PCNX3

Summary

PCNX3 (pecanex 3, HGNC:18760) is a protein-coding gene on chromosome 11q13.1, encoding Pecanex-like protein 3 (Q9H6A9). It is a selective cancer dependency (DepMap: 41.3% of cell lines).

Predicted to be located in membrane.

Source: NCBI Gene 399909 — RefSeq curated summary.

At a glance

• GWAS associations: 27
• Clinical variants (ClinVar): 62 total — 1 likely-pathogenic
• Cancer dependency (DepMap): dependent in 41.3% of screened cell lines
• MANE Select transcript: NM_032223

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18760
Approved symbol	PCNX3
Name	pecanex 3
Location	11q13.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ22427
Ensembl gene	ENSG00000197136
Ensembl biotype	protein_coding
OMIM	617657
Entrez	399909

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 10 protein_coding, 2 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000355703, ENST00000439247, ENST00000530174, ENST00000531045, ENST00000531280, ENST00000913353, ENST00000913354, ENST00000913355, ENST00000913356, ENST00000913357, ENST00000913358, ENST00000913359, ENST00000913360, ENST00000913361

RefSeq mRNA: 1 — MANE Select: NM_032223 NM_032223

CCDS: CCDS44650

Canonical transcript exons

ENST00000355703 — 35 exons

Exon	Start	End
ENSE00001191523	65624471	65624581
ENSE00001191534	65624195	65624366
ENSE00001191539	65623929	65623961
ENSE00001191545	65623491	65623644
ENSE00001191554	65622245	65622366
ENSE00001191568	65620339	65620429
ENSE00001191577	65619754	65619932
ENSE00001191584	65619537	65619660
ENSE00001191593	65617940	65619067
ENSE00001191600	65617611	65617706
ENSE00001191606	65617470	65617509
ENSE00001191612	65617250	65617349
ENSE00001406209	65626904	65627048
ENSE00001426083	65636766	65637439
ENSE00001534698	65616824	65617011
ENSE00001534700	65615776	65616464
ENSE00001550980	65625904	65626054
ENSE00001559150	65625171	65625280
ENSE00001561315	65624925	65625016
ENSE00003466888	65620831	65620966
ENSE00003473643	65625652	65625744
ENSE00003513089	65634538	65634641
ENSE00003522614	65625405	65625510
ENSE00003532624	65627405	65627582
ENSE00003549214	65629520	65629735
ENSE00003553196	65636391	65636689
ENSE00003559951	65628595	65628703
ENSE00003562093	65635529	65635803
ENSE00003576512	65634973	65635120
ENSE00003605883	65634126	65634356
ENSE00003612982	65635218	65635448
ENSE00003640012	65628819	65628948
ENSE00003643828	65636174	65636307
ENSE00003667590	65629357	65629415
ENSE00003679736	65630351	65630604

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 93.93.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 38.9699 / max 250.1828, expressed in 1819 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
115182	38.5045	1819
115181	0.3569	173
115183	0.1085	38

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	93.93	gold quality
stromal cell of endometrium	CL:0002255	91.86	gold quality
mucosa of transverse colon	UBERON:0004991	91.68	gold quality
spleen	UBERON:0002106	91.56	gold quality
blood	UBERON:0000178	91.03	gold quality
sural nerve	UBERON:0015488	90.68	gold quality
small intestine Peyer’s patch	UBERON:0003454	90.47	gold quality
adenohypophysis	UBERON:0002196	90.14	gold quality
pituitary gland	UBERON:0000007	90.12	gold quality
metanephros cortex	UBERON:0010533	90.05	gold quality
apex of heart	UBERON:0002098	89.91	gold quality
right hemisphere of cerebellum	UBERON:0014890	89.86	gold quality
body of stomach	UBERON:0001161	89.84	gold quality
right lobe of thyroid gland	UBERON:0001119	89.82	gold quality
left testis	UBERON:0004533	89.76	gold quality
transverse colon	UBERON:0001157	89.69	gold quality
small intestine	UBERON:0002108	89.49	gold quality
right testis	UBERON:0004534	89.44	gold quality
lower esophagus mucosa	UBERON:0035834	89.42	gold quality
left lobe of thyroid gland	UBERON:0001120	89.17	gold quality
upper lobe of left lung	UBERON:0008952	89.06	gold quality
cerebellum	UBERON:0002037	89.04	gold quality
cerebellar hemisphere	UBERON:0002245	89.02	gold quality
right uterine tube	UBERON:0001302	88.99	gold quality
cerebellar cortex	UBERON:0002129	88.98	gold quality
fundus of stomach	UBERON:0001160	88.85	gold quality
esophagus mucosa	UBERON:0002469	88.83	gold quality
skin of leg	UBERON:0001511	88.71	gold quality
left uterine tube	UBERON:0001303	88.70	gold quality
thyroid gland	UBERON:0002046	88.69	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.63
E-MTAB-6142	no	51.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

16 targeting PCNX3, 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-3613-3P	100.00	76.36	7965
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-4255	99.72	67.70	1541
HSA-MIR-4530	99.69	66.47	1509
HSA-MIR-4761-5P	99.51	66.69	804
HSA-MIR-4641	99.28	66.64	744
HSA-MIR-3190-5P	98.87	64.89	1345
HSA-MIR-4277	98.34	67.17	1323
HSA-MIR-338-3P	98.14	67.38	1137
HSA-MIR-4257	97.86	68.05	1190
HSA-MIR-1972	97.67	67.38	1172
HSA-MIR-8057	97.64	66.54	897
HSA-MIR-4690-3P	97.02	64.72	981
HSA-MIR-5685	97.02	64.34	1004
HSA-MIR-1296-5P	93.94	67.71	305

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 41.3% of screened cell lines.

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	pcnx3	ENSDARG00000019501
mus_musculus	Pcnx3	ENSMUSG00000054874
rattus_norvegicus	Pcnx3	ENSRNOG00000020742
drosophila_melanogaster	pcx	FBGN0003048
caenorhabditis_elegans	B0511.12	WBGENE00015237

Paralogs (3): PCNX1 (ENSG00000100731), PCNX4 (ENSG00000126773), PCNX2 (ENSG00000135749)

Protein

Protein identifiers

Pecanex-like protein 3 — Q9H6A9 (reviewed: Q9H6A9)

Alternative names: Pecanex homolog protein 3

All UniProt accessions (1): Q9H6A9

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Membrane.

Similarity. Belongs to the pecanex family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9H6A9-1	1	yes
Q9H6A9-2	2
Q9H6A9-3	3

RefSeq proteins (1): NP_115599* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007735	Pecanex_C	Domain
IPR039797	Pecanex	Family

Pfam: PF05041

UniProt features (49 total): transmembrane region 13, modified residue 10, compositionally biased region 9, region of interest 5, sequence variant 5, splice variant 4, glycosylation site 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H6A9-F1	61.06	0.15

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 (10): 127, 129, 370, 392, 431, 505, 1025, 1697, 1909, 1955

Glycosylation sites (2): 319, 1770

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 77 (showing top): GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, chr11q13, SCHAEFFER_PROSTATE_DEVELOPMENT_6HR_DN, MILI_PSEUDOPODIA_CHEMOTAXIS_DN, MARSON_BOUND_BY_FOXP3_UNSTIMULATED, GSE13522_WT_VS_IFNG_KO_SKIN_DN, LU_EZH2_TARGETS_UP, E2F3_UP.V1_DN, CBX5_TARGET_GENES, CEBPZ_TARGET_GENES, DLX4_TARGET_GENES, E2F2_TARGET_GENES, FEV_TARGET_GENES, FOXG1_TARGET_GENES

GO Biological Process (0):

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

GO Cellular Component (1): membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

922 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PCNX3	MIF4GD	A9UHW6	505
PCNX3	MPHOSPH9	Q99550	454
PCNX3	TNFAIP1	Q13829	443
PCNX3	STARD9	Q9P2P6	440
PCNX3	FAM89B	Q8N5H3	437
PCNX3	KIF22	Q14807	433
PCNX3	RSBN1L	Q6PCB5	401
PCNX3	KIF14	Q15058	400
PCNX3	SIPA1	Q96FS4	386
PCNX3	RNASEH2C	Q8TDP1	382
PCNX3	KIFC3	Q9BVG8	376
PCNX3	C12orf43	Q96C57	367
PCNX3	TMIGD1	Q6UXZ0	364
PCNX3	SNAPC1	Q16533	362
PCNX3	TASOR2	Q5VWN6	349

IntAct

69 interactions, top by confidence:

A	B	Type	Score
ENTREP1	WWP2	psi-mi:“MI:0914”(association)	0.850
PCNX3	ENTREP1	psi-mi:“MI:0915”(physical association)	0.550
YIPF3	TMEM120B	psi-mi:“MI:0914”(association)	0.530
LRRTM1	UPK3BL1	psi-mi:“MI:0914”(association)	0.530
ZNRF4	UPK3BL1	psi-mi:“MI:0914”(association)	0.530
TMEM31	PSMD11	psi-mi:“MI:0914”(association)	0.530
TM2D2	TMEM97	psi-mi:“MI:0914”(association)	0.530
SLC30A2	ESYT2	psi-mi:“MI:0914”(association)	0.530
TCIRG1	AP3D1	psi-mi:“MI:0914”(association)	0.530
PCNX3	USP20	psi-mi:“MI:0915”(physical association)	0.500
Cdh1	ARVCF	psi-mi:“MI:0914”(association)	0.350
LIMA1	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
Coro1c	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
KCNA2	TMEM129	psi-mi:“MI:0914”(association)	0.350
ATP2B2	ESYT2	psi-mi:“MI:0914”(association)	0.350
TTMP	TMEM223	psi-mi:“MI:0914”(association)	0.350
TTYH1	TMEM223	psi-mi:“MI:0914”(association)	0.350
KCNK18	TMEM223	psi-mi:“MI:0914”(association)	0.350
HCST	TMEM120B	psi-mi:“MI:0914”(association)	0.350
ZDHHC12	NBAS	psi-mi:“MI:0914”(association)	0.350
CLRN2	FAM234B	psi-mi:“MI:0914”(association)	0.350
RXFP1	UPK3BL1	psi-mi:“MI:0914”(association)	0.350
KCNE3	PIK3R2	psi-mi:“MI:0914”(association)	0.350
MARCHF4	C2CD2L	psi-mi:“MI:0914”(association)	0.350
NAT8B	COX7A2L	psi-mi:“MI:0914”(association)	0.350
MS4A15	ABCD4	psi-mi:“MI:0914”(association)	0.350
SLC17A2	ABCD4	psi-mi:“MI:0914”(association)	0.350

BioGRID (97): PCNXL3 (Affinity Capture-MS), PCNXL3 (Affinity Capture-MS), PCNXL3 (Affinity Capture-MS), PCNXL3 (Affinity Capture-MS), PCNXL3 (Affinity Capture-MS), PCNXL3 (Affinity Capture-MS), PCNXL3 (Affinity Capture-MS), PCNXL3 (Affinity Capture-MS), PCNXL3 (Affinity Capture-MS), PCNXL3 (Affinity Capture-MS), PCNXL3 (Affinity Capture-MS), PCNXL3 (Affinity Capture-MS), PCNXL3 (Affinity Capture-MS), PCNXL3 (Affinity Capture-MS), PCNXL3 (Affinity Capture-MS)

ESM2 similar proteins: A0A1B0GTI1, A2BIL8, A5PKK9, C5DY61, E2QSX5, E7F555, O35147, O43151, P11805, P19416, P24940, P27579, Q06616, Q17QE3, Q1LZE2, Q1RMQ5, Q1T763, Q28CW2, Q2HR82, Q2TBN9, Q3B8E9, Q3ZBS1, Q567C6, Q5RDK8, Q62417, Q68FW2, Q6AY26, Q6DFB0, Q6P6I6, Q6PKN7, Q80U49, Q86YL5, Q8C3W1, Q8QVM1, Q8VEB3, Q8VI59, Q96FT9, Q96GV9, Q96GY3, Q99618

Diamond homologs: A2RUW7, A6NKB5, E9PSU6, P18490, Q3UVY5, Q5DU28, Q5HZQ9, Q63HM2, Q8VI59, Q96RV3, Q98UF7, Q9H6A9, Q9QYC1

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	14
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
982224	NM_032223.4(PCNX3):c.229_230del (p.Val77fs)	Likely pathogenic

SpliceAI

6156 predictions. Top by Δscore:

Variant	Effect	Δscore
11:65616977:G:GT	donor_gain	1.0000
11:65616992:G:GT	donor_gain	1.0000
11:65617009:CAGGT:C	donor_loss	1.0000
11:65617010:AGGTG:A	donor_gain	1.0000
11:65617012:G:T	donor_loss	1.0000
11:65617013:T:A	donor_loss	1.0000
11:65617244:C:CA	acceptor_gain	1.0000
11:65617246:CCAGG:C	acceptor_loss	1.0000
11:65617247:CAGGG:C	acceptor_loss	1.0000
11:65617248:A:AG	acceptor_gain	1.0000
11:65617248:AG:A	acceptor_gain	1.0000
11:65617249:G:GG	acceptor_gain	1.0000
11:65617249:GG:G	acceptor_gain	1.0000
11:65617345:TCTCG:T	donor_loss	1.0000
11:65617350:G:GG	donor_gain	1.0000
11:65617350:GT:G	donor_loss	1.0000
11:65617351:T:G	donor_loss	1.0000
11:65617352:GA:G	donor_loss	1.0000
11:65617450:AT:A	acceptor_gain	1.0000
11:65617451:T:G	acceptor_gain	1.0000
11:65617697:G:GT	donor_gain	1.0000
11:65617702:ACTGA:A	donor_gain	1.0000
11:65617703:C:CG	donor_gain	1.0000
11:65617703:C:G	donor_gain	1.0000
11:65617703:CTGAG:C	donor_loss	1.0000
11:65617704:TGA:T	donor_gain	1.0000
11:65617704:TGAG:T	donor_loss	1.0000
11:65617705:GA:G	donor_gain	1.0000
11:65617705:GAG:G	donor_gain	1.0000
11:65617705:GAGTG:G	donor_loss	1.0000

AlphaMissense

13102 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:65616426:T:A	W39R	1.000
11:65616426:T:C	W39R	1.000
11:65616912:T:C	L81P	1.000
11:65619911:C:G	H663D	1.000
11:65619917:T:C	F665L	1.000
11:65619918:T:C	F665S	1.000
11:65619919:C:A	F665L	1.000
11:65619919:C:G	F665L	1.000
11:65620353:T:G	Y675D	1.000
11:65620359:T:C	F677L	1.000
11:65620360:T:C	F677S	1.000
11:65620361:T:A	F677L	1.000
11:65620361:T:G	F677L	1.000
11:65623552:G:C	G807R	1.000
11:65623619:C:A	A829D	1.000
11:65624203:C:A	N851K	1.000
11:65624203:C:G	N851K	1.000
11:65624219:A:C	S857R	1.000
11:65624221:C:A	S857R	1.000
11:65624221:C:G	S857R	1.000
11:65625721:A:C	S1069R	1.000
11:65625723:C:A	S1069R	1.000
11:65625723:C:G	S1069R	1.000
11:65628646:T:A	W1252R	1.000
11:65628646:T:C	W1252R	1.000
11:65628658:T:A	W1256R	1.000
11:65628658:T:C	W1256R	1.000
11:65628660:G:C	W1256C	1.000
11:65628660:G:T	W1256C	1.000
11:65628661:G:C	G1257R	1.000

dbSNP variants (sampled 300 via entrez): RS1000016935 (11:65625718 G>A), RS1000204726 (11:65620146 C>A,G,T), RS1000264077 (11:65615806 G>A), RS1000302448 (11:65630709 C>G), RS1000439950 (11:65615942 G>A,T), RS1000507781 (11:65619158 G>A,C), RS1000538920 (11:65619277 C>G,T), RS1000580499 (11:65620015 C>A,G,T), RS1000844285 (11:65624859 C>A,G,T), RS1000914446 (11:65632011 A>G), RS1000923582 (11:65628268 G>A), RS1000923733 (11:65626521 C>T), RS1001051301 (11:65614506 G>A,C), RS1001538281 (11:65633885 C>T), RS1001547843 (11:65636807 C>T)

Disease associations

OMIM: gene MIM:617657 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (1): Moyamoya angiopathy (Orphanet:477768)

HPO phenotypes

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

GWAS associations

27 associations (top):

Study	Trait	p-value
GCST002481_8	Acne (severe)	3.000000e-11
GCST003252_19	Systemic lupus erythematosus	7.000000e-06
GCST005195_134	Coronary artery disease	2.000000e-11
GCST005196_50	Coronary artery disease	3.000000e-11
GCST005196_51	Coronary artery disease	4.000000e-08
GCST006166_10	Diastolic blood pressure x alcohol consumption interaction (2df test)	2.000000e-16
GCST006167_9	Mean arterial pressure x alcohol consumption interaction (2df test)	8.000000e-09
GCST006169_18	Diastolic blood pressure x alcohol consumption (light vs heavy) interaction (2df test)	1.000000e-10
GCST006170_39	Systolic blood pressure x alcohol consumption (light vs heavy) interaction (2df test)	2.000000e-10
GCST006172_2	Mean arterial pressure x alcohol consumption (light vs heavy) interaction (2df test)	3.000000e-11
GCST006231_49	Mean arterial pressure	4.000000e-11
GCST006288_182	Heel bone mineral density	2.000000e-06
GCST006288_40	Heel bone mineral density	3.000000e-16
GCST006288_733	Heel bone mineral density	7.000000e-10
GCST006434_31	Systolic blood pressure x alcohol consumption interaction (2df test)	4.000000e-17
GCST006434_9	Systolic blood pressure x alcohol consumption interaction (2df test)	1.000000e-20
GCST006979_401	Heel bone mineral density	9.000000e-17
GCST007483_10	Waist-to-hip ratio adjusted for BMI (additive genetic model)	2.000000e-08
GCST007487_17	Waist-to-hip ratio adjusted for BMI (additive genetic model)	3.000000e-08
GCST007500_20	Waist-to-hip ratio adjusted for BMI (additive genetic model)	9.000000e-06
GCST007876_2	Estimated glomerular filtration rate	2.000000e-20
GCST007918_16	Serum uric acid levels	2.000000e-07
GCST010002_240	Refractive error	3.000000e-11
GCST010320_69	PR interval	3.000000e-07
GCST010321_67	PR interval	4.000000e-08
GCST010479_20	Coronary artery disease	2.000000e-08
GCST90002395_89	Mean platelet volume	1.000000e-39

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0004329	alcohol drinking
EFO:0006336	diastolic blood pressure
EFO:0006340	mean arterial pressure
EFO:0006335	systolic blood pressure
EFO:0009270	heel bone mineral density
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0004761	uric acid measurement
EFO:0004462	PR interval

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

24 total (human), top 24 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases abundance, increases expression	4
Air Pollutants	affects expression, increases abundance, increases expression	2
Smoke	decreases expression, increases abundance, increases expression	2
FR900359	affects phosphorylation	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
kojic acid	decreases expression	1
mono-(2-ethylhexyl)phthalate	decreases expression	1
aflatoxin B2	increases methylation	1
CGP 52608	affects binding, increases reaction	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Sunitinib	increases expression	1
Acetaminophen	increases expression	1
Arsenic	decreases expression, increases abundance	1
Benzo(a)pyrene	affects methylation	1
Caffeine	decreases phosphorylation	1
Doxorubicin	decreases expression	1
Ozone	increases abundance, affects expression	1
Quercetin	increases expression	1
Selenomethionine	affects expression	1
Valproic Acid	increases methylation	1
Cyclosporine	decreases expression	1
Aflatoxin B1	increases methylation	1
Acrylamide	decreases expression	1

Clinical trials (associated diseases)

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