PNN

Summary

PNN (pinin, desmosome associated protein, HGNC:9162) is a protein-coding gene on chromosome 14q21.1, encoding Pinin (Q9H307). Transcriptional activator binding to the E-box 1 core sequence of the E-cadherin promoter gene; the core-binding sequence is 5’CAGGTG-3’. It is a common-essential gene (DepMap: required in 93.2% of cancer cell lines).

Enables RNA binding activity. Predicted to be involved in cell adhesion and mRNA splicing, via spliceosome. Predicted to act upstream of or within cell-cell adhesion. Located in exon-exon junction complex and nuclear speck. Part of catalytic step 2 spliceosome.

Source: NCBI Gene 5411 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 95 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 93.2% of screened cell lines (common-essential)
• MANE Select transcript: NM_002687

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9162
Approved symbol	PNN
Name	pinin, desmosome associated protein
Location	14q21.1
Locus type	gene with protein product
Status	Approved
Aliases	memA
Ensembl gene	ENSG00000100941
Ensembl biotype	protein_coding
OMIM	603154
Entrez	5411

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 6 protein_coding, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000216832, ENST00000553331, ENST00000554117, ENST00000554902, ENST00000556530, ENST00000557680, ENST00000859942, ENST00000911270, ENST00000911271

RefSeq mRNA: 1 — MANE Select: NM_002687 NM_002687

CCDS: CCDS9671

Canonical transcript exons

ENST00000216832 — 9 exons

Exon	Start	End
ENSE00000656406	39176078	39176149
ENSE00000656407	39176527	39176595
ENSE00000656408	39177412	39177484
ENSE00000656409	39177593	39177687
ENSE00000889803	39180503	39183220
ENSE00002444446	39175254	39175392
ENSE00003479237	39179091	39179246
ENSE00003625334	39177841	39177916
ENSE00003675752	39179324	39179462

Expression profiles

Bgee: expression breadth ubiquitous, 303 present calls, max score 99.39.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 125.4116 / max 9118.0577, expressed in 1821 samples.

FANTOM5 promoters (19 alternative TSS)

Promoter ID	TPM avg	Samples expressed
139345	79.3370	1815
139344	12.5920	1745
139352	5.9963	1241
139359	3.9167	1161
139355	3.4927	1012
139357	3.2138	1006
139353	3.1284	978
139348	2.1991	763
139360	1.8319	771
139356	1.8033	729

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tendon of biceps brachii	UBERON:0008188	99.39	gold quality
corpus epididymis	UBERON:0004359	99.04	gold quality
sural nerve	UBERON:0015488	98.69	gold quality
epithelium of nasopharynx	UBERON:0001951	98.52	gold quality
nasopharynx	UBERON:0001728	98.50	gold quality
ventricular zone	UBERON:0003053	98.19	gold quality
tendon	UBERON:0000043	98.02	gold quality
pylorus	UBERON:0001166	97.83	gold quality
cardia of stomach	UBERON:0001162	97.77	gold quality
medial globus pallidus	UBERON:0002477	97.77	gold quality
seminal vesicle	UBERON:0000998	97.72	gold quality
endometrium	UBERON:0001295	97.71	gold quality
right uterine tube	UBERON:0001302	97.71	gold quality
adenohypophysis	UBERON:0002196	97.58	gold quality
tibia	UBERON:0000979	97.53	gold quality
embryo	UBERON:0000922	97.50	gold quality
calcaneal tendon	UBERON:0003701	97.43	gold quality
parotid gland	UBERON:0001831	97.42	gold quality
pituitary gland	UBERON:0000007	97.37	gold quality
globus pallidus	UBERON:0001875	97.37	gold quality
ganglionic eminence	UBERON:0004023	97.36	gold quality
body of uterus	UBERON:0009853	97.34	gold quality
small intestine Peyer’s patch	UBERON:0003454	97.27	gold quality
left lobe of thyroid gland	UBERON:0001120	97.26	gold quality
left ovary	UBERON:0002119	97.24	gold quality
body of pancreas	UBERON:0001150	97.23	gold quality
caput epididymis	UBERON:0004358	97.21	gold quality
tonsil	UBERON:0002372	97.18	gold quality
thyroid gland	UBERON:0002046	97.12	gold quality
cartilage tissue	UBERON:0002418	97.08	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-10042	yes	5.51
E-MTAB-7052	no	527.31
E-MTAB-7606	no	439.93
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CUX1

miRNA regulators (miRDB)

142 targeting PNN, 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-4795-3P	100.00	74.62	4024
HSA-MIR-8485	100.00	77.57	4731
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-12136	99.98	72.81	5713
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-3617-3P	99.98	67.86	918
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-557	99.96	70.01	1640

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 93.2% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 20)

• Pinin functions as a splicing regulator which participates itself directly in splicing reaction or indirectly via other components of splicing machinery (PMID:12051732)
• Pnn may participate, via its interaction with RNPS1, in mRNA metabolism in the nucleus, including mRNA splicing and export (PMID:14517304)
• the interaction of Pnn with the corepressor CtBP1 may modulate repression of E-cadherin transcription by CtBP1 (PMID:15542832)
• Pnn may play a general role in the control of the cellular amount of family SR proteins through down-regulation of its own expression (PMID:16430868)
• Corepressor CtBP and PNN/DRS differentially modulate transcription and splicing of the E-cadherin gene. (PMID:18086895)
• Urinary desmosine level is an important biologoical marker, in patients treated with bilateral knee replacement and hydrocortison therapy. (PMID:23097096)
• ESRP1 and PNN modulate alternative splicing of a specific subset of target genes, but not general splicing events, in HCET cells to maintain or enhance epithelial characteristics. (PMID:23299472)
• PNN has an important role in alternative splicing of a specific subset of lncRNAs of the corneal epithelium. (PMID:25489234)
• Pinin and CtBP are oncotargets that closely interact with each other to regulate transcription and pre-mRNA alternative splicing and promote cell adhesion and other epithelial characteristics of ovarian cancer cells. (PMID:26871283)
• These data suggest that lowering of PNN levels in epithelial cells results in dramatic transformation in the number and composition of splicing variants and that PNN plays a crucial role in the selection of which RNA isoforms differentiating cells produce. (PMID:26900324)
• Our findings suggested that PNN, as a valuable marker of prognosis, has important influence on the progression of colorectal cancer (PMID:27107420)
• Pinin contributes to hepatocellular carcinoma progression and resistance to glucose deprivation-induced apoptosis via maintaining ERK1/2 activation (PMID:27175589)
• Data suggest that SNRPA1, SNRPD1, and PNN are key players in the regulation of pluripotency-specific spliceosome assembly and the acquisition and maintenance of pluripotency. (PMID:28595116)
• By a transcriptomic approach and validates PNN and KCNQ1OT1 as molecular biomarkers. (PMID:30973654)
• It has been shown that in the absence of piRNAs, human PIWIL1 in pancreatic ductal adenocarcinoma (PDAC) functions as an oncoprotein by activating the anaphase promoting complex/cyclosome (APC/C) E3 complex, which then targets a critical cell adhesion-related protein, Pinin, to enhance PDAC metastasis. (PMID:32203416)
• Hsa_circ_0032463 acts as the tumor promoter in osteosarcoma by regulating the miR3303p/PNN axis. (PMID:33786605)
• Pinin acts as a poor prognostic indicator for renal cell carcinoma by reducing apoptosis and promoting cell migration and invasion. (PMID:33811436)
• The prognostic effect of PNN in digestive tract cancers and its correlation with the tumor immune landscape in colon adenocarcinoma. (PMID:35257416)
• Methyltransferase like 3 enhances pinin mRNA stability through N(6) -methyladenosine modification to augment tumourigenesis of colon adenocarcinoma. (PMID:35996844)
• Identification of a Novel miR-195-5p/PNN Axis in Colorectal Cancer. (PMID:38892168)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	pnn	ENSDARG00000015851
mus_musculus	Pnn	ENSMUSG00000020994
rattus_norvegicus	Pnn	ENSRNOG00000004061
drosophila_melanogaster	Pnn	FBGN0037737
caenorhabditis_elegans		WBGENE00011308

Protein

Protein identifiers

Pinin — Q9H307 (reviewed: Q9H307)

Alternative names: 140 kDa nuclear and cell adhesion-related phosphoprotein, Desmosome-associated protein, Domain-rich serine protein, Melanoma metastasis clone A protein, Nuclear protein SDK3, SR-like protein

All UniProt accessions (3): Q9H307, G3V579, G3V5F0

UniProt curated annotations — full annotation on UniProt →

Function. Transcriptional activator binding to the E-box 1 core sequence of the E-cadherin promoter gene; the core-binding sequence is 5’CAGGTG-3’. Capable of reversing CTBP1-mediated transcription repression. Auxiliary component of the splicing-dependent multiprotein exon junction complex (EJC) deposited at splice junction on mRNAs. The EJC is a dynamic structure consisting of core proteins and several peripheral nuclear and cytoplasmic associated factors that join the complex only transiently either during EJC assembly or during subsequent mRNA metabolism. Participates in the regulation of alternative pre-mRNA splicing. Associates to spliced mRNA within 60 nt upstream of the 5’-splice sites. Component of the PSAP complex which binds RNA in a sequence-independent manner and is proposed to be recruited to the EJC prior to or during the splicing process and to regulate specific excision of introns in specific transcription subsets. Involved in the establishment and maintenance of epithelia cell-cell adhesion. Potential tumor suppressor for renal cell carcinoma.

Subunit / interactions. Found in a mRNA splicing-dependent exon junction complex (EJC). Found in a complex with SR proteins. Found in a mRNP complex with RNPS1. Component of the PSAP complex consisting of RNPS1, SAP18 and PNN. Interacts with PNISR, CTBP1, CTBP2, KRT8, KRT18, KRT19, PS1D/PNO40, PPIG, RNPS1, SFRS4 and SRRM2. Identified in the spliceosome C complex.

Subcellular location. Nucleus speckle. Cell junction. Desmosome.

Tissue specificity. Expressed in placenta, lung, liver, kidney, pancreas, spleen, thymus, prostate, testis, ovary, small intestine, colon, heart, epidermis, esophagus, brain and smooth and skeletal muscle. Expressed strongly in melanoma metastasis lesions and advanced primary tumors.

Similarity. Belongs to the pinin family.

RefSeq proteins (1): NP_002678* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006786	Pinin_SDK_MemA	Domain
IPR006787	Pinin_SDK_N	Domain
IPR039853	Pinin	Family

Pfam: PF04696, PF04697

UniProt features (93 total): sequence conflict 25, modified residue 21, compositionally biased region 15, cross-link 15, region of interest 7, coiled-coil region 4, mutagenesis site 3, initiator methionine 1, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H307-F1	58.30	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 (36): 2, 48, 54, 58, 66, 96, 100, 114, 115, 124, 238, 238, 347, 375, 381, 443, 450, 552, 658, 692 …

Mutagenesis-validated functional residues (3):

Position	Phenotype
8	abolishes interaction with krt18.
19	abolishes interaction with krt18.
502–503	abolishes interaction with ctbp1 and shows moderate relief of ctbp1-mediated repression.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-72163	mRNA Splicing - Major Pathway

MSigDB gene sets: 254 (showing top): RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, TAATAAT_MIR126, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, YAGI_AML_WITH_INV_16_TRANSLOCATION, TGCGCANK_UNKNOWN, GOBP_REGULATION_OF_MRNA_CATABOLIC_PROCESS, GCM_NPM1, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, THEILGAARD_NEUTROPHIL_AT_SKIN_WOUND_DN, MONNIER_POSTRADIATION_TUMOR_ESCAPE_UP, PUJANA_CHEK2_PCC_NETWORK, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, MUELLER_PLURINET

GO Biological Process (4): mRNA splicing, via spliceosome (GO:0000398), cell adhesion (GO:0007155), mRNA processing (GO:0006397), RNA splicing (GO:0008380)

GO Molecular Function (4): DNA binding (GO:0003677), RNA binding (GO:0003723), structural molecule activity (GO:0005198), protein binding (GO:0005515)

GO Cellular Component (12): nucleoplasm (GO:0005654), intermediate filament (GO:0005882), plasma membrane (GO:0005886), cell-cell junction (GO:0005911), membrane (GO:0016020), nuclear speck (GO:0016607), desmosome (GO:0030057), catalytic step 2 spliceosome (GO:0071013), nucleus (GO:0005634), spliceosomal complex (GO:0005681), exon-exon junction complex (GO:0035145), anchoring junction (GO:0070161)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
mRNA Splicing	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA processing	2
nucleic acid binding	2
cellular anatomical structure	2
nuclear protein-containing complex	2
RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	1
mRNA processing	1
cellular process	1
mRNA metabolic process	1
molecular_function	1
binding	1
nuclear lumen	1
intermediate filament cytoskeleton	1
polymeric cytoskeletal fiber	1
membrane	1
cell periphery	1
anchoring junction	1
nuclear ribonucleoprotein granule	1
cell-cell junction	1
Prp19 complex	1
spliceosomal complex	1
U5 snRNP	1
catalytic complex	1
intracellular membrane-bounded organelle	1
ribonucleoprotein complex	1
cell junction	1

Protein interactions and networks

STRING

1386 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PNN	RNPS1	Q15287	978
PNN	SAP18	O00422	926
PNN	SRRM1	Q8IYB3	916
PNN	ACIN1	Q9UKV3	817
PNN	TRA2B	P62995	816
PNN	SRSF11	Q05519	813
PNN	RBM8A	Q9Y5S9	775
PNN	UPF3A	Q9H1J1	760
PNN	NXF1	Q9UBU9	754
PNN	MAGOH	P50606	751
PNN	MAGOHB	Q96A72	744
PNN	UPF3B	Q9BZI7	728
PNN	UPF2	Q9HAU5	728
PNN	DDX39B	Q13838	699
PNN	DSP	P15924	693

IntAct

320 interactions, top by confidence:

A	B	Type	Score
MAGOH	CASC3	psi-mi:“MI:0914”(association)	0.970
NDUFAF1	NDUFS3	psi-mi:“MI:0914”(association)	0.790
PNN	ACIN1	psi-mi:“MI:0915”(physical association)	0.740
MED19	MED19	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
SNRPD2	GEMIN2	psi-mi:“MI:0914”(association)	0.710
PNN	SNW1	psi-mi:“MI:0915”(physical association)	0.670
PNN	CASC3	psi-mi:“MI:0914”(association)	0.640
CAMKV	AP3B1	psi-mi:“MI:0914”(association)	0.640
SF3B1	SAP18	psi-mi:“MI:0914”(association)	0.640
PNN	SAP18	psi-mi:“MI:0915”(physical association)	0.620
SARNP	ZC3H11A	psi-mi:“MI:0914”(association)	0.610
PNN	RNPS1	psi-mi:“MI:0407”(direct interaction)	0.600
PNN	RNPS1	psi-mi:“MI:0915”(physical association)	0.600
PNN	CSNK2A1	psi-mi:“MI:0217”(phosphorylation reaction)	0.590
KRT27	PNN	psi-mi:“MI:0915”(physical association)	0.560
DLD	PDHB	psi-mi:“MI:0914”(association)	0.530
PTGER3	PIK3R2	psi-mi:“MI:0914”(association)	0.530
PIP4K2A	AP3B1	psi-mi:“MI:0914”(association)	0.530
PES1	AP3B1	psi-mi:“MI:0914”(association)	0.530
EPB41L2	AP3B1	psi-mi:“MI:0914”(association)	0.530
FAM9A	AP3B1	psi-mi:“MI:0914”(association)	0.530
MDK	SETD1A	psi-mi:“MI:0914”(association)	0.530
RSBN1	SETD1A	psi-mi:“MI:0914”(association)	0.530
SNIP1	CASC3	psi-mi:“MI:0914”(association)	0.530
RALYL	CDC40	psi-mi:“MI:0914”(association)	0.530
DDX41	NOS1AP	psi-mi:“MI:0914”(association)	0.530

BioGRID (492): PNN (Affinity Capture-MS), PNN (Affinity Capture-MS), PNN (Affinity Capture-MS), PNN (Affinity Capture-MS), PNN (Affinity Capture-MS), PNN (Affinity Capture-MS), PNN (Affinity Capture-MS), PNN (Affinity Capture-MS), PNN (Affinity Capture-MS), PNN (Affinity Capture-MS), PNN (Affinity Capture-MS), PNN (Affinity Capture-MS), PNN (Affinity Capture-MS), PNN (Affinity Capture-MS), PNN (Affinity Capture-MS)

ESM2 similar proteins: A0JNI5, A2AJT4, D3ZTQ1, O35691, O75376, P79149, Q05519, Q12872, Q14241, Q149C2, Q3USH5, Q4KKX4, Q4R6F6, Q53F19, Q568R1, Q569Z6, Q5BJ39, Q5BL56, Q5HZB6, Q5M7V8, Q5R5X0, Q5SFM8, Q5T8P6, Q5ZM19, Q60974, Q63187, Q6DFQ2, Q6NZN0, Q6PJT7, Q6WKW9, Q6ZPZ3, Q8BZR9, Q8BZX4, Q8CB77, Q8CFC7, Q8K019, Q8K3W3, Q8K3X0, Q8N2M8, Q8QG78

Diamond homologs: O35691, P79122, P79149, Q5R5X0, Q9H307

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
APC-c	“down-regulates quantity by destabilization”	PNN	polyubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 209 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Transport of Mature Transcript to Cytoplasm	9	23.5×	6e-09
mRNA 3’-end processing	15	20.2×	4e-14
mRNA Splicing	25	18.8×	4e-23
RNA Polymerase II Transcription Termination	12	18.1×	1e-10
Processing of Capped Intron-Containing Pre-mRNA	28	15.8×	1e-23
Transport of Mature mRNA derived from an Intron-Containing Transcript	15	15.6×	2e-12
mRNA Polyadenylation	24	14.4×	3e-19
mRNA Splicing - Major Pathway	38	14.2×	7e-31

GO biological processes:

GO term	Partners	Fold	FDR
negative regulation of mRNA splicing, via spliceosome	9	37.5×	3e-10
regulation of mRNA splicing, via spliceosome	7	33.7×	1e-07
regulation of mRNA processing	6	28.9×	5e-06
U2-type prespliceosome assembly	8	27.1×	7e-08
spliceosomal complex assembly	8	26.2×	8e-08
positive regulation of transcription by RNA polymerase III	5	25.4×	1e-04
mRNA splice site recognition	5	21.8×	2e-04
RNA splicing, via transesterification reactions	6	20.4×	4e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	78
Likely benign	1
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

898 predictions. Top by Δscore:

Variant	Effect	Δscore
14:39175388:GTGAG:G	donor_gain	1.0000
14:39175390:GAG:G	donor_gain	1.0000
14:39175390:GAGGT:G	donor_loss	1.0000
14:39175391:AGG:A	donor_loss	1.0000
14:39175392:GGTA:G	donor_loss	1.0000
14:39175393:G:GG	donor_gain	1.0000
14:39175393:GT:G	donor_loss	1.0000
14:39176073:TACA:T	acceptor_loss	1.0000
14:39176075:CA:C	acceptor_loss	1.0000
14:39176076:A:AG	acceptor_gain	1.0000
14:39176076:AG:A	acceptor_gain	1.0000
14:39176077:G:GA	acceptor_gain	1.0000
14:39176077:GG:G	acceptor_gain	1.0000
14:39176077:GGC:G	acceptor_gain	1.0000
14:39176077:GGCC:G	acceptor_gain	1.0000
14:39176077:GGCCC:G	acceptor_gain	1.0000
14:39176147:GAG:G	donor_gain	1.0000
14:39176148:AGGT:A	donor_loss	1.0000
14:39176149:GGTA:G	donor_loss	1.0000
14:39176150:GTAAG:G	donor_loss	1.0000
14:39176151:T:A	donor_loss	1.0000
14:39176592:GTAG:G	donor_gain	1.0000
14:39176593:TAG:T	donor_loss	1.0000
14:39176594:AG:A	donor_loss	1.0000
14:39176595:GGTA:G	donor_loss	1.0000
14:39176597:T:G	donor_loss	1.0000
14:39177407:GACAG:G	acceptor_loss	1.0000
14:39177409:CAG:C	acceptor_loss	1.0000
14:39177410:AGG:A	acceptor_loss	1.0000
14:39177410:AGGCT:A	acceptor_gain	1.0000

AlphaMissense

4785 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:39175302:T:C	L8S	1.000
14:39175314:T:C	L12P	1.000
14:39175322:G:C	A15P	1.000
14:39175335:T:A	L19H	1.000
14:39175335:T:C	L19P	1.000
14:39175346:G:C	D23H	1.000
14:39175356:T:A	I26N	1.000
14:39175356:T:C	I26T	1.000
14:39175356:T:G	I26S	1.000
14:39175359:G:C	R27P	1.000
14:39175365:T:C	L29P	1.000
14:39175370:G:A	G31R	1.000
14:39175370:G:C	G31R	1.000
14:39175370:G:T	G31W	1.000
14:39175371:G:A	G31E	1.000
14:39175371:G:T	G31V	1.000
14:39177612:T:A	V116D	1.000
14:39177648:T:C	L128P	1.000
14:39177677:G:A	G138R	1.000
14:39177677:G:C	G138R	1.000
14:39177687:G:C	R141T	1.000
14:39177687:G:T	R141M	1.000
14:39177841:G:C	R141S	1.000
14:39177841:G:T	R141S	1.000
14:39177844:C:A	N142K	1.000
14:39177844:C:G	N142K	1.000
14:39177846:G:C	R143P	1.000
14:39177848:C:G	R144G	1.000
14:39177849:G:C	R144P	1.000
14:39177852:T:A	I145K	1.000

dbSNP variants (sampled 300 via entrez): RS1000079015 (14:39176199 TAA>T), RS1000427340 (14:39182492 G>A), RS1000568076 (14:39182710 G>C,T), RS1000995685 (14:39176952 A>G), RS1001138235 (14:39175536 G>C), RS1001261658 (14:39180095 A>G), RS1001583210 (14:39183028 CTG>C), RS1001606253 (14:39182814 A>G), RS1001750042 (14:39177361 G>C), RS1002141873 (14:39183175 T>C), RS1002193 (14:39175568 C>G,T), RS1002569581 (14:39180123 A>G), RS1002728611 (14:39175237 G>A,C), RS1002996488 (14:39175158 A>T), RS1003430576 (14:39178558 G>A)

Disease associations

OMIM: gene MIM:603154 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5725146 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,538 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1232461	MOLIBRESIB	2	1,538

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.00	IC50	10	nM	MOLIBRESIB
7.82	Kd	15	nM	MOLIBRESIB

PubChem BioAssay actives

2 with measured affinity, of 7 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2178813: Inhibition of PNN (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	0.0100	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression	5
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	4
Arsenic	affects cotreatment, increases abundance, increases expression	2
Benzo(a)pyrene	decreases expression	2
Lipopolysaccharides	decreases reaction, increases expression, affects expression, affects response to substance, decreases expression	2
Tetrachlorodibenzodioxin	decreases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
Asbestos, Crocidolite	decreases expression, increases expression	2
Cadmium Chloride	decreases expression, decreases methylation, increases expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
TAK-243	decreases sumoylation	1
daidzein	affects cotreatment, increases expression	1
methylmercuric chloride	decreases expression	1
bisphenol A	decreases expression	1
deoxynivalenol	increases expression	1
arsenite	affects expression	1
cobaltous chloride	decreases expression	1
nickel chloride	decreases expression	1
potassium chromate(VI)	affects cotreatment, increases expression	1
ferrous chloride	increases expression	1
coumarin	decreases phosphorylation	1
resorcinol	increases expression	1
epigallocatechin gallate	affects cotreatment, increases expression	1
tamibarotene	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
glycitein	increases expression, affects cotreatment	1
CGP 52608	affects binding, increases reaction	1
tanespimycin	increases expression	1

ChEMBL screening assays

7 unique, capped per target: 7 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5697543	Binding	Inhibition of PNN (unknown origin) assessed as fold change at 10 uM incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia. — Nature

Clinical trials (associated diseases)

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