PCNX2

Summary

PCNX2 (pecanex 2, HGNC:8736) is a protein-coding gene on chromosome 1q42.2, encoding Pecanex-like protein 2 (A6NKB5). May play a role in tumorigenesis of colorectal carcinomas with high microsatellite instability (MSI-H).

This gene contains coding mononucleotide repeats that are associated with tumors of high mcrosatellite instability (MSI-H). Defects in this gene are involved in the tumorigenesis of MSI-H colorectal carcinomas.

Source: NCBI Gene 80003 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 86 total
• MANE Select transcript: NM_014801

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8736
Approved symbol	PCNX2
Name	pecanex 2
Location	1q42.2
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0435, FLJ11383
Ensembl gene	ENSG00000135749
Ensembl biotype	protein_coding
OMIM	617656
Entrez	80003

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 7 retained_intron, 6 protein_coding, 5 nonsense_mediated_decay, 5 protein_coding_CDS_not_defined

ENST00000258229, ENST00000324142, ENST00000344698, ENST00000429988, ENST00000462233, ENST00000462762, ENST00000467336, ENST00000475463, ENST00000484041, ENST00000484347, ENST00000486012, ENST00000488780, ENST00000490102, ENST00000496510, ENST00000496675, ENST00000497623, ENST00000498302, ENST00000517808, ENST00000518351, ENST00000519530, ENST00000520463, ENST00000522067, ENST00000912675

RefSeq mRNA: 1 — MANE Select: NM_014801 NM_014801

CCDS: CCDS44335

Canonical transcript exons

ENST00000258229 — 34 exons

Exon	Start	End
ENSE00000921423	233054268	233054483
ENSE00001380374	233025146	233025399
ENSE00001442199	233057232	233057290
ENSE00001442200	233090061	233090190
ENSE00003463113	232983435	232984477
ENSE00003467016	233261285	233261321
ENSE00003482931	233252354	233252499
ENSE00003491179	233262045	233262165
ENSE00003494683	233262958	233263163
ENSE00003496680	233250739	233250832
ENSE00003497137	232998251	232998438
ENSE00003498010	233139714	233139855
ENSE00003500072	233000305	233000535
ENSE00003512529	232986092	232986540
ENSE00003527656	233135013	233135190
ENSE00003542886	232999105	232999379
ENSE00003551739	233161271	233161363
ENSE00003554184	233095755	233095863
ENSE00003554572	233179066	233179175
ENSE00003565913	233208518	233208689
ENSE00003576559	233252641	233252788
ENSE00003600093	233198939	233199030
ENSE00003610001	233016921	233017154
ENSE00003616143	233217899	233217931
ENSE00003625542	233227226	233227371
ENSE00003627298	233258028	233259344
ENSE00003644324	233001537	233001681
ENSE00003659735	233236845	233236980
ENSE00003676554	233177802	233177898
ENSE00003687106	233200154	233200264
ENSE00003687654	233160283	233160433
ENSE00003688292	233014665	233014777
ENSE00003691340	233295326	233295725
ENSE00003728058	233218031	233218184

Expression profiles

Bgee: expression breadth ubiquitous, 266 present calls, max score 96.36.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.6145 / max 163.4476, expressed in 1535 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
18018	11.6145	1535

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	96.36	gold quality
middle temporal gyrus	UBERON:0002771	95.66	gold quality
cerebellar vermis	UBERON:0004720	94.26	gold quality
primary visual cortex	UBERON:0002436	93.94	gold quality
cerebellar cortex	UBERON:0002129	93.17	gold quality
cerebellar hemisphere	UBERON:0002245	93.15	gold quality
Brodmann (1909) area 23	UBERON:0013554	93.10	gold quality
cerebellum	UBERON:0002037	93.06	gold quality
right hemisphere of cerebellum	UBERON:0014890	93.06	gold quality
endothelial cell	CL:0000115	92.73	gold quality
postcentral gyrus	UBERON:0002581	91.71	gold quality
occipital lobe	UBERON:0002021	91.48	gold quality
lateral nuclear group of thalamus	UBERON:0002736	91.37	gold quality
parietal lobe	UBERON:0001872	91.33	gold quality
superior frontal gyrus	UBERON:0002661	90.78	gold quality
right frontal lobe	UBERON:0002810	90.30	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	89.97	gold quality
Brodmann (1909) area 9	UBERON:0013540	89.58	gold quality
entorhinal cortex	UBERON:0002728	89.54	gold quality
frontal cortex	UBERON:0001870	89.46	gold quality
cortical plate	UBERON:0005343	89.33	gold quality
frontal pole	UBERON:0002795	89.27	gold quality
neocortex	UBERON:0001950	89.19	gold quality
prefrontal cortex	UBERON:0000451	89.17	gold quality
pituitary gland	UBERON:0000007	89.03	gold quality
cerebral cortex	UBERON:0000956	88.99	gold quality
adenohypophysis	UBERON:0002196	88.43	gold quality
paraflocculus	UBERON:0005351	88.43	gold quality
telencephalon	UBERON:0001893	88.03	gold quality
Ammon’s horn	UBERON:0001954	87.91	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.25

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

8 targeting PCNX2, 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-3692-3P	99.98	70.27	2139
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-4324	99.04	70.14	1569
HSA-MIR-4277	98.34	67.17	1323
HSA-MIR-450A-2-3P	97.91	67.56	1459
HSA-MIR-3665	97.73	65.08	975
HSA-MIR-939-5P	97.10	65.80	1579
HSA-MIR-1343-5P	96.48	66.06	1506

Literature-anchored findings (GeneRIF, showing 2)

• Identification of MARCKS, FLJ11383 and TAF1B as putative novel target genes in colorectal carcinomas with microsatellite instability. (PMID:12140758)
• Genetic polymorphisms in the PCNXL2 gene are risk factors for thyroid cancer in the Chinese population. (PMID:34747634)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	pcnx2	ENSDARG00000055698
mus_musculus	Pcnx2	ENSMUSG00000060212
rattus_norvegicus	Pcnx2	ENSRNOG00000028580
drosophila_melanogaster	pcx	FBGN0003048
caenorhabditis_elegans	B0511.12	WBGENE00015237

Paralogs (3): PCNX1 (ENSG00000100731), PCNX4 (ENSG00000126773), PCNX3 (ENSG00000197136)

Protein

Protein identifiers

Pecanex-like protein 2 — A6NKB5 (reviewed: A6NKB5)

Alternative names: Pecanex homolog protein 2

All UniProt accessions (9): A6NKB5, E7EVZ6, H0YAR6, H0YAV6, H0YB15, H0YB30, H0YBD1, H0YBD6, H0YBF4

UniProt curated annotations — full annotation on UniProt →

Function. May play a role in tumorigenesis of colorectal carcinomas with high microsatellite instability (MSI-H).

Subcellular location. Membrane.

Miscellaneous. PCNXL2 is characterized by high mutational frequencies and biallelic mutations in MSI-H colorectal tumors, and is thus likely to be a target gene in these tumors.

Similarity. Belongs to the pecanex family.

Isoforms (5)

UniProt ID	Names	Canonical?
A6NKB5-1	1	yes
A6NKB5-2	2
A6NKB5-3	3
A6NKB5-5	5
A6NKB5-4	4

RefSeq proteins (1): NP_055616* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007735	Pecanex_C	Domain
IPR039797	Pecanex	Family

Pfam: PF05041

UniProt features (60 total): transmembrane region 15, compositionally biased region 11, glycosylation site 11, splice variant 10, region of interest 8, sequence variant 4, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A6NKB5-F1	57.79	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.

Glycosylation sites (11): 136, 449, 550, 572, 587, 598, 613, 1412, 1553, 1818, 2054

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 81 (showing top): CAGGTCC_MIR492, CAGCAGG_MIR370, TAATGTG_MIR323, CCAGGGG_MIR331, CTGAGCC_MIR24, MODULE_13, ZHOU_INFLAMMATORY_RESPONSE_LIVE_UP, SENGUPTA_EBNA1_ANTICORRELATED, CAGTGTT_MIR141_MIR200A, MEISSNER_NPC_HCP_WITH_H3_UNMETHYLATED, MIKKELSEN_MCV6_HCP_WITH_H3K27ME3, MIKKELSEN_MEF_HCP_WITH_H3K27ME3, FORTSCHEGGER_PHF8_TARGETS_DN, MTOR_UP.N4.V1_DN, OISHI_CHOLANGIOMA_STEM_CELL_LIKE_UP

GO Biological Process (1): biological_process (GO:0008150)

GO Molecular Function (1): molecular_function (GO:0003674)

GO Cellular Component (2): membrane (GO:0016020), cellular_component (GO:0005575)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	1

Protein interactions and networks

STRING

334 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PCNX2	TAF1B	Q53T94	540
PCNX2	EPB41L4A	Q9HCS5	493
PCNX2	ASTE1	Q2TB18	474
PCNX2	TMEM253	P0C7T8	447
PCNX2	STN1	Q9H668	431
PCNX2	HEPH	Q9BQS7	427
PCNX2	LRRC34	Q8IZ02	380
PCNX2	NREP	Q16612	369
PCNX2	FOXE1	O00358	349
PCNX2	GRIA4	P48058	344
PCNX2	SEPTIN11	Q9NVA2	339
PCNX2	SLC38A12	Q8NE00	324
PCNX2	OR2Z1	Q8NG97	323
PCNX2	TBC1D8	O95759	311
PCNX2	MS4A14	Q96JA4	311

IntAct

3 interactions, top by confidence:

A	B	Type	Score
KLHL22	TRAV18	psi-mi:“MI:0914”(association)	0.350
FMR1	PCNX2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (14): PCNXL2 (Synthetic Growth Defect), PCNXL2 (Synthetic Growth Defect), PCNXL2 (Affinity Capture-RNA), PCNXL2 (Affinity Capture-RNA), PCNXL2 (Affinity Capture-MS), PCNXL2 (Two-hybrid), PCNXL2 (Two-hybrid), SLC30A2 (Two-hybrid), PCNXL2 (Affinity Capture-MS), PCNXL2 (Affinity Capture-RNA), PCNXL2 (Protein-peptide), PCNXL2 (Affinity Capture-MS), PCNXL2 (Affinity Capture-MS), PCNXL2 (Affinity Capture-RNA)

ESM2 similar proteins: A0A140LFM6, A0A1B0GUA6, A0JMD2, A4IGV6, A6H5Y1, A6NFA0, A6NKB5, A8E653, B3DHS1, D3ZJ47, D3ZMK9, E9Q309, O14513, O60284, P0CAX8, Q1RMQ5, Q32LN6, Q3URK1, Q3UTJ2, Q3ZBS1, Q49A88, Q5DU28, Q5RDK8, Q5REU9, Q5SW75, Q5VT06, Q60664, Q62417, Q642A3, Q68D20, Q6A065, Q6DFB0, Q6NRK3, Q6NWJ0, Q6ZVD7, Q76I79, Q7TSH4, Q8K2J4, Q8K3V7, Q8VEB3

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	22
Likely benign	6
Benign	6

Top pathogenic / likely-pathogenic (0)

SpliceAI

7427 predictions. Top by Δscore:

Variant	Effect	Δscore
1:232984476:TG:T	acceptor_gain	1.0000
1:232984478:C:CC	acceptor_gain	1.0000
1:232984482:C:CT	acceptor_gain	1.0000
1:232984482:C:T	acceptor_gain	1.0000
1:232984483:A:T	acceptor_gain	1.0000
1:232998435:CATC:C	acceptor_gain	1.0000
1:232998437:TC:T	acceptor_gain	1.0000
1:232998437:TCC:T	acceptor_loss	1.0000
1:232998438:CC:C	acceptor_gain	1.0000
1:232998439:C:CA	acceptor_loss	1.0000
1:232998439:C:CC	acceptor_gain	1.0000
1:232998440:T:C	acceptor_loss	1.0000
1:233000300:CATA:C	donor_loss	1.0000
1:233000301:ATAC:A	donor_loss	1.0000
1:233000302:TA:T	donor_loss	1.0000
1:233000531:TGGTC:T	acceptor_gain	1.0000
1:233000533:GTC:G	acceptor_gain	1.0000
1:233000534:TC:T	acceptor_gain	1.0000
1:233000535:CCTGG:C	acceptor_gain	1.0000
1:233000536:C:CC	acceptor_gain	1.0000
1:233001531:TTTTA:T	donor_loss	1.0000
1:233001532:TTTAC:T	donor_loss	1.0000
1:233001533:TTACC:T	donor_loss	1.0000
1:233001534:TA:T	donor_loss	1.0000
1:233001535:A:AT	donor_loss	1.0000
1:233001536:C:G	donor_loss	1.0000
1:233001677:CCAGG:C	acceptor_gain	1.0000
1:233001678:CAGG:C	acceptor_gain	1.0000
1:233001678:CAGGC:C	acceptor_gain	1.0000
1:233001680:GG:G	acceptor_gain	1.0000

AlphaMissense

14050 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:233016953:A:G	W1603R	0.999
1:233016953:A:T	W1603R	0.999
1:233000430:A:G	W1735R	0.998
1:233000430:A:T	W1735R	0.998
1:233001611:A:G	W1675R	0.998
1:233001611:A:T	W1675R	0.998
1:233017152:A:C	S1536R	0.998
1:233017152:A:T	S1536R	0.998
1:233017154:T:G	S1536R	0.998
1:233054391:A:G	W1410R	0.998
1:233054391:A:T	W1410R	0.998
1:232999216:A:T	V1831D	0.997
1:233001544:A:G	L1697P	0.997
1:233054272:G:C	F1449L	0.997
1:233054272:G:T	F1449L	0.997
1:233054274:A:G	F1449L	0.997
1:233054330:A:T	V1430D	0.997
1:233090117:A:C	S1340R	0.997
1:233090117:A:T	S1340R	0.997
1:233090119:T:G	S1340R	0.997
1:232999293:A:C	S1805R	0.996
1:232999293:A:T	S1805R	0.996
1:232999295:T:G	S1805R	0.996
1:233000393:A:G	L1747P	0.996
1:233014703:C:A	R1638S	0.996
1:233014703:C:G	R1638S	0.996
1:233054273:A:G	F1449S	0.996
1:233054288:A:G	L1444P	0.996
1:232999267:C:G	R1814P	0.995
1:232999330:A:G	L1793P	0.995

dbSNP variants (sampled 300 via entrez): RS1000004338 (1:233157474 G>A,T), RS1000005011 (1:233116730 A>G), RS1000016882 (1:233155193 T>C), RS1000023011 (1:233155577 TC>T), RS1000027423 (1:233214234 C>T), RS1000066013 (1:233123885 G>A), RS1000067946 (1:233245456 G>A), RS1000069360 (1:233164142 C>T), RS1000072231 (1:233286890 C>G,T), RS1000074870 (1:233144076 G>T), RS1000075243 (1:233027909 T>C), RS1000075465 (1:233204531 C>G), RS1000083800 (1:233161983 TAC>T), RS1000100157 (1:233244969 T>G), RS1000104344 (1:233131937 T>A)

Disease associations

OMIM: gene MIM:617656 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST001033_2	Type 2 diabetes	4.000000e-07
GCST002251_1	Homeostasis model assessment of beta-cell function (dietary factor interaction)	1.000000e-06
GCST002783_465	Body mass index	2.000000e-06
GCST003654_3	Bone mineral density (Ward’s triangle area)	4.000000e-06
GCST004144_6	Thyroid cancer	4.000000e-11
GCST004493_2	Lower body strength	2.000000e-06
GCST004753_5	Papillary thyroid cancer	9.000000e-08
GCST004798_6	Differentiated thyroid cancer	6.000000e-08

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004469	HOMA-B
EFO:0008111	diet measurement
EFO:0004340	body mass index
EFO:0007785	femoral neck bone mineral density
EFO:0007999	lower body strength measurement

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 expression, increases expression	5
Aflatoxin B1	decreases methylation, increases methylation	2
bisphenol F	affects cotreatment, decreases methylation	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, affects methylation, decreases methylation	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
benzo(e)pyrene	increases methylation	1
coumarin	increases phosphorylation	1
di-n-butylphosphoric acid	affects expression	1
entinostat	increases expression	1
abrine	increases expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	affects cotreatment, increases expression	1
Fulvestrant	affects methylation, decreases methylation, affects cotreatment	1
Air Pollutants	increases expression, increases abundance	1
Arbutin	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Demecolcine	increases expression	1
Doxorubicin	decreases expression	1
Ethyl Methanesulfonate	increases expression	1
Folic Acid	decreases expression	1
Formaldehyde	increases expression	1
Methapyrilene	increases methylation	1
Methyl Methanesulfonate	increases expression	1
Naled	affects expression	1
Tetrachlorodibenzodioxin	affects cotreatment, increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Vincristine	increases expression	1
Antirheumatic Agents	increases expression	1
Particulate Matter	increases abundance, increases expression	1

Clinical trials (associated diseases)

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