PROCA1

Summary

PROCA1 (protein interacting with cyclin A1, HGNC:28600) is a protein-coding gene on chromosome 17q11.2, encoding Protein PROCA1 (Q8NCQ7). It is a selective cancer dependency (DepMap: 13.5% of cell lines).

Enables cyclin binding activity. Predicted to be involved in arachidonate secretion and phospholipid metabolic process.

Source: NCBI Gene 147011 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 74 total — 1 pathogenic
• Cancer dependency (DepMap): dependent in 13.5% of screened cell lines
• MANE Select transcript: NM_001366301

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28600
Approved symbol	PROCA1
Name	protein interacting with cyclin A1
Location	17q11.2
Locus type	gene with protein product
Status	Approved
Aliases	MGC39650
Ensembl gene	ENSG00000167525
Ensembl biotype	protein_coding
OMIM	617376
Entrez	147011

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 5 protein_coding_CDS_not_defined, 4 protein_coding, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000301039, ENST00000415329, ENST00000422880, ENST00000473751, ENST00000495203, ENST00000578097, ENST00000579650, ENST00000581289, ENST00000584073, ENST00000674362, ENST00000682792

RefSeq mRNA: 8 — MANE Select: NM_001366301 NM_001304949, NM_001304951, NM_001304952, NM_001304953, NM_001304954, NM_001366301, NM_001366303, NM_152465

CCDS: CCDS11239, CCDS92283

Canonical transcript exons

ENST00000682792 — 5 exons

Exon	Start	End
ENSE00001933005	28703197	28704212
ENSE00003616703	28706680	28706763
ENSE00003663159	28704708	28704843
ENSE00003686051	28704307	28704435
ENSE00003917090	28711570	28711888

Expression profiles

Bgee: expression breadth ubiquitous, 168 present calls, max score 98.64.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 3.9135 / max 217.8740, expressed in 1020 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
165053	3.4564	969
165052	0.2978	55
165054	0.1297	39
165051	0.0297	8

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	98.64	gold quality
right testis	UBERON:0004534	98.36	gold quality
sperm	CL:0000019	97.02	gold quality
testis	UBERON:0000473	96.26	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.60	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.40	gold quality
right uterine tube	UBERON:0001302	85.05	gold quality
granulocyte	CL:0000094	82.02	gold quality
sural nerve	UBERON:0015488	81.72	gold quality
parotid gland	UBERON:0001831	80.80	gold quality
adult organism	UBERON:0007023	79.18	gold quality
spleen	UBERON:0002106	79.11	gold quality
cerebellar hemisphere	UBERON:0002245	78.29	gold quality
right hemisphere of cerebellum	UBERON:0014890	78.23	gold quality
cerebellar cortex	UBERON:0002129	78.15	gold quality
monocyte	CL:0000576	77.94	gold quality
leukocyte	CL:0000738	77.65	gold quality
left ovary	UBERON:0002119	77.63	gold quality
cerebellum	UBERON:0002037	76.86	gold quality
metanephros cortex	UBERON:0010533	76.10	gold quality
kidney epithelium	UBERON:0004819	75.48	gold quality
right ovary	UBERON:0002118	75.32	gold quality
apex of heart	UBERON:0002098	75.05	gold quality
ventricular zone	UBERON:0003053	74.94	gold quality
tibial nerve	UBERON:0001323	74.82	gold quality
ganglionic eminence	UBERON:0004023	74.60	gold quality
cortical plate	UBERON:0005343	74.45	gold quality
secondary oocyte	CL:0000655	74.44	silver quality
C1 segment of cervical spinal cord	UBERON:0006469	73.70	gold quality
cortex of kidney	UBERON:0001225	73.68	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-GEOD-134144	yes	32.71
E-ANND-3	no	1.58

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

18 targeting PROCA1, 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-12136	99.98	72.81	5713
HSA-MIR-1249-5P	99.61	66.55	2049
HSA-MIR-6797-5P	99.61	66.55	2084
HSA-MIR-1260A	99.61	66.67	1098
HSA-MIR-1260B	99.61	66.67	1098
HSA-MIR-6751-5P	99.56	64.99	1145
HSA-MIR-6803-5P	99.19	63.90	1026
HSA-MIR-6734-3P	99.15	66.27	1627
HSA-MIR-4795-5P	99.11	66.90	876
HSA-MIR-4297	98.77	66.95	2013
HSA-MIR-3166	98.24	66.63	1223
HSA-MIR-876-5P	97.99	68.49	1345
HSA-MIR-676-3P	97.86	65.70	668
HSA-MIR-214-5P	97.34	66.50	617
HSA-MIR-6515-5P	97.08	65.48	1219
HSA-MIR-3167	96.81	67.09	1236
HSA-MIR-1468-5P	94.18	69.04	176
HSA-MIR-639	88.87	61.76	78

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 13.5% of screened cell lines.

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
danio_rerio	pla2g3	ENSDARG00000008948
danio_rerio	proca1	ENSDARG00000069823
danio_rerio		ENSDARG00000098989
mus_musculus	Proca1	ENSMUSG00000044122
rattus_norvegicus	Proca1	ENSRNOG00000023381
drosophila_melanogaster	GIIIspla2	FBGN0030013
drosophila_melanogaster	sPLA2	FBGN0033170
drosophila_melanogaster	CG30503	FBGN0050503
drosophila_melanogaster	CG42237	FBGN0250862

Paralogs (1): PLA2G3 (ENSG00000100078)

Protein

Protein identifiers

Protein PROCA1 — Q8NCQ7 (reviewed: Q8NCQ7)

Alternative names: Protein interacting with cyclin A1

All UniProt accessions (5): A0A804HIV4, Q8NCQ7, J3QQU2, J3QSA8, K7ESJ9

UniProt curated annotations — full annotation on UniProt →

Tissue specificity. High expressed in testis.

Similarity. Belongs to the PROCA1 family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q8NCQ7-1	1	yes
Q8NCQ7-2	2
Q8NCQ7-3	3

RefSeq proteins (7): NP_001291878, NP_001291880, NP_001291881, NP_001291882, NP_001353230, NP_001353232, NP_689678 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR016090	PLA2-like_dom	Domain
IPR036444	PLipase_A2_dom_sf	Homologous_superfamily

Pfam: PF05826

UniProt features (19 total): modified residue 6, compositionally biased region 5, splice variant 3, sequence variant 2, chain 1, region of interest 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NCQ7-F1	46.25	0.00

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 (6): 319, 355, 364, 276, 308, 318

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 65 (showing top): GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_UP, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, chr17q11, GOBP_ORGANIC_ACID_TRANSPORT, GOBP_ORGANIC_ANION_TRANSPORT, GOBP_SECRETION, GOBP_LIPID_METABOLIC_PROCESS, GOBP_MONOCARBOXYLIC_ACID_TRANSPORT, GOBP_LONG_CHAIN_FATTY_ACID_TRANSPORT, GOBP_LIPID_LOCALIZATION, GOBP_FATTY_ACID_TRANSPORT, GOMF_CYCLIN_BINDING, GOMF_HYDROLASE_ACTIVITY_ACTING_ON_ESTER_BONDS, GOMF_CARBOXYLIC_ESTER_HYDROLASE_ACTIVITY

GO Biological Process (2): phospholipid metabolic process (GO:0006644), arachidonate secretion (GO:0050482)

GO Molecular Function (3): A2-type glycerophospholipase activity (GO:0004623), cyclin binding (GO:0030332), protein binding (GO:0005515)

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
lipid metabolic process	1
organophosphate metabolic process	1
icosanoid secretion	1
arachidonate transport	1
glycerophospholipase activity	1
carboxylic ester hydrolase activity	1
protein binding	1
binding	1

Protein interactions and networks

STRING

1550 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PROCA1	TBC1D22B	Q9NU19	708
PROCA1	PPP2R2D	Q66LE6	651
PROCA1	GRPR	P30550	615
PROCA1	SPATA31F1	Q6ZU69	525
PROCA1	KLHDC9	Q8NEP7	495
PROCA1	SPEM3	A0A1B0GUW6	487
PROCA1	TMCO2	Q7Z6W1	466
PROCA1	CCDC187	A0A096LP49	464
PROCA1	GARIN3	Q8TC56	463
PROCA1	CCNA1	P78396	462
PROCA1	GPS2	Q13227	458
PROCA1	GRP	P07491	454
PROCA1	CCDC54	Q8NEL0	450
PROCA1	INCA1	Q0VD86	443
PROCA1	FAM209A	Q5JX71	429

IntAct

2 interactions, top by confidence:

A	B	Type	Score
PROCA1	VIM	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (6): PROCA1 (Two-hybrid), PROCA1 (Reconstituted Complex), PROCA1 (Affinity Capture-MS), PROCA1 (Synthetic Lethality), PROCA1 (Proximity Label-MS), PROCA1 (Affinity Capture-RNA)

ESM2 similar proteins: A0A1B0GR13, A3GGV1, A7E371, B0QZF7, B4NU50, B6KJ32, E9Q7F5, F4J6F6, K9N4Q4, O55777, P04605, P05909, P0C1C6, P0C1K0, P0C569, P11459, P24109, P32772, P46012, P46916, Q09221, Q32KL7, Q3UZB0, Q4R309, Q4V7B4, Q5BI31, Q5M948, Q5RCX3, Q66H17, Q6PB60, Q6R7G9, Q6UW49, Q71HP2, Q873B8, Q8JSZ3, Q8LAX3, Q8NCQ7, Q8QVM1, Q8WWF3, Q95LJ2

Diamond homologs: A7E371, B0QZF7, Q4V7B4, Q8NCQ7

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	52
Likely benign	11
Benign	3

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1526572	GRCh37/hg19 17p11.2-q11.2(chr17:21690653-28281232)	Pathogenic

SpliceAI

894 predictions. Top by Δscore:

Variant	Effect	Δscore
17:28704210:CAC:C	acceptor_gain	1.0000
17:28704845:T:C	acceptor_loss	1.0000
17:28704208:TGCAC:T	acceptor_gain	0.9900
17:28704209:GCAC:G	acceptor_gain	0.9900
17:28704210:CACC:C	acceptor_gain	0.9900
17:28704213:C:CC	acceptor_gain	0.9900
17:28704300:CACT:C	donor_loss	0.9900
17:28704301:ACTC:A	donor_loss	0.9900
17:28704303:T:TA	donor_loss	0.9900
17:28704304:C:CC	donor_loss	0.9900
17:28704305:A:AC	donor_gain	0.9900
17:28704305:ACCAG:A	donor_gain	0.9900
17:28704306:C:CC	donor_gain	0.9900
17:28704306:CCAGC:C	donor_gain	0.9900
17:28704703:CTCAC:C	donor_loss	0.9900
17:28704704:TCACC:T	donor_loss	0.9900
17:28704841:CAC:C	acceptor_gain	0.9900
17:28711564:TCTTA:T	donor_loss	0.9900
17:28711565:CTTA:C	donor_loss	0.9900
17:28711566:TTACC:T	donor_loss	0.9900
17:28711567:TA:T	donor_loss	0.9900
17:28711568:A:AC	donor_gain	0.9900
17:28711568:A:T	donor_loss	0.9900
17:28711569:C:CC	donor_gain	0.9900
17:28711569:CCG:C	donor_gain	0.9900
17:28711622:AGT:A	donor_gain	0.9900
17:28704211:AC:A	acceptor_gain	0.9800
17:28704212:CC:C	acceptor_gain	0.9800
17:28704301:A:AC	donor_gain	0.9800
17:28704302:C:CC	donor_gain	0.9800

AlphaMissense

2399 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:28711657:A:G	W2R	0.934
17:28711657:A:T	W2R	0.934
17:28711655:C:A	W2C	0.927
17:28711655:C:G	W2C	0.927
17:28704001:A:G	W218R	0.900
17:28704001:A:T	W218R	0.900
17:28703999:C:A	W218C	0.899
17:28703999:C:G	W218C	0.899
17:28704003:A:G	I217T	0.879
17:28711625:C:A	W12C	0.876
17:28711625:C:G	W12C	0.876
17:28703987:G:C	S222R	0.874
17:28703987:G:T	S222R	0.874
17:28703989:T:G	S222R	0.874
17:28704177:A:G	I159T	0.865
17:28704003:A:C	I217S	0.850
17:28704003:A:T	I217N	0.845
17:28704009:A:G	I215T	0.845
17:28711649:C:A	R4S	0.838
17:28711649:C:G	R4S	0.838
17:28704183:G:T	A157E	0.835
17:28706741:C:A	W37C	0.835
17:28706741:C:G	W37C	0.835
17:28704009:A:C	I215S	0.829
17:28711627:A:G	W12R	0.824
17:28711627:A:T	W12R	0.824
17:28704177:A:C	I159S	0.817
17:28704009:A:T	I215N	0.806
17:28704773:G:C	F82L	0.802
17:28704773:G:T	F82L	0.802

dbSNP variants (sampled 300 via entrez): RS1000544647 (17:28706106 C>T), RS1000789179 (17:28705097 C>T), RS1000847800 (17:28709494 A>G), RS1000879019 (17:28709877 G>A), RS1001158659 (17:28713224 C>A,T), RS1001365519 (17:28707031 G>A), RS1001818020 (17:28707240 T>C,G), RS1002209371 (17:28704086 T>C,G), RS1002440814 (17:28710450 T>C), RS1002950887 (17:28707514 TTCTC>T), RS1003109326 (17:28713346 T>C), RS1003214463 (17:28705373 C>G), RS1003410375 (17:28711516 GGGTCT>G), RS1004112387 (17:28711869 G>A,C,T), RS1004573377 (17:28703398 G>C)

Disease associations

OMIM: gene MIM:617376 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST90002395_246	Mean platelet volume	1.000000e-10
GCST90002405_331	Reticulocyte count	4.000000e-19

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007986	reticulocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

30 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression	6
glycidyl methacrylate	increases expression	1
ethyl-p-hydroxybenzoate	decreases expression	1
trichostatin A	decreases expression	1
butyraldehyde	decreases expression	1
benzo(e)pyrene	decreases methylation	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	increases expression	1
(+)-JQ1 compound	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Acetaminophen	decreases expression	1
Allergens	affects cotreatment, decreases expression, increases abundance	1
Vehicle Emissions	affects cotreatment, decreases expression, increases abundance	1
Benzo(a)pyrene	increases methylation	1
Cadmium	increases abundance, decreases expression	1
Estradiol	decreases expression	1
Methapyrilene	decreases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Toluene	decreases expression	1
Urethane	increases expression	1
Aflatoxin B1	increases methylation	1
Aflatoxin M1	increases expression	1
Cadmium Chloride	decreases expression, increases abundance	1
Particulate Matter	affects cotreatment, decreases expression, increases abundance	1

Clinical trials (associated diseases)

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