CSTL1

Summary

CSTL1 (cystatin like 1, HGNC:15958) is a protein-coding gene on chromosome 20p11.21, encoding Cystatin-like 1 (Q9H114).

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 at the telomeric end of the cystatin locus and encodes a type 2 cystatin-like protein. The specific function of this protein has not been determined.

Source: NCBI Gene 128817 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 32 total — 1 pathogenic
• MANE Select transcript: NM_138283

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15958
Approved symbol	CSTL1
Name	cystatin like 1
Location	20p11.21
Locus type	gene with protein product
Status	Approved
Aliases	dJ322G13.4, CTES1
Ensembl gene	ENSG00000125823
Ensembl biotype	protein_coding
Entrez	128817

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 2 protein_coding, 2 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000246020, ENST00000347397, ENST00000472140, ENST00000485969, ENST00000619238

RefSeq mRNA: 1 — MANE Select: NM_138283 NM_138283

CCDS: CCDS13153

Canonical transcript exons

ENST00000347397 — 4 exons

Exon	Start	End
ENSE00001129203	23439685	23439806
ENSE00001131433	23444771	23444930
ENSE00001376763	23443934	23444044
ENSE00003523083	23440144	23440486

Expression profiles

Bgee: expression breadth broad, 64 present calls, max score 85.68.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.68	gold quality
right testis	UBERON:0004534	75.24	gold quality
left testis	UBERON:0004533	74.83	gold quality
testis	UBERON:0000473	72.52	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	61.59	gold quality
sperm	CL:0000019	57.18	gold quality
lower esophagus mucosa	UBERON:0035834	49.56	gold quality
buccal mucosa cell	CL:0002336	49.24	gold quality
esophagus mucosa	UBERON:0002469	47.74	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	43.37	gold quality
secondary oocyte	CL:0000655	42.57	gold quality
lower lobe of lung	UBERON:0008949	42.35	silver quality
granulocyte	CL:0000094	41.92	silver quality
right lobe of liver	UBERON:0001114	41.62	silver quality
vastus lateralis	UBERON:0001379	41.41	gold quality
quadriceps femoris	UBERON:0001377	41.37	gold quality
superficial temporal artery	UBERON:0001614	41.33	gold quality
oviduct epithelium	UBERON:0004804	41.17	gold quality
palpebral conjunctiva	UBERON:0001812	41.10	gold quality
mucosa of paranasal sinus	UBERON:0005030	40.98	gold quality
skin of leg	UBERON:0001511	40.82	gold quality
amniotic fluid	UBERON:0000173	40.69	gold quality
jejunal mucosa	UBERON:0000399	40.59	gold quality
biceps brachii	UBERON:0001507	40.57	gold quality
epithelium of nasopharynx	UBERON:0001951	40.45	gold quality
myocardium	UBERON:0002349	40.45	gold quality
gingival epithelium	UBERON:0001949	40.43	gold quality
germinal epithelium of ovary	UBERON:0001304	40.33	gold quality
esophagus squamous epithelium	UBERON:0006920	40.29	gold quality
zone of skin	UBERON:0000014	40.28	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	2.61

Regulation

Is transcription factor: no

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	si:busm1-57f23.1	ENSDARG00000074425
mus_musculus	Cstl1	ENSMUSG00000055177
rattus_norvegicus	Cstl1	ENSRNOG00000004779
caenorhabditis_elegans		WBGENE00000534
caenorhabditis_elegans		WBGENE00000535
caenorhabditis_elegans		WBGENE00023486

Paralogs (11): CST7 (ENSG00000077984), CST9L (ENSG00000101435), CST3 (ENSG00000101439), CST4 (ENSG00000101441), CST8 (ENSG00000125815), CST11 (ENSG00000125831), CST5 (ENSG00000170367), CST2 (ENSG00000170369), CST1 (ENSG00000170373), CST9 (ENSG00000173335), CST6 (ENSG00000175315)

Protein

Protein identifiers

Cystatin-like 1 — Q9H114 (reviewed: Q9H114)

Alternative names: RCET11

All UniProt accessions (1): Q9H114

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Secreted.

Similarity. Belongs to the cystatin family.

RefSeq proteins (1): NP_612140* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000010	Cystatin_dom	Domain
IPR042921	CSTL1	Family
IPR046350	Cystatin_sf	Homologous_superfamily

Pfam: PF00031

UniProt features (11 total): sequence variant 5, disulfide bond 2, signal peptide 1, chain 1, domain 1, glycosylation site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H114-F1	85.45	0.61

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): 91–101, 114–134

Glycosylation sites (1): 42

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 32 (showing top): GOBP_PROTEIN_MATURATION, GOMF_CYSTEINE_TYPE_PEPTIDASE_ACTIVITY, GOBP_PROTEOLYSIS, GOMF_PEPTIDASE_REGULATOR_ACTIVITY, GOMF_PEPTIDASE_ACTIVITY, chr20p11, GOMF_ENZYME_INHIBITOR_ACTIVITY, GOMF_ENZYME_REGULATOR_ACTIVITY, GSE13762_CTRL_VS_125_VITAMIND_DAY12_DC_DN, GOMF_CYSTEINE_TYPE_ENDOPEPTIDASE_INHIBITOR_ACTIVITY, GOBP_PROTEIN_PROCESSING, GOMF_ENDOPEPTIDASE_REGULATOR_ACTIVITY, GOBP_SIGNALING_RECEPTOR_LIGAND_PRECURSOR_PROCESSING, NABA_ECM_REGULATORS, GSE11884_WT_VS_FURIN_KO_NAIVE_CD4_TCELL_DN

GO Biological Process (3): transmission of nerve impulse (GO:0019226), G protein-coupled opioid receptor signaling pathway (GO:0038003), signaling receptor ligand precursor processing (GO:0140448)

GO Molecular Function (3): cysteine-type endopeptidase inhibitor activity (GO:0004869), cysteine-type peptidase activity (GO:0008234), peptidase inhibitor activity (GO:0030414)

GO Cellular Component (1): extracellular region (GO:0005576)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
peptidase activity	2
action potential	1
cell communication	1
chemical synaptic transmission	1
nervous system process	1
G protein-coupled receptor signaling pathway	1
protein processing	1
cysteine-type endopeptidase activity	1
endopeptidase inhibitor activity	1
enzyme inhibitor activity	1
peptidase regulator activity	1
cellular anatomical structure	1

Protein interactions and networks

STRING

318 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CSTL1	CST9	Q5W186	582
CSTL1	GZF1	Q9H116	512
CSTL1	IQCF6	A8MYZ5	471
CSTL1	NXT1	Q9UKK6	451
CSTL1	CTSB	P07858	428
CSTL1	CST3	P01034	421
CSTL1	ACSS1	Q9NUB1	404
CSTL1	OR1F1	O43749	400
CSTL1	PATE3	B3GLJ2	399
CSTL1	KRTAP5-7	Q6L8G8	397
CSTL1	OR2AE1	Q8NHA4	394
CSTL1	RNF32	Q9H0A6	373
CSTL1	TPM3	P06753	368
CSTL1	NPIPB13	A6NJU9	359
CSTL1	L3HYPDH	Q96EM0	348

IntAct

2 interactions, top by confidence:

A	B	Type	Score
CSTL1	DENND11	psi-mi:“MI:0914”(association)	0.350

BioGRID (56): HBA2 (Affinity Capture-MS), GOLIM4 (Affinity Capture-MS), MZT2B (Affinity Capture-MS), RCCD1 (Affinity Capture-MS), FN1 (Affinity Capture-MS), FBXO2 (Affinity Capture-MS), SUSD5 (Affinity Capture-MS), KDM8 (Affinity Capture-MS), TMEM131 (Affinity Capture-MS), DHFRL1 (Affinity Capture-MS), PTPRK (Affinity Capture-MS), LOXL2 (Affinity Capture-MS), PPTC7 (Affinity Capture-MS), UBE2Q1 (Affinity Capture-MS), GPR98 (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, E3P6N3, E3P6N7, E3P6N8, E3P6N9, E3P6P0, E3P6P3, J3RYX9, J3SE80, O19092, O19093, O89098, O97862, P01034, P01035, P01038, P08935, P14841, P19313, P21460, P35481, P81061, Q15828, Q2XXN5, Q6T6T4, Q80ZN5, Q91195, Q98967, Q9H114, B1P1J3, E3P6N4, E3P6N5, E3P6N6, E3P6P1, E3P6P2, E3P6P4, O60676, O76096, O88969, P01036

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	24
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
3024619	GRCh37/hg19 20p13-11.21(chr20:68351-23860313)x3	Pathogenic

SpliceAI

504 predictions. Top by Δscore:

Variant	Effect	Δscore
20:23443932:A:AG	acceptor_gain	0.9900
20:23443933:G:GG	acceptor_gain	0.9900
20:23444769:A:AG	acceptor_gain	0.9700
20:23444770:G:GG	acceptor_gain	0.9700
20:23444770:GA:G	acceptor_gain	0.9700
20:23439802:GGAAG:G	donor_gain	0.9500
20:23439803:GAAGG:G	donor_gain	0.9500
20:23443933:GCT:G	acceptor_gain	0.9500
20:23439804:A:T	donor_gain	0.9400
20:23439804:AAGGT:A	donor_loss	0.9400
20:23439806:GGTAA:G	donor_loss	0.9400
20:23439808:T:G	donor_loss	0.9400
20:23443928:C:CA	acceptor_gain	0.9400
20:23443680:G:GC	acceptor_gain	0.9300
20:23443929:GGCA:G	acceptor_loss	0.9300
20:23443930:GCA:G	acceptor_loss	0.9300
20:23443931:CA:C	acceptor_loss	0.9300
20:23443928:CGGCA:C	acceptor_loss	0.9200
20:23440482:TGCAG:T	donor_loss	0.9000
20:23440483:GCAGG:G	donor_loss	0.9000
20:23440484:CAG:C	donor_loss	0.9000
20:23440485:AG:A	donor_loss	0.9000
20:23440486:GGTT:G	donor_loss	0.9000
20:23440487:G:T	donor_loss	0.9000
20:23440488:T:A	donor_loss	0.9000
20:23443679:TG:T	acceptor_gain	0.9000
20:23443929:G:A	acceptor_gain	0.9000
20:23443933:GC:G	acceptor_gain	0.9000
20:23444036:C:G	donor_gain	0.9000
20:23440489:TTG:T	donor_loss	0.8900

AlphaMissense

954 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:23440406:T:C	F47L	0.898
20:23440408:C:A	F47L	0.898
20:23440408:C:G	F47L	0.898
20:23440358:T:C	F31L	0.897
20:23440360:C:A	F31L	0.897
20:23440360:C:G	F31L	0.897
20:23444809:G:C	W123C	0.847
20:23444809:G:T	W123C	0.847
20:23444830:G:C	W130C	0.811
20:23444830:G:T	W130C	0.811
20:23444819:T:C	F127L	0.791
20:23444821:C:A	F127L	0.791
20:23444821:C:G	F127L	0.791
20:23440359:T:G	F31C	0.789
20:23440475:A:C	S70R	0.774
20:23440477:T:A	S70R	0.774
20:23440477:T:G	S70R	0.774
20:23440418:T:C	S51P	0.768
20:23443959:T:A	V82D	0.768
20:23444786:T:C	S116P	0.762
20:23444780:T:A	C114S	0.758
20:23444781:G:C	C114S	0.758
20:23443980:C:T	T89I	0.753
20:23440426:C:A	N53K	0.740
20:23440426:C:G	N53K	0.740
20:23444793:T:A	I118K	0.736
20:23440421:T:G	Y52D	0.717
20:23440479:A:C	Q71P	0.715
20:23440433:A:C	S56R	0.713
20:23440435:C:A	S56R	0.713

dbSNP variants (sampled 300 via entrez): RS1000081997 (20:23459473 T>C), RS1000253936 (20:23455664 G>A,C,T), RS1000283614 (20:23455991 A>T), RS1000436925 (20:23438481 C>T), RS1000512010 (20:23450768 G>A), RS1000549848 (20:23442286 C>T), RS1000648510 (20:23445060 C>A,T), RS1001038963 (20:23447907 T>C), RS1001116216 (20:23458501 T>G), RS1001125831 (20:23438901 C>A), RS1001286524 (20:23454639 G>A), RS1001410668 (20:23454050 AACAC>A,AAC), RS1001488160 (20:23446742 C>G), RS1001610805 (20:23443449 A>C), RS1001646257 (20:23460882 G>A)

Disease associations

OMIM: gene `` | 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

10 total (human), top 10 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
perfluorooctanoic acid	increases expression	1
perfluorooctane sulfonic acid	increases expression	1
CGP 52608	affects binding, increases reaction	1
perfluoro-n-nonanoic acid	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Arsenic Trioxide	increases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Cadmium	decreases expression	1
Copper	affects cotreatment, decreases expression	1
Aflatoxin B1	increases methylation	1

Clinical trials (associated diseases)

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