CST11

Summary

CST11 (cystatin 11, HGNC:15959) is a protein-coding gene on chromosome 20p11.21, encoding Cystatin-11 (Q9H112). Has antibacterial activity against the Gram-negative bacteria E.coli.

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.

Source: NCBI Gene 140880 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 25 total — 1 pathogenic
• MANE Select transcript: NM_130794

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15959
Approved symbol	CST11
Name	cystatin 11
Location	20p11.21
Locus type	gene with protein product
Status	Approved
Aliases	dJ322G13.6, CTES2
Ensembl gene	ENSG00000125831
Ensembl biotype	protein_coding
OMIM	609731
Entrez	140880

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000377007, ENST00000377009, ENST00000915941

RefSeq mRNA: 2 — MANE Select: NM_130794 NM_080830, NM_130794

CCDS: CCDS13154, CCDS13155

Canonical transcript exons

ENST00000377009 — 3 exons

Exon	Start	End
ENSE00000859441	23451816	23451920
ENSE00001472449	23452584	23452876
ENSE00003842518	23450412	23450589

Expression profiles

Bgee: expression breadth broad, 59 present calls, max score 99.61.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0654 / max 113.6559, expressed in 1 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
186702	0.0561	1
186701	0.0092	1

Top tissues by expression

225 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
corpus epididymis	UBERON:0004359	99.61	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	94.97	gold quality
buccal mucosa cell	CL:0002336	85.23	gold quality
cardiac muscle of right atrium	UBERON:0003379	77.08	gold quality
left ventricle myocardium	UBERON:0006566	76.23	gold quality
upper arm skin	UBERON:0004263	75.33	gold quality
caput epididymis	UBERON:0004358	73.96	gold quality
kidney epithelium	UBERON:0004819	73.63	gold quality
myocardium	UBERON:0002349	72.02	gold quality
cauda epididymis	UBERON:0004360	70.17	gold quality
decidua	UBERON:0002450	67.44	gold quality
vena cava	UBERON:0004087	67.43	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	67.05	gold quality
vastus lateralis	UBERON:0001379	66.70	gold quality
nasal cavity epithelium	UBERON:0005384	66.47	gold quality
quadriceps femoris	UBERON:0001377	66.46	gold quality
tendon of biceps brachii	UBERON:0008188	65.07	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	64.05	gold quality
parotid gland	UBERON:0001831	63.49	gold quality
superficial temporal artery	UBERON:0001614	63.47	gold quality
secondary oocyte	CL:0000655	62.26	gold quality
gingival epithelium	UBERON:0001949	61.66	gold quality
biceps brachii	UBERON:0001507	61.62	gold quality
body of tongue	UBERON:0011876	60.68	gold quality
substantia nigra pars compacta	UBERON:0001965	60.06	gold quality
gingiva	UBERON:0001828	60.01	gold quality
heart right ventricle	UBERON:0002080	59.97	gold quality
jejunum	UBERON:0002115	59.89	gold quality
subthalamic nucleus	UBERON:0001906	59.75	gold quality
cerebellar vermis	UBERON:0004720	59.48	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-HCAD-38	yes	1876.02
E-ANND-3	no	0.65

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

5 targeting CST11, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-3123	99.47	67.15	2693
HSA-MIR-4774-3P	98.90	67.82	737
HSA-MIR-12125	98.59	67.54	1044
HSA-MIR-541-5P	98.24	67.77	1181

Literature-anchored findings (GeneRIF, showing 1)

• CST11 is an antimicrobial peptide that has shown to be effective against E. coli. (PMID:12072414)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	si:busm1-57f23.1	ENSDARG00000074425
mus_musculus	Cst11	ENSMUSG00000036958
rattus_norvegicus	Cst11	ENSRNOG00000004808
caenorhabditis_elegans		WBGENE00000534
caenorhabditis_elegans		WBGENE00000535
caenorhabditis_elegans		WBGENE00023486

Paralogs (11): CST7 (ENSG00000077984), CST9L (ENSG00000101435), CST3 (ENSG00000101439), CST4 (ENSG00000101441), CST8 (ENSG00000125815), CSTL1 (ENSG00000125823), CST5 (ENSG00000170367), CST2 (ENSG00000170369), CST1 (ENSG00000170373), CST9 (ENSG00000173335), CST6 (ENSG00000175315)

Protein

Protein identifiers

Cystatin-11 — Q9H112 (reviewed: Q9H112)

All UniProt accessions (2): Q9H112, A0A384P5Z6

UniProt curated annotations — full annotation on UniProt →

Function. Has antibacterial activity against the Gram-negative bacteria E.coli. May play a role in sperm maturation and fertilization.

Subcellular location. Secreted.

Tissue specificity. Detected in the epithelium and lumen of the epididymis, and in sperm (at protein level).

Similarity. Belongs to the cystatin family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9H112-1	1	yes
Q9H112-2	2

RefSeq proteins (2): NP_543020, NP_570612* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000010	Cystatin_dom	Domain
IPR042930	CST11	Family
IPR046350	Cystatin_sf	Homologous_superfamily

Pfam: PF00031

UniProt features (6 total): disulfide bond 2, signal peptide 1, chain 1, glycosylation site 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H112-F1	91.03	0.76

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Disulfide bonds (2): 94–102, 115–135

Glycosylation sites (1): 132

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 62 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_DN, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_HORMONE_MEDIATED_SIGNALING_PATHWAY, GOBP_CELLULAR_RESPONSE_TO_HORMONE_STIMULUS, GOBP_DEFENSE_RESPONSE_TO_GRAM_NEGATIVE_BACTERIUM, GOBP_RESPONSE_TO_STEROID_HORMONE, GOBP_RESPONSE_TO_HORMONE, GOBP_RESPONSE_TO_LIPID, GOBP_CELLULAR_RESPONSE_TO_STEROID_HORMONE_STIMULUS, GOBP_INTRACELLULAR_RECEPTOR_SIGNALING_PATHWAY, GOBP_STEROID_HORMONE_RECEPTOR_SIGNALING_PATHWAY, GOBP_DEFENSE_RESPONSE_TO_BACTERIUM, GOBP_CELL_KILLING, GOBP_ANDROGEN_RECEPTOR_SIGNALING_PATHWAY, GOCC_MOTILE_CILIUM

GO Biological Process (4): androgen receptor signaling pathway (GO:0030521), killing of cells of another organism (GO:0031640), defense response to Gram-negative bacterium (GO:0050829), defense response to bacterium (GO:0042742)

GO Molecular Function (2): cysteine-type endopeptidase inhibitor activity (GO:0004869), peptidase inhibitor activity (GO:0030414)

GO Cellular Component (5): extracellular region (GO:0005576), nucleus (GO:0005634), cytoplasm (GO:0005737), sperm flagellum (GO:0036126), sperm head (GO:0061827)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
nuclear receptor-mediated steroid hormone signaling pathway	1
cell killing	1
disruption of cell in another organism	1
defense response to bacterium	1
defense response	1
response to bacterium	1
cysteine-type endopeptidase activity	1
endopeptidase inhibitor activity	1
enzyme inhibitor activity	1
peptidase activity	1
peptidase regulator activity	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
9+2 motile cilium	1

Protein interactions and networks

STRING

585 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CST11	SPMIP1	A0A1B0GUX0	624
CST11	LCN8	Q6JVE9	587
CST11	TECR	Q9NZ01	582
CST11	LCN9	Q8WX39	545
CST11	TEDDM1	Q5T9Z0	542
CST11	CST9	Q5W186	541
CST11	LCN6	P62502	538
CST11	DEFB128	Q7Z7B8	473
CST11	RNASE10	Q5GAN6	461
CST11	GZF1	Q9H116	452
CST11	CST9L	Q9H4G1	437
CST11	CCDC127	Q96BQ5	435
CST11	NXT1	Q9UKK6	406
CST11	LCN10	Q6JVE6	406
CST11	TPM3	P06753	397

IntAct

3 interactions, top by confidence:

A	B	Type	Score
CST11	DHRS4	psi-mi:“MI:0914”(association)	0.350
CST11	PLXNB2	psi-mi:“MI:0914”(association)	0.350

BioGRID (73): CST11 (Affinity Capture-MS), DHRS4 (Affinity Capture-MS), DNAJB9 (Affinity Capture-MS), CCPG1 (Affinity Capture-MS), LOXL2 (Affinity Capture-MS), LAMB2 (Affinity Capture-MS), ADAMTS7 (Affinity Capture-MS), CNNM3 (Affinity Capture-MS), ART5 (Affinity Capture-MS), MR1 (Affinity Capture-MS), HKDC1 (Affinity Capture-MS), PDIA4 (Affinity Capture-MS), IGF1R (Affinity Capture-MS), SQSTM1 (Affinity Capture-MS), TUBA4A (Affinity Capture-MS)

ESM2 similar proteins: A0A0K0IP23, A0A1S3PBB7, B2Z450, E3P6N3, E3P6N4, E3P6N5, E3P6N6, E3P6N7, E3P6N8, E3P6N9, E3P6P0, E3P6P1, E3P6P2, E3P6P3, E3P6P4, J3RYX9, J3SE80, O60676, O88969, O97862, P01036, P01037, P01038, P01048, P08932, P08935, P09228, P19313, P28325, P32766, P33046, P35481, P49928, P49929, P49930, P54229, P54230, P81714, Q15828, Q2XXN5

Diamond homologs: B2Z450, J3SE80, O19092, O19093, O60676, O88969, P01034, P01035, P14841, P21460, P22085, P32766, P81061, Q80Y72, Q80ZN5, Q8K5A3, Q9D269, Q9H112, Q9H114, O97862, P01037, P09228, Q5W188, B1P1J3, E3P6N3, E3P6N4, E3P6N5, E3P6N6, E3P6N7, E3P6N8, E3P6N9, E3P6P0, E3P6P1, E3P6P2, E3P6P3, E3P6P4, G5EDZ9, J3RYX9, O76096, O89098

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

25 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	21
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
424642	GRCh37/hg19 20p13-q11.21(chr20:80198-26208081)x3	Pathogenic

SpliceAI

213 predictions. Top by Δscore:

Variant	Effect	Δscore
20:23452639:T:A	donor_gain	1.0000
20:23450586:CTTG:C	acceptor_gain	0.9900
20:23452579:CTCA:C	donor_loss	0.9900
20:23452580:TCAC:T	donor_loss	0.9900
20:23452581:CA:C	donor_loss	0.9900
20:23452582:A:AG	donor_loss	0.9900
20:23452582:ACCTG:A	donor_gain	0.9900
20:23452583:C:CT	donor_loss	0.9900
20:23452583:CCTG:C	donor_gain	0.9900
20:23452583:CCTGC:C	donor_gain	0.9900
20:23452586:G:A	donor_gain	0.9800
20:23450590:C:CC	acceptor_gain	0.9700
20:23450587:TTG:T	acceptor_gain	0.9600
20:23452582:A:AC	donor_gain	0.9600
20:23452583:C:CC	donor_gain	0.9600
20:23450588:TG:T	acceptor_gain	0.9200
20:23450687:C:CT	donor_gain	0.9000
20:23452578:ACTC:A	donor_loss	0.8500
20:23452088:C:CT	acceptor_gain	0.8400
20:23450587:T:C	acceptor_gain	0.8200
20:23450587:TTGC:T	acceptor_loss	0.8200
20:23450588:TGCT:T	acceptor_loss	0.8200
20:23450589:GCTAA:G	acceptor_loss	0.8200
20:23450590:CTAAA:C	acceptor_loss	0.8200
20:23450591:T:G	acceptor_loss	0.8200
20:23451832:T:A	donor_gain	0.8200
20:23452089:A:T	acceptor_gain	0.8000
20:23450603:C:CT	acceptor_loss	0.7700
20:23450604:A:T	acceptor_loss	0.7500
20:23452576:ACACT:A	donor_loss	0.7500

AlphaMissense

931 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:23450572:G:C	F117L	0.869
20:23450572:G:T	F117L	0.869
20:23450574:A:G	F117L	0.869
20:23450563:A:C	F120L	0.867
20:23450563:A:T	F120L	0.867
20:23450565:A:G	F120L	0.867
20:23452617:G:C	F65L	0.819
20:23452617:G:T	F65L	0.819
20:23452619:A:G	F65L	0.819
20:23452719:A:C	F31L	0.784
20:23452719:A:T	F31L	0.784
20:23452721:A:G	F31L	0.784
20:23450551:C:A	W124C	0.753
20:23450551:C:G	W124C	0.753
20:23452671:G:C	S47R	0.753
20:23452671:G:T	S47R	0.753
20:23452673:T:G	S47R	0.753
20:23451883:A:G	M89T	0.715
20:23452651:T:G	Q54P	0.684
20:23452612:A:G	I67T	0.678
20:23451895:A:G	L85P	0.673
20:23450575:G:C	F116L	0.668
20:23450575:G:T	F116L	0.668
20:23450577:A:G	F116L	0.668
20:23450553:A:G	W124R	0.659
20:23450553:A:T	W124R	0.659
20:23450567:A:T	V119E	0.656
20:23450573:A:C	F117C	0.650
20:23452594:A:T	V73D	0.648
20:23452669:A:G	L48S	0.639

dbSNP variants (sampled 300 via entrez): RS1000512010 (20:23450768 G>A), RS1001286524 (20:23454639 G>A), RS1001410668 (20:23454050 AACAC>A,AAC), RS1002986022 (20:23451390 C>T), RS1003429150 (20:23451650 G>A), RS1003747737 (20:23452226 C>A,T), RS1004797504 (20:23451546 C>T), RS1004811434 (20:23451433 C>A), RS1004842632 (20:23451733 A>T), RS1005176856 (20:23450254 A>G), RS1006128117 (20:23454403 C>A), RS1006188356 (20:23453744 C>A), RS1008192437 (20:23451597 C>A), RS1008587928 (20:23452120 G>A), RS1010074718 (20:23452358 G>A)

Disease associations

OMIM: gene MIM:609731 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

4 total (human), top 4 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, increases methylation	2
CGP 52608	affects binding, increases reaction	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Aflatoxin B1	increases methylation	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.