RIPOR1

Summary

RIPOR1 (RHO family interacting cell polarization regulator 1, HGNC:25836) is a protein-coding gene on chromosome 16q22.1, encoding Rho family-interacting cell polarization regulator 1 (Q6ZS17). Downstream effector protein for Rho-type small GTPases that plays a role in cell polarity and directional migration.

Enables 14-3-3 protein binding activity. Involved in several processes, including establishment of Golgi localization; negative regulation of Rho guanyl-nucleotide exchange factor activity; and negative regulation of Rho protein signal transduction. Located in several cellular components, including Golgi apparatus; cell leading edge; and cytosol.

Source: NCBI Gene 79567 — automated summary from GO annotations (Alliance of Genome Resources).

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 201 total
• GTEx eGene: eQTL in 10 tissues, sQTL in 6 (q < 0.05)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.61 (unconstrained)
• MANE Select transcript: NM_024519
• Notable: 201 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25836
Approved symbol	RIPOR1
Name	RHO family interacting cell polarization regulator 1
Location	16q22.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ13725
Ensembl gene	ENSG00000039523
Ensembl biotype	protein_coding
OMIM	619842
Entrez	79567

Gene structure

Transcript identifiers

Ensembl transcripts: 41 — 32 protein_coding, 7 retained_intron, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

MANE Select: ENST00000042381

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 2: 8, TSL 3: 3, TSL 4: 5, TSL 5: 7

ENST00000042381, ENST00000379312, ENST00000422602, ENST00000428437, ENST00000540839, ENST00000561534, ENST00000562116, ENST00000562755, ENST00000564616, ENST00000565176, ENST00000565190, ENST00000565679, ENST00000566522, ENST00000566559, ENST00000566730, ENST00000566815, ENST00000566907, ENST00000566920, ENST00000568959, ENST00000569179, ENST00000569253, ENST00000569474, ENST00000569733, ENST00000860989, ENST00000860990, ENST00000860991, ENST00000860992, ENST00000860993, ENST00000860994, ENST00000860995, ENST00000860996, ENST00000860997, ENST00000860998, ENST00000860999, ENST00000861000, ENST00000861001, ENST00000861002, ENST00000861003, ENST00000965781, ENST00000965782, ENST00001134117

RefSeq mRNA: 5 — MANE Select: NM_024519 NM_001193522, NM_001193523, NM_001193524, NM_001410885, NM_024519

CCDS: CCDS10840, CCDS54026, CCDS54027, CCDS54028, CCDS92176

Canonical transcript exons

ENST00000042381 — 22 exons

Exon	Start	End
ENSE00001380181	67528829	67528914
ENSE00003505157	67546366	67546786
ENSE00003539957	67538424	67538550
ENSE00003801384	67540300	67540363
ENSE00003801433	67544956	67545117
ENSE00003801861	67539846	67539899
ENSE00003803162	67545664	67545860
ENSE00003803502	67540579	67540704
ENSE00003803768	67543348	67543469
ENSE00003804977	67539728	67539751
ENSE00003805247	67540053	67540205
ENSE00003805827	67545376	67545534
ENSE00003805966	67544299	67544431
ENSE00003806300	67540458	67540501
ENSE00003806516	67546141	67546231
ENSE00003806764	67538990	67539068
ENSE00003806783	67541430	67541578
ENSE00003806883	67541653	67541782
ENSE00003807048	67545949	67546032
ENSE00003807054	67538672	67538824
ENSE00003809764	67541867	67543264
ENSE00003810335	67544695	67544830

Expression profiles

Bgee: expression breadth ubiquitous, 274 present calls, max score 97.83.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 30.5908 / max 908.5516, expressed in 1805 samples.

Highest expression (Bgee): apex of heart, lung, upper lobe of left lung, renal glomerulus, spleen.

Genetic regulation across tissues (GTEx eQTL / sQTL)

RIPOR1 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 10 tissues and its splicing (sQTL) in 6 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

16 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Brain Cerebellum	eqtl	1.1e-06	+0.64	16:67534414:G:A
Whole Blood	eqtl	6.8e-06	-0.13	16:67547980:A:G
Thyroid	eqtl	6.9e-06	-0.28	16:67763231:T:C
Brain Cerebellar Hemisphere	eqtl	1.3e-03	+0.19	16:68217881:C:G
Cells Cultured fibroblasts	eqtl	8.8e-03	+0.32	16:68194852:ATATAT:A
Colon Sigmoid	eqtl	1.3e-02	+0.53	16:67408313:G:A
Muscle Skeletal	eqtl	1.6e-02	+0.09	16:68343030:C:A
Prostate	eqtl	1.7e-02	-0.61	16:68368843:C:T
Artery Tibial	sqtl	1.9e-02	-0.61	16:67532667:G:C
Skin Sun Exposed Lower leg	eqtl	2.0e-02	+0.19	16:66697720:C:CT
Esophagus Muscularis	sqtl	2.4e-02	-0.67	16:67544354:C:T
Adipose Subcutaneous	eqtl	2.7e-02	-0.15	16:66597874:C:T
Brain Cortex	sqtl	2.8e-02	-2.46	16:68463290:G:A
Minor Salivary Gland	sqtl	4.0e-02	+1.37	16:67156074:C:G
Stomach	sqtl	4.1e-02	-1.27	16:67140970:G:A
Testis	sqtl	4.6e-02	-1.27	16:66659353:C:T

FANTOM5 promoters

showing 10 of 11 alternative TSS:

Promoter ID	TPM avg	Samples expressed
154641	19.8221	1778
154645	6.0305	1350
154654	2.1436	916
154655	1.1631	463
154656	0.9720	359
154657	0.3136	109
154643	0.0534	9
154639	0.0371	9
154642	0.0308	12
154640	0.0167	6

Top tissues by expression

showing 100 of 288 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	97.83	gold quality
right lung	UBERON:0002167	97.50	gold quality
upper lobe of left lung	UBERON:0008952	96.63	gold quality
renal glomerulus	UBERON:0000074	96.53	gold quality
spleen	UBERON:0002106	96.47	gold quality
right hemisphere of cerebellum	UBERON:0014890	96.46	gold quality
metanephric glomerulus	UBERON:0004736	96.28	gold quality
right coronary artery	UBERON:0001625	96.22	gold quality
right frontal lobe	UBERON:0002810	96.19	gold quality
upper lobe of lung	UBERON:0008948	96.17	gold quality
metanephros cortex	UBERON:0010533	96.07	gold quality
cerebellar hemisphere	UBERON:0002245	96.03	gold quality
cerebellar cortex	UBERON:0002129	95.98	gold quality
ascending aorta	UBERON:0001496	95.78	gold quality
cortical plate	UBERON:0005343	95.74	gold quality
thoracic aorta	UBERON:0001515	95.73	gold quality
body of uterus	UBERON:0009853	95.73	gold quality
left uterine tube	UBERON:0001303	95.68	gold quality
omental fat pad	UBERON:0010414	95.51	gold quality
sural nerve	UBERON:0015488	95.49	gold quality
peritoneum	UBERON:0002358	95.47	gold quality
lower esophagus muscularis layer	UBERON:0035833	95.43	gold quality
lower esophagus	UBERON:0013473	95.41	gold quality
descending thoracic aorta	UBERON:0002345	95.38	gold quality
aorta	UBERON:0000947	95.31	gold quality
left coronary artery	UBERON:0001626	95.28	gold quality
cortex of kidney	UBERON:0001225	95.25	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	95.22	gold quality
endocervix	UBERON:0000458	95.19	gold quality
mucosa of stomach	UBERON:0001199	95.17	gold quality
popliteal artery	UBERON:0002250	95.08	gold quality
tibial artery	UBERON:0007610	95.08	gold quality
anterior cingulate cortex	UBERON:0009835	95.08	gold quality
cingulate cortex	UBERON:0003027	95.06	gold quality
cerebellum	UBERON:0002037	95.03	gold quality
adipose tissue of abdominal region	UBERON:0007808	95.03	gold quality
coronary artery	UBERON:0001621	94.98	gold quality
heart left ventricle	UBERON:0002084	94.97	gold quality
right atrium auricular region	UBERON:0006631	94.94	gold quality
cardiac ventricle	UBERON:0002082	94.82	gold quality
right lobe of thyroid gland	UBERON:0001119	94.81	gold quality
tibial nerve	UBERON:0001323	94.63	gold quality
left lobe of thyroid gland	UBERON:0001120	94.58	gold quality
stromal cell of endometrium	CL:0002255	94.55	gold quality
nucleus accumbens	UBERON:0001882	94.42	gold quality
caudate nucleus	UBERON:0001873	94.35	gold quality
ectocervix	UBERON:0012249	94.22	gold quality
right ovary	UBERON:0002118	94.16	gold quality
adult mammalian kidney	UBERON:0000082	94.10	gold quality
putamen	UBERON:0001874	94.06	gold quality
lower esophagus mucosa	UBERON:0035834	94.03	gold quality
thyroid gland	UBERON:0002046	93.92	gold quality
muscle layer of sigmoid colon	UBERON:0035805	93.92	gold quality
subcutaneous adipose tissue	UBERON:0002190	93.91	gold quality
prefrontal cortex	UBERON:0000451	93.90	gold quality
neocortex	UBERON:0001950	93.83	gold quality
granulocyte	CL:0000094	93.79	gold quality
heart	UBERON:0000948	93.77	gold quality
frontal cortex	UBERON:0001870	93.75	gold quality
monocyte	CL:0000576	93.56	gold quality
cardiac atrium	UBERON:0002081	93.55	gold quality
amygdala	UBERON:0001876	93.52	gold quality
mononuclear cell	CL:0000842	93.47	gold quality
left ovary	UBERON:0002119	93.43	gold quality
adenohypophysis	UBERON:0002196	93.38	gold quality
gall bladder	UBERON:0002110	93.36	gold quality
leukocyte	CL:0000738	93.26	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	93.26	gold quality
Brodmann (1909) area 9	UBERON:0013540	92.98	gold quality
telencephalon	UBERON:0001893	92.97	gold quality
cerebral cortex	UBERON:0000956	92.92	gold quality
forebrain	UBERON:0001890	92.82	gold quality
brain	UBERON:0000955	92.69	gold quality
left adrenal gland cortex	UBERON:0035825	92.66	gold quality
pituitary gland	UBERON:0000007	92.64	gold quality
colonic epithelium	UBERON:0000397	92.60	gold quality
left adrenal gland	UBERON:0001234	92.56	gold quality
cerebellar vermis	UBERON:0004720	92.52	silver quality
body of pancreas	UBERON:0001150	92.48	gold quality
right adrenal gland	UBERON:0001233	92.34	gold quality
right adrenal gland cortex	UBERON:0035827	92.34	gold quality
myometrium	UBERON:0001296	92.31	gold quality
temporal lobe	UBERON:0001871	92.26	gold quality
hypothalamus	UBERON:0001898	92.22	gold quality
adipose tissue	UBERON:0001013	92.19	gold quality
adrenal cortex	UBERON:0001235	92.15	gold quality
small intestine Peyer’s patch	UBERON:0003454	92.06	gold quality
connective tissue	UBERON:0002384	92.00	gold quality
Ammon’s horn	UBERON:0001954	91.97	gold quality
fundus of stomach	UBERON:0001160	91.95	gold quality
body of stomach	UBERON:0001161	91.84	gold quality
hindlimb stylopod muscle	UBERON:0004252	91.82	gold quality
lung	UBERON:0002048	91.79	gold quality
esophagus	UBERON:0001043	91.78	gold quality
bone marrow cell	CL:0002092	91.53	gold quality
gastrocnemius	UBERON:0001388	91.51	gold quality
ganglionic eminence	UBERON:0004023	91.46	gold quality
smooth muscle tissue	UBERON:0001135	91.43	gold quality
muscle of leg	UBERON:0001383	91.30	gold quality
minor salivary gland	UBERON:0001830	91.24	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-CURD-119	yes	28.50
E-ANND-3	yes	12.95
E-MTAB-9543	yes	7.72
E-CURD-112	no	2.72

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 76 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Hippocampus	tissue	109.2	not detected
Postcentral gyrus	tissue	99.9
Nucleus accumbens	tissue	94.5
Locus coeruleus	tissue	88.1
Choroid plexus	tissue	64.5
Retina	tissue	40.7
Spleen	tissue	40.6	not detected
Heart muscle	tissue	37.1	not detected
Frontal cortex	tissue	33.6
Vagina	tissue	28.3	not detected
Placenta	tissue	28.0	not detected
Cerebellum	tissue	28.0	low
Caudate putamen	tissue	28.0
Prefrontal cortex	tissue	27.9
Cerebral cortex	tissue	27.9	not detected
Lung	tissue	27.9	low
Skeletal muscle	tissue	27.7	not detected
Adipose tissue	tissue	27.0	not detected
Insular cortex	tissue	26.0
Motor cortex	tissue	25.8
Bone marrow	tissue	25.7	not detected
Occipital cortex	tissue	25.7
Somatosensory cortex	tissue	25.2
Retrosplenial cortex	tissue	25.0
Pituitary gland	tissue	24.8
Retrosplenial and cingulate cortex	tissue	24.7
Hippocampal formation	tissue	24.5
Entorhinal cortex	tissue	24.4
Basal ganglia	tissue	24.1	not detected
Temporal cortex	tissue	23.8
Smooth muscle	tissue	23.5	not detected
Putamen	tissue	23.5
Ventral forebrain	tissue	23.5
Amygdala	tissue	22.9
Pancreas	tissue	22.6	low
Olfactory bulb	tissue	22.4
Superior colliculi	tissue	22.1
Appendix	tissue	22.1	medium
Substantia nigra	tissue	21.5
Kidney	tissue	21.2	low
Corpus callosum	tissue	21.2
Hypothalamus	tissue	21.1
Midbrain	tissue	21.0
Tongue	tissue	20.8
Thalamus	tissue	20.8
Septum	tissue	20.8
Gallbladder	tissue	20.1	low
Pons	tissue	19.8
Endometrium 1	tissue	19.7	not detected
Lymph node	tissue	19.5	not detected
Medulla oblongata	tissue	19.5
Spinal cord	tissue	19.4
Parathyroid gland	tissue	19.3	not detected
Seminal vesicle	tissue	19.0	not detected
Ovary	tissue	18.9	not detected
Urinary bladder	tissue	18.0	medium
Cervix	tissue	17.0	not detected
Periaqueductal gray	tissue	16.8
Tonsil	tissue	16.4	not detected
Thyroid gland	tissue	15.9	not detected

Brain sub-regions (HPA Brain Atlas): detected in 190; highest nTPM — Precentral gyrus (125.3), Hippocampus, CA3 (119.8), Dentate gyrus (115.3), Temporo-occipital transitional zone (112.4), Entorhinal gyrus (111.4).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting RIPOR1 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 38 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-345-3P	99.89	70.23	1421
HSA-MIR-3140-3P	99.88	68.47	2069
HSA-MIR-3151-5P	99.86	63.83	1069
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-4760-5P	99.80	69.88	1619
HSA-MIR-6885-3P	99.75	70.36	3187
HSA-MIR-6752-3P	99.72	66.71	1587
HSA-MIR-1825	99.72	68.11	1089
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-8061	99.63	69.44	1411
HSA-MIR-4663	99.62	65.33	957
HSA-MIR-4472	99.56	66.08	1478
HSA-MIR-4688	99.48	64.68	828
HSA-MIR-6743-5P	99.48	63.60	721
HSA-MIR-6507-5P	99.36	70.46	2524
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-10522-5P	99.26	68.50	2087
HSA-MIR-5787	99.22	67.86	2628
HSA-MIR-491-5P	99.13	65.98	1468
HSA-MIR-6809-5P	99.13	68.45	1223
HSA-MIR-3688-5P	99.12	69.67	1091
HSA-MIR-4764-5P	98.88	65.53	894

Functional genomics

gnomAD constraint: pLI 2.89e-06, LOEUF 0.609, missense Z 2.27 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000042381 splits into 3 regions with different missense tolerance; 0 are missense-constrained. Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
16:67,538,447–67,539,052	165 / 145.5	1.13	no
16:67,539,053–67,541,691	202 / 295.9	0.68	no
16:67,541,692–67,546,460	1005 / 1144.7	0.88	no

Literature-anchored findings (GeneRIF, showing 1)

• These results reveal a previously unidentified pathway downstream of RHO that regulates the polarity of migrating cells through Golgi reorientation in a FAM65A-, CCM3- and MST3- and MST4-dependent manner. (PMID:27807006)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	ripor1	ENSDARG00000062178
mus_musculus	Ripor1	ENSMUSG00000038604
rattus_norvegicus	Ripor1	ENSRNOG00000017604
caenorhabditis_elegans		WBGENE00045063

Paralogs (2): RIPOR3 (ENSG00000042062), RIPOR2 (ENSG00000111913)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1922937) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 1 distinct phenotype terms.

Mouse phenotype (MP)	Records
preweaning lethality, complete penetrance	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Gallus gallus	Q5F3L9	83.4%	Diamond
Coturnix japonica	A9ZLX4	83.1%	Diamond
Bos taurus	Q3B7M3	82.7%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
ATP6V0D1-DT	ncRNA	101927837
CTCF	protein-coding	10664
CTCF-DT	ncRNA	107984813
AGRP	protein-coding	181
ATP6V0D1	protein-coding	9114
HSD11B2	protein-coding	3291
CARMIL2	protein-coding	146206
PARD6A	protein-coding	50855
ACD	protein-coding	65057
ZDHHC1	protein-coding	29800

Protein

Protein identifiers

Rho family-interacting cell polarization regulator 1 — Q6ZS17 (reviewed: Q6ZS17)

All UniProt accessions (12): A0A0A0MTL6, A0A0G2JLA4, Q6ZS17, H3BMG9, H3BP86, H3BQI5, H3BS40, H3BSV5, H3BSX9, H3BU12, H3BUP6, H3BV02

UniProt curated annotations — full annotation on UniProt →

Function. Downstream effector protein for Rho-type small GTPases that plays a role in cell polarity and directional migration. Acts as an adapter protein, linking active Rho proteins to STK24 and STK26 kinases, and hence positively regulates Golgi reorientation in polarized cell migration upon Rho activation. Involved in the subcellular relocation of STK26 from the Golgi to cytoplasm punctae in a Rho- and PDCD10-dependent manner upon serum stimulation.

Subunit / interactions. Interacts (via N-terminus) with RHOA (GTP-bound form); this interaction links active RHOA to STK24 and STK26 kinases. Interacts with RHOB. Interacts with RHOC. Interacts (via C-terminus) with PDCD10; this interaction occurs in a Rho-independent manner. Interacts (via C-terminus) with STK24; this interaction occurs in a PDCD10-dependent and Rho-independent manner. Interacts (via C-terminus) with STK26; this interaction occurs in a PDCD10-dependent and Rho-independent manner. Interacts (via N-terminus) with 14-3-3 proteins; these interactions occur in a Rho-dependent manner.

Subcellular location. Cytoplasm. Golgi apparatus.

Similarity. Belongs to the RIPOR family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q6ZS17-1	1	yes
Q6ZS17-2	2
Q6ZS17-3	3
Q6ZS17-4	4

RefSeq proteins (5): NP_001180451, NP_001180452, NP_001180453, NP_001397814, NP_078795* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011989	ARM-like	Homologous_superfamily
IPR016024	ARM-type_fold	Homologous_superfamily
IPR026136	RIPOR3	Family
IPR031780	RIPOR1-3_N	Domain

Pfam: PF15903

UniProt features (29 total): compositionally biased region 8, modified residue 8, sequence conflict 5, region of interest 3, splice variant 3, chain 1, coiled-coil region 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6ZS17-F1	63.47	0.33

Human Protein Atlas

Protein class: Predicted intracellular proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): golgi apparatus; cytosol

Antibody reliability (HPA): IH uncertain · IF supported

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 (8)

Type	Positions
Phosphoserine	22, 349, 351, 456, 459, 874, 875
Phosphothreonine	355

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 0; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

MSigDB gene sets: 231 (showing top): ATF_B, WANG_CLIM2_TARGETS_UP, chr16q22, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_RESPONSE_TO_PEPTIDE, RORA1_01, GOBP_POSITIVE_REGULATION_OF_INTRACELLULAR_PROTEIN_TRANSPORT, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GOBP_REGULATION_OF_GTPASE_ACTIVITY, GOBP_REGULATION_OF_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, AP4_Q6, MEF2_02, GGGTGGRR_PAX4_03

GO Biological Process (10): Rho protein signal transduction (GO:0007266), cellular response to starvation (GO:0009267), response to wounding (GO:0009611), positive regulation of cell migration (GO:0030335), protein localization to Golgi apparatus (GO:0034067), negative regulation of Rho protein signal transduction (GO:0035024), establishment of Golgi localization (GO:0051683), positive regulation of intracellular protein transport (GO:0090316), cellular response to chemokine (GO:1990869), negative regulation of Rho guanyl-nucleotide exchange factor activity (GO:2001107)

GO Molecular Function (2): 14-3-3 protein binding (GO:0071889), protein binding (GO:0005515)

GO Cellular Component (7): cytoplasm (GO:0005737), Golgi apparatus (GO:0005794), cytosol (GO:0005829), vesicle membrane (GO:0012506), membrane (GO:0016020), cell leading edge (GO:0031252), extracellular exosome (GO:0070062)

GO top-level categories

32 GO namespaces:

Category	Terms
cellular anatomical structure	4
cytoplasm	2
small GTPase-mediated signal transduction	1
cellular response to nutrient levels	1
cellular response to stress	1
response to starvation	1
response to stress	1
cell migration	1
regulation of cell migration	1
positive regulation of cell motility	1
protein localization to organelle	1
Rho protein signal transduction	1
regulation of Rho protein signal transduction	1
negative regulation of small GTPase mediated signal transduction	1
Golgi localization	1
establishment of localization in cell	1
establishment of organelle localization	1
intracellular protein transport	1
positive regulation of intracellular transport	1
regulation of intracellular protein transport	1
positive regulation of protein transport	1
cellular response to cytokine stimulus	1
response to chemokine	1
negative regulation of guanyl-nucleotide exchange factor activity	1
protein binding	1
binding	1
intracellular anatomical structure	1
endomembrane system	1
intracellular membrane-bounded organelle	1
organelle membrane	1
vesicle	1
extracellular vesicle	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 17 of 19 annotations. The rest are phylogenetic / computational / electronic (IEA).

17 experimentally-supported GO terms:

GO term	NS	Evidence
Rho protein signal transduction	BP	mutant phenotype
cellular response to chemokine	BP	mutant phenotype
cellular response to starvation	BP	mutant phenotype
establishment of Golgi localization	BP	mutant phenotype
negative regulation of Rho guanyl-nucleotide exchange factor activity	BP	mutant phenotype
negative regulation of Rho protein signal transduction	BP	mutant phenotype
positive regulation of cell migration	BP	mutant phenotype
positive regulation of intracellular protein transport	BP	mutant phenotype
protein localization to Golgi apparatus	BP	mutant phenotype
response to wounding	BP	mutant phenotype
Golgi apparatus	CC	direct assay
cell leading edge	CC	direct assay
cytoplasm	CC	direct assay
cytosol	CC	direct assay
extracellular exosome	CC	high-throughput assay
membrane	CC	direct assay
14-3-3 protein binding	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 732 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RIPOR1	PSKH1	P11801	553
RIPOR1	STK26	Q9P289	460
RIPOR1	RNF17	Q9BXT8	438
RIPOR1	R3HDM2	Q9Y2K5	431
RIPOR1	PARP4	Q9UKK3	417
RIPOR1	ZMYM5	Q9UJ78	416
RIPOR1	PDCD10	Q9BUL8	400
RIPOR1	PLA2G15	Q8NCC3	397
RIPOR1	EDC4	Q6P2E9	395
RIPOR1	PPP4R3B	Q5MIZ7	386
RIPOR1	NPEPL1	Q8NDH3	383
RIPOR1	HIPK1	Q86Z02	379
RIPOR1	TTC7A	Q9ULT0	375
RIPOR1	NUCKS1	Q9H1E3	374
RIPOR1	STRIP1	Q5VSL9	354

IntAct

Human interaction partners of RIPOR1 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

4 partners by confidence:

Partner	Interaction type	MIscore	Records
MAP1LC3B	physical association	0.370	1
STK25	association	0.350	1
FMR1	physical association	0.000	1
MYO7A	physical association	0.000	1

Disease & clinical

Genetic variants

Variant evidence for RIPOR1: 201 ClinVar records (0 pathogenic / likely pathogenic); 4 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	166
Likely benign	10
Benign	0

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 25 predictions of 1,761):

Position(s)	Effect	Δscore	Sites
16:67538551–67538552	donor_loss	1.0000	3
16:67539719	acceptor_gain	1.0000
16:67539848	acceptor_gain	1.0000
16:67539900–67539901	donor_loss	1.0000	3
16:67540044	acceptor_gain	1.0000
16:67540206–67540207	donor_loss	1.0000	5
16:67540364–67540365	donor_loss	1.0000	4
16:67541428–67541429	acceptor_loss	1.0000	5
16:67541556	donor_gain	1.0000
16:67541565	donor_gain	1.0000

AlphaMissense

2,635 missense substitutions predicted likely pathogenic (of 7,843 scored), across 645 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M163	9	0.878	0.986
M213	9	0.878	0.994
D226	8	0.988	0.998
D305	8	0.982	0.994
F854	8	0.975	0.998
D123	8	0.970	0.996
F1223	8	0.970	0.997
F219	8	0.965	1.000
D1176	8	0.963	0.994
F295	8	0.960	0.995
F856	8	0.955	0.997
F209	8	0.954	0.999
F23	8	0.953	0.996
F118	8	0.951	0.998
F138	8	0.949	0.999
D121	8	0.946	0.990
F1213	8	0.923	0.985
F260	8	0.918	0.993
F323	8	0.918	0.982
F363	8	0.914	0.991

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

3 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	1.12e-07
Lung Squamous Cell Carcinoma (TCGA)	unfavorable	5.18e-05
Pancreatic Adenocarcinoma (validation)	unfavorable	0.000412

Disease associations

OMIM: gene MIM:619842 | disease phenotypes:

GWAS associations

4 associations:

Study	Trait	p-value
GCST006979_878	Heel bone mineral density	5e-15
GCST010002_165	Refractive error	2e-14
GCST90002388_355	Lymphocyte count	7e-11
GCST010083_159	Hemoglobin levels	1e-10

EFO canonical traits (from GWAS)

3 canonical traits:

EFO ID	Trait name
EFO:0009270	heel bone mineral density
EFO:0004509	hemoglobin measurement
EFO:0004587	lymphocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Arsenic	affects methylation, increases abundance, increases expression	2
aristolochic acid I	increases expression	1
FR900359	increases phosphorylation	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases methylation	1
lead acetate	increases expression	1
sodium arsenate	increases abundance, increases expression	1
ethyl-p-hydroxybenzoate	increases expression	1
beta-lapachone	increases expression	1
beta-methylcholine	affects expression	1
ICG 001	increases expression	1
Decitabine	affects expression	1
Sunitinib	increases expression	1
Leflunomide	increases expression	1
Acetaminophen	increases expression	1
Cadmium	decreases expression, increases abundance	1
Caffeine	affects phosphorylation	1
Calcitriol	decreases expression	1
Cisplatin	affects expression	1
Doxorubicin	decreases expression	1
Rotenone	decreases expression	1
Silicon Dioxide	increases expression	1
Tetrachlorodibenzodioxin	increases expression	1
Valproic Acid	affects expression	1
Vanadates	increases expression	1
Cyclosporine	increases expression	1
Aflatoxin B1	increases methylation	1
Sodium Selenite	increases expression	1
Cadmium Chloride	decreases expression, increases abundance	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B2DV	Abcam HeLa RIPOR1 KO	Cancer cell line	Female

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.