PGCKA1

Summary

PGCKA1 (PDCD10 and GCKIII kinases associated 1, HGNC:25618) is a protein-coding gene on chromosome 4p14, encoding PDCD10 and GCKIII kinases-associated protein 1 (Q8IY42). Acts as a tumor suppressor.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 4 total
• MANE Select transcript: NM_001104629

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25618
Approved symbol	PGCKA1
Name	PDCD10 and GCKIII kinases associated 1
Location	4p14
Locus type	gene with protein product
Status	Approved
Aliases	FLJ11017
Ensembl gene	ENSG00000154274
Ensembl biotype	protein_coding
Entrez	55286

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 13 protein_coding

ENST00000284437, ENST00000381980, ENST00000508175, ENST00000858659, ENST00000858660, ENST00000858661, ENST00000858662, ENST00000858663, ENST00000858664, ENST00000858665, ENST00000858666, ENST00000971264, ENST00000971265

RefSeq mRNA: 2 — MANE Select: NM_001104629 NM_001104629, NM_018302

CCDS: CCDS3442

Canonical transcript exons

ENST00000381980 — 4 exons

Exon	Start	End
ENSE00001157595	37588846	37588899
ENSE00001322320	37558027	37558076
ENSE00001490484	37453925	37454040
ENSE00003847729	37590088	37593510

Expression profiles

Bgee: expression breadth ubiquitous, 224 present calls, max score 95.55.

FANTOM5 (CAGE): breadth broad, TPM avg 1.8848 / max 116.1187, expressed in 430 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
47299	1.8848	430

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
amniotic fluid	UBERON:0000173	95.55	gold quality
pancreatic ductal cell	CL:0002079	95.03	gold quality
mucosa of sigmoid colon	UBERON:0004993	93.48	gold quality
colonic mucosa	UBERON:0000317	93.38	gold quality
parotid gland	UBERON:0001831	92.45	gold quality
oocyte	CL:0000023	92.32	gold quality
secondary oocyte	CL:0000655	91.28	gold quality
ileal mucosa	UBERON:0000331	89.70	gold quality
rectum	UBERON:0001052	89.10	gold quality
mucosa of transverse colon	UBERON:0004991	88.96	gold quality
islet of Langerhans	UBERON:0000006	87.94	gold quality
body of pancreas	UBERON:0001150	87.73	gold quality
right lobe of liver	UBERON:0001114	87.31	gold quality
jejunal mucosa	UBERON:0000399	87.21	gold quality
pancreas	UBERON:0001264	86.91	gold quality
liver	UBERON:0002107	86.89	gold quality
duodenum	UBERON:0002114	86.22	gold quality
nasal cavity epithelium	UBERON:0005384	85.87	gold quality
sperm	CL:0000019	84.71	gold quality
placenta	UBERON:0001987	84.43	gold quality
palpebral conjunctiva	UBERON:0001812	83.82	gold quality
saliva-secreting gland	UBERON:0001044	82.54	gold quality
male germ cell	CL:0000015	81.78	gold quality
nasal cavity mucosa	UBERON:0001826	81.32	gold quality
gall bladder	UBERON:0002110	80.80	gold quality
minor salivary gland	UBERON:0001830	80.40	gold quality
transverse colon	UBERON:0001157	79.76	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	79.67	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.57	gold quality
small intestine	UBERON:0002108	78.38	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	11.04

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

93 targeting PGCKA1, 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-4668-3P	100.00	68.74	2635
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-8087	99.90	69.55	1351
HSA-MIR-345-3P	99.89	70.23	1421
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-4495	99.82	72.08	3080
HSA-MIR-448	99.79	72.37	2103
HSA-MIR-5002-5P	99.76	70.84	1763
HSA-MIR-4802-3P	99.72	70.13	1273
HSA-MIR-670-5P	99.67	69.94	1565
HSA-MIR-5197-5P	99.64	69.08	1494

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Pgcka1	ENSMUSG00000060512
rattus_norvegicus	C14h4orf19	ENSRNOG00000002191

Protein

Protein identifiers

PDCD10 and GCKIII kinases-associated protein 1 — Q8IY42 (reviewed: Q8IY42)

All UniProt accessions (2): Q8IY42, D6RFF1

UniProt curated annotations — full annotation on UniProt →

Function. Acts as a tumor suppressor. Acts as a tumor suppressor for colorectal cancer cell proliferation by targeting KEAP1/USP17/ELK1/CDK6 axis.

Subunit / interactions. Interacts with KEAP1; this interaction prevents the ubiquitination of KEAP1 by TRIM25, thus protecting KEAP1 from degradation. Found in association with PDCD10 and members of the STE20 kinases, such as STK24, STK25 and STK26.

Subcellular location. Cell membrane.

Induction. Markedly down-regulated in colorectal cancer tissues.

RefSeq proteins (2): NP_001098099, NP_060772 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR031528	C4orf19	Family

Pfam: PF15770

UniProt features (13 total): modified residue 4, sequence variant 3, compositionally biased region 3, region of interest 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IY42-F1	54.55	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 (4): 30, 106, 238, 241

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 99 (showing top): FREAC2_01, HNF3ALPHA_Q6, DOANE_RESPONSE_TO_ANDROGEN_DN, GOBP_REGULATION_OF_CELL_CYCLE, HAN_SATB1_TARGETS_DN, MODULE_342, CHARAFE_BREAST_CANCER_LUMINAL_VS_MESENCHYMAL_UP, STEIN_ESRRA_TARGETS_UP, DODD_NASOPHARYNGEAL_CARCINOMA_DN, MEISSNER_BRAIN_HCP_WITH_H3K4ME3_AND_H3K27ME3, WAMUNYOKOLI_OVARIAN_CANCER_LMP_UP, BRUINS_UVC_RESPONSE_VIA_TP53_GROUP_A, ONKEN_UVEAL_MELANOMA_DN, LTE2_UP.V1_UP, RAF_UP.V1_UP

GO Biological Process (1): regulation of cell cycle (GO:0051726)

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

GO Cellular Component (3): plasma membrane (GO:0005886), cell periphery (GO:0071944), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
cell cycle	1
regulation of cellular process	1
binding	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

408 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PGCKA1	KIAA0930	Q6ICG6	447
PGCKA1	FAM221A	A4D161	447
PGCKA1	FAM219B	Q5XKK7	432
PGCKA1	MCRIP2	Q9BUT9	419
PGCKA1	C3orf52	Q5BVD1	417
PGCKA1	FAM120C	Q9NX05	402
PGCKA1	DISP2	A7MBM2	396
PGCKA1	METTL26	Q96S19	394
PGCKA1	CCDC148	Q8NFR7	391
PGCKA1	SOWAHB	A6NEL2	371
PGCKA1	KATNBL1	Q9H079	370
PGCKA1	CA8	P35219	360
PGCKA1	ZNF256	Q9Y2P7	356
PGCKA1	MRPS24	P82668	348
PGCKA1	ZNF814	B7Z6K7	348
PGCKA1	ZNF461	Q8TAF7	348

IntAct

22 interactions, top by confidence:

A	B	Type	Score
PDCD10	PGCKA1	psi-mi:“MI:0915”(physical association)	0.870
PGCKA1	PDCD10	psi-mi:“MI:0915”(physical association)	0.870
PGCKA1	EIF3E	psi-mi:“MI:0915”(physical association)	0.670
EIF3E	PGCKA1	psi-mi:“MI:0915”(physical association)	0.670
PGCKA1	ABITRAM	psi-mi:“MI:0915”(physical association)	0.560
PGCKA1	CEP19	psi-mi:“MI:0915”(physical association)	0.560
PGCKA1	STK25	psi-mi:“MI:0914”(association)	0.530
NFKB1	NFKB1	psi-mi:“MI:0914”(association)	0.350
PDCD10	PGCKA1	psi-mi:“MI:0915”(physical association)	0.000
ABITRAM	PGCKA1	psi-mi:“MI:0915”(physical association)	0.000
CEP19	PGCKA1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (23): C4orf19 (Two-hybrid), C4orf19 (Two-hybrid), EEF1A2 (Affinity Capture-MS), STK25 (Affinity Capture-MS), STK26 (Affinity Capture-MS), STK24 (Affinity Capture-MS), PDCD10 (Affinity Capture-MS), STK24 (Affinity Capture-MS), PDCD10 (Affinity Capture-MS), STK25 (Affinity Capture-MS), STK26 (Affinity Capture-MS), EEF1A2 (Affinity Capture-MS), C4orf19 (Affinity Capture-RNA), C4orf19 (Two-hybrid), C4orf19 (Two-hybrid)

ESM2 similar proteins: A0A1B0GUA9, A0JNH1, A1L170, A2TJV2, A6H7B4, A6NFA0, A6NGY1, A6X8Z5, A7YY35, B2RQL2, D3Z1D3, M0RD54, P43359, Q05860, Q0VF49, Q1RMX6, Q1RN00, Q2M1Z3, Q32LI3, Q3URK1, Q5EBJ4, Q5M831, Q5RJL0, Q62100, Q640N3, Q64256, Q642A3, Q66H53, Q66LM6, Q68D20, Q68DA7, Q68US1, Q6AXN6, Q6AYA8, Q6IR42, Q711Q0, Q80VY2, Q86UF4, Q8IY42, Q8TDR4

Diamond homologs: Q6AYA8, Q8IY42, Q99K99

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

1644 predictions. Top by Δscore:

Variant	Effect	Δscore
4:37516187:G:GT	donor_gain	1.0000
4:37558076:GGTAA:G	donor_loss	1.0000
4:37590083:T:A	acceptor_gain	1.0000
4:37613216:C:A	donor_gain	1.0000
4:37454036:CCCAG:C	donor_loss	0.9900
4:37454037:CCAGG:C	donor_loss	0.9900
4:37454038:CAGGT:C	donor_loss	0.9900
4:37454040:GGTAG:G	donor_loss	0.9900
4:37454041:GT:G	donor_loss	0.9900
4:37454042:T:G	donor_loss	0.9900
4:37588840:TTCCA:T	acceptor_loss	0.9900
4:37588841:TCCAG:T	acceptor_loss	0.9900
4:37588842:CCAGG:C	acceptor_loss	0.9900
4:37588843:CA:C	acceptor_loss	0.9900
4:37588844:A:C	acceptor_loss	0.9900
4:37588844:AGGT:A	acceptor_gain	0.9900
4:37588845:G:GT	acceptor_loss	0.9900
4:37588845:GGTG:G	acceptor_gain	0.9900
4:37590086:A:AG	acceptor_gain	0.9900
4:37590087:G:GG	acceptor_gain	0.9900
4:37593476:CA:C	acceptor_gain	0.9900
4:37613213:ATTC:A	donor_gain	0.9900
4:37558025:A:AG	acceptor_gain	0.9800
4:37558026:G:GG	acceptor_gain	0.9800
4:37588119:A:T	donor_gain	0.9800
4:37590087:GCT:G	acceptor_gain	0.9800
4:37590087:GCTAT:G	acceptor_gain	0.9800
4:37590103:A:AG	acceptor_gain	0.9800
4:37590104:G:GG	acceptor_gain	0.9800
4:37593475:CCA:C	acceptor_gain	0.9800

AlphaMissense

2091 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:37590957:T:C	L301S	0.993
4:37590962:G:C	A303P	0.990
4:37590965:G:C	A304P	0.987
4:37590944:G:C	A297P	0.986
4:37590953:G:C	A300P	0.985
4:37590950:G:C	A299P	0.982
4:37590948:T:A	L298H	0.980
4:37590948:T:C	L298P	0.976
4:37588874:T:C	C3R	0.972
4:37590971:G:C	A306P	0.972
4:37588880:T:C	C5R	0.969
4:37590938:G:C	A295P	0.969
4:37588883:T:C	C6R	0.968
4:37588893:T:C	I9T	0.966
4:37590966:C:A	A304D	0.966
4:37588883:T:A	C6S	0.961
4:37588884:G:A	C6Y	0.961
4:37588884:G:C	C6S	0.961
4:37588871:G:A	G2R	0.960
4:37588871:G:C	G2R	0.960
4:37588893:T:A	I9K	0.958
4:37588874:T:A	C3S	0.957
4:37588875:G:C	C3S	0.957
4:37588885:T:G	C6W	0.954
4:37588880:T:A	C5S	0.949
4:37588881:G:C	C5S	0.949
4:37590954:C:A	A300D	0.949
4:37588887:A:T	K7I	0.946
4:37588872:G:A	G2E	0.944
4:37588888:A:C	K7N	0.939

dbSNP variants (sampled 300 via entrez): RS1000026101 (4:37559641 C>G), RS1000077403 (4:37484266 A>G), RS1000088711 (4:37454071 A>C), RS1000128089 (4:37568201 C>T), RS1000168069 (4:37463038 C>G,T), RS1000264155 (4:37511647 A>C), RS1000268916 (4:37518295 G>A), RS1000280783 (4:37586621 T>C), RS1000289182 (4:37545794 C>A), RS1000295183 (4:37580003 T>C), RS10003039 (4:37560793 T>A,C,G), RS1000316313 (4:37504114 A>C,G), RS1000326592 (4:37460556 T>C), RS1000327181 (4:37466408 A>G), RS1000342819 (4:37541422 C>T)

Disease associations

OMIM: gene `` | 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
GCST000783_1	Multiple sclerosis–Brain Glutamate Levels	7.000000e-06
GCST008764_10	Perceived intensity of neohesperidin dihydrochalcone	6.000000e-06
GCST009391_2089	Metabolite levels	3.000000e-06
GCST009391_460	Metabolite levels	4.000000e-06
GCST009391_98	Metabolite levels	6.000000e-06
GCST010303_33	Nevus count or cutaneous melanoma	1.000000e-08

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0010373	phosphatidylcholine 32:1 measurement
EFO:0010522	phosphoenolpyruvic acid measurement
EFO:0010473	cyclic adenosine monophosphate measurement
EFO:0004632	nevus count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	7
entinostat	increases expression, affects cotreatment	2
(+)-JQ1 compound	decreases expression	2
Acetaminophen	decreases expression	2
Benzo(a)pyrene	affects methylation	2
Cyclosporine	decreases expression	2
Aflatoxin B1	decreases methylation, increases methylation	2
aristolochic acid I	decreases expression	1
triphenyl phosphate	affects expression	1
terbufos	increases methylation	1
trichostatin A	increases expression	1
aflatoxin B2	decreases methylation, increases methylation	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
mercuric bromide	increases expression	1
di-n-butylphosphoric acid	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
bisphenol S	affects cotreatment, increases methylation	1
theaflavin-3,3’-digallate	affects expression	1
Sunitinib	decreases expression	1
Zoledronic Acid	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Panobinostat	affects cotreatment, increases expression	1
Caffeine	decreases phosphorylation	1
Diethylhexyl Phthalate	increases expression	1
Fonofos	increases methylation	1
Estradiol	increases expression	1
Etoposide	affects response to substance	1
Lead	increases expression	1

Clinical trials (associated diseases)

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