GeneBe

CARD14

caspase recruitment domain family member 14, the group of PDZ domain containing|Membrane associated guanylate kinases|Caspase recruitment domain containing

Basic information

Region (hg38): 17:80169992-80216073

Previous symbols: [ "PSORS2" ]

Links

ENSG00000141527 ∙ NCBI:79092 ∙ OMIM:607211 ∙ HGNC:16446 ∙ Uniprot:Q9BXL6 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

  • familial pityriasis rubra pilaris (Strong), mode of inheritance: AD
  • psoriasis 2 (Strong), mode of inheritance: AD
  • familial pityriasis rubra pilaris (Supportive), mode of inheritance: AD
  • familial pityriasis rubra pilaris (Strong), mode of inheritance: AD
  • psoriasis 2 (Strong), mode of inheritance: AD
  • psoriasis 2 (Definitive), mode of inheritance: AD
  • familial pityriasis rubra pilaris (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Pityriasis rubra pilaris; Psoriasis 2ADGeneralGenetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testingDermatologic8178173; 15689454; 22521418

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CARD14 gene.

  • Psoriasis_2 (1108 variants)
  • Pityriasis_rubra_pilaris (1106 variants)
  • Inborn_genetic_diseases (163 variants)
  • not_provided (154 variants)
  • Autoinflammatory_syndrome (132 variants)
  • CARD14-related_disorder (51 variants)
  • not_specified (11 variants)
  • Papulosquamous_eruptions (9 variants)
  • Familial_pityriasis_rubra_pilaris (1 variants)
  • PSORIASIS_2,_PUSTULAR (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CARD14 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001366385.1. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
13
clinvar
261
clinvar
14
clinvar
 288
missense
9
clinvar
2
clinvar
546
clinvar
56
clinvar
8
clinvar
 621
nonsense
22
clinvar
1
clinvar
 23
start loss
0
frameshift
28
clinvar
 28
splice donor/acceptor (+/-2bp)
2
clinvar
17
clinvar
 19
Total 11 2 626 318 22

Highest pathogenic variant AF is 0.000006840647

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
CARD14protein_codingprotein_codingENST00000573882 2039340
pLI Probability
LOF Intolerant 		pRec Probability
LOF Recessive 		Individuals with
no LOFs 		Individuals with
Homozygous LOFs 		Individuals with
Heterozygous LOFs 		Defined p
1.21e-190.22612558901591257480.000632
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense0.6085766190.9310.00004166456
Missense in Polyphen164175.010.937081900
Synonymous-1.392982691.110.00001881960
Loss of Function1.583647.80.7530.00000242535

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.001730.00171
Ashkenazi Jewish0.0008950.000893
East Asian0.001850.00185
Finnish0.00005390.0000462
European (Non-Finnish)0.0004090.000396
Middle Eastern0.001850.00185
South Asian0.0008840.000882
Other0.0003320.000326

dbNSFP

Source: dbNSFP

Function
FUNCTION: Acts as a scaffolding protein that can activate the inflammatory transcription factor NF-kappa-B and p38/JNK MAP kinase signaling pathways. Forms a signaling complex with BCL10 and MALT1, and activates MALT1 proteolytic activity and inflammatory gene expression. MALT1 is indispensable for CARD14- induced activation of NF-kappa-B and p38/JNK MAP kinases (PubMed:11278692, PubMed:21302310, PubMed:27113748, PubMed:27071417). May play a role in signaling mediated by TRAF2, TRAF3 and TRAF6 and protects cells against apoptosis. {ECO:0000269|PubMed:11278692, ECO:0000269|PubMed:21302310, ECO:0000269|PubMed:27071417, ECO:0000269|PubMed:27113748}.;
Disease
DISEASE: Psoriasis 2 (PSORS2) [MIM:602723]: A common, chronic inflammatory disease of the skin with multifactorial etiology. It is characterized by red, scaly plaques usually found on the scalp, elbows and knees. These lesions are caused by abnormal keratinocyte proliferation and infiltration of inflammatory cells into the dermis and epidermis. {ECO:0000269|PubMed:22521418, ECO:0000269|PubMed:22521419, ECO:0000269|PubMed:26358359, ECO:0000269|PubMed:27071417, ECO:0000269|PubMed:27113748}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.; DISEASE: Pityriasis rubra pilaris (PRP) [MIM:173200]: A rare, papulosquamous skin disease characterized by the appearance of keratotic follicular papules, well-demarcated salmon-colored erythematous plaques covered with fine powdery scales interspersed with distinct islands of uninvolved skin, and palmoplantar keratoderma. Most cases are sporadic. The rare familial cases show autosomal dominant inheritance with incomplete penetrance and variable expression. Familial PRP usually presents at birth or appears during the first years of life and runs a chronic course. It is characterized by prominent follicular hyperkeratosis, diffuse palmoplantar keratoderma, and erythema. {ECO:0000269|PubMed:22703878, ECO:0000269|PubMed:27760266}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway
NF-kappa B signaling pathway - Homo sapiens (human);Apoptosis-related network due to altered Notch3 in ovarian cancer (Consensus)

Recessive Scores

pRec
0.128

Intolerance Scores

loftool
0.832
rvis_EVS
0.89
rvis_percentile_EVS
89.08

Haploinsufficiency Scores

pHI
0.0925
hipred
N
hipred_score
0.170
ghis
0.536

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
gene_indispensability_pred
E
gene_indispensability_score
0.705

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumHigh
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Card14
Phenotype

Gene ontology

Biological process
positive regulation of protein phosphorylation;apoptotic process;activation of NF-kappaB-inducing kinase activity;tumor necrosis factor-mediated signaling pathway;negative regulation of apoptotic process;positive regulation of NF-kappaB transcription factor activity
Cellular component
cytoplasm;plasma membrane
Molecular function
CARD domain binding