CCNI2

Summary

CCNI2 (cyclin I family member 2, HGNC:33869) is a protein-coding gene on chromosome 5q31.1, encoding Cyclin-I2 (Q6ZMN8).

Predicted to enable cyclin-dependent protein serine/threonine kinase regulator activity. Predicted to be involved in G1/S transition of mitotic cell cycle. Predicted to be part of cyclin-dependent protein kinase holoenzyme complex. Predicted to be active in cytoplasm and nucleus.

Source: NCBI Gene 645121 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 70 total
• MANE Select transcript: NM_001039780

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:33869
Approved symbol	CCNI2
Name	cyclin I family member 2
Location	5q31.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ16793
Ensembl gene	ENSG00000205089
Ensembl biotype	protein_coding
OMIM	620419
Entrez	645121

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 7 protein_coding, 1 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000378731, ENST00000468733, ENST00000492179, ENST00000614847, ENST00000878146, ENST00000878147, ENST00000878148, ENST00000878149, ENST00000971609

RefSeq mRNA: 3 — MANE Select: NM_001039780 NM_001039780, NM_001287252, NM_001287253

CCDS: CCDS34236, CCDS75297

Canonical transcript exons

ENST00000378731 — 6 exons

Exon	Start	End
ENSE00001478547	132751966	132752196
ENSE00001478548	132750857	132750997
ENSE00001478549	132749348	132749422
ENSE00001478552	132748347	132748475
ENSE00003714234	132752866	132754403
ENSE00003903577	132747426	132747924

Expression profiles

Bgee: expression breadth ubiquitous, 133 present calls, max score 96.79.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.4246 / max 39.7032, expressed in 154 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
58495	0.2755	117
58494	0.1491	84

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primary visual cortex	UBERON:0002436	96.79	gold quality
right frontal lobe	UBERON:0002810	96.29	gold quality
right hemisphere of cerebellum	UBERON:0014890	96.26	gold quality
cerebellar cortex	UBERON:0002129	95.46	gold quality
cerebellar hemisphere	UBERON:0002245	95.44	gold quality
cerebellum	UBERON:0002037	95.43	gold quality
Brodmann (1909) area 9	UBERON:0013540	95.00	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	94.95	gold quality
temporal lobe	UBERON:0001871	94.49	gold quality
amygdala	UBERON:0001876	94.46	gold quality
putamen	UBERON:0001874	94.37	gold quality
superior frontal gyrus	UBERON:0002661	94.36	gold quality
anterior cingulate cortex	UBERON:0009835	94.00	gold quality
frontal cortex	UBERON:0001870	93.92	gold quality
Ammon’s horn	UBERON:0001954	93.71	gold quality
cerebral cortex	UBERON:0000956	93.62	gold quality
hypothalamus	UBERON:0001898	93.45	gold quality
substantia nigra	UBERON:0002038	93.44	gold quality
caudate nucleus	UBERON:0001873	93.13	gold quality
prefrontal cortex	UBERON:0000451	92.56	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	92.36	gold quality
nucleus accumbens	UBERON:0001882	92.31	gold quality
brain	UBERON:0000955	92.27	gold quality
corpus callosum	UBERON:0002336	87.76	gold quality
mucosa of transverse colon	UBERON:0004991	84.83	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.62	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	80.78	gold quality
apex of heart	UBERON:0002098	79.37	gold quality
tibial nerve	UBERON:0001323	79.19	gold quality
pituitary gland	UBERON:0000007	78.66	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-GEOD-76312	no	11.77
E-ANND-3	no	1.51

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

66 targeting CCNI2, 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-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-6740-5P	100.00	65.64	932
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-22-3P	99.93	68.13	917
HSA-MIR-329-3P	99.91	66.56	1234
HSA-MIR-362-3P	99.91	66.38	1267
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-548D-3P	99.87	70.67	4362
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-204-5P	99.79	71.62	2439
HSA-MIR-211-5P	99.79	71.65	2440
HSA-MIR-4255	99.72	67.70	1541
HSA-MIR-7-5P	99.67	70.53	1809
HSA-MIR-29B-2-5P	99.67	68.98	1726
HSA-MIR-6757-3P	99.63	66.88	1089
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-802	99.61	67.70	1254
HSA-MIR-24-3P	99.59	69.97	1934
HSA-MIR-642A-5P	99.51	65.10	1152
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-6828-5P	99.31	69.21	1433
HSA-MIR-422A	99.18	65.83	550

Literature-anchored findings (GeneRIF, showing 2)

• Here the authors show that cyclin I-like (CCNI2), a homolog of CCNI, interacts with CDK5 and activates the kinase activity of CDK5. Different from CCNI, which colocalizes with CDK5 in the nuclei in transfected cells, CCNI2 mainly retains CDK5 in the cytoplasm as well as on the cell membrane. (PMID:28112194)
• CCNI2 plays a promoting role in the progression of colorectal cancer. (PMID:33620152)

Cross-species orthologs

13 orthologs

Organism	Symbol	Gene ID
danio_rerio	ccni2	ENSDARG00000033046
drosophila_melanogaster	CycA	FBGN0000404
drosophila_melanogaster	CycB	FBGN0000405
drosophila_melanogaster	CycD	FBGN0010315
drosophila_melanogaster	CycE	FBGN0010382
caenorhabditis_elegans		WBGENE00000863
caenorhabditis_elegans		WBGENE00000864
caenorhabditis_elegans		WBGENE00000865
caenorhabditis_elegans		WBGENE00000866
caenorhabditis_elegans	cyb-2.2	WBGENE00000867
caenorhabditis_elegans		WBGENE00000870
caenorhabditis_elegans	cye-1	WBGENE00000871
caenorhabditis_elegans		WBGENE00017259

Paralogs (18): CCNE1 (ENSG00000105173), CCNP (ENSG00000105219), CCNJ (ENSG00000107443), CCND1 (ENSG00000110092), CCND3 (ENSG00000112576), CCNG1 (ENSG00000113328), CCNI (ENSG00000118816), CCND2 (ENSG00000118971), CCNA1 (ENSG00000133101), CCNB1 (ENSG00000134057), CCNJL (ENSG00000135083), CCNG2 (ENSG00000138764), CCNA2 (ENSG00000145386), CCNB3 (ENSG00000147082), CCNO (ENSG00000152669), CCNB2 (ENSG00000157456), CCNF (ENSG00000162063), CCNE2 (ENSG00000175305)

Protein

Protein identifiers

Cyclin-I2 — Q6ZMN8 (reviewed: Q6ZMN8)

All UniProt accessions (1): Q6ZMN8

UniProt curated annotations — full annotation on UniProt →

Similarity. Belongs to the cyclin family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q6ZMN8-1	1	yes
Q6ZMN8-2	2
Q6ZMN8-3	3

RefSeq proteins (3): NP_001034869, NP_001274181, NP_001274182 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006671	Cyclin_N	Domain
IPR013763	Cyclin-like_dom	Domain
IPR036915	Cyclin-like_sf	Homologous_superfamily
IPR039361	Cyclin	Family

Pfam: PF00134

UniProt features (7 total): compositionally biased region 2, splice variant 2, chain 1, region of interest 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6ZMN8-F1	75.87	0.55

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 0 (showing top):

GO Biological Process (1): G1/S transition of mitotic cell cycle (GO:0000082)

GO Molecular Function (1): cyclin-dependent protein serine/threonine kinase regulator activity (GO:0016538)

GO Cellular Component (3): cyclin-dependent protein kinase holoenzyme complex (GO:0000307), nucleus (GO:0005634), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
mitotic cell cycle	1
mitotic cell cycle phase transition	1
cell cycle G1/S phase transition	1
cyclin-dependent protein serine/threonine kinase activity	1
cyclin-dependent protein kinase regulator activity	1
serine/threonine protein kinase complex	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1327 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CCNI2	MORN3	Q6PF18	456
CCNI2	CCDC148	Q8NFR7	443
CCNI2	SHROOM1	Q2M3G4	435
CCNI2	FAM24B	Q8N5W8	433
CCNI2	J3KQ18	J3KQ18	431
CCNI2	ZNF525	Q8N782	431
CCNI2	IZUMO4	Q1ZYL8	422
CCNI2	SOWAHA	Q2M3V2	420
CCNI2	ZNF253	O75346	420
CCNI2	CDK5	Q00535	416
CCNI2	CDK18	Q07002	409
CCNI2	MCMDC2	Q4G0Z9	391
CCNI2	MOB3A	Q96BX8	383
CCNI2	ZNF254	O75437	374
CCNI2	QSER1	Q2KHR3	373

IntAct

5 interactions, top by confidence:

A	B	Type	Score
CCNI2	HSPA8	psi-mi:“MI:0914”(association)	0.530
CCNI2	ZNF609	psi-mi:“MI:0914”(association)	0.350
VASH1	NAA30	psi-mi:“MI:0914”(association)	0.350

BioGRID (14): HSPA1B (Affinity Capture-MS), HSPA8 (Affinity Capture-MS), HSPA6 (Affinity Capture-MS), HSPA1L (Affinity Capture-MS), LARP1B (Affinity Capture-MS), CDK5 (Affinity Capture-MS), CDK5 (Affinity Capture-MS), LARP1B (Affinity Capture-MS), HSPA8 (Affinity Capture-MS), LARP1B (Affinity Capture-MS), HSPA8 (Affinity Capture-MS), CDK5 (Affinity Capture-MS), CCNI (Negative Genetic), CCNI2 (Positive Genetic)

ESM2 similar proteins: A0A087WVF3, A0A087WXS9, A0A087X179, A0A087X1G2, A6NDS4, A6NER0, A6QPT6, B9A6J9, M3WHG5, O14771, O15482, O15553, O19110, O76081, P0C7X1, P0C7X3, P0C7X4, P35125, P48778, P48967, P79209, Q13670, Q15697, Q2TBC4, Q3T191, Q3UZD7, Q4R2Z8, Q5DRQ5, Q5SSQ6, Q5XFX8, Q69ZB3, Q6DHY5, Q6IPX1, Q6ZMN8, Q8BLR5, Q8BWA8, Q8IYF1, Q8IZP1, Q8JZW5, Q8N7G0

Diamond homologs: O08918, P13351, P24868, P24869, P25011, P25012, P25322, P30183, P30278, P30279, P30280, P39950, P46277, P46278, P51945, P51959, Q04827, Q0JIF2, Q0P5D3, Q14094, Q16589, Q39068, Q39069, Q52QT8, Q5E9I1, Q5R5D0, Q61456, Q6AY13, Q6ZMN8, Q8WNW2, Q92161, Q95TJ9, Q9Z2V9, A0MEB5, O15995, O48790, O96020, P04962, P14785, P18606

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	58
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1089 predictions. Top by Δscore:

Variant	Effect	Δscore
5:132748475:GGTAG:G	donor_loss	1.0000
5:132748476:G:GA	donor_loss	1.0000
5:132748477:T:A	donor_loss	1.0000
5:132749420:G:GT	donor_gain	1.0000
5:132750852:TACAG:T	acceptor_loss	1.0000
5:132750853:ACAGT:A	acceptor_loss	1.0000
5:132750854:C:G	acceptor_gain	1.0000
5:132750855:A:AG	acceptor_gain	1.0000
5:132750856:G:GT	acceptor_gain	1.0000
5:132750856:GT:G	acceptor_gain	1.0000
5:132750856:GTT:G	acceptor_gain	1.0000
5:132750856:GTTT:G	acceptor_gain	1.0000
5:132750856:GTTTA:G	acceptor_gain	1.0000
5:132747920:CCCAG:C	donor_loss	0.9900
5:132747921:CCAG:C	donor_loss	0.9900
5:132747922:CAGG:C	donor_loss	0.9900
5:132747923:AGGT:A	donor_loss	0.9900
5:132747924:GG:G	donor_loss	0.9900
5:132747925:G:GA	donor_loss	0.9900
5:132747926:T:A	donor_loss	0.9900
5:132748473:AAG:A	donor_gain	0.9900
5:132749339:ATACT:A	acceptor_gain	0.9900
5:132749342:CTGCA:C	acceptor_loss	0.9900
5:132749343:TGCA:T	acceptor_loss	0.9900
5:132749344:GCAGG:G	acceptor_loss	0.9900
5:132749345:CAGGT:C	acceptor_loss	0.9900
5:132749347:G:GA	acceptor_loss	0.9900
5:132749436:G:GT	donor_gain	0.9900
5:132750998:G:GG	donor_gain	0.9900
5:132751007:G:GT	donor_gain	0.9900

AlphaMissense

2362 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:132750986:T:C	F255L	0.994
5:132750988:C:A	F255L	0.994
5:132750988:C:G	F255L	0.994
5:132750930:A:T	E236V	0.991
5:132752095:T:C	F302L	0.987
5:132752097:C:A	F302L	0.987
5:132752097:C:G	F302L	0.987
5:132750987:T:C	F255S	0.986
5:132752180:T:C	L330P	0.983
5:132749397:C:A	A203D	0.982
5:132749404:A:C	K205N	0.982
5:132749404:A:T	K205N	0.982
5:132752138:T:C	L316P	0.982
5:132750930:A:C	E236A	0.980
5:132752114:C:A	A308D	0.979
5:132752060:T:C	L290P	0.976
5:132750929:G:A	E236K	0.973
5:132750879:T:C	F219S	0.970
5:132750931:G:C	E236D	0.969
5:132750931:G:T	E236D	0.969
5:132752101:G:C	G304R	0.968
5:132748438:C:A	A174D	0.967
5:132750930:A:G	E236G	0.967
5:132750956:T:A	W245R	0.967
5:132750956:T:C	W245R	0.967
5:132752048:T:C	L286P	0.967
5:132750958:G:C	W245C	0.966
5:132750958:G:T	W245C	0.966
5:132750987:T:G	F255C	0.966
5:132751966:T:C	F259L	0.966

dbSNP variants (sampled 300 via entrez): RS1000861189 (5:132750369 G>A), RS1000893645 (5:132750028 G>A), RS1001225027 (5:132751583 A>G,T), RS1001519375 (5:132755458 T>C), RS1001569119 (5:132747945 G>A), RS1001947574 (5:132755809 C>A), RS1002105270 (5:132747154 C>T), RS1002171565 (5:132745885 G>A), RS1002179588 (5:132754993 C>A,T), RS1002434871 (5:132747328 G>A), RS1002872515 (5:132753628 G>A), RS1002903795 (5:132753371 A>T), RS1003241762 (5:132754906 T>C), RS1003277653 (5:132749715 CAG>C), RS1003615472 (5:132755339 A>G)

Disease associations

OMIM: gene MIM:620419 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST007564_19	Asthma or allergic disease (pleiotropy)	2.000000e-10
GCST007995_20	Asthma (childhood onset)	3.000000e-22
GCST008916_112	Asthma	2.000000e-11
GCST008916_34	Asthma	2.000000e-09
GCST009798_39	Asthma	5.000000e-29
GCST009798_75	Asthma	9.000000e-24

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

7 total (human), top 7 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases methylation	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Fluorescein-5-isothiocyanate	affects binding	1
Lactic Acid	decreases expression	1
Particulate Matter	increases expression	1

Clinical trials (associated diseases)

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