CDSN

corneodesmosin

Basic information

Region (hg38): 6:31115086-31120446

Links

ENSG00000204539 ∙ NCBI:1041 ∙ OMIM:602593 ∙ HGNC:1802 ∙ Uniprot:Q15517 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hypotrichosis 2 (Strong), mode of inheritance: AD
• peeling skin syndrome 1 (Strong), mode of inheritance: AR
• peeling skin syndrome 1 (Strong), mode of inheritance: AR
• hypotrichosis simplex of the scalp (Supportive), mode of inheritance: AD
• peeling skin syndrome 1 (Moderate), mode of inheritance: AR
• hypotrichosis 2 (Moderate), mode of inheritance: AD
• peeling skin syndrome 1 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hypotrichosis 2; Peeling skin syndrome 1	AD/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	Allergy/Immunology/Infectious; Dermatologic	3652491; 10793007; 12754508; 20691404; 21191406; 21777220; 22146835

ClinVar

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

• not provided (85 variants)
• Inborn genetic diseases (14 variants)
• Peeling skin syndrome 1 (7 variants)
• not specified (3 variants)
• CDSN-related condition (1 variants)
• Hypotrichosis 2 (1 variants)
• Hypotrichosis 2;Peeling skin syndrome 1 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CDSN 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				11	13	24
missense		1	32	6	15	54
nonsense	1	1				2
start loss						0
frameshift		1	3			4
inframe indel					1	1
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding					17	17
Total	1	3	35	17	46

Highest pathogenic variant AF is 0.0000394

Variants in CDSN

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

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

Position	Type	Phenotype	Significance	ClinVar
6-31115879-G-A			Benign (Nov 10, 2018)
6-31115887-G-A			Benign (Nov 10, 2018)
6-31115952-A-C			Benign (Nov 11, 2018)
6-31116020-ACTT-A			Benign (Oct 27, 2021)
6-31116034-GT-G			Uncertain significance (Nov 27, 2023)
6-31116036-T-C		Peeling skin syndrome 1	Benign (Jan 31, 2024)
6-31116048-C-T			Uncertain significance (Apr 06, 2020)
6-31116083-G-A			Uncertain significance (Jul 10, 2023)
6-31116089-A-G		CDSN-related disorder	Likely benign (Dec 30, 2023)
6-31116090-G-A		Hypotrichosis 2;Peeling skin syndrome 1	Benign/Likely benign (Dec 21, 2023)
6-31116099-C-T		Inborn genetic diseases	Uncertain significance (Dec 16, 2023)
6-31116100-T-C			Likely benign (Mar 08, 2023)
6-31116117-G-A			Uncertain significance (Oct 12, 2022)
6-31116125-C-T		not specified	Uncertain significance (Jan 01, 2019)
6-31116156-C-T		Peeling skin syndrome 1	Likely pathogenic (May 28, 2019)
6-31116168-C-T		not specified • CDSN-related disorder	Benign/Likely benign (Jan 22, 2024)
6-31116171-C-T			Uncertain significance (Mar 31, 2023)
6-31116174-C-A			Uncertain significance (Jul 13, 2023)
6-31116174-C-T		Inborn genetic diseases	Uncertain significance (Oct 06, 2022)
6-31116202-G-A		CDSN-related disorder	Benign/Likely benign (Oct 09, 2023)
6-31116203-G-A		Inborn genetic diseases	Uncertain significance (Nov 17, 2023)
6-31116250-AG-A			Uncertain significance (Nov 28, 2022)
6-31116257-C-T		Peeling skin syndrome 1 • CDSN-related disorder	Benign (Jan 29, 2024)
6-31116271-A-G			Benign (Jan 29, 2024)
6-31116275-G-A		Hypotrichosis 2 • Inborn genetic diseases	Uncertain significance (Mar 01, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CDSN	protein_coding	protein_coding	ENST00000376288	2	5357

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.464	0.531	125737	0	9	125746	0.0000358

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.01	247	296	0.834	0.0000164	3361
Missense in Polyphen		23	22.991	1.0004		199
Synonymous	0.862	113	125	0.902	0.00000793	1143
Loss of Function	2.35	2	10.0	0.200	4.95e-7	115

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.000100	0.0000992
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000470	0.0000352
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000980	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Important for the epidermal barrier integrity. {ECO:0000269|PubMed:20691404}.
• Disease: DISEASE: Hypotrichosis 2 (HYPT2) [MIM:146520]: A condition characterized by the presence of less than the normal amount of hair. Affected individuals have normal hair in early childhood but experience progressive hair loss limited to the scalp beginning in the middle of the first decade and almost complete baldness by the third decade. Body hair, beard, eyebrows, axillary hair, teeth, and nails develop normally. {ECO:0000269|PubMed:12754508}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Peeling skin syndrome 1 (PSS1) [MIM:270300]: A genodermatosis characterized by generalized, continuous shedding of the outer layers of the epidermis. Two main PSS subtypes have been suggested. Patients with non-inflammatory PSS (type A) manifest white scaling, with painless and easy removal of the skin, irritation when in contact with water, dust and sand, and no history of erythema, pruritis or atopy. Inflammatory PSS (type B) is associated with generalized erythema, pruritus and atopy. It is an ichthyosiform erythroderma characterized by lifelong patchy peeling of the entire skin with onset at birth or shortly after. Several patients have been reported with high IgE levels. {ECO:0000269|PubMed:20691404}. Note=The disease is caused by mutations affecting the gene represented in this entry. CDNS mutations are responsible for generalized, inflammatory peeling skin syndrome type B (PubMed:20691404). {ECO:0000269|PubMed:20691404}.
• Pathway: Keratinization;Developmental Biology;Formation of the cornified envelope (Consensus)

Intolerance Scores

• loftool: 0.599
• rvis_EVS: 2.11
• rvis_percentile_EVS: 97.89

Haploinsufficiency Scores

• pHI: 0.0925
• hipred: N
• hipred_score: 0.179
• ghis: 0.500

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.522

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cdsn
• Phenotype: neoplasm; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); immune system phenotype; endocrine/exocrine gland 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); growth/size/body region phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: corneocyte desquamation;cell adhesion;epidermis development;keratinocyte differentiation;skin morphogenesis;cornification;cell-cell adhesion;negative regulation of cornification
• Cellular component: cornified envelope;extracellular region;plasma membrane;cell-cell junction;desmosome
• Molecular function: protein homodimerization activity