PNISR

Summary

PNISR (PNN interacting serine and arginine rich protein, HGNC:21222) is a protein-coding gene on chromosome 6q16.2, encoding Arginine/serine-rich protein PNISR (Q8TF01). It is a selective cancer dependency (DepMap: 16.9% of cell lines).

Enables RNA binding activity. Located in cytosol; nuclear speck; and plasma membrane.

Source: NCBI Gene 25957 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 119 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 16.9% of screened cell lines
• MANE Select transcript: NM_032870

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21222
Approved symbol	PNISR
Name	PNN interacting serine and arginine rich protein
Location	6q16.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ14752, bA98I9.2, DKFZp564B0769, SRrp130
Ensembl gene	ENSG00000132424
Ensembl biotype	protein_coding
OMIM	616653
Entrez	25957

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 15 protein_coding, 4 retained_intron, 3 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000369239, ENST00000438806, ENST00000460600, ENST00000463021, ENST00000466057, ENST00000476159, ENST00000478777, ENST00000481229, ENST00000492294, ENST00000498075, ENST00000647811, ENST00000679525, ENST00000681611, ENST00000681615, ENST00000899536, ENST00000928590, ENST00000928591, ENST00000928592, ENST00000928593, ENST00000950807, ENST00000950808, ENST00000950809, ENST00000950810

RefSeq mRNA: 13 — MANE Select: NM_032870 NM_001322405, NM_001322406, NM_001322408, NM_001322410, NM_001322412, NM_001322413, NM_001322414, NM_001322415, NM_001322416, NM_001322417, NM_001322419, NM_015491, NM_032870

CCDS: CCDS5043, CCDS93977, CCDS93978

Canonical transcript exons

ENST00000369239 — 12 exons

Exon	Start	End
ENSE00001345743	99403829	99403882
ENSE00001402214	99416349	99416428
ENSE00001860096	99425215	99425308
ENSE00002155399	99408081	99408271
ENSE00002157662	99410741	99410964
ENSE00002163893	99409173	99409344
ENSE00002192283	99406031	99406168
ENSE00003492215	99402540	99402710
ENSE00003518977	99412551	99412739
ENSE00003607259	99414572	99414690
ENSE00003674417	99404603	99404702
ENSE00003842230	99398050	99401630

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 99.15.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 105.7196 / max 7381.2848, expressed in 1817 samples.

FANTOM5 promoters (14 alternative TSS)

Promoter ID	TPM avg	Samples expressed
74810	86.7762	1817
74794	5.3692	1091
74797	3.4134	933
74802	1.6003	522
74800	1.5249	616
74798	1.4493	555
74801	1.2654	545
74796	1.1834	440
74795	1.1029	401
74805	0.6643	284

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	99.15	gold quality
sural nerve	UBERON:0015488	99.14	gold quality
right uterine tube	UBERON:0001302	99.09	gold quality
left ovary	UBERON:0002119	99.06	gold quality
adenohypophysis	UBERON:0002196	99.06	gold quality
left lobe of thyroid gland	UBERON:0001120	99.03	gold quality
cerebellar hemisphere	UBERON:0002245	99.03	gold quality
right ovary	UBERON:0002118	99.01	gold quality
cerebellar cortex	UBERON:0002129	98.99	gold quality
body of uterus	UBERON:0009853	98.92	gold quality
pituitary gland	UBERON:0000007	98.91	gold quality
right lobe of thyroid gland	UBERON:0001119	98.91	gold quality
calcaneal tendon	UBERON:0003701	98.89	gold quality
thyroid gland	UBERON:0002046	98.85	gold quality
Brodmann (1909) area 23	UBERON:0013554	98.83	gold quality
muscle layer of sigmoid colon	UBERON:0035805	98.82	gold quality
endocervix	UBERON:0000458	98.81	gold quality
fundus of stomach	UBERON:0001160	98.77	gold quality
lower esophagus	UBERON:0013473	98.72	gold quality
lower esophagus muscularis layer	UBERON:0035833	98.72	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	98.72	gold quality
middle temporal gyrus	UBERON:0002771	98.71	gold quality
tibial nerve	UBERON:0001323	98.68	gold quality
mucosa of stomach	UBERON:0001199	98.67	gold quality
pylorus	UBERON:0001166	98.64	gold quality
right lung	UBERON:0002167	98.62	gold quality
cerebellum	UBERON:0002037	98.60	gold quality
cardia of stomach	UBERON:0001162	98.54	gold quality
small intestine Peyer’s patch	UBERON:0003454	98.53	gold quality
lymph node	UBERON:0000029	98.44	gold quality

Single-cell (SCXA)

Detected in 12 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-MTAB-9221	yes	19.78
E-CURD-122	yes	19.11
E-MTAB-8142	yes	18.44
E-MTAB-2983	no	2929.49
E-MTAB-8381	no	1231.25
E-CURD-89	no	1087.77
E-MTAB-10432	no	1038.09
E-HCAD-4	no	92.32
E-HCAD-6	no	51.36
E-GEOD-137537	no	6.34
E-GEOD-83139	no	4.10
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

194 targeting PNISR, 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-LET-7F-1-3P	100.00	74.02	3928
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-3163	100.00	77.23	8605
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-4795-3P	100.00	74.62	4024
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-6870-5P	99.99	68.55	2115

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 16.9% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 2)

• results indicate that LUC7L3, PPIG, and SFRS18 are not only implicated in EDA+ fibronectin formation, but also that they could possess multiple roles in psoriasis-associated molecular abnormalities. (PMID:28589370)
• In our present RNA-Seq experiment, we demonstrated that the LUC7L3 and SFRS18 splicing factors contribute to the regulation of several well-known psoriasis-associated pathways, including the IFN signalling pathway, antiviral immunity and ubiquitination. (PMID:29512856)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	pnisr	ENSDARG00000069855
mus_musculus	Pnisr	ENSMUSG00000028248
rattus_norvegicus	Pnisr	ENSRNOG00000008782
drosophila_melanogaster	CG31211	FBGN0051211
caenorhabditis_elegans	rsy-1	WBGENE00013177

Protein

Protein identifiers

Arginine/serine-rich protein PNISR — Q8TF01 (reviewed: Q8TF01)

Alternative names: PNN-interacting serine/arginine-rich protein, SR-related protein, SR-rich protein, Serine/arginine-rich-splicing regulatory protein 130, Splicing factor, arginine/serine-rich 130, Splicing factor, arginine/serine-rich 18

All UniProt accessions (5): Q8TF01, A0A2R8Y2Y1, A0A7P0T9Z6, A0A7P0Z4K1, A0A7P0Z4P8

UniProt curated annotations — full annotation on UniProt →

Subunit / interactions. Interacts with PNN.

Subcellular location. Nucleus speckle.

Tissue specificity. Expressed in heart, skeletal muscle, thymus, spleen, kidney, liver, placenta and leukocytes.

Similarity. Belongs to the splicing factor SR family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8TF01-1	1	yes
Q8TF01-2	2

RefSeq proteins (12): NP_001309334, NP_001309335, NP_001309337, NP_001309339, NP_001309341, NP_001309342, NP_001309343, NP_001309344, NP_001309345, NP_001309346, NP_056306, NP_116259* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR031937	PNISR	Family

Pfam: PF15996

UniProt features (48 total): compositionally biased region 19, modified residue 10, sequence conflict 8, coiled-coil region 3, cross-link 3, region of interest 2, splice variant 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TF01-F1	54.69	0.08

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 (13): 204, 211, 290, 304, 313, 321, 465, 467, 485, 726, 218, 496, 703

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 243 (showing top): BROWNE_HCMV_INFECTION_6HR_DN, CAFFAREL_RESPONSE_TO_THC_UP, ONKEN_UVEAL_MELANOMA_UP, DEURIG_T_CELL_PROLYMPHOCYTIC_LEUKEMIA_DN, BLALOCK_ALZHEIMERS_DISEASE_UP, DACOSTA_UV_RESPONSE_VIA_ERCC3_COMMON_DN, BENPORATH_NOS_TARGETS, BASAKI_YBX1_TARGETS_DN, BILBAN_B_CLL_LPL_DN, POU3F2_02, NOUZOVA_TRETINOIN_AND_H4_ACETYLATION, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_DN, GOCC_NUCLEAR_SPECK, BENPORATH_OCT4_TARGETS, GOCC_NUCLEAR_BODY

GO Biological Process (0):

GO Molecular Function (1): RNA binding (GO:0003723)

GO Cellular Component (6): nucleoplasm (GO:0005654), cytosol (GO:0005829), plasma membrane (GO:0005886), nuclear speck (GO:0016607), presynaptic active zone (GO:0048786), nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
nucleic acid binding	1
nuclear lumen	1
cytoplasm	1
membrane	1
cell periphery	1
nuclear ribonucleoprotein granule	1
presynapse	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1766 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PNISR	SCAF11	Q99590	869
PNISR	U2AF2	P26368	848
PNISR	SRSF2	Q01130	787
PNISR	SNRNP70	P08621	711
PNISR	PNN	Q9H307	679
PNISR	PRPF39	Q86UA1	589
PNISR	SRRM2	Q9UQ35	585
PNISR	FAXC	Q5TGI0	539
PNISR	SRSF6	Q13247	513
PNISR	FBXL4	Q9UKA2	511
PNISR	SREK1	Q8WXA9	508
PNISR	TRA2B	P62995	461
PNISR	COQ3	Q9NZJ6	456
PNISR	LUC7L3	O95232	452
PNISR	RNPS1	Q15287	446

IntAct

39 interactions, top by confidence:

A	B	Type	Score
CDK8	MED19	psi-mi:“MI:2364”(proximity)	0.850
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
CAMKV	AP3B1	psi-mi:“MI:0914”(association)	0.640
PIP4K2A	AP3B1	psi-mi:“MI:0914”(association)	0.530
EPB41L1	AP3B1	psi-mi:“MI:0914”(association)	0.530
PIH1D1	PNISR	psi-mi:“MI:0915”(physical association)	0.400
RPS24	PNISR	psi-mi:“MI:0915”(physical association)	0.370
HSPB1	PNISR	psi-mi:“MI:0915”(physical association)	0.370
Papss1	TCOF1	psi-mi:“MI:0914”(association)	0.350
Shoc2	GABPB1	psi-mi:“MI:0914”(association)	0.350
Kifc5b	KPNA3	psi-mi:“MI:0914”(association)	0.350
CDC42	BBX	psi-mi:“MI:0914”(association)	0.350
Naa10	MYO9A	psi-mi:“MI:0914”(association)	0.350
EDEM1	P4HB	psi-mi:“MI:0914”(association)	0.350
BAG3	HTT	psi-mi:“MI:0914”(association)	0.350
Xpo1	IFT56	psi-mi:“MI:0914”(association)	0.350
Mecom	ESYT2	psi-mi:“MI:0914”(association)	0.350
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
CAMKV	AP3B1	psi-mi:“MI:0914”(association)	0.350
AKR7L	KIF2A	psi-mi:“MI:0914”(association)	0.350
AFG2B	MMP24OS	psi-mi:“MI:0914”(association)	0.350
BTK	BLTP3B	psi-mi:“MI:0914”(association)	0.350
LUC7L2	SAP18	psi-mi:“MI:0914”(association)	0.350
PIP4K2A	SAP18	psi-mi:“MI:0914”(association)	0.350
SRPK2	SAP18	psi-mi:“MI:0914”(association)	0.350
SYT2	SMAP	psi-mi:“MI:0914”(association)	0.350

BioGRID (60): PNISR (Affinity Capture-RNA), PNISR (Affinity Capture-RNA), PNISR (Two-hybrid), PNISR (Co-fractionation), PNISR (Co-fractionation), PNISR (Co-fractionation), PNISR (Proximity Label-MS), PNISR (Biochemical Activity), PNISR (Affinity Capture-MS), PNISR (Affinity Capture-MS), PNISR (Affinity Capture-MS), PNISR (Affinity Capture-MS), PNISR (Affinity Capture-MS), PNISR (Affinity Capture-MS), PNISR (Affinity Capture-MS)

ESM2 similar proteins: A0JNI5, A2AJT4, A2AQ19, A4IFB1, B1H1X4, D3ZTQ1, O43290, P35269, Q05519, Q12872, Q13435, Q3THK3, Q3UJB0, Q3UQU0, Q3USH5, Q4V7C9, Q53F19, Q568R1, Q5EA53, Q5HZB6, Q5PQQ2, Q5R539, Q5RAD5, Q5XIW8, Q5ZM19, Q66I22, Q6AY96, Q6DDA4, Q6GLZ8, Q6INH5, Q6ZPZ3, Q8BZR9, Q8CFC7, Q8K194, Q8N2M8, Q8N5F7, Q8TF01, Q8VHI6, Q8WVK2, Q923D5

Diamond homologs: A2AJT4, Q8TF01

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 49 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
Viral Infection Pathways	9	8.4×	9e-05
Infectious disease	11	8.3×	1e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	103
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2345 predictions. Top by Δscore:

Variant	Effect	Δscore
6:99401425:T:TA	donor_gain	1.0000
6:99401434:A:AC	donor_gain	1.0000
6:99401434:ACT:A	donor_gain	1.0000
6:99401435:C:CC	donor_gain	1.0000
6:99401435:CTC:C	donor_gain	1.0000
6:99401440:T:TA	donor_gain	1.0000
6:99401511:T:TA	donor_gain	1.0000
6:99401631:C:CC	acceptor_gain	1.0000
6:99402542:T:A	donor_gain	1.0000
6:99402554:T:C	donor_gain	1.0000
6:99402564:G:C	donor_gain	1.0000
6:99402596:T:TA	donor_gain	1.0000
6:99402597:C:A	donor_gain	1.0000
6:99403891:C:CT	acceptor_gain	1.0000
6:99403893:C:CT	acceptor_gain	1.0000
6:99403896:C:CT	acceptor_gain	1.0000
6:99403897:A:T	acceptor_gain	1.0000
6:99403903:A:T	acceptor_gain	1.0000
6:99403908:CAACA:C	acceptor_gain	1.0000
6:99403911:CA:C	acceptor_gain	1.0000
6:99403912:A:AC	acceptor_gain	1.0000
6:99403912:A:C	acceptor_gain	1.0000
6:99404602:CCTTT:C	donor_gain	1.0000
6:99404700:CAT:C	acceptor_gain	1.0000
6:99404703:C:CC	acceptor_gain	1.0000
6:99406039:A:AC	donor_gain	1.0000
6:99406040:C:CC	donor_gain	1.0000
6:99406040:CT:C	donor_gain	1.0000
6:99406047:T:TA	donor_gain	1.0000
6:99406164:CTATC:C	acceptor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000091060 (6:99415779 T>A,G), RS1000163148 (6:99400188 A>T), RS1000467600 (6:99415147 A>C,G), RS1000491571 (6:99401414 C>G,T), RS1000523440 (6:99415444 G>A), RS1000551333 (6:99408386 C>G,T), RS1000561773 (6:99420361 A>G,T), RS1000633829 (6:99420184 T>C), RS1000747521 (6:99425960 C>G,T), RS1000761020 (6:99401886 G>A), RS1000844174 (6:99401747 C>A), RS1000978166 (6:99421213 A>C), RS1000982687 (6:99408675 T>C), RS1001108245 (6:99414775 C>A,T), RS1001129937 (6:99413781 T>C)

Disease associations

OMIM: gene MIM:616653 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST009391_89	Metabolite levels	9.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5725138 (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

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

pChembl	Type	Value	Unit	Molecule
8.10	Kd	8	nM	MOLIBRESIB

PubChem BioAssay actives

1 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	2179233: Binding affinity against SFRS18 (unknown origin) assessed as apparent dissociation constant incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	kd	0.0080	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression	8
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Dronabinol	increases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
Cyclosporine	decreases expression, decreases methylation	2
FR900359	affects phosphorylation	1
TAK-243	decreases sumoylation	1
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
bisphenol A	decreases expression	1
trichostatin A	affects expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
beta-lapachone	decreases expression	1
sodium arsenite	decreases expression	1
butyraldehyde	decreases expression	1
nickel chloride	decreases expression	1
zinc chromate	increases expression, increases abundance	1
resorcinol	increases expression	1
avobenzone	increases expression	1
cyanoginosin LR	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
chromium hexavalent ion	increases abundance, increases expression	1
perfluorooctane sulfonic acid	decreases expression	1
entinostat	decreases expression	1
monomethylarsonous acid	decreases expression	1
K 7174	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
dimethylarsinous acid	decreases expression	1
ICG 001	decreases expression	1
dorsomorphin	affects cotreatment, decreases 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
CHEMBL5697684	Binding	Inhibition of SFRS18 (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.