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

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Pityriasis rubra pilaris; Psoriasis 2	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Dermatologic	8178173; 15689454; 22521418

ClinVar

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

• not provided (3 variants)
• Psoriasis 2 (2 variants)
• Pityriasis rubra pilaris;Psoriasis 2 (2 variants)
• Papulosquamous eruptions (2 variants)
• Pityriasis rubra pilaris (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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			10	212	15	237
missense	2	2	480	16	8	508
nonsense			19	1		20
start loss						0
frameshift			21			21
inframe indel		1	4			5
splice donor/acceptor (+/-2bp)	1		16			17
splice region	1		30	34	1	66
non coding			9	122	72	203
Total	3	3	559	351	95

Variants in CARD14

This is a list of pathogenic ClinVar variants found in the CARD14 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
17-80181089-TA-T			Benign (Oct 06, 2019)
17-80181089-T-TAAAA			Benign (Oct 05, 2019)
17-80181205-G-A			Benign (Jul 09, 2018)
17-80181299-G-A			Benign (Jul 10, 2018)
17-80181383-A-C		not specified	Benign (Nov 12, 2023)
17-80181431-G-T		Autoinflammatory syndrome • CARD14-related disorder	Benign (May 01, 2019)
17-80181442-G-A		Pityriasis rubra pilaris;Psoriasis 2	Uncertain significance (Nov 20, 2022)
17-80181445-G-A		Pityriasis rubra pilaris;Psoriasis 2	Likely benign (Jan 26, 2024)
17-80181447-A-G		Pityriasis rubra pilaris;Psoriasis 2	Likely benign (Jun 23, 2018)
17-80181448-CTG-C		Pityriasis rubra pilaris;Psoriasis 2	Uncertain significance (May 05, 2023)
17-80181454-C-T		Pityriasis rubra pilaris;Psoriasis 2 • Autoinflammatory syndrome	Uncertain significance (Oct 13, 2023)
17-80181457-A-T		Pityriasis rubra pilaris;Psoriasis 2	Uncertain significance (Dec 19, 2023)
17-80181459-G-A		Pityriasis rubra pilaris;Psoriasis 2	Likely benign (Jul 25, 2022)
17-80181464-C-G		Pityriasis rubra pilaris;Psoriasis 2	Uncertain significance (Nov 29, 2019)
17-80181465-C-T		Pityriasis rubra pilaris;Psoriasis 2 • Autoinflammatory syndrome • CARD14-related disorder	Benign/Likely benign (Jan 14, 2024)
17-80181468-A-G		Pityriasis rubra pilaris;Psoriasis 2	Likely benign (Apr 07, 2023)
17-80181473-C-T		Pityriasis rubra pilaris;Psoriasis 2 • Autoinflammatory syndrome	Conflicting classifications of pathogenicity (Jan 08, 2024)
17-80181474-G-A			Likely benign (Jan 01, 2023)
17-80181474-G-C		Pityriasis rubra pilaris;Psoriasis 2	Likely benign (Apr 24, 2022)
17-80181478-C-G		Pityriasis rubra pilaris;Psoriasis 2	Uncertain significance (Jul 20, 2018)
17-80181483-C-T		Pityriasis rubra pilaris;Psoriasis 2 • Autoinflammatory syndrome	Conflicting classifications of pathogenicity (Oct 13, 2023)
17-80181484-G-A		Pityriasis rubra pilaris;Psoriasis 2	Uncertain significance (Dec 13, 2023)
17-80181487-G-A		Pityriasis rubra pilaris;Psoriasis 2	Uncertain significance (Oct 26, 2022)
17-80181492-A-G		Pityriasis rubra pilaris;Psoriasis 2	Likely benign (Jun 13, 2020)
17-80181494-T-C		Pityriasis rubra pilaris;Psoriasis 2	Uncertain significance (Aug 01, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CARD14	protein_coding	protein_coding	ENST00000573882	20	39340

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.21e-19	0.226	125589	0	159	125748	0.000632

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.608	576	619	0.931	0.0000416	6456
Missense in Polyphen		164	175.01	0.93708		1900
Synonymous	-1.39	298	269	1.11	0.0000188	1960
Loss of Function	1.58	36	47.8	0.753	0.00000242	535

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00173	0.00171
Ashkenazi Jewish	0.000895	0.000893
East Asian	0.00185	0.00185
Finnish	0.0000539	0.0000462
European (Non-Finnish)	0.000409	0.000396
Middle Eastern	0.00185	0.00185
South Asian	0.000884	0.000882
Other	0.000332	0.000326

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
• gene_indispensability_pred: E
• gene_indispensability_score: 0.705

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	High
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Card14

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