CDKN2B-AS1

Summary

CDKN2B-AS1 (CDKN2B and CDKN2A antisense cis and trans regulatory RNA 1, HGNC:34341) is a long non-coding RNA gene on chromosome 9p21.3.

This gene is located within the CDKN2B-CDKN2A gene cluster at chromosome 9p21. The gene product is a functional RNA molecule that interacts with polycomb repressive complex-1 (PRC1) and -2 (PRC2), leading to epigenetic silencing of other genes in this cluster. This region is a significant genetic susceptibility locus for cardiovascular disease, and has also been linked to a number of other pathologies, including several cancers, intracranial aneurysm, type-2 diabetes, periodontitis, Alzheimer’s disease, endometriosis, frailty in the elderly, and glaucoma. Multiple alternatively processed transcript variants have been detected, some of which may take the form of circular RNA molecules (PMID:21151960).

Source: NCBI Gene 100048912 — RefSeq curated summary.

At a glance

• Gene type: non-coding (lncRNA) — no protein product; not a drug target. Variant/disease associations are omitted (they would be positional, from an overlapping protein-coding gene).

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:34341
Approved symbol	CDKN2B-AS1
Name	CDKN2B and CDKN2A antisense cis and trans regulatory RNA 1
Location	9p21.3
Locus type	RNA, long non-coding
Status	Approved
Aliases	ANRIL, RP11-145E5.4, NCRNA00089, p15AS, CDKN2B-AS, PCAT12, 66CTG
Ensembl gene	ENSG00000240498
Ensembl biotype	lncRNA
OMIM	613149
Entrez	100048912
RNAcentral	URS00026A21AD — lncRNA, 3453 nt, 1 organism(s)

Gene structure

Transcript identifiers

Ensembl transcripts: 37 — 37 lncRNA

ENST00000421632, ENST00000422420, ENST00000428597, ENST00000455933, ENST00000468603, ENST00000577551, ENST00000580467, ENST00000580576, ENST00000581051, ENST00000582072, ENST00000582301, ENST00000583719, ENST00000584020, ENST00000584351, ENST00000584637, ENST00000584816, ENST00000585267, ENST00000643286, ENST00000644233, ENST00000645223, ENST00000645313, ENST00000650946, ENST00000651519, ENST00000651588, ENST00000651784, ENST00000651904, ENST00000652420, ENST00000658981, ENST00000755351, ENST00000755352, ENST00000806148, ENST00000806149, ENST00000806150, ENST00000806151, ENST00000806152, ENST00000806153, ENST00000806154

RefSeq mRNA: 0 — MANE Select: None

Canonical transcript exons

ENST00000421632 — 9 exons

Exon	Start	End
ENSE00001607196	22112320	22112395
ENSE00001634408	22049106	22049228
ENSE00001694999	22118644	22118767
ENSE00001712751	22120200	22120410
ENSE00001762254	22113666	22113799
ENSE00001781056	22046751	22046900
ENSE00002699013	21995095	21995161
ENSE00003460498	22029433	22029594
ENSE00003844945	22120504	22120689

Expression profiles

Bgee: expression breadth ubiquitous, 169 present calls, max score 98.11.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 3.9993 / max 137.4912, expressed in 1073 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
96300	1.9372	624
96301	0.7774	445
96297	0.3996	81
96296	0.3723	167
96308	0.1957	16
96298	0.1600	68
96299	0.1514	60
96309	0.0055	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of transverse colon	UBERON:0004991	98.11	gold quality
rectum	UBERON:0001052	96.50	gold quality
transverse colon	UBERON:0001157	88.56	gold quality
small intestine Peyer’s patch	UBERON:0003454	85.06	gold quality
small intestine	UBERON:0002108	81.32	gold quality
colonic epithelium	UBERON:0000397	80.80	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.14	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	76.41	gold quality
right uterine tube	UBERON:0001302	75.38	gold quality
intestine	UBERON:0000160	75.19	gold quality
adenohypophysis	UBERON:0002196	74.31	gold quality
colon	UBERON:0001155	74.23	gold quality
pancreatic ductal cell	CL:0002079	73.85	silver quality
tibialis anterior	UBERON:0001385	73.80	gold quality
large intestine	UBERON:0000059	73.45	gold quality
sural nerve	UBERON:0015488	72.95	gold quality
pituitary gland	UBERON:0000007	72.81	gold quality
stromal cell of endometrium	CL:0002255	72.26	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	70.43	gold quality
buccal mucosa cell	CL:0002336	70.16	silver quality
bone marrow cell	CL:0002092	68.53	gold quality
muscle layer of sigmoid colon	UBERON:0035805	66.95	gold quality
calcaneal tendon	UBERON:0003701	65.98	gold quality
monocyte	CL:0000576	65.91	gold quality
mononuclear cell	CL:0000842	65.90	gold quality
leukocyte	CL:0000738	65.61	gold quality
ventricular zone	UBERON:0003053	65.06	gold quality
lower esophagus muscularis layer	UBERON:0035833	64.73	gold quality
right adrenal gland	UBERON:0001233	64.71	gold quality
spleen	UBERON:0002106	64.70	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.64

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CTNNBL1, E2F1

Literature-anchored findings (GeneRIF, showing 40)

• CDKN2A CDKN2B and ANRIL is the susceptibility locus for coronary heart disease (CHD) and periodontitis. (PMID:19214202)
• ANRIL splice variants have a role in cardiovascular disease (PMID:19888323)
• study suggests that modulation of ANRIL expression mediates susceptibility to several important human diseases. (PMID:20386740)
• Data show that chromobox 7 (CBX7) within the polycomb repressive complex 1 binds to ANRIL, and both CBX7 and ANRIL are found at elevated levels in prostate cancer tissues. (PMID:20541999)
• genome wide association study identified association of endometriosis with rs10965235 which is located in CDKN2BAS; SNP showing strongest association was located in intron 16 of CDKN2BAS and was implicated in regulating expression of p15, p16 and p14 (PMID:20601957)
• Results indicate that co-regulation of ANRIL and p14ARF could be coupled by their unique intergenic region potentially through E2F1. (PMID:20664976)
• results suggest a model in which ANRIL binds to and recruits PRC2 to repress the expression of p15(INK4B) locus (PMID:21151178)
• We report a genome-wide association study for open-angle glaucoma (OAG) blindness showing an association at cdkn2b locus (PMID:21532571)
• Our findings indicated that the ANRIL may serve as a novel genetic marker for the risk of atherothrombotic and hemorrhagic stroke and their recurrence. (PMID:22034006)
• in neurofibromatosis type 1(NF1)-associated plexiform neurofibromas(PNFs),rs2151280 was associated with number of PNFs in NF1; allele T associated with reduced ANRIL transcript levels suggesting modulation of ANRIL expression mediates PNF susceptibility (PMID:22034633)
• ANRIL on 9p21 and BRAP were both associated with ankle brachial index in a Taiwanese population. (PMID:22122968)
• Suggest that several atherosclerosis-associated SNPs in the 9p21 locus affect the expression of ANRIL, which, in turn modulate cell growth, possibly via CDKN2A/B regulation. (PMID:22178423)
• ANRIL splicing variants play a role in coordinating tissue remodeling, by modulating the expression of genes involved in cell proliferation, apoptosis, extra-cellular matrix remodeling and inflammatory response to finally impact in the risk of cardiovascular disease and other pathologies. (PMID:22382030)
• Common variants in CDKN2B-AS1 associated with optic-nerve vulnerability of glaucoma identified by genome-wide association studies in Japanese. (PMID:22428042)
• Patients with primary open-angle glaucoma (POAG) carrying the glaucoma risk alleles at the 9p21 locus have larger vertical cup-to-disc ratio and lower IOP than POAG patients without these alleles. (PMID:22521085)
• ANRIL long non-coding RNA, human plays a role in plexiform neurofibromas (PMID:22578354)
• The 9p21 coronary artery disease risk genotype was associated with reduced expression of p16(INK4a), p15(INK4b) and ANRIL. (PMID:22706276)
• we provide further evidence that variants in CDKN2BAS contribute to intracranial aneurysm (PMID:22961961)
• The epigenetic changes in p15(INK4b) methylation and ANRIL expression may involve in the mechanisms of chromosome 9p21 on CAD development. (PMID:23091611)
• Alleles of CDKN2B-AS1 SNPs, which influence risk of developing POAG (primary open-angle glaucoma), also modulate optic nerve degeneration among POAG patients, underscoring the role of CDKN2B-AS1 in POAG. (PMID:23111177)
• We confirm WNT4, CDKN2BAS and FN1 as the first identified common loci for endometriosis. (PMID:23142796)
• A single nucleotide polymorphism in the ANRIL locus is implicated in statin therapy response and serum lipid profile. (PMID:23266621)
• Complex regulatory variation affecting ANRIL and CDKN2B gene expression may contribute to increased risk for clinically apparent and subclinical coronary artery disease and aortic disease. (PMID:23315372)
• An elevated levels of ANRIL suppress the expression of INK4a, INK4b and ARF at the late-stage of DNA damage response. (PMID:23416462)
• Homozygous deletion of ANRIL gene is associated with haploid lymphoblastic leukemia. (PMID:23508829)
• Evidence shows that specific isoforms of ANRIL regulate key genes of glucose and fatty acid metabolism. (PMID:23813974)
• Our study provides a molecular mechanism for pro-atherogenic effects of ANRIL at Chr9p21 and suggests a novel role for Alu elements in epigenetic gene regulation by long ncRNAs. (PMID:23861667)
• we observed a significant association of SNP rs10120688 in the CDKN2B-AS1 region with Primary open angle glaucoma. (PMID:23963167)
• ANRIL may increase the risk of ischemic stroke through regulation of the CARD8 pathway (PMID:24385277)
• genetic polymorphism, risk factor for coronary artery diseases in Asian Indians, is associated with altered smooth muscle cell proliferation (PMID:24452806)
• All the family members were homozygotes for the risk allele G for the rs1333049 variant in the CDKN2BAS locus. (PMID:24642913)
• Data suggest that WT1-as, MEG3 and ANRIL could potentially be used as new primary myelofibrosis (PMF) diagnostic biomarkers with prognostic implications. (PMID:24707949)
• these findings suggest a significant role of ANRIL in the occurrence and development of esophageal squamous cell carcinoma through TGFbeta1 signaling pathways. (PMID:24747824)
• ANRIL-mediated growth promotion is in part due to epigenetic repression of miR-99a/miR-449a in gastric cancer (PMID:24810364)
• The sequence variant rs1333049 affects the expression of ANRIL, a noncoding RNA transcript playing a key role in the regulation of inflammatory processes. These results are suggesting that genetic information on the rs1333049 variant might be a useful predictor of adverse cardiac events. Thus, we could successfully replicate the predictive value of the 9p21 risk allele in an Austrian cohort. (PMID:25032714)
• meta-analysis of two Caucasian cohorts did not show an association between five aneurysm associated loci and sporadic brain Arteriovenous malformations. (PMID:25053769)
• Our results suggest that the rs10965235 SNP in the CDKN2B-AS gene and the rs16826658 SNP near the WNT4 gene were significantly associated with endometriosis in this Korean population. (PMID:25154675)
• six novel lncRNAs (CDKN2B-AS1, MIR22HG, GABPB1-AS1, FLJ33630, LINC00152, and LINC0541471_v2) that respond to model chemical stresses (cycloheximide, hydrogen peroxide, cadmium, or arsenic) in hiPSCs. (PMID:25171338)
• Replicated evidence showed that one SNP, rs2069416, in CDKN2B-AS1 significantly modified the association between diastolic blood pressure and coronary artery calcification quantity. (PMID:25185447)
• A significant association of rs4977574 with the risk of coronary heart disease under a recessive inheritance model in females. (PMID:25268619)

Cross-species orthologs

0 orthologs

Protein

Non-coding RNA — no protein product; not a drug target.

Function

No curated pathway, Gene-Ontology, or interaction data.

Disease & clinical

No curated disease, variant, or cancer-driver associations.

Drugs & pharmacology

No drug or pharmacology data — not an established drug target.