687.3(NLRP12): c.2755C> T (p.Arg919Trp) single nucleotide variant Benign/Likely benign rs61741349 GRCh37 Chromosome 19, 54304482: 54304482
27 NLRP12 NM_144687.3(NLRP12): c.2141A> G (p.Asn714Ser) single nucleotide variant Benign/Likely benign rs150848917 GRCh37 Chromosome 19, 54310851: 54310851
28 NLRP12 NM_144687.3(NLRP12): c.2141A> G (p.Asn714Ser) single nucleotide variant Benign/Likely benign rs150848917 GRCh38 Chromosome 19, 53807597: 53807597
29 NLRP12 NM_144687.3(NLRP12): c.960G> A (p.Thr320=) single nucleotide variant Benign/Likely benign rs77625808 GRCh37 Chromosome 19, 54313953: 54313953
30 NLRP12 NM_144687.3(NLRP12): c.960G> A (p.Thr320=) single nucleotide variant Benign/Likely benign rs77625808 GRCh38 Chromosome 19, 53810699: 53810699
31 NLRP12 NM_144687.3(NLRP12): c.1996T> C (p.Tyr666His) single nucleotide variant Uncertain significance rs766112183 GRCh37 Chromosome 19, 54312917: 54312917
32 NLRP12 NM_144687.3(NLRP12): c.1996T> C (p.Tyr666His) single nucleotide variant Uncertain significance rs766112183 GRCh38 Chromosome 19, 53809663: 53809663
33 NLRP12 NM_144687.3(NLRP12): c.1349C> T (p.Pro450Leu) single nucleotide variant Conflicting interpretations of pathogenicity rs143640165 GRCh37 Chromosome 19, 54313564: 54313564
34 NLRP12 NM_144687.3(NLRP12): c.1349C> T (p.Pro450Leu) single nucleotide variant Conflicting interpretations of pathogenicity rs143640165 GRCh38 Chromosome 19, 53810310: 53810310
35 NLRP12 NM_144687.3(NLRP12): c.1347C> G (p.Ala449=) single nucleotide variant Benign rs111234757 GRCh37 Chromosome 19, 54313566: 54313566
36 NLRP12 NM_144687.3(NLRP12): c.1347C> G (p.Ala449=) single nucleotide variant Benign rs111234757 GRCh38 Chromosome 19, 53810312: 53810312
37 NLRP12 NM_144687.3(NLRP12): c.2754G> C (p.Leu918=) single nucleotide variant Benign/Likely benign rs61741347 GRCh38 Chromosome 19, 53801229: 53801229
38 NLRP12 NM_144687.3(NLRP12): c.2754G> C (p.Leu918=) single nucleotide variant Benign/Likely benign rs61741347 GRCh37 Chromosome 19, 54304483: 54304483
39 NLRP12 NM_144687.3(NLRP12): c.2748G> A (p.Gln916=) single nucleotide variant Likely benign rs368633277 GRCh38 Chromosome 19, 53801235: 53801235
40 NLRP12 NM_144687.3(NLRP12): c.2748G> A (p.Gln916=) single nucleotide variant Likely benign rs368633277 GRCh37 Chromosome 19, 54304489: 54304489
41 NLRP12 NM_144687.3(NLRP12): c.2576G> A (p.Arg859Gln) single nucleotide variant Benign/Likely benign rs79884502 GRCh38 Chromosome 19, 53803961: 53803961
42 NLRP12 NM_144687.3(NLRP12): c.2576G> A (p.Arg859Gln) single nucleotide variant Benign/Likely benign rs79884502 GRCh37 Chromosome 19, 54307215: 54307215
43 NLRP12 NM_144687.3(NLRP12): c.779C> T (p.Thr260Met) single nucleotide variant Conflicting interpretations of pathogenicity rs150280940 GRCh37 Chromosome 19, 54314134: 54314134
44 NLRP12 NM_144687.3(NLRP12): c.779C> T (p.Thr260Met) single nucleotide variant Conflicting interpretations of pathogenicity rs150280940 GRCh38 Chromosome 19, 53810880: 53810880
45 NLRP12 NM_144687.3(NLRP12): c.291T> C (p.Asp97=) single nucleotide variant Likely benign rs201046901 GRCh38 Chromosome 19, 53814987: 53814987
46 NLRP12 NM_144687.3(NLRP12): c.291T> C (p.Asp97=) single nucleotide variant Likely benign rs201046901 GRCh37 Chromosome 19, 54318241: 54318241
47 NLRP12 NM_144687.3(NLRP12): c.2750C> T (p.Thr917Ile) single nucleotide variant Uncertain significance rs760120881 GRCh38 Chromosome 19, 53801233: 53801233
48 NLRP12 NM_144687.3(NLRP12): c.2750C> T (p.Thr917Ile) single nucleotide variant Uncertain significance rs760120881 GRCh37 Chromosome 19, 54304487: 54304487
49 NLRP12 NC_000019.10: g.(?_53807475)_(53807688_?)del deletion Uncertain significance GRCh38 Chromosome 19, 53807475: 53807688
50 NLRP12 NC_000019.10: g.(?_53807475)_(53807688_?)del deletion Uncertain significance GRCh37 Chromosome 19, 54310729: 54310942

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

GO Terms for Familial Cold Autoinflammatory Syndrome 2

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

# Name GO ID Score Top Affiliating Genes
1 activation of cysteine-type endopeptidase activity involved in apoptotic process GO:0006919 9.43 NLRP12 NLRP3
2 cholesterol metabolic process GO:0008203 9.4 LDLR PON1
3 positive regulation of inflammatory response GO:0050729 9.37 LDLR NLRP12
4 negative regulation of NF-kappaB transcription factor activity GO:0032088 9.32 NLRP12 NLRP3
5 positive regulation of interleukin-1 beta secretion GO:0050718 9.26 NLRP12 NLRP3
6 negative regulation of NIK/NF-kappaB signaling GO:1901223 9.16 NLRP12 NLRP3
7 olfactory bulb development GO:0021772 8.96 CHD7 ENPP1
8 negative regulation of protein autophosphorylation GO:0031953 8.62 ENPP1 NLRP12

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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