CST5

protein-coding

cystatin D, the group of Cystatins, type 2

Gene summary

The cystatin superfamily encompasses proteins that contain multiple cystatin-like sequences. Some of the members are active cysteine protease inhibitors, while others have lost or perhaps never acquired this inhibitory activity. There are three inhibitory families in the superfamily, including the type 1 cystatins (stefins), type 2 cystatins and the kininogens. The type 2 cystatin proteins are a class of cysteine proteinase inhibitors found in a variety of human fluids and secretions. The cystatin locus on chromosome 20 contains the majority of the type 2 cystatin genes and pseudogenes. This gene is located in the cystatin locus and encodes a protein found in saliva and tears. The encoded protein may play a protective role against proteinases present in the oral cavity. [provided by RefSeq, Jul 2008]

MANE transcript

NM_001900.5

Inheritance

—

ClinVar variants

U:32

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 1.28

Max pathogenic AF

—

Genomic locus

chr20:23,875,934-23,879,748

External References & Databases

Ensembl (ENSG00000170367)

Transcript & Mutation Effects

hg38 • Region Span ~3.8 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CST5 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 32

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001900.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous						0
missense			32 clinvar			32
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	32	0	0	32

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 6 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001900.5	RefSeq	NP_001891.2	3	MANE Select
ENST00000304710.5	Ensembl	ENSP00000307132.4	3	MANE Select
ENST00000967458.1	Ensembl	ENSP00000637517.1	3	Standard
ENST00000967458.2	Ensembl	ENSP00000637517.1	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Salivary secretion - Homo sapiens (human)
Endochondral Ossification

Biological Process

negative regulation of endopeptidase activity

Molecular Function

cysteine-type endopeptidase inhibitor activity
protein binding

Cellular Component

extracellular region
extracellular space
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000304710
Coding exons: 3
Length: 3816
Individuals with no LoFs: 125712
Homozygous LoFs: 0
Heterozygous LoFs: 21
Defined: 125733
p: 0.0000835

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-1.34	113	79.3	1.42	0.00000421	934
Missense (PolyPhen)		26	16.918	1.5368		204
Synonymous	-1.25	42	32.9	1.28	0.00000184	265
Loss of Function	-0.606	7	5.47	1.28	2.99e-7	55

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0.000092	0.000092	rare
European (Non-Finnish)	0.00011	0.00011	rare
South Asian	0.00016	0.00016	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Cysteine proteinase inhibitor that possibly plays a protective role against proteinases present in the oral cavity. The order of preference for inhibition is cathepsin S > cathepsin H > cathepsin L > cathepsin B. {ECO:0000269|PubMed:8083219}.;

Recessive Scores

pRec: 0.0862

Intolerance Scores

LoFtool: 0.627
RVIS EVS: 0.53
RVIS percentile EVS: 80.73

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.539

Gene Damage Prediction

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