CSTA

cystatin A, the group of Cystatins, type 1

Basic information

Region (hg38): 3:122325248-122341969

Previous symbols: [ "STF1", "STFA" ]

Links

ENSG00000121552 ∙ NCBI:1475 ∙ OMIM:184600 ∙ HGNC:2481 ∙ Uniprot:P01040 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• peeling skin syndrome 4 (Strong), mode of inheritance: AR
• peeling skin syndrome 4 (Strong), mode of inheritance: AR
• peeling skin syndrome 4 (Moderate), mode of inheritance: AR
• peeling skin syndrome 4 (Strong), mode of inheritance: AR
• peeling skin syndrome 4 (Strong), mode of inheritance: AR
• acral peeling skin syndrome (Supportive), mode of inheritance: AR
• exfoliative ichthyosis (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Peeling skin syndrome 4	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	21944047; 25400170

ClinVar

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

• not provided (1 variants)
• Peeling skin syndrome 4 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CSTA 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					1	1
missense			5		2	7
nonsense	1	1				2
start loss						0
frameshift		1				1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding				1	3	4
Total	1	2	5	1	6

Highest pathogenic variant AF is 0.0000263

Variants in CSTA

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

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

Position	Type	Phenotype	Significance	ClinVar
3-122325312-C-T		Inborn genetic diseases	Uncertain significance (Jan 19, 2024)
3-122325324-C-A		Inborn genetic diseases	Uncertain significance (Aug 26, 2024)
3-122325326-G-A		Inborn genetic diseases	Uncertain significance (Jun 24, 2022)
3-122325342-A-G		Inborn genetic diseases	Uncertain significance (Mar 16, 2024)
3-122325356-A-T		Peeling skin syndrome 4	Pathogenic (Feb 14, 2019)
3-122337545-A-T		Peeling skin syndrome 4	Pathogenic (Oct 07, 2011)
3-122337581-CTT-C			Likely pathogenic (Oct 04, 2024)
3-122337585-C-T			Benign (Nov 10, 2018)
3-122337605-A-G		Inborn genetic diseases	Uncertain significance (Jan 03, 2024)
3-122341102-C-T			Benign (Nov 11, 2018)
3-122341230-G-A			Benign (Nov 10, 2018)
3-122341427-A-C			Benign (Nov 10, 2018)
3-122341442-C-T		Peeling skin syndrome 4	Likely pathogenic (Oct 08, 2021)
3-122341443-G-A		Inborn genetic diseases	Uncertain significance (Oct 08, 2024)
3-122341462-T-A		CSTA-related disorder	Pathogenic (Jul 01, 2024)
3-122341520-G-A			Uncertain significance (Sep 01, 2022)
3-122341526-C-T		Peeling skin syndrome 4	Pathogenic (Oct 07, 2011)
3-122341543-G-T			Benign (May 05, 2021)
3-122341550-G-A		Inborn genetic diseases	Uncertain significance (Aug 19, 2024)
3-122341557-C-T			Benign (Nov 10, 2018)
3-122341577-C-T		CSTA-related disorder	Likely benign (Mar 25, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CSTA	protein_coding	protein_coding	ENST00000264474	3	16729

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000153	0.261	125732	0	13	125745	0.0000517

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.0715	50	51.4	0.972	0.00000253	632
Missense in Polyphen		16	19.456	0.82236		249
Synonymous	-0.322	22	20.2	1.09	0.00000122	176
Loss of Function	-0.626	5	3.70	1.35	1.56e-7	45

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000261	0.000261
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000352	0.0000352
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: This is an intracellular thiol proteinase inhibitor. Has an important role in desmosome-mediated cell-cell adhesion in the lower levels of the epidermis. {ECO:0000269|PubMed:21944047}.
• Pathway: Keratinization;Developmental Biology;Formation of the cornified envelope (Consensus)

Recessive Scores

• pRec: 0.161

Intolerance Scores

• loftool: 0.764
• rvis_EVS: 0.33
• rvis_percentile_EVS: 73.11

Haploinsufficiency Scores

• pHI: 0.142
• hipred: N
• hipred_score: 0.233
• ghis: 0.383

Essentials

• essential_gene_CRISPR: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.671

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Stfa3

Gene ontology

• Biological process: negative regulation of peptidase activity;negative regulation of endopeptidase activity;peptide cross-linking;keratinocyte differentiation;negative regulation of proteolysis;cornification;cell-cell adhesion
• Cellular component: cornified envelope;extracellular space;nucleus;cytoplasm;cytosol
• Molecular function: protease binding;cysteine-type endopeptidase inhibitor activity;structural molecule activity;protein binding, bridging