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

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Ichthyosis, congenital, autosomal recessive 12	AR	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	27494380

ClinVar

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

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.

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				2	3	5
missense			25	2	2	29
nonsense			2			2
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				2		2
non coding				1	15	16
Total	0	0	27	5	20

Variants in CASP14

This is a list of pathogenic ClinVar variants found in the CASP14 region.

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

Position	Type	Phenotype	Significance	ClinVar
19-15051944-C-T			Benign (Nov 10, 2018)
19-15051947-A-G			Benign (Nov 10, 2018)
19-15052105-T-A			Benign (Nov 10, 2018)
19-15052242-C-T		CASP14-related disorder	Likely benign (Feb 17, 2020)
19-15052249-G-A		CASP14-related disorder	Likely benign (Jul 16, 2019)
19-15052265-G-A		not specified	Likely benign (Sep 16, 2021)
19-15053211-T-G			Benign (Nov 10, 2018)
19-15053309-T-C			Benign (Jun 20, 2021)
19-15053506-C-T		not specified	Uncertain significance (Dec 14, 2023)
19-15053507-G-A		not specified	Uncertain significance (Sep 21, 2023)
19-15053523-G-A			Benign (Dec 31, 2019)
19-15053540-G-A		not specified	Uncertain significance (Feb 21, 2024)
19-15053560-C-G		not specified	Uncertain significance (Dec 28, 2022)
19-15053564-A-G		not specified	Uncertain significance (Apr 12, 2022)
19-15053584-C-T		CASP14-related disorder	Benign (Jun 10, 2019)
19-15053615-G-C		not specified	Uncertain significance (Dec 19, 2023)
19-15053628-C-T			Benign/Likely benign (Oct 01, 2023)
19-15053631-G-A			Likely benign (Apr 10, 2018)
19-15053748-C-G			Benign (Jan 18, 2018)
19-15053779-G-C		not specified	Uncertain significance (Dec 16, 2022)
19-15053780-G-C		CASP14-related disorder	Benign (Oct 28, 2019)
19-15053818-C-A		not specified	Uncertain significance (Jul 12, 2023)
19-15053827-G-C		not specified	Uncertain significance (Apr 08, 2024)
19-15053883-G-A		Ichthyosis, congenital, autosomal recessive 12	Uncertain significance (Feb 18, 2019)
19-15053887-C-T		Ichthyosis, congenital, autosomal recessive 12	Uncertain significance (May 09, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CASP14	protein_coding	protein_coding	ENST00000427043	6	8910

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000287	0.545	125562	0	183	125745	0.000728

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.175	156	150	1.04	0.00000925	1575
Missense in Polyphen		60	64.067	0.93653		683
Synonymous	-0.369	62	58.4	1.06	0.00000356	470
Loss of Function	0.804	10	13.1	0.761	7.92e-7	140

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00293	0.00293
Ashkenazi Jewish	0.00149	0.00149
East Asian	0.00103	0.00103
Finnish	0.0000463	0.0000462
European (Non-Finnish)	0.000344	0.000343
Middle Eastern	0.00103	0.00103
South Asian	0.0000653	0.0000653
Other	0.00147	0.00147

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

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

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