RITA1

Summary

RITA1 (RBPJ interacting and tubulin associated 1, HGNC:25925) is a protein-coding gene on chromosome 12q24.13, encoding RBPJ-interacting and tubulin-associated protein 1 (Q96K30). Tubulin-binding protein that acts as a negative regulator of Notch signaling pathway.

Enables tubulin binding activity. Involved in negative regulation of Notch signaling pathway and nuclear export. Located in centrosome; cytoplasm; and nucleoplasm.

Source: NCBI Gene 84934 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 43 total
• MANE Select transcript: NM_032848

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25925
Approved symbol	RITA1
Name	RBPJ interacting and tubulin associated 1
Location	12q24.13
Locus type	gene with protein product
Status	Approved
Aliases	FLJ14827, RITA
Ensembl gene	ENSG00000139405
Ensembl biotype	protein_coding
OMIM	620696
Entrez	84934

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 14 protein_coding

ENST00000548278, ENST00000549621, ENST00000552495, ENST00000615042, ENST00000865301, ENST00000865302, ENST00000865303, ENST00000865304, ENST00000932688, ENST00000932689, ENST00000960881, ENST00000960882, ENST00000960883, ENST00000960884

RefSeq mRNA: 2 — MANE Select: NM_032848 NM_001286215, NM_032848

CCDS: CCDS66473, CCDS9166

Canonical transcript exons

ENST00000548278 — 4 exons

Exon	Start	End
ENSE00001512417	113186185	113186316
ENSE00002339420	113191310	113192368
ENSE00003532017	113186683	113187048
ENSE00003848107	113185721	113186021

Expression profiles

Bgee: expression breadth ubiquitous, 254 present calls, max score 88.94.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 23.7192 / max 114.8056, expressed in 1809 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
128150	8.8426	1745
128148	5.1566	1664
128149	3.1305	1302
128151	2.4951	1478
128146	1.9429	783
128152	1.6761	1066
128153	0.2640	95
128147	0.2114	81

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left adrenal gland cortex	UBERON:0035825	88.94	gold quality
left adrenal gland	UBERON:0001234	88.89	gold quality
right adrenal gland	UBERON:0001233	88.83	gold quality
right adrenal gland cortex	UBERON:0035827	88.69	gold quality
gastrocnemius	UBERON:0001388	88.00	gold quality
right lobe of liver	UBERON:0001114	87.96	gold quality
muscle of leg	UBERON:0001383	87.47	gold quality
adrenal cortex	UBERON:0001235	87.30	gold quality
prefrontal cortex	UBERON:0000451	87.24	gold quality
right frontal lobe	UBERON:0002810	87.17	gold quality
hindlimb stylopod muscle	UBERON:0004252	87.16	gold quality
mucosa of transverse colon	UBERON:0004991	86.74	gold quality
adrenal gland	UBERON:0002369	86.50	gold quality
anterior cingulate cortex	UBERON:0009835	86.48	gold quality
cingulate cortex	UBERON:0003027	86.42	gold quality
muscle organ	UBERON:0001630	86.00	gold quality
parotid gland	UBERON:0001831	85.72	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	85.54	gold quality
apex of heart	UBERON:0002098	85.44	gold quality
right uterine tube	UBERON:0001302	85.23	gold quality
frontal cortex	UBERON:0001870	85.05	gold quality
neocortex	UBERON:0001950	84.84	gold quality
triceps brachii	UBERON:0001509	84.63	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	84.39	gold quality
right hemisphere of cerebellum	UBERON:0014890	84.19	gold quality
Brodmann (1909) area 9	UBERON:0013540	84.17	gold quality
nucleus accumbens	UBERON:0001882	84.10	gold quality
gluteal muscle	UBERON:0002000	83.98	gold quality
caudate nucleus	UBERON:0001873	83.81	gold quality
heart left ventricle	UBERON:0002084	83.74	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.58
E-MTAB-6524	no	72.86

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

19 targeting RITA1, 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-548AN	99.97	70.91	2817
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-1271-5P	99.91	71.99	1972
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-4696	99.48	67.48	1040
HSA-MIR-7515	99.31	68.22	1795
HSA-MIR-1273H-3P	99.29	67.55	980
HSA-MIR-4292	99.16	65.57	1767
HSA-MIR-6791-5P	99.16	65.92	1844
HSA-MIR-3160-3P	99.07	64.78	955
HSA-MIR-4477A	98.83	69.75	2952
HSA-MIR-7851-3P	98.72	64.88	980
HSA-MIR-31-5P	98.58	68.35	1239
HSA-MIR-6864-5P	98.38	66.59	1079
HSA-MIR-874-5P	96.93	63.92	1014
HSA-MIR-758-5P	93.99	64.46	534
HSA-MIR-6746-5P	92.37	63.66	103
HSA-MIR-6771-5P	86.50	65.30	81

Literature-anchored findings (GeneRIF, showing 9)

• RITA might suppress tumor growth and induce apoptosis in hepatocellular carcinoma. (PMID:24308154)
• RITA overexpression increased expression of p53 and Fbxw7 and downregulated expression of cyclin D1, cyclin E, CDK2, Hes-1 and NF-kappaB p65. These changes led to growth inhibition and induced G0/G1 cell cycle arrest and apoptosis in SMMC7721 and HepG2 cells. (PMID:25445601)
• human RITA, binding to Drosophila Su(H) and tubulin, cannot influence the Notch signalling pathway in the fly (PMID:25588307)
• structural and biophysical studies demonstrate that RITA binds RBP-J similarly to the RAM (RBP-J-associated molecule) domain of Notch, our biochemical and cellular assays suggest that RITA interacts with additional regions in RBP-J. (PMID:28487372)
• Data indicate that elevated levels of pretreatment RITA expression are correlated with unfavourable clinical outcome in anal carcinoma treated with concomitant chemoradiotherapy. (PMID:29122359)
• A potential role for RITA in the activation of Aurora A. (PMID:30705408)
• This study identifies RITA as a novel crucial player in cell migration and invasion by affecting the turnover of focal adhesions through its interference with the dynamics of actin filaments and microtubules. Its deregulation may contribute to malignant progression. (PMID:31353815)
• RITA Is Expressed in Trophoblastic Cells and Is Involved in Differentiation Processes of the Placenta. (PMID:31766533)
• RITA1 drives the growth of bladder cancer cells by recruiting TRIM25 to facilitate the proteasomal degradation of RBPJ. (PMID:35701858)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Rita1	ENSMUSG00000029600
rattus_norvegicus	Rita1	ENSRNOG00000037720
rattus_norvegicus	Rita1l1	ENSRNOG00000062346

Protein

Protein identifiers

RBPJ-interacting and tubulin-associated protein 1 — Q96K30 (reviewed: Q96K30)

Alternative names: RBPJ-interacting and tubulin-associated protein

All UniProt accessions (2): A0A087X1G3, Q96K30

UniProt curated annotations — full annotation on UniProt →

Function. Tubulin-binding protein that acts as a negative regulator of Notch signaling pathway. Shuttles between the cytoplasm and the nucleus and mediates the nuclear export of RBPJ/RBPSUH, thereby preventing the interaction between RBPJ/RBPSUH and NICD product of Notch proteins (Notch intracellular domain), leading to down-regulate Notch-mediated transcription. May play a role in neurogenesis.

Subunit / interactions. Interacts with RBPJ/RBPSUH.

Subcellular location. Cytoplasm. Nucleus. Cytoskeleton. Microtubule organizing center. Centrosome.

Similarity. Belongs to the RITA family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q96K30-1	1	yes
Q96K30-2	2
Q96K30-3	3

RefSeq proteins (2): NP_001273144, NP_116237* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR031418	RITA1	Family

Pfam: PF17066

UniProt features (21 total): region of interest 4, mutagenesis site 4, splice variant 3, sequence variant 2, sequence conflict 2, short sequence motif 2, compositionally biased region 2, chain 1, strand 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
5EG6	X-RAY DIFFRACTION	2.09

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96K30-F1	60.11	0.00

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Mutagenesis-validated functional residues (4):

Position	Phenotype
7	results in nuclear accumulation; when associated with a-12 and a-15.
12	results in nuclear accumulation; when associated with a-7 and a-15.
15	results in nuclear accumulation; when associated with a-7 and a-12.
95–97	abolishes nuclear localization.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 112 (showing top): GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_NEUROGENESIS, GOBP_NEGATIVE_REGULATION_OF_NOTCH_SIGNALING_PATHWAY, GOCC_MICROTUBULE_ORGANIZING_CENTER, TERAMOTO_OPN_TARGETS_CLUSTER_6, GOBP_NUCLEAR_TRANSPORT, GOCC_CENTROSOME, GOBP_REGULATION_OF_NOTCH_SIGNALING_PATHWAY, GOBP_NUCLEAR_EXPORT, BOCHKIS_FOXA2_TARGETS, chr12q24, GOMF_CYTOSKELETAL_PROTEIN_BINDING, MANALO_HYPOXIA_DN, KRIGE_RESPONSE_TO_TOSEDOSTAT_6HR_DN

GO Biological Process (6): negative regulation of transcription by RNA polymerase II (GO:0000122), Notch signaling pathway (GO:0007219), neurogenesis (GO:0022008), negative regulation of Notch signaling pathway (GO:0045746), nuclear export (GO:0051168), nervous system development (GO:0007399)

GO Molecular Function (2): tubulin binding (GO:0015631), protein binding (GO:0005515)

GO Cellular Component (5): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), centrosome (GO:0005813), cytoskeleton (GO:0005856)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
cell surface receptor signaling pathway	1
nervous system development	1
cell differentiation	1
Notch signaling pathway	1
regulation of Notch signaling pathway	1
negative regulation of signal transduction	1
nucleocytoplasmic transport	1
intercellular transport	1
system development	1
cytoskeletal protein binding	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
centriole	1
microtubule organizing center	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

514 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RITA1	RBPJ	Q06330	559
RITA1	CFAP73	A6NFT4	533
RITA1	LPP	Q93052	533
RITA1	MRPL15	Q9P015	470
RITA1	HIPK4	Q8NE63	469
RITA1	HIPK1	Q86Z02	462
RITA1	MEGF6	O75095	451
RITA1	MEGF11	A6BM72	447
RITA1	DRC10	Q96DY2	436
RITA1	KDM1A	O60341	424
RITA1	HIPK3	Q9H422	404
RITA1	MAP2K5	Q13163	395
RITA1	KCNN4	O15554	392
RITA1	NEURL1B	A8MQ27	389
RITA1	HIPK2	Q9H2X6	388

IntAct

29 interactions, top by confidence:

A	B	Type	Score
RITA1	RBPJ	psi-mi:“MI:0915”(physical association)	0.730
RBPJ	RITA1	psi-mi:“MI:0407”(direct interaction)	0.730
RITA1	RBPJ	psi-mi:“MI:0407”(direct interaction)	0.730
RBPJ	RITA1	psi-mi:“MI:0915”(physical association)	0.730
RBPJ	RITA1	psi-mi:“MI:0403”(colocalization)	0.730
GOLGA2	RITA1	psi-mi:“MI:0915”(physical association)	0.670
DCP1A	RITA1	psi-mi:“MI:0915”(physical association)	0.670
RITA1	DCP1A	psi-mi:“MI:0915”(physical association)	0.670
RITA1	CEP43	psi-mi:“MI:0915”(physical association)	0.500
RITA1	rbpj	psi-mi:“MI:0407”(direct interaction)	0.440
“Su	RITA1	psi-mi:“MI:0407”(direct interaction)	0.440
	RITA1	psi-mi:“MI:0407”(direct interaction)	0.440
RITA1	HOOK2	psi-mi:“MI:0915”(physical association)	0.370
RBPJ	SAMD1	psi-mi:“MI:0914”(association)	0.350
RBPJ	RPA2	psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
RITA1	PLOD3	psi-mi:“MI:0914”(association)	0.350
NEK2	RITA1	psi-mi:“MI:0403”(colocalization)	0.270
RITA1	PCNT	psi-mi:“MI:0403”(colocalization)	0.270
	RITA1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (57): RITA1 (Two-hybrid), RITA1 (Two-hybrid), RITA1 (Reconstituted Complex), RITA1 (Two-hybrid), RITA1 (Two-hybrid), RITA1 (Affinity Capture-MS), COL4A2 (Affinity Capture-MS), PPP3CC (Affinity Capture-MS), PPP2R3C (Affinity Capture-MS), COLGALT2 (Affinity Capture-MS), COLGALT1 (Affinity Capture-MS), CEP350 (Affinity Capture-MS), FGFR1OP (Affinity Capture-MS), PLOD3 (Affinity Capture-MS), RBPJ (Affinity Capture-Western)

ESM2 similar proteins: A0A1B0GTD5, A0A1B0GTJ6, A0A1B0GUX0, A0A3Q1MT14, A0JNL1, A5PJD8, B9EJX3, E1B9R1, E1BNS6, F1MMV1, Q0P591, Q148A4, Q14BB9, Q1JPL0, Q2KJ10, Q2MH31, Q2T9T0, Q2TA11, Q32L72, Q32L77, Q3V0Q6, Q5BN46, Q5PQN4, Q5RBH3, Q5RHU7, Q5SPV6, Q5SVJ3, Q5VTT2, Q5VZQ5, Q66HR9, Q6AYM0, Q7Z5V6, Q8CDU5, Q8N5S3, Q8N865, Q8NA69, Q8NCR6, Q8NEG2, Q95LU0, Q96K30

Diamond homologs: D2HS03, P0CJ62, Q2HJ75, Q2KJ10, Q96K30, Q9D1H0

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
RITA1	down-regulates	RBPJ	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	35
Likely benign	8
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

384 predictions. Top by Δscore:

Variant	Effect	Δscore
12:113185273:CCTA:C	donor_loss	1.0000
12:113185275:TAC:T	donor_loss	1.0000
12:113185276:A:AC	donor_gain	1.0000
12:113185276:A:C	donor_loss	1.0000
12:113185276:ACCTT:A	donor_gain	1.0000
12:113185277:C:CC	donor_gain	1.0000
12:113185277:C:CG	donor_loss	1.0000
12:113185277:CCTT:C	donor_gain	1.0000
12:113185277:CCTTC:C	donor_gain	1.0000
12:113185280:T:A	donor_gain	1.0000
12:113185276:AC:A	donor_gain	0.9900
12:113185277:CC:C	donor_gain	0.9900
12:113185300:T:TA	donor_gain	0.9900
12:113186951:G:GT	donor_gain	0.9900
12:113187031:G:GT	donor_gain	0.9900
12:113187045:ACAG:A	donor_loss	0.9900
12:113187047:AG:A	donor_loss	0.9900
12:113187048:GGTA:G	donor_loss	0.9900
12:113187049:G:A	donor_loss	0.9900
12:113187050:T:G	donor_loss	0.9900
12:113191308:A:AG	acceptor_gain	0.9900
12:113191309:G:GA	acceptor_gain	0.9900
12:113191309:GACCC:G	acceptor_gain	0.9900
12:113185601:G:GG	donor_gain	0.9800
12:113186020:AGG:A	donor_loss	0.9800
12:113186022:GTA:G	donor_loss	0.9800
12:113191302:T:G	acceptor_gain	0.9800
12:113191307:CAG:C	acceptor_loss	0.9800
12:113191309:GA:G	acceptor_gain	0.9800
12:113191309:GACC:G	acceptor_gain	0.9800

AlphaMissense

1696 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:113186861:T:C	F39L	0.975
12:113186863:T:A	F39L	0.975
12:113186863:T:G	F39L	0.975
12:113191350:T:C	F115L	0.973
12:113191352:T:A	F115L	0.973
12:113191352:T:G	F115L	0.973
12:113186912:T:A	W56R	0.961
12:113186912:T:C	W56R	0.961
12:113186914:G:C	W56C	0.955
12:113186914:G:T	W56C	0.955
12:113186900:T:C	F52L	0.929
12:113186902:C:A	F52L	0.929
12:113186902:C:G	F52L	0.929
12:113191809:T:A	W268R	0.927
12:113191809:T:C	W268R	0.927
12:113186861:T:A	F39I	0.911
12:113186862:T:G	F39C	0.905
12:113191811:G:C	W268C	0.905
12:113191811:G:T	W268C	0.905
12:113186853:A:T	E36V	0.899
12:113191337:T:G	C110W	0.895
12:113191336:G:A	C110Y	0.885
12:113186861:T:G	F39V	0.883
12:113191310:A:C	R101S	0.882
12:113191310:A:T	R101S	0.882
12:113191351:T:G	F115C	0.880
12:113191350:T:A	F115I	0.874
12:113186862:T:C	F39S	0.873
12:113191339:A:T	D111V	0.863
12:113186859:T:A	L38Q	0.860

dbSNP variants (sampled 300 via entrez): RS1000000451 (12:113192184 G>C,T), RS1000200284 (12:113191908 G>A), RS1000295980 (12:113185426 G>A,C), RS1000714909 (12:113190096 G>A), RS1000916684 (12:113190440 C>T), RS1001314438 (12:113184926 T>C), RS1001346527 (12:113185157 C>T), RS1001502366 (12:113184639 A>T), RS1001820418 (12:113184973 C>G), RS1001947116 (12:113190698 T>A), RS1002187764 (12:113185110 C>A,G), RS1002221577 (12:113189689 A>G), RS1002347947 (12:113184072 G>A,T), RS1002595083 (12:113189173 G>A), RS1002609682 (12:113187523 G>A)

Disease associations

OMIM: gene MIM:620696 | 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
GCST005951_2	Body mass index	9.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

20 total (human), top 20 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
FR900359	decreases phosphorylation	1
sodium arsenite	decreases expression	1
cobaltous chloride	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
K 7174	decreases expression	1
ICG 001	increases expression	1
jinfukang	increases expression, affects cotreatment	1
NSC 689534	affects binding, decreases expression	1
Sunitinib	increases expression	1
Cisplatin	affects cotreatment, increases expression	1
Copper	affects binding, decreases expression	1
Formaldehyde	decreases expression	1
Smoke	decreases expression	1
Thiram	decreases expression	1
Tretinoin	decreases expression	1
Valproic Acid	increases expression	1
Cadmium Chloride	decreases expression	1
Copper Sulfate	decreases expression	1
Lactic Acid	decreases expression	1
Vitamin K 3	affects expression	1

Clinical trials (associated diseases)

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