GeneBe

CASP14

caspase 14, the group of Caspases

Basic information

Region (hg38): 19:15049480-15058293

Links

ENSG00000105141 ∙ NCBI:23581 ∙ OMIM:605848 ∙ HGNC:1502 ∙ Uniprot:P31944 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

  • ichthyosis, congenital, autosomal recessive 12 (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Ichthyosis, congenital, autosomal recessive 12ARGeneralGenetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testingDermatologic27494380

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CASP14 gene.

  • not_specified (58 variants)
  • not_provided (8 variants)
  • Ichthyosis,_congenital,_autosomal_recessive_12 (3 variants)
  • CASP14-related_disorder (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CASP14 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000012114.3. 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
3
clinvar
3
clinvar
 6
missense
55
clinvar
2
clinvar
2
clinvar
 59
nonsense
2
clinvar
 2
start loss
0
frameshift
1
clinvar
 1
splice donor/acceptor (+/-2bp)
0
Total 0 0 57 6 5
Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
CASP14protein_codingprotein_codingENST00000427043 68910
pLI Probability
LOF Intolerant 		pRec Probability
LOF Recessive 		Individuals with
no LOFs 		Individuals with
Homozygous LOFs 		Individuals with
Heterozygous LOFs 		Defined p
0.000002870.54512556201831257450.000728
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense-0.1751561501.040.000009251575
Missense in Polyphen6064.0670.93653683
Synonymous-0.3696258.41.060.00000356470
Loss of Function0.8041013.10.7617.92e-7140

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.002930.00293
Ashkenazi Jewish0.001490.00149
East Asian0.001030.00103
Finnish0.00004630.0000462
European (Non-Finnish)0.0003440.000343
Middle Eastern0.001030.00103
South Asian0.00006530.0000653
Other0.001470.00147

dbNSFP

Source: dbNSFP

Function
FUNCTION: Non-apoptotic caspase involved in epidermal differentiation. Is the predominant caspase in epidermal stratum corneum (PubMed:15556625). Seems to play a role in keratinocyte differentiation and is required for cornification. Regulates maturation of the epidermis by proteolytically processing filaggrin (By similarity). In vitro has a preference for the substrate [WY]-X-X-D motif and is active on the synthetic caspase substrate WEHD-ACF (PubMed:16854378, PubMed:19960512). Involved in processing of prosaposin in the epidermis (By similarity). May be involved in retinal pigment epithelium cell barrier function (PubMed:25121097). Involved in DNA degradation in differentiated keratinocytes probably by cleaving DFFA/ICAD leading to liberation of DFFB/CAD (PubMed:24743736). {ECO:0000250|UniProtKB:O89094, ECO:0000269|PubMed:15301553, ECO:0000269|PubMed:15556625, ECO:0000269|PubMed:16854378, ECO:0000269|PubMed:19960512, ECO:0000269|PubMed:22825846, ECO:0000269|PubMed:24743736, ECO:0000305|PubMed:25121097}.;
Disease
DISEASE: Ichthyosis, congenital, autosomal recessive 12 (ARCI12) [MIM:617320]: A form of autosomal recessive congenital ichthyosis, a disorder of keratinization with abnormal differentiation and desquamation of the epidermis, resulting in abnormal skin scaling over the whole body. The main skin phenotypes are lamellar ichthyosis (LI) and non-bullous congenital ichthyosiform erythroderma (NCIE), although phenotypic overlap within the same patient or among patients from the same family can occur. Lamellar ichthyosis is a condition often associated with an embedment in a collodion-like membrane at birth; skin scales later develop, covering the entire body surface. Non-bullous congenital ichthyosiform erythroderma characterized by fine whitish scaling on an erythrodermal background; larger brownish scales are present on the buttocks, neck and legs. {ECO:0000269|PubMed:27494380}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway
Vitamin D Receptor Pathway;Keratinization;Developmental Biology;DroToll-like;Formation of the cornified envelope (Consensus)

Recessive Scores

pRec
0.0980

Intolerance Scores

loftool
0.825
rvis_EVS
-0.2
rvis_percentile_EVS
38.98

Haploinsufficiency Scores

pHI
0.349
hipred
N
hipred_score
0.146
ghis
0.525

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
N
gene_indispensability_pred
N
gene_indispensability_score
0.346

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Casp14
Phenotype
integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); homeostasis/metabolism phenotype;

Gene ontology

Biological process
proteolysis;apoptotic process;epidermis development;intrinsic apoptotic signaling pathway in response to DNA damage;keratinization;cornification
Cellular component
nucleus;cytoplasm;mitochondrion;cytosol;keratin filament
Molecular function
endopeptidase activity;cysteine-type endopeptidase activity;protein binding;cysteine-type endopeptidase activity involved in apoptotic process