PRKRIP1

Summary

PRKRIP1 (PRKR interacting protein 1, HGNC:21894) is a protein-coding gene on chromosome 7q22.1, encoding PRKR-interacting protein 1 (Q9H875). Required for pre-mRNA splicing as component of the spliceosome. It is a selective cancer dependency (DepMap: 27.1% of cell lines).

Predicted to enable double-stranded RNA binding activity; protein kinase binding activity; and protein kinase inhibitor activity. Involved in renal system process. Located in extracellular exosome.

Source: NCBI Gene 79706 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 1 total
• Cancer dependency (DepMap): dependent in 27.1% of screened cell lines
• MANE Select transcript: NM_024653

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21894
Approved symbol	PRKRIP1
Name	PRKR interacting protein 1
Location	7q22.1
Locus type	gene with protein product
Status	Approved
Aliases	C114, FLJ13902, KRBOX3
Ensembl gene	ENSG00000128563
Ensembl biotype	protein_coding
OMIM	617458
Entrez	79706

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 6 protein_coding, 5 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000397912, ENST00000462601, ENST00000468316, ENST00000469763, ENST00000477886, ENST00000482465, ENST00000482549, ENST00000496391, ENST00000891277, ENST00000933080, ENST00000933081, ENST00000943279

RefSeq mRNA: 1 — MANE Select: NM_024653 NM_024653

CCDS: CCDS34714

Canonical transcript exons

ENST00000397912 — 6 exons

Exon	Start	End
ENSE00001399629	102396363	102396537
ENSE00003484940	102397620	102397698
ENSE00003626794	102407434	102407498
ENSE00003655506	102399548	102399648
ENSE00003669049	102425014	102426666
ENSE00003694424	102404598	102404683

Expression profiles

Bgee: expression breadth ubiquitous, 254 present calls, max score 93.55.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 27.4717 / max 155.7563, expressed in 1821 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
80251	21.6500	1817
80250	5.7976	1641
204622	0.0241	1

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	93.55	gold quality
cerebellar hemisphere	UBERON:0002245	93.20	gold quality
cerebellar cortex	UBERON:0002129	93.11	gold quality
right hemisphere of cerebellum	UBERON:0014890	92.95	gold quality
left testis	UBERON:0004533	92.72	gold quality
cerebellum	UBERON:0002037	92.33	gold quality
right testis	UBERON:0004534	92.10	gold quality
granulocyte	CL:0000094	91.71	gold quality
adenohypophysis	UBERON:0002196	91.55	gold quality
pituitary gland	UBERON:0000007	91.29	gold quality
metanephros cortex	UBERON:0010533	91.29	gold quality
skin of leg	UBERON:0001511	91.03	gold quality
mucosa of stomach	UBERON:0001199	90.88	gold quality
body of stomach	UBERON:0001161	90.73	gold quality
testis	UBERON:0000473	90.66	gold quality
ventricular zone	UBERON:0003053	90.65	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	90.43	gold quality
minor salivary gland	UBERON:0001830	90.37	gold quality
apex of heart	UBERON:0002098	90.10	gold quality
skin of abdomen	UBERON:0001416	90.08	gold quality
left lobe of thyroid gland	UBERON:0001120	90.03	gold quality
right frontal lobe	UBERON:0002810	89.97	gold quality
right lobe of thyroid gland	UBERON:0001119	89.88	gold quality
muscle layer of sigmoid colon	UBERON:0035805	89.68	gold quality
tibial nerve	UBERON:0001323	89.65	gold quality
left adrenal gland cortex	UBERON:0035825	89.61	gold quality
right adrenal gland	UBERON:0001233	89.60	gold quality
tendon of biceps brachii	UBERON:0008188	89.55	gold quality
lower esophagus	UBERON:0013473	89.54	gold quality
lower esophagus muscularis layer	UBERON:0035833	89.54	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.10

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

38 targeting PRKRIP1, 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-6783-3P	99.89	67.92	2059
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-204-5P	99.79	71.62	2439
HSA-MIR-211-5P	99.79	71.65	2440
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-4755-5P	99.71	70.34	2716
HSA-MIR-5006-3P	99.71	70.26	2728
HSA-MIR-1208	99.70	68.28	1533
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-24-3P	99.59	69.97	1934
HSA-MIR-3153	99.55	67.59	2337
HSA-MIR-4437	99.52	65.29	1266
HSA-MIR-6727-3P	99.49	65.92	1333
HSA-MIR-4688	99.48	64.68	828
HSA-MIR-6743-5P	99.48	63.60	721
HSA-MIR-4722-3P	99.35	65.22	1099
HSA-MIR-6878-3P	99.24	64.23	920
HSA-MIR-6071	99.16	67.77	1780
HSA-MIR-6809-5P	99.13	68.45	1223
HSA-MIR-485-5P	99.10	64.78	1889
HSA-MIR-6884-5P	99.10	64.50	1987
HSA-MIR-3168	99.08	67.75	1384
HSA-MIR-4297	98.77	66.95	2013
HSA-MIR-767-3P	98.61	67.69	1192
HSA-MIR-5088-3P	98.29	66.63	1310
HSA-MIR-5581-5P	97.91	66.50	965
HSA-MIR-146B-3P	97.83	65.29	782

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 27.1% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 1)

• PRKRIP1, A Splicing Complex Factor, Is a Marker of Poor Prognosis in Colorectal Cancer. (PMID:36192001)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	prkrip1	ENSDARG00000033126
mus_musculus	Prkrip1	ENSMUSG00000039737
rattus_norvegicus	Prkrip1	ENSRNOG00000063308
drosophila_melanogaster	CG8441	FBGN0034086
caenorhabditis_elegans		WBGENE00018132

Protein

Protein identifiers

PRKR-interacting protein 1 — Q9H875 (reviewed: Q9H875)

All UniProt accessions (1): Q9H875

UniProt curated annotations — full annotation on UniProt →

Function. Required for pre-mRNA splicing as component of the spliceosome. Binds double-stranded RNA. Inhibits EIF2AK2 kinase activity.

Subunit / interactions. Component of the pre-catalytic and post-catalytic spliceosome complexes. Interacts with EIF2AK2.

Subcellular location. Nucleus. Nucleolus.

Similarity. Belongs to the PRKRIP1 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9H875-1	1	yes
Q9H875-2	2

RefSeq proteins (1): NP_078929* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR009548	Prkrip1	Family

Pfam: PF06658

UniProt features (16 total): region of interest 6, compositionally biased region 3, splice variant 2, sequence variant 2, chain 1, helix 1, coiled-coil region 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
8C6J	ELECTRON MICROSCOPY	2.8
6ICZ	ELECTRON MICROSCOPY	3
6QDV	ELECTRON MICROSCOPY	3.3
9FMD	ELECTRON MICROSCOPY	3.3
5XJC	ELECTRON MICROSCOPY	3.6
7W5A	ELECTRON MICROSCOPY	3.6
7W5B	ELECTRON MICROSCOPY	4.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H875-F1	81.88	0.59

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

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

MSigDB gene sets: 121 (showing top): GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, FOSTER_TOLERANT_MACROPHAGE_DN, REACTOME_PROCESSING_OF_CAPPED_INTRON_CONTAINING_PRE_MRNA, GOBP_RNA_SPLICING, REACTOME_MRNA_SPLICING, RYTTCCTG_ETS2_B, GRYDER_PAX3FOXO1_ENHANCERS_IN_TADS, GOBP_RENAL_SYSTEM_PROCESS, REACTOME_METABOLISM_OF_RNA, GOCC_U2_TYPE_SPLICEOSOMAL_COMPLEX, BENPORATH_OCT4_TARGETS, CTGAGCC_MIR24, GOCC_CATALYTIC_STEP_2_SPLICEOSOME, GOCC_SPLICEOSOMAL_COMPLEX, CHEN_HOXA5_TARGETS_9HR_UP

GO Biological Process (3): renal system process (GO:0003014), mRNA processing (GO:0006397), RNA splicing (GO:0008380)

GO Molecular Function (4): double-stranded RNA binding (GO:0003725), protein kinase inhibitor activity (GO:0004860), protein kinase binding (GO:0019901), protein binding (GO:0005515)

GO Cellular Component (5): nucleoplasm (GO:0005654), spliceosomal complex (GO:0005681), nucleolus (GO:0005730), extracellular exosome (GO:0070062), nucleus (GO:0005634)

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
nuclear lumen	2
system process	1
mRNA metabolic process	1
RNA binding	1
protein kinase activity	1
kinase inhibitor activity	1
protein kinase regulator activity	1
kinase binding	1
binding	1
cellular anatomical structure	1
nuclear protein-containing complex	1
ribonucleoprotein complex	1
intracellular membraneless organelle	1
extracellular vesicle	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

666 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PRKRIP1	FAM32A	Q9Y421	665
PRKRIP1	SDE2	Q6IQ49	595
PRKRIP1	SLU7	O95391	543
PRKRIP1	YJU2	Q9BW85	541
PRKRIP1	CPNE2	Q96FN4	521
PRKRIP1	CACTIN	Q8WUQ7	506
PRKRIP1	CRNKL1	Q9BZJ0	464
PRKRIP1	SPDYE2	Q495Y8	446
PRKRIP1	RAD1	O60671	444
PRKRIP1	YJU2B	P13994	437
PRKRIP1	RPL3L	Q92901	436
PRKRIP1	GLRX5	Q86SX6	425
PRKRIP1	TTC14	Q96N46	422
PRKRIP1	NFS1	Q9Y697	415
PRKRIP1	DHX8	Q14562	401

IntAct

32 interactions, top by confidence:

A	B	Type	Score
SNRPF	GEMIN2	psi-mi:“MI:0914”(association)	0.910
SNRPE	GEMIN2	psi-mi:“MI:0914”(association)	0.770
SNRPG	GEMIN2	psi-mi:“MI:0914”(association)	0.710
SNRPA1	HTATSF1	psi-mi:“MI:0914”(association)	0.640
SNRPA1	U2SURP	psi-mi:“MI:0914”(association)	0.640
SNRPB	SART1	psi-mi:“MI:0914”(association)	0.640
PRKRIP1	TRAF2	psi-mi:“MI:0915”(physical association)	0.560
PRKRIP1	CEP70	psi-mi:“MI:0915”(physical association)	0.560
TRAF2	PRKRIP1	psi-mi:“MI:0915”(physical association)	0.560
SNRPE	PRMT5	psi-mi:“MI:0914”(association)	0.530
SNRPN	PRMT5	psi-mi:“MI:0914”(association)	0.530
SNRPE	SNRPGP15	psi-mi:“MI:0914”(association)	0.530
SNRPB2	CDC40	psi-mi:“MI:0914”(association)	0.530
GSK3B	PRKRIP1	psi-mi:“MI:0915”(physical association)	0.370
MAGEA11	PRKRIP1	psi-mi:“MI:0915”(physical association)	0.370
LRP8	TYK2	psi-mi:“MI:0914”(association)	0.350
PDGFRA	RNPS1	psi-mi:“MI:0914”(association)	0.350
Xpo1	IFT56	psi-mi:“MI:0914”(association)	0.350
SNRPGP15	GEMIN2	psi-mi:“MI:0914”(association)	0.350
BMI1	HMGB1P1	psi-mi:“MI:0914”(association)	0.350
BMI1	MEIS3P1	psi-mi:“MI:0914”(association)	0.350
SNRPB2	U2SURP	psi-mi:“MI:0914”(association)	0.350
FEM1A	RNF113A	psi-mi:“MI:0914”(association)	0.350

BioGRID (52): PRKRIP1 (Two-hybrid), CEP70 (Two-hybrid), PRKRIP1 (Affinity Capture-MS), PRKRIP1 (Two-hybrid), PRKRIP1 (Affinity Capture-MS), PRKRIP1 (Affinity Capture-MS), PRKRIP1 (Affinity Capture-MS), PRKRIP1 (Affinity Capture-MS), PRKRIP1 (Affinity Capture-MS), PRKRIP1 (Affinity Capture-MS), PRKRIP1 (Affinity Capture-MS), PRKRIP1 (Affinity Capture-RNA), PRKRIP1 (Affinity Capture-RNA), PRKRIP1 (Affinity Capture-MS), EIF2AK2 (Affinity Capture-Western)

ESM2 similar proteins: A0JNI5, A2AQ19, D3ZTQ1, O43290, O43395, P21675, P35269, P49140, Q02614, Q12872, Q13435, Q2KIA6, Q2KIT1, Q3THK3, Q3TIV5, Q3U155, Q3UJB0, Q3USH5, Q53F19, Q5EA53, Q5HZB6, Q5R5F1, Q5R5J3, Q5RAD5, Q5U3K5, Q5XIW8, Q5ZIH9, Q5ZJ85, Q5ZM19, Q60544, Q6AY96, Q6PII3, Q6U6G5, Q75QI0, Q80UV9, Q8BVA4, Q8BZR9, Q8CFC7, Q8N2M8, Q8WU90

Diamond homologs: P41880, Q28IN9, Q2KIT1, Q568A0, Q5R5J3, Q5ZKU0, Q6GNG8, Q9CWV6, Q9H875

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 31 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
Metabolism of non-coding RNA	5	122.0×	8e-09
mRNA Splicing	12	50.7×	1e-16
RNA Polymerase II Transcription Termination	6	50.7×	3e-08
snRNP Assembly	6	48.8×	3e-08
SARS-CoV-2 modulates host translation machinery	5	43.1×	1e-06
Processing of Capped Intron-Containing Pre-mRNA	12	37.9×	3e-15
mRNA Polyadenylation	10	33.8×	4e-12
CHD1 and CHD2 subfamily	8	33.5×	1e-09

GO biological processes:

GO term	Partners	Fold	FDR
U2-type prespliceosome assembly	7	161.8×	1e-12
spliceosomal snRNP assembly	7	150.7×	2e-12
mRNA splicing, via spliceosome	14	47.5×	1e-18
RNA splicing	7	22.9×	9e-07

Disease & clinical

Clinical variants and AI predictions

ClinVar

1 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

1866 predictions. Top by Δscore:

Variant	Effect	Δscore
7:102364407:GGAGG:G	donor_gain	1.0000
7:102364408:GAGG:G	donor_gain	1.0000
7:102364408:GAGGG:G	donor_gain	1.0000
7:102364410:GG:G	donor_gain	1.0000
7:102364411:GG:G	donor_gain	1.0000
7:102364412:G:GG	donor_gain	1.0000
7:102366073:GCAG:G	donor_gain	1.0000
7:102366074:CAGG:C	donor_loss	1.0000
7:102366075:AGG:A	donor_loss	1.0000
7:102366076:GGTG:G	donor_loss	1.0000
7:102366077:G:C	donor_loss	1.0000
7:102366078:T:A	donor_loss	1.0000
7:102375910:G:GT	donor_gain	1.0000
7:102375910:G:T	donor_gain	1.0000
7:102375946:GTGG:G	donor_gain	1.0000
7:102376207:AACAG:A	acceptor_gain	1.0000
7:102376210:A:AG	acceptor_gain	1.0000
7:102376210:AG:A	acceptor_gain	1.0000
7:102376211:G:GG	acceptor_gain	1.0000
7:102376211:GG:G	acceptor_gain	1.0000
7:102376211:GGGT:G	acceptor_gain	1.0000
7:102376211:GGGTA:G	acceptor_gain	1.0000
7:102376324:T:G	donor_loss	1.0000
7:102404596:A:AG	acceptor_gain	1.0000
7:102404597:G:GG	acceptor_gain	1.0000
7:102404597:GCAA:G	acceptor_gain	1.0000
7:102404681:GCG:G	donor_gain	1.0000
7:102404682:CGGT:C	donor_loss	1.0000
7:102404683:GGTA:G	donor_loss	1.0000
7:102404684:G:GG	donor_gain	1.0000

AlphaMissense

1203 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:102397680:T:C	F63L	1.000
7:102397682:T:A	F63L	1.000
7:102397682:T:G	F63L	1.000
7:102397698:G:C	G69R	1.000
7:102399553:A:C	S71R	1.000
7:102399555:T:A	S71R	1.000
7:102399555:T:G	S71R	1.000
7:102399557:C:A	A72D	1.000
7:102399560:G:A	G73E	1.000
7:102399563:C:A	A74D	1.000
7:102399568:A:C	S76R	1.000
7:102399570:T:A	S76R	1.000
7:102399570:T:G	S76R	1.000
7:102399577:T:C	F79L	1.000
7:102399578:T:C	F79S	1.000
7:102399578:T:G	F79C	1.000
7:102399579:C:A	F79L	1.000
7:102399579:C:G	F79L	1.000
7:102399580:C:A	H80N	1.000
7:102399580:C:G	H80D	1.000
7:102399582:C:A	H80Q	1.000
7:102399582:C:G	H80Q	1.000
7:102399590:G:C	R83T	1.000
7:102399591:A:C	R83S	1.000
7:102399591:A:T	R83S	1.000
7:102399596:T:C	L85P	1.000
7:102399598:C:A	R86S	1.000
7:102399602:G:C	R87P	1.000
7:102397684:T:A	V64D	0.999
7:102397693:T:A	V67D	0.999

dbSNP variants (sampled 300 via entrez): RS1000327248 (7:102399369 A>G), RS1000632699 (7:102426327 C>T), RS1000664994 (7:102398161 A>G,T), RS1000779649 (7:102397964 G>A,T), RS1000917457 (7:102403227 T>C), RS1001444623 (7:102400603 C>G,T), RS1001716875 (7:102394553 T>C), RS1001735057 (7:102411973 C>T), RS1001764717 (7:102411728 T>G), RS1002065419 (7:102410372 G>A,T), RS1002096662 (7:102410070 C>G,T), RS1002134645 (7:102417056 T>C), RS1002202643 (7:102418413 A>G), RS1002228186 (7:102422867 T>G), RS1002364054 (7:102422527 A>G)

Disease associations

OMIM: gene MIM:617458 | 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: no

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

Binding affinities (BindingDB)

3 measured of 3 human assays (8 total across all organisms); most potent 3 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
H-1152	KI	6 nM
5-(1,4-diazepan-1-ylsulfonyl)isoquinoline	KD	50 nM	US-11198680: Rho kinase inhibitor BA-1049 (R) and active metabolites thereof
belumosudil	IC50	13100 nM	US-10183931: Rho kinase inhibitors

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases methylation, affects expression	2
aristolochic acid I	increases expression	1
FR900359	increases phosphorylation	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
cylindrospermopsin	increases expression	1
tanespimycin	increases expression	1
abrine	increases expression	1
Benzo(a)pyrene	increases methylation, affects methylation	1
Cadmium	increases abundance, decreases expression	1
Carcinogens	decreases expression	1
Doxorubicin	decreases expression	1
Mercuric Chloride	decreases expression	1
Methyl Methanesulfonate	increases expression	1
Potassium Dichromate	increases expression	1
Quercetin	increases expression	1
Smoke	decreases expression	1
Thimerosal	decreases expression	1
Thiram	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	increases expression	1
Tunicamycin	increases expression	1
Cyclosporine	increases expression	1
Aflatoxin B1	increases methylation	1
Cadmium Chloride	decreases expression, increases abundance	1
Copper Sulfate	increases expression	1
Lactic Acid	decreases expression	1

Clinical trials (associated diseases)

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