CYS1

Summary

CYS1 (cystin 1, HGNC:18525) is a protein-coding gene on chromosome 2p25.1, encoding Cystin-1 (Q717R9).

Predicted to enable chromatin binding activity and transcription corepressor activity. Predicted to act upstream of or within inner ear development; kidney development; and regulation of DNA-templated transcription. Predicted to be located in cytoskeleton; membrane; and nucleus. Biomarker of stomach cancer.

Source: NCBI Gene 192668 — RefSeq curated summary.

At a glance

• Gene–disease (curated): polycystic kidney disease (Limited, ClinGen)
• GWAS associations: 2
• Clinical variants (ClinVar): 52 total — 1 pathogenic
• MANE Select transcript: NM_001037160

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18525
Approved symbol	CYS1
Name	cystin 1
Location	2p25.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000205795
Ensembl biotype	protein_coding
OMIM	618713
Entrez	192668

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 1 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000381813, ENST00000477304

RefSeq mRNA: 1 — MANE Select: NM_001037160 NM_001037160

CCDS: CCDS33145

Canonical transcript exons

ENST00000381813 — 3 exons

Exon	Start	End
ENSE00001489934	10056473	10058958
ENSE00001489936	10079906	10080411
ENSE00003465323	10065904	10065956

Expression profiles

Bgee: expression breadth ubiquitous, 186 present calls, max score 99.64.

FANTOM5 (CAGE): breadth broad, TPM avg 1.1750 / max 154.1962, expressed in 350 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
26854	1.1750	350

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
kidney epithelium	UBERON:0004819	99.64	gold quality
renal medulla	UBERON:0000362	97.89	gold quality
adult mammalian kidney	UBERON:0000082	97.26	gold quality
metanephros cortex	UBERON:0010533	97.24	gold quality
kidney	UBERON:0002113	93.61	gold quality
adult organism	UBERON:0007023	88.46	gold quality
metanephros	UBERON:0000081	87.75	gold quality
cortex of kidney	UBERON:0001225	87.21	gold quality
body of pancreas	UBERON:0001150	84.13	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.63	gold quality
pancreatic ductal cell	CL:0002079	82.33	gold quality
ascending aorta	UBERON:0001496	82.01	gold quality
thoracic aorta	UBERON:0001515	81.86	gold quality
aorta	UBERON:0000947	81.06	gold quality
parotid gland	UBERON:0001831	81.03	silver quality
lower esophagus muscularis layer	UBERON:0035833	80.79	gold quality
lower esophagus	UBERON:0013473	80.67	gold quality
tibial artery	UBERON:0007610	80.50	gold quality
popliteal artery	UBERON:0002250	80.49	gold quality
gall bladder	UBERON:0002110	80.21	gold quality
calcaneal tendon	UBERON:0003701	80.21	gold quality
pancreas	UBERON:0001264	79.68	gold quality
descending thoracic aorta	UBERON:0002345	79.21	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	79.17	gold quality
cardiac muscle of right atrium	UBERON:0003379	79.16	gold quality
right coronary artery	UBERON:0001625	78.75	gold quality
layer of synovial tissue	UBERON:0007616	78.59	silver quality
mucosa of stomach	UBERON:0001199	77.20	gold quality
muscle layer of sigmoid colon	UBERON:0035805	77.15	gold quality
saphenous vein	UBERON:0007318	76.96	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.30

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

63 targeting CYS1, 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-4795-3P	100.00	74.62	4024
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-1200	99.71	70.42	1838
HSA-MIR-4677-5P	99.70	70.09	1940
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-4708-3P	99.51	67.99	870
HSA-MIR-4666A-5P	99.41	69.72	1887
HSA-MIR-4251	99.40	69.19	3363
HSA-MIR-3140-5P	99.39	69.04	1136
HSA-MIR-185-5P	99.35	68.60	2497
HSA-MIR-4644	99.35	69.12	2514
HSA-MIR-520A-5P	99.35	66.72	1632
HSA-MIR-525-5P	99.35	66.85	1615
HSA-MIR-6505-3P	99.34	67.39	1071

Literature-anchored findings (GeneRIF, showing 2)

• genomic region comprises three coding exons, which span 22 kb and the transcript harbors an open reading frame of 477 nucleotides encoding a protein with 158 amino acid residues, which is called cystin (PMID:12733055)
• Cystin genetic variants cause autosomal recessive polycystic kidney disease associated with altered Myc expression. (PMID:34521872)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Cys1	ENSMUSG00000062563
rattus_norvegicus	Cys1	ENSRNOG00000058891

Protein

Protein identifiers

Cystin-1 — Q717R9 (reviewed: Q717R9)

Alternative names: Cilia-associated protein

All UniProt accessions (1): Q717R9

UniProt curated annotations — full annotation on UniProt →

Subunit / interactions. Interacts (when myristoylated) with UNC119 and UNC119B; interaction is required for localization to cilium.

Subcellular location. Cell projection. Cilium membrane. Cytoplasm. Cytoskeleton. Cilium axoneme.

Tissue specificity. Expressed at high levels in the kidney and pancreas. Moderate expression seen in the skeletal muscle, liver and heart. A weak expression seen in the brain, lung, uterus, prostate, testis, small intestine and colon.

RefSeq proteins (1): NP_001032237* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR058884	Cys1	Family

Pfam: PF26203

UniProt features (8 total): compositionally biased region 3, initiator methionine 1, chain 1, region of interest 1, short sequence motif 1, lipid moiety-binding region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q717R9-F1	66.42	0.20

Functional residue map

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

Post-translational modifications (1): 2

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-5624138	Trafficking of myristoylated proteins to the cilium

MSigDB gene sets: 55 (showing top): chr2p25, GAUSSMANN_MLL_AF4_FUSION_TARGETS_C_DN, SCHAEFFER_PROSTATE_DEVELOPMENT_12HR_UP, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_UP, BASAKI_YBX1_TARGETS_DN, GOCC_CYTOPLASMIC_REGION, GOCC_CELL_PROJECTION_MEMBRANE, GOCC_PLASMA_MEMBRANE_REGION, GOCC_CILIARY_MEMBRANE, GOCC_CILIUM, LIU_PROSTATE_CANCER_DN, MEISSNER_NPC_HCP_WITH_H3K4ME2, BRUINS_UVC_RESPONSE_VIA_TP53_GROUP_D, WANG_MLL_TARGETS, REACTOME_ORGANELLE_BIOGENESIS_AND_MAINTENANCE

GO Biological Process (0):

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (9): cytosol (GO:0005829), cilium (GO:0005929), axoneme (GO:0005930), ciliary membrane (GO:0060170), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), plasma membrane (GO:0005886), membrane (GO:0016020), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Cargo trafficking to the periciliary membrane	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
binding	1
cytoplasm	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1
cytoskeleton	1
microtubule	1
ciliary plasm	1
cilium	1
cell projection membrane	1
bounding membrane of organelle	1
intracellular anatomical structure	1
intracellular membraneless organelle	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

494 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CYS1	PKHD1	P08F94	820
CYS1	IFT88	Q13099	752
CYS1	PKD1	P98161	631
CYS1	PKD2	Q13563	599
CYS1	PTGER2	P43116	599
CYS1	PTGER4	P35408	581
CYS1	TIMP1	P01033	578
CYS1	AQP2	P41181	568
CYS1	UNC119B	A6NIH7	552
CYS1	KIF7	Q2M1P5	546
CYS1	KIF3A	Q9Y496	520
CYS1	PIK3C2A	O00443	518
CYS1	OXT	P01178	506
CYS1	SCN9A	Q15858	495
CYS1	PGP	A6NDG6	493

IntAct

6 interactions, top by confidence:

A	B	Type	Score
UNC119	UNC119B	psi-mi:“MI:0914”(association)	0.640
CYS1	UNC119B	psi-mi:“MI:0914”(association)	0.350
NMS	MANBA	psi-mi:“MI:0914”(association)	0.350

BioGRID (24): CYS1 (Affinity Capture-MS), CYS1 (Affinity Capture-MS), EDRF1 (Affinity Capture-MS), KLHDC2 (Affinity Capture-MS), PLCG1 (Affinity Capture-MS), UNC119B (Affinity Capture-MS), NMT1 (Affinity Capture-MS), DPP9 (Affinity Capture-MS), NMT2 (Affinity Capture-MS), UNC119 (Affinity Capture-MS), TBC1D15 (Affinity Capture-MS), TBC1D17 (Affinity Capture-MS), CYS1 (Affinity Capture-MS), THEM6 (Affinity Capture-MS), COPG2 (Affinity Capture-MS)

ESM2 similar proteins: A2VDX9, A6NCS6, A6NEL2, A6NJG2, A6NK89, A6NLJ0, A8MVW0, B2RU40, B7ZBB8, C9JH25, D3YXK1, D4A9R4, M0QZC1, O15049, P03971, P03972, P0C1Z6, P0CG25, P0DPE3, P27106, P49000, P79295, Q17QH7, Q1HCM0, Q1LZD1, Q29RM6, Q2M3G4, Q2M3V2, Q3SX20, Q4G0M1, Q6NY19, Q6PCT2, Q6PJ61, Q6ZS72, Q6ZW31, Q717R9, Q86SH2, Q8BLS7, Q8N4B5, Q8N9M5

Diamond homologs: Q717R9, Q8R4T1

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	46
Likely benign	3
Benign	1

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1693276	NM_001037160.3(CYS1):c.318+5G>A	Pathogenic

SpliceAI

444 predictions. Top by Δscore:

Variant	Effect	Δscore
2:10058957:CT:C	acceptor_gain	1.0000
2:10058959:C:CC	acceptor_gain	1.0000
2:10058954:GGGCT:G	acceptor_gain	0.9900
2:10058955:GGCT:G	acceptor_gain	0.9900
2:10058956:GCT:G	acceptor_gain	0.9900
2:10058957:CTC:C	acceptor_gain	0.9900
2:10058958:TCT:T	acceptor_gain	0.9900
2:10058959:C:G	acceptor_gain	0.9900
2:10058959:C:T	acceptor_loss	0.9900
2:10058960:T:G	acceptor_loss	0.9900
2:10058967:C:CT	acceptor_gain	0.9900
2:10058968:A:T	acceptor_gain	0.9900
2:10079905:CCGCG:C	donor_gain	0.9900
2:10058956:GCTCT:G	acceptor_gain	0.9800
2:10079899:CACT:C	donor_loss	0.9800
2:10079900:ACTC:A	donor_loss	0.9800
2:10079901:CT:C	donor_loss	0.9800
2:10079902:T:TC	donor_loss	0.9800
2:10079903:CAC:C	donor_loss	0.9800
2:10079904:A:AC	donor_gain	0.9800
2:10079904:A:AT	donor_loss	0.9800
2:10079905:C:CC	donor_gain	0.9800
2:10079905:CCG:C	donor_gain	0.9800
2:10058955:GGCTC:G	acceptor_gain	0.9700
2:10066052:TTCA:T	donor_gain	0.9700
2:10065902:A:AC	donor_gain	0.9600
2:10065903:C:CC	donor_gain	0.9600
2:10058961:G:C	acceptor_gain	0.9500
2:10065903:CT:C	donor_gain	0.9500
2:10079898:ACACT:A	donor_loss	0.9500

AlphaMissense

994 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:10058875:A:T	I152N	0.989
2:10058883:C:A	M149I	0.987
2:10058883:C:G	M149I	0.987
2:10058883:C:T	M149I	0.987
2:10058884:A:G	M149T	0.986
2:10079994:A:G	L77P	0.981
2:10058875:A:C	I152S	0.980
2:10058864:A:G	Y156H	0.973
2:10058875:A:G	I152T	0.964
2:10058863:T:G	Y156S	0.963
2:10058887:A:G	L148P	0.960
2:10058872:T:A	E153V	0.958
2:10058863:T:C	Y156C	0.957
2:10080209:G:C	S5R	0.957
2:10080209:G:T	S5R	0.957
2:10080211:T:G	S5R	0.957
2:10058895:T:A	E145D	0.954
2:10058895:T:G	E145D	0.954
2:10080220:C:G	G2R	0.954
2:10080206:G:C	S6R	0.948
2:10080206:G:T	S6R	0.948
2:10080208:T:G	S6R	0.948
2:10058864:A:C	Y156D	0.946
2:10058882:C:G	A150P	0.946
2:10080000:T:A	D75V	0.944
2:10058884:A:T	M149K	0.942
2:10080215:G:C	S3R	0.934
2:10080215:G:T	S3R	0.934
2:10080217:T:G	S3R	0.934
2:10080006:A:G	L73P	0.933

dbSNP variants (sampled 300 via entrez): RS1000024767 (2:10081770 C>T), RS1000035721 (2:10058890 C>T), RS1000073136 (2:10082358 C>A), RS1000150545 (2:10076021 T>A), RS1000231666 (2:10076252 G>C,T), RS1000286979 (2:10070886 C>T), RS1000350327 (2:10082056 G>C), RS1000581355 (2:10072848 G>A), RS1000674375 (2:10059656 T>C), RS1000746816 (2:10061397 G>A,C), RS1001050254 (2:10072618 C>G,T), RS1001079418 (2:10080713 G>A,C), RS1001317529 (2:10059459 G>T), RS1001324542 (2:10064197 TG>T), RS1001405567 (2:10056492 T>C)

Disease associations

OMIM: gene MIM:618713 | disease phenotypes: MIM:173900

GenCC curated gene-disease

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
polycystic kidney disease	Limited	AR

Mondo (2): autosomal recessive polycystic kidney disease (MONDO:0009889), polycystic kidney disease (MONDO:0020642)

Orphanet (2): Autosomal recessive polycystic kidney disease (Orphanet:731), (Orphanet:8378)

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST001942_5	Prostate cancer	3.000000e-08
GCST002625_10	Chronic bronchitis and chronic obstructive pulmonary disease	3.000000e-08

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D007690	Polycystic Kidney Diseases	C12.050.351.968.419.403.875; C12.200.777.419.403.875; C12.950.419.403.875; C16.131.077.717; C16.320.184.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

20 total (human), top 20 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	2
aristolochic acid I	decreases expression	1
bisphenol A	increases methylation	1
2,5,2’,5’-tetrachlorobiphenyl	increases expression	1
trichostatin A	increases expression	1
sodium arsenite	increases abundance, increases expression	1
ferrous chloride	decreases expression	1
CGP 52608	affects binding, increases reaction	1
abrine	decreases expression	1
jinfukang	increases expression	1
Zoledronic Acid	decreases expression	1
Arsenic	increases expression, increases abundance	1
Benzo(a)pyrene	decreases methylation, increases methylation	1
Cadmium	increases abundance, increases expression	1
Nickel	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Aflatoxin B1	increases methylation	1
Antirheumatic Agents	increases expression	1
Cadmium Chloride	increases abundance, increases expression	1
Okadaic Acid	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04782258	PHASE3	RECRUITING	A Study to See Iftolvaptan is Safe in Infants and Children Who at Enrollment Are 28 Days to Less Than 18 Years Old withAutosomal Recessive Polycystic Kidney Disease (ARPKD)
NCT04786574	PHASE3	WITHDRAWN	A Study to See if Tolvaptan Can Delay Dialysis in Infants and Children Who at Enrollment Are 28 Days to Less Than 12 Weeks Old With Autosomal Recessive Polycystic Kidney Disease (ARPKD)
NCT02140814	PHASE2	COMPLETED	Uncontrolled, Open Label, Pilot and Feasibility Study of Niacinamide in Polycystic Kidney Disease
NCT02558595	PHASE2	COMPLETED	Pilot Study of Niacinamide in Polycystic Kidney Disease (NIAC-PKD2)
NCT02697617	PHASE2	COMPLETED	Use of Low Dose Pioglitazone to Treat Autosomal Dominant Polycystic Kidney Disease
NCT02166489	PHASE1	COMPLETED	Mesenchymal Stem Cells Transplantation in Patients With Chronic Renal Failure Due to Polycystic Kidney Disease
NCT01401998	Not specified	RECRUITING	ARPKD Database Study
NCT06065852	Not specified	RECRUITING	National Registry of Rare Kidney Diseases
NCT06147414	Not specified	RECRUITING	Development of Non-Invasive Prenatal Diagnosis for Single Gene Disorders
NCT07201025	Not specified	RECRUITING	Imaging Assessments of ARPKD Kidney Disease Progression
NCT01009957	PHASE2/PHASE3	TERMINATED	Everolimus on CKD Progression in ADPKD Patients
NCT01680250	PHASE2/PHASE3	UNKNOWN	Sirolimus for Massive Polycystic Liver
NCT00286156	PHASE1/PHASE2	COMPLETED	Pilot Study of Rapamycin as Treatment for Autosomal Dominant Polycystic Kidney Disease (ADPKD)
NCT03423810	EARLY_PHASE1	COMPLETED	Assessing a Dose-Response Relationship of Hydralazine and Its Effects on DNA Methyltransferase 1 in Polycystic Kidney Disease Patients
NCT00792155	Not specified	RECRUITING	Polycystic Kidney Disease Data Repository
NCT01873235	Not specified	RECRUITING	PKD Clinical and Translational Core Study
NCT01931644	Not specified	COMPLETED	At-Home Research Study for Patients With Autoimmune, Inflammatory, Genetic, Hematological, Infectious, Neurological, CNS, Oncological, Respiratory, Metabolic Conditions
NCT02142101	Not specified	COMPLETED	Evaluation of Gut Bacteria in Patients With Polycystic Kidney Disease
NCT02739750	Not specified	COMPLETED	Pioglitazone and Lumbar Bone Marrow Fat in Chronic Kidney Disease
NCT02936791	Not specified	RECRUITING	Early PKD Observational Cohort Study
NCT03726463	Not specified	UNKNOWN	Evaluation of Iliac and Renal Artery for Mechanism of Intracranial Aneurysm in ADPKD
NCT03889392	Not specified	COMPLETED	Evaluation of Nephrectomy Specimen for Intracranial Aneurysm Development in ADPKD
NCT03948113	Not specified	COMPLETED	Outcome of Autosomal Dominant Polycystic Kidney Disease Patients on Peritoneal Dialysis: a National Retrospective Study Based on Two French Registries (the French Language Peritoneal Dialysis Registry and the French Renal Epidemiology and Information Network).
NCT04039061	Not specified	RECRUITING	ADPKD Patient Registry
NCT05215964	Not specified	UNKNOWN	The Association Between Skeletal Muscle Mass and Severity of Polycystic Liver Disease and Polycystic Kidney Disease
NCT06036992	Not specified	ACTIVE_NOT_RECRUITING	Study and Management of Cystic Complications in Autosomal Dominant Polycystic Kidney Disease
NCT06325644	Not specified	RECRUITING	Well-Formulated Ketogenic Diet Polycystic Kidney Disease
NCT06728228	Not specified	RECRUITING	Amnioinfusion for Fetal Renal Failure
NCT06841224	Not specified	ENROLLING_BY_INVITATION	The Factors Affecting IPP in Peritoneal Dialysis Patients with Polycystic Kidney Disease
NCT06867471	Not specified	RECRUITING	Effects of Exogenous Ketosis on Proteinuria and Renal Function
NCT07310641	Not specified	COMPLETED	Descriptive Analysis of Preimplantation Genetic Test (PGT)in Couples With Polycystic Kidney Disease (PKD). In the ADPKD Subgroup Evaluation of Outcomes and Complications Comparing Couples in Which the Father is Affected With Couples in Which the Mother is Affected