CST11

protein-coding

cystatin 11, 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 an epididymal-specific protein shown to have antimicrobial activity against E. coli. Alternative splicing yields two variants encoding distinct isoforms. [provided by RefSeq, Sep 2014]

Previous symbols:

CST8L

MANE transcript

NM_130794.2

Inheritance

—

ClinVar variants

U:21B:3

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 1.05

Max pathogenic AF

—

Genomic locus

chr20:23,450,403-23,452,876

External References & Databases

Ensembl (ENSG00000125831)

Transcript & Mutation Effects

hg38 • Region Span ~2.5 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 CST11 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 24

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_130794.2. 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			21 clinvar	3 clinvar		24
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	21	3	0	24

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 8 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_130794.2	RefSeq	NP_570612.1	3	MANE Select
ENST00000377009.8	Ensembl	ENSP00000366208.3	3	MANE Select
NM_080830.3	RefSeq	NP_543020.2	2	Standard
ENST00000377007.3	Ensembl	ENSP00000366206.3	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

negative regulation of endopeptidase activity
androgen receptor signaling pathway
killing of cells of other organism
defense response to Gram-negative bacterium

Molecular Function

cysteine-type endopeptidase inhibitor activity

Cellular Component

extracellular region
nucleus
cytoplasm
sperm flagellum
sperm head

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000377009
Coding exons: 3
Length: 2455
Individuals with no LoFs: 125468
Homozygous LoFs: 0
Heterozygous LoFs: 277
Defined: 125745
p: 0.00110

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.391	80	70.7	1.13	0.00000341	928
Missense (PolyPhen)		11	19.578	0.56185		268
Synonymous	-0.380	30	27.5	1.09	0.00000143	230
Loss of Function	-0.105	6	5.73	1.05	2.45e-7	62

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.00015	0.00014	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.013	0.014	notable
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00013	0.00012	rare
South Asian	0.00020	0.00020	rare
Other	0.00049	0.00049	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Has antibacterial activity against the Gram-negative bacteria E.coli. May play a role in sperm maturation and fertilization. {ECO:0000269|PubMed:12072414}.;

Recessive Scores

pRec: 0.0678

Intolerance Scores

LoFtool: 0.820
RVIS EVS: -0.07
RVIS percentile EVS: 48.12

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.0602

Gene Damage Prediction

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