CST6

cystatin E/M, the group of Cystatins, type 2

Basic information

Region (hg38): 11:66012008-66013505

Links

ENSG00000175315

∙ NCBI:1474 ∙ OMIM:601891 ∙ HGNC:2478 ∙ Uniprot:Q15828 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

ectodermal dysplasia 15, hypohidrotic/hair type (Limited), mode of inheritance: AR
ectodermal dysplasia 15, hypohidrotic/hair type (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Ectodermal dysplasia 15, hypohydrotic/hair type	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	30425301

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CST6 gene.

not_specified (19 variants)
Ectodermal_dysplasia_15,_hypohidrotic/hair_type (3 variants)
not_provided (1 variants)
CST6-related_disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CST6 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000001323.4. 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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous				1 clinvar		1
missense			19 clinvar	1 clinvar	1 clinvar	21
nonsense	1 clinvar		1 clinvar			2
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	1	0	20	2	1

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CST6	protein_coding	protein_coding	ENST00000312134	3	1665

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.372	0.585	114431	0	1	114432	0.00000437

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.25	58	91.7	0.632	0.00000523	949
Missense in Polyphen		15	27.452	0.54641		309
Synonymous	-0.0857	42	41.3	1.02	0.00000259	305
Loss of Function	1.59	1	4.75	0.211	2.50e-7	51

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.0000348	0.0000348
Other	0.00	0.00

dbNSFP

Source: dbNSFP

Function: FUNCTION: Shows moderate inhibition of cathepsin B but is not active against cathepsin C.;
Pathway: Vitamin D Receptor Pathway (Consensus)

Recessive Scores

pRec: 0.147

Haploinsufficiency Scores

pHI: 0.121
hipred: N
hipred_score: 0.274
ghis: 0.537

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: N
gene_indispensability_score: 0.246

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Cst6
Phenotype: 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); cellular phenotype; endocrine/exocrine gland phenotype; growth/size/body region 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);

Gene ontology

Biological process: epidermis development;anatomical structure morphogenesis;negative regulation of endopeptidase activity
Cellular component: cornified envelope;extracellular exosome
Molecular function: cysteine-type endopeptidase inhibitor activity