INCA1

Summary

INCA1 (inhibitor of CDK, cyclin A1 interacting protein 1, HGNC:32224) is a protein-coding gene on chromosome 17p13.2, encoding Protein INCA1 (Q0VD86). Binds to CDK2-bound cyclins and inhibits the kinase activity of CDK2; binding to cyclins is critical for its function as CDK inhibitor.

Enables cyclin binding activity; cyclin-dependent protein serine/threonine kinase inhibitor activity; and identical protein binding activity. Acts upstream of or within negative regulation of cyclin-dependent protein serine/threonine kinase activity. Located in cytoplasm and nuclear body.

Source: NCBI Gene 388324 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 15 total
• MANE Select transcript: NM_001394789

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:32224
Approved symbol	INCA1
Name	inhibitor of CDK, cyclin A1 interacting protein 1
Location	17p13.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000196388
Ensembl biotype	protein_coding
OMIM	617374
Entrez	388324

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 20 protein_coding

ENST00000355025, ENST00000574617, ENST00000575780, ENST00000576820, ENST00000695324, ENST00000895019, ENST00000895020, ENST00000895021, ENST00000895022, ENST00000895023, ENST00000895024, ENST00000895025, ENST00000895026, ENST00000895027, ENST00000949043, ENST00000949044, ENST00000949045, ENST00000949046, ENST00000949047, ENST00000949048

RefSeq mRNA: 8 — MANE Select: NM_001394789 NM_001167985, NM_001167986, NM_001167987, NM_001394788, NM_001394789, NM_001394790, NM_001394791, NM_213726

CCDS: CCDS11064, CCDS54074

Canonical transcript exons

ENST00000695324 — 7 exons

Exon	Start	End
ENSE00001418684	4994394	4994475
ENSE00001421154	4997496	4997522
ENSE00001421288	4990152	4990265
ENSE00001428360	4989890	4989929
ENSE00001431647	4988779	4988944
ENSE00001432898	4989428	4989624
ENSE00002668194	4988130	4988554

Expression profiles

Bgee: expression breadth ubiquitous, 133 present calls, max score 94.84.

FANTOM5 (CAGE): breadth broad, TPM avg 0.9814 / max 69.4671, expressed in 452 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
164011	0.5538	270
164012	0.3158	137
164010	0.0957	38
164009	0.0160	7

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right testis	UBERON:0004534	94.84	gold quality
left testis	UBERON:0004533	94.15	gold quality
testis	UBERON:0000473	93.21	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	91.87	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.19	gold quality
apex of heart	UBERON:0002098	84.55	gold quality
gastrocnemius	UBERON:0001388	82.13	gold quality
muscle of leg	UBERON:0001383	81.87	gold quality
hindlimb stylopod muscle	UBERON:0004252	81.12	gold quality
metanephros cortex	UBERON:0010533	80.55	gold quality
duodenum	UBERON:0002114	80.53	gold quality
right lobe of thyroid gland	UBERON:0001119	80.43	gold quality
mucosa of transverse colon	UBERON:0004991	80.43	gold quality
body of uterus	UBERON:0009853	79.90	gold quality
left lobe of thyroid gland	UBERON:0001120	79.77	gold quality
rectum	UBERON:0001052	79.75	gold quality
thyroid gland	UBERON:0002046	79.70	gold quality
mucosa of stomach	UBERON:0001199	79.68	gold quality
transverse colon	UBERON:0001157	79.65	gold quality
lower esophagus muscularis layer	UBERON:0035833	79.60	gold quality
small intestine Peyer’s patch	UBERON:0003454	79.55	gold quality
lower esophagus	UBERON:0013473	79.55	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	79.50	gold quality
skeletal muscle tissue	UBERON:0001134	79.14	gold quality
ectocervix	UBERON:0012249	79.09	gold quality
right ovary	UBERON:0002118	79.06	gold quality
left ovary	UBERON:0002119	79.05	gold quality
smooth muscle tissue	UBERON:0001135	78.99	gold quality
right coronary artery	UBERON:0001625	78.85	gold quality
endocervix	UBERON:0000458	78.72	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-MTAB-6075	no	4.28
E-HCAD-13	no	3.06
E-ANND-3	no	2.46

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

13 targeting INCA1, 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-6739-5P	99.80	67.87	2806
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-3714	99.71	70.74	2671
HSA-MIR-3153	99.55	67.59	2337
HSA-MIR-766-5P	99.47	67.91	2225
HSA-MIR-3123	99.47	67.15	2693
HSA-MIR-185-5P	99.35	68.60	2497
HSA-MIR-4644	99.35	69.12	2514
HSA-MIR-6804-5P	98.39	65.77	1084
HSA-MIR-6847-5P	97.93	66.74	1808
HSA-MIR-2278	97.30	66.19	1130
HSA-MIR-6880-3P	85.95	63.83	83

Literature-anchored findings (GeneRIF, showing 2)

• Inhibitor of cyclin-dependent kinase (CDK) interacting with cyclin A1 (INCA1) regulates proliferation and is repressed by oncogenic signaling (PMID:21540187)
• Results indicate that ING5 is a growth suppressor with suppressed expression in AML whose functions depend on its interaction with INCA1. (PMID:21750715)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Inca1	ENSMUSG00000057054
rattus_norvegicus	Inca1	ENSRNOG00000037418

Protein

Protein identifiers

Protein INCA1 — Q0VD86 (reviewed: Q0VD86)

Alternative names: Inhibitor of CDK interacting with cyclin A1

All UniProt accessions (1): Q0VD86

UniProt curated annotations — full annotation on UniProt →

Function. Binds to CDK2-bound cyclins and inhibits the kinase activity of CDK2; binding to cyclins is critical for its function as CDK inhibitor. Inhibits cell growth and cell proliferation and may play a role in cell cycle control. Required for ING5-mediated regulation of S-phase progression, enhancement of Fas-induced apoptosis and inhibition of cell growth.

Subunit / interactions. Interacts with CCNA1. Interacts with CCNA2, CCNB1 and CCNE1. Found in a complex with CCNA1 and CDK2. Interacts with ZNF16; the interaction inhibits INCA1 activity and induces the cell cycle process. Interacts with SPACA9. Interacts with the CCNA1/CDK2 complex. Interacts with ING5, DAZAP2, RNF26, USP15, SPOUT1, DPH7, TRIM26 and RAB5C.

Subcellular location. Nucleus. Cytoplasm.

Tissue specificity. Detected in testis, and at lower levels in ovary. Detected at very low levels in testis tumors. Down-regulated in bone marrow cells in acute myeloid and lymphoid leukemia patients as compared with normal bone marrow cells.

Post-translational modifications. Phosphorylated when part of a complex with CCNA1 and CDK2. Strongly phosphorylated by CDK2 on its C-terminal region spanning amino acid 149-221. Less intensively phosphorylated by CDK2 on its first 75 amino acid residues.

Induction. By serum starvation.

Similarity. Belongs to the INCA family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q0VD86-1	1	yes
Q0VD86-2	2

RefSeq proteins (8): NP_001161457, NP_001161458, NP_001161459, NP_001381717, NP_001381718, NP_001381719, NP_001381720, NP_998891 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026238	INCA1	Family

Pfam: PF15142

UniProt features (13 total): mutagenesis site 4, modified residue 4, chain 1, region of interest 1, sequence conflict 1, short sequence motif 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q0VD86-F1	60.75	0.11

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 (4): 23, 182, 191, 194

Mutagenesis-validated functional residues (4):

Position	Phenotype
191	strongly reduced phosphorylation. phosphorylation is almost abolished; when associated with a-182.
194	reduced phosphorylation.
23	loss of phosphorylation site.
182	reduced phosphorylation. phosphorylation is almost abolished; when associated with a-191.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 94 (showing top): RNGTGGGC_UNKNOWN, GOBP_REGULATION_OF_PHOSPHORYLATION, GOBP_NEGATIVE_REGULATION_OF_KINASE_ACTIVITY, LFA1_Q6, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GOBP_REGULATION_OF_TRANSFERASE_ACTIVITY, TGACCTY_ERR1_Q2, GGGTGGRR_PAX4_03, SREBP1_02, UEDA_PERIFERAL_CLOCK, GOBP_APOPTOTIC_SIGNALING_PATHWAY, GOBP_NEGATIVE_REGULATION_OF_CELL_CYCLE, GOBP_REGULATION_OF_CELL_CYCLE, GOBP_NEGATIVE_REGULATION_OF_PHOSPHORUS_METABOLIC_PROCESS, TCF11_01

GO Biological Process (6): negative regulation of cell population proliferation (GO:0008285), negative regulation of cyclin-dependent protein serine/threonine kinase activity (GO:0045736), fibroblast proliferation (GO:0048144), negative regulation of fibroblast proliferation (GO:0048147), apoptotic signaling pathway (GO:0097190), positive regulation of apoptotic signaling pathway (GO:2001235)

GO Molecular Function (6): cyclin-dependent protein serine/threonine kinase inhibitor activity (GO:0004861), cyclin binding (GO:0030332), identical protein binding (GO:0042802), protein-containing complex binding (GO:0044877), protein kinase inhibitor activity (GO:0004860), protein binding (GO:0005515)

GO Cellular Component (4): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), nuclear body (GO:0016604)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell population proliferation	2
cyclin-dependent protein serine/threonine kinase activity	2
protein binding	2
binding	2
cellular anatomical structure	2
regulation of cell population proliferation	1
negative regulation of cellular process	1
regulation of cyclin-dependent protein serine/threonine kinase activity	1
negative regulation of cell cycle	1
negative regulation of protein serine/threonine kinase activity	1
negative regulation of cyclin-dependent protein kinase activity	1
negative regulation of cell population proliferation	1
fibroblast proliferation	1
regulation of fibroblast proliferation	1
apoptotic process	1
signal transduction	1
positive regulation of signal transduction	1
positive regulation of apoptotic process	1
apoptotic signaling pathway	1
regulation of apoptotic signaling pathway	1
cyclin-dependent protein serine/threonine kinase regulator activity	1
protein serine/threonine kinase inhibitor activity	1
protein kinase activity	1
kinase inhibitor activity	1
protein kinase regulator activity	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
nucleoplasm	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

298 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
INCA1	CCNA1	P78396	850
INCA1	ING5	Q8WYH8	517
INCA1	KLHDC9	Q8NEP7	446
INCA1	PROCA1	Q8NCQ7	443
INCA1	BRAT1	Q6PJG6	441
INCA1	ARHGAP30	Q7Z6I6	433
INCA1	ZNF16	P17020	431
INCA1	NKX1-1	Q15270	430
INCA1	GPS2	Q13227	410
INCA1	PXT1	Q8NFP0	404
INCA1	XRCC6	P12956	400
INCA1	KASH5	Q8N6L0	392
INCA1	BPIFB3	P59826	368
INCA1	PRDM13	Q9H4Q3	355
INCA1	DMC1	Q14565	340

IntAct

829 interactions, top by confidence:

A	B	Type	Score
INCA1	CABP5	psi-mi:“MI:0915”(physical association)	0.830
CABP5	INCA1	psi-mi:“MI:0915”(physical association)	0.830
INCA1	COL8A1	psi-mi:“MI:0915”(physical association)	0.780
CDKN2D	INCA1	psi-mi:“MI:0915”(physical association)	0.780
COL8A1	INCA1	psi-mi:“MI:0915”(physical association)	0.780
EPHB6	INCA1	psi-mi:“MI:0915”(physical association)	0.720
INCA1	STK16	psi-mi:“MI:0915”(physical association)	0.720
UBXN2B	INCA1	psi-mi:“MI:0915”(physical association)	0.720
INCA1	RAMAC	psi-mi:“MI:0915”(physical association)	0.720
INCA1	DMRT3	psi-mi:“MI:0915”(physical association)	0.720
SPG21	INCA1	psi-mi:“MI:0915”(physical association)	0.720
OSGIN1	INCA1	psi-mi:“MI:0915”(physical association)	0.720
STK16	INCA1	psi-mi:“MI:0915”(physical association)	0.720
RAMAC	INCA1	psi-mi:“MI:0915”(physical association)	0.720
DMRT3	INCA1	psi-mi:“MI:0915”(physical association)	0.720
INCA1	SPG21	psi-mi:“MI:0915”(physical association)	0.720
INCA1	EPHB6	psi-mi:“MI:0915”(physical association)	0.720

BioGRID (267): INCA1 (Two-hybrid), INCA1 (Two-hybrid), INCA1 (Two-hybrid), INCA1 (Two-hybrid), INCA1 (Two-hybrid), INCA1 (Two-hybrid), INCA1 (Two-hybrid), INCA1 (Two-hybrid), INCA1 (Two-hybrid), INCA1 (Two-hybrid), INCA1 (Two-hybrid), INCA1 (Two-hybrid), INCA1 (Two-hybrid), INCA1 (Two-hybrid), INCA1 (Two-hybrid)

ESM2 similar proteins: A0A1B0GTK4, A0A1B0GTK5, A0JNL8, A2RUT3, A4D250, B2KGE5, F1MQW7, F2Z3F1, F5HHT4, O93195, O95411, P04610, P05905, P0C733, P0C7M3, P0DP71, P16722, P17758, P47939, P47940, P57738, Q0VD86, Q1HVB5, Q1RN00, Q1X6Y7, Q1X6Z1, Q1X6Z2, Q3ZN08, Q5PR19, Q5PXH1, Q5TC04, Q5TEZ4, Q64902, Q66669, Q66HF0, Q67863, Q6DGF6, Q6UYE1, Q7L4S7, Q8AZJ3

Diamond homologs: Q0VD86, Q6PKN7

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
CyclinA2/CDK2	unknown	INCA1	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	11
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1152 predictions. Top by Δscore:

Variant	Effect	Δscore
17:4988813:T:TA	donor_gain	1.0000
17:4989426:A:AC	donor_gain	1.0000
17:4989427:C:CC	donor_gain	1.0000
17:4989925:TGGGG:T	acceptor_gain	1.0000
17:4989930:C:CC	acceptor_gain	1.0000
17:4994392:A:AC	donor_gain	1.0000
17:4994393:C:CC	donor_gain	1.0000
17:4994476:C:CC	acceptor_gain	1.0000
17:4998154:GAGGT:G	donor_loss	1.0000
17:4998155:AGGTG:A	donor_loss	1.0000
17:4998156:GGTG:G	donor_loss	1.0000
17:4998157:G:GA	donor_loss	1.0000
17:4998158:T:A	donor_loss	1.0000
17:4988573:T:TC	acceptor_gain	0.9900
17:4988957:TAGG:T	acceptor_gain	0.9900
17:4988961:C:CC	acceptor_gain	0.9900
17:4989417:C:CA	donor_gain	0.9900
17:4989421:T:TA	donor_gain	0.9900
17:4989427:CT:C	donor_gain	0.9900
17:4989623:CT:C	acceptor_gain	0.9900
17:4989625:C:CC	acceptor_gain	0.9900
17:4989627:G:C	acceptor_gain	0.9900
17:4989631:C:CT	acceptor_gain	0.9900
17:4989632:A:T	acceptor_gain	0.9900
17:4989886:TTA:T	donor_loss	0.9900
17:4989887:TA:T	donor_loss	0.9900
17:4989889:C:CA	donor_loss	0.9900
17:4989926:GGGG:G	acceptor_gain	0.9900
17:4989927:GGG:G	acceptor_gain	0.9900
17:4989927:GGGC:G	acceptor_loss	0.9900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000464490 (17:4999457 C>T), RS1000917238 (17:4999485 A>C), RS1001073394 (17:4993984 C>G,T), RS1001194001 (17:4988534 G>A,T), RS1001225120 (17:4988222 A>C,T), RS1001652467 (17:4992031 A>G), RS1001673259 (17:4995265 G>A), RS1001683470 (17:4992341 G>A), RS1001706702 (17:4995587 G>A), RS1001974347 (17:4998516 A>G), RS1002039675 (17:4993440 A>G), RS1002042087 (17:4997702 G>A,T), RS1002194829 (17:4990148 T>A,G), RS1002323680 (17:4998219 G>A,T), RS1002628942 (17:4996662 G>A,T)

Disease associations

OMIM: gene MIM:617374 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST001762_456	Obesity-related traits	6.000000e-06
GCST005170_15	Intraocular pressure	2.000000e-14
GCST90013442_27	Keratoconus	2.000000e-14

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004695	intraocular pressure measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

12 total (human), top 12 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
triphenyl phosphate	affects expression	1
jinfukang	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Sunitinib	increases expression	1
Benzo(a)pyrene	affects methylation	1
Niclosamide	increases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	increases methylation	1
Gold Compounds	increases expression	1

Clinical trials (associated diseases)

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