RHPN1

Summary

RHPN1 (rhophilin Rho GTPase binding protein 1, HGNC:19973) is a protein-coding gene on chromosome 8q24.3, encoding Rhophilin-1 (Q8TCX5). Has no enzymatic activity. It is a selective cancer dependency (DepMap: 17.5% of cell lines).

Predicted to be involved in negative regulation of stress fiber assembly. Predicted to act upstream of or within several processes, including focal adhesion assembly; glomerular filtration; and renal albumin absorption. Predicted to be located in plasma membrane.

Source: NCBI Gene 114822 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 186 total
• Cancer dependency (DepMap): dependent in 17.5% of screened cell lines
• MANE Select transcript: NM_052924

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19973
Approved symbol	RHPN1
Name	rhophilin Rho GTPase binding protein 1
Location	8q24.3
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1929, RHPN, ODF5
Ensembl gene	ENSG00000158106
Ensembl biotype	protein_coding
OMIM	601031
Entrez	114822

Gene structure

Transcript identifiers

Ensembl transcripts: 44 — 42 protein_coding, 2 retained_intron

ENST00000289013, ENST00000522335, ENST00000522899, ENST00000715591, ENST00000857760, ENST00000857761, ENST00000857762, ENST00000857763, ENST00000857764, ENST00000857765, ENST00000857766, ENST00000857767, ENST00000857768, ENST00000857769, ENST00000857770, ENST00000857771, ENST00000857772, ENST00000857773, ENST00000857774, ENST00000857775, ENST00000857776, ENST00000857777, ENST00000857778, ENST00000857779, ENST00000857780, ENST00000857781, ENST00000857782, ENST00000857783, ENST00000857784, ENST00000857785, ENST00000930055, ENST00000930056, ENST00000930057, ENST00000930058, ENST00000930059, ENST00000930060, ENST00000930061, ENST00000964538, ENST00000964539, ENST00000964540, ENST00000964541, ENST00000964542, ENST00000964543, ENST00000964544

RefSeq mRNA: 1 — MANE Select: NM_052924 NM_052924

CCDS: CCDS47927

Canonical transcript exons

ENST00000289013 — 15 exons

Exon	Start	End
ENSE00001139743	143380062	143380175
ENSE00001328129	143368876	143369047
ENSE00003474215	143378912	143379078
ENSE00003474548	143378269	143378346
ENSE00003491955	143378696	143378820
ENSE00003506371	143377380	143377455
ENSE00003518918	143381268	143381344
ENSE00003550871	143375553	143375668
ENSE00003586031	143376525	143376653
ENSE00003588153	143379315	143379508
ENSE00003615003	143380589	143380783
ENSE00003659226	143379829	143379985
ENSE00004027325	143381572	143381718
ENSE00004027326	143382436	143384221
ENSE00004027327	143381807	143381968

Expression profiles

Bgee: expression breadth ubiquitous, 205 present calls, max score 95.48.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.0485 / max 269.1854, expressed in 1076 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
91403	2.9825	718
91402	2.2854	799
91401	0.7807	448

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of thyroid gland	UBERON:0001119	95.48	gold quality
left lobe of thyroid gland	UBERON:0001120	95.06	gold quality
adenohypophysis	UBERON:0002196	94.78	gold quality
pituitary gland	UBERON:0000007	94.26	gold quality
right uterine tube	UBERON:0001302	93.85	gold quality
thyroid gland	UBERON:0002046	93.58	gold quality
pancreatic ductal cell	CL:0002079	92.76	silver quality
metanephros cortex	UBERON:0010533	92.72	gold quality
right frontal lobe	UBERON:0002810	92.00	gold quality
kidney epithelium	UBERON:0004819	91.34	gold quality
nucleus accumbens	UBERON:0001882	91.02	gold quality
Brodmann (1909) area 9	UBERON:0013540	90.66	gold quality
amygdala	UBERON:0001876	90.48	gold quality
anterior cingulate cortex	UBERON:0009835	89.93	gold quality
caudate nucleus	UBERON:0001873	89.67	gold quality
hypothalamus	UBERON:0001898	89.60	gold quality
nasal cavity epithelium	UBERON:0005384	89.27	silver quality
putamen	UBERON:0001874	89.00	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	88.96	gold quality
vena cava	UBERON:0004087	88.83	silver quality
thymus	UBERON:0002370	88.69	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	88.30	gold quality
cortex of kidney	UBERON:0001225	88.29	gold quality
upper arm skin	UBERON:0004263	88.11	gold quality
forebrain	UBERON:0001890	87.71	gold quality
parotid gland	UBERON:0001831	87.10	silver quality
tibial nerve	UBERON:0001323	87.05	gold quality
neocortex	UBERON:0001950	87.01	gold quality
frontal cortex	UBERON:0001870	86.81	gold quality
Ammon’s horn	UBERON:0001954	86.70	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.04

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

55 targeting RHPN1, 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-6748-5P	100.00	65.81	1057
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-6762-3P	99.66	66.94	1188
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-6836-5P	99.60	65.62	1538
HSA-MIR-6132	99.60	65.83	1554
HSA-MIR-24-3P	99.59	69.97	1934
HSA-MIR-4328	99.57	71.06	4094
HSA-MIR-1275	99.47	67.90	2749
HSA-MIR-6165	99.44	67.12	1389
HSA-MIR-6837-5P	99.25	65.47	1632
HSA-MIR-4685-5P	99.25	65.99	1563
HSA-MIR-7974	99.24	65.48	1137
HSA-MIR-8052	99.17	65.01	719
HSA-MIR-6071	99.16	67.77	1780
HSA-MIR-4254	99.11	65.15	1315
HSA-MIR-7160-5P	99.11	67.17	2207
HSA-MIR-3619-5P	99.00	68.87	2308
HSA-MIR-939-3P	98.97	65.07	2347

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 17.5% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 2)

• The positive feedback loop of RHPN1-AS1/miR-1299/ETS1 accelerates the deterioration of gastric cancer. (PMID:31982726)
• LncRNA RHPN1-AS1 accelerates proliferation, migration, and invasion via regulating miR-485-5p/BSG axis in hepatocellular carcinoma. (PMID:32435875)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	rhpn1	ENSDARG00000052454
mus_musculus	Rhpn1	ENSMUSG00000022580
rattus_norvegicus	Rhpn1	ENSRNOG00000007597
drosophila_melanogaster	Rhp	FBGN0026374
caenorhabditis_elegans	ego-2	WBGENE00001215

Paralogs (1): RHPN2 (ENSG00000131941)

Protein

Protein identifiers

Rhophilin-1 — Q8TCX5 (reviewed: Q8TCX5)

Alternative names: GTP-Rho-binding protein 1

All UniProt accessions (2): A0AAQ5BIJ1, Q8TCX5

UniProt curated annotations — full annotation on UniProt →

Function. Has no enzymatic activity. May serve as a target for Rho, and interact with some cytoskeletal component upon Rho binding or relay a Rho signal to other molecules.

Subunit / interactions. Binds specifically to GTP-Rho. Interacts with ROPN1.

Domain organisation. The PDZ domain mediates interaction with ROPN1.

Similarity. Belongs to the RHPN family.

RefSeq proteins (1): NP_443156* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001478	PDZ	Domain
IPR004328	BRO1_dom	Domain
IPR011072	HR1_rho-bd	Domain
IPR036034	PDZ_sf	Homologous_superfamily
IPR036274	HR1_rpt_sf	Homologous_superfamily
IPR038499	BRO1_sf	Homologous_superfamily
IPR042715	Rhophilin-1_BRO1	Domain
IPR047138	RHPN1_2	Family

Pfam: PF00595, PF02185, PF03097

UniProt features (8 total): domain 3, region of interest 2, chain 1, compositionally biased region 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TCX5-F1	78.85	0.57

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 (1): 24

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-5666185	RHO GTPases Activate Rhotekin and Rhophilins
R-HSA-8980692	RHOA GTPase cycle

MSigDB gene sets: 76 (showing top): GOBP_ACTIN_FILAMENT_BUNDLE_ORGANIZATION, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION, GOBP_REGULATION_OF_ACTIN_FILAMENT_BASED_PROCESS, GOBP_NEGATIVE_REGULATION_OF_ACTIN_FILAMENT_BUNDLE_ASSEMBLY, GOBP_ACTIN_FILAMENT_ORGANIZATION, GOBP_ACTOMYOSIN_STRUCTURE_ORGANIZATION, GOBP_REGULATION_OF_ACTIN_FILAMENT_BUNDLE_ASSEMBLY, CUI_TCF21_TARGETS_2_DN, GOBP_REGULATION_OF_CYTOSKELETON_ORGANIZATION, GOBP_NEGATIVE_REGULATION_OF_ORGANELLE_ORGANIZATION, CHARAFE_BREAST_CANCER_LUMINAL_VS_MESENCHYMAL_UP, MODULE_69, NIKOLSKY_BREAST_CANCER_8Q23_Q24_AMPLICON, MOREAUX_MULTIPLE_MYELOMA_BY_TACI_UP

GO Biological Process (2): signal transduction (GO:0007165), negative regulation of stress fiber assembly (GO:0051497)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (1): cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
RHO GTPase Effectors	1
RHO GTPase cycle	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
negative regulation of actin filament bundle assembly	1
stress fiber assembly	1
regulation of stress fiber assembly	1
binding	1
cytoplasm	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1022 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RHPN1	ROPN1	Q9HAT0	974
RHPN1	RTKN	Q9BST9	874
RHPN1	PKN1	Q16512	872
RHPN1	ROPN1L	Q96C74	853
RHPN1	AKAP3	O75969	825
RHPN1	CNKSR1	Q969H4	789
RHPN1	CABYR	O75952	761
RHPN1	RGS14	O43566	716
RHPN1	SPA17	Q15506	682
RHPN1	RHOA	P06749	656
RHPN1	RALGDS	Q12967	603
RHPN1	RGS12	O14924	577
RHPN1	PTGDR	Q13258	528
RHPN1	PTS	Q03393	490
RHPN1	RHOD	O00212	471

IntAct

423 interactions, top by confidence:

A	B	Type	Score
GOLGA2	RHPN1	psi-mi:“MI:0915”(physical association)	0.740
RHPN1	PODXL	psi-mi:“MI:0914”(association)	0.690
PODXL	RHPN1	psi-mi:“MI:0407”(direct interaction)	0.690
RHPN1	MTUS2	psi-mi:“MI:0915”(physical association)	0.670
MTUS2	RHPN1	psi-mi:“MI:0915”(physical association)	0.670
TRIM27	RHPN1	psi-mi:“MI:0915”(physical association)	0.560
RHPN1	TRIM27	psi-mi:“MI:0915”(physical association)	0.560
KRT31	RHPN1	psi-mi:“MI:0915”(physical association)	0.560
RHPN1	GPRASP2	psi-mi:“MI:0915”(physical association)	0.560
RHPN1	LZTS1	psi-mi:“MI:0915”(physical association)	0.560
HAP1	RHPN1	psi-mi:“MI:0915”(physical association)	0.560
CEP70	RHPN1	psi-mi:“MI:0915”(physical association)	0.560
RHPN1	GFAP	psi-mi:“MI:0915”(physical association)	0.560
GRN	RHPN1	psi-mi:“MI:0915”(physical association)	0.560
LMNA	RHPN1	psi-mi:“MI:0915”(physical association)	0.560
RHPN1	NEFL	psi-mi:“MI:0915”(physical association)	0.560
RHPN1	PEX1	psi-mi:“MI:0915”(physical association)	0.560
RHPN1	WFS1	psi-mi:“MI:0915”(physical association)	0.560
RHPN1	SPRED1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (87): RHPN1 (Two-hybrid), RHPN1 (Two-hybrid), RHPN1 (Two-hybrid), RHPN1 (Two-hybrid), RHPN1 (Two-hybrid), RHPN1 (Two-hybrid), RHPN1 (Affinity Capture-Western), RHPN1 (Affinity Capture-Western), RHPN1 (Reconstituted Complex), RHPN1 (Reconstituted Complex), CNKSR1 (Affinity Capture-Western), CEP70 (Two-hybrid), PTPN14 (Affinity Capture-MS), PTPN21 (Affinity Capture-MS), WWC1 (Affinity Capture-MS)

ESM2 similar proteins: A1L3C1, A2RRU4, A6QM06, A6QNS9, F1LQY6, O94827, P29372, P29590, P97260, Q01113, Q02833, Q04841, Q12770, Q13505, Q29RM4, Q32KT5, Q32L49, Q3UGX3, Q4R5F9, Q5BK01, Q5I0I4, Q5MNU5, Q5SQH8, Q66T02, Q69Z89, Q6GQT6, Q6RFZ7, Q6UXT9, Q6ZN54, Q70EL4, Q7Z6G3, Q86WI3, Q86YD3, Q8IW40, Q8N1F8, Q8N531, Q8N9H8, Q8TCX5, Q91ZP9, Q920N2

Diamond homologs: A0A1D5P556, A0A8C0TYJ0, A4D2P6, A5PKA5, A8MUH7, B7WN72, G5ECY0, O08774, O14745, O14924, O15085, O60879, P31007, P31016, P70175, P70441, P78352, P97879, Q09506, Q0D5P3, Q0QWG9, Q12959, Q13425, Q15599, Q15700, Q28619, Q28C55, Q3T0X8, Q3UHD6, Q4R6G4, Q5PYH5, Q5PYH6, Q5PYH7, Q5RCF7, Q5T2W1, Q5ZM14, Q61085, Q61235, Q62108, Q62696

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 164 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
Ca2+ pathway	6	9.2×	5e-03
G alpha (12/13) signalling events	7	8.2×	5e-03
GPCR downstream signalling	12	4.5×	5e-03
Signaling by GPCR	12	4.1×	5e-03

GO biological processes:

GO term	Partners	Fold	FDR
transport across blood-brain barrier	7	8.2×	8e-03
phospholipase C-activating G protein-coupled receptor signaling pathway	9	7.7×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	142
Likely benign	15
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3275 predictions. Top by Δscore:

Variant	Effect	Δscore
8:143375667:AGGT:A	donor_loss	1.0000
8:143375669:G:GA	donor_loss	1.0000
8:143376651:G:GT	donor_gain	1.0000
8:143376651:G:T	donor_gain	1.0000
8:143377378:A:AG	acceptor_gain	1.0000
8:143377379:G:GG	acceptor_gain	1.0000
8:143377379:GC:G	acceptor_gain	1.0000
8:143377379:GCGA:G	acceptor_gain	1.0000
8:143377452:GAAG:G	donor_gain	1.0000
8:143377456:G:GC	donor_loss	1.0000
8:143377456:G:GG	donor_gain	1.0000
8:143379506:CAGG:C	donor_loss	1.0000
8:143379508:GGTG:G	donor_loss	1.0000
8:143379983:CCCG:C	donor_loss	1.0000
8:143379984:CCGTG:C	donor_loss	1.0000
8:143379985:CG:C	donor_loss	1.0000
8:143379986:G:GG	donor_gain	1.0000
8:143379986:GTGA:G	donor_loss	1.0000
8:143379987:T:A	donor_loss	1.0000
8:143380060:A:AG	acceptor_gain	1.0000
8:143380061:G:GA	acceptor_gain	1.0000
8:143380061:GCA:G	acceptor_gain	1.0000
8:143380782:GC:G	donor_gain	1.0000
8:143380784:G:GG	donor_gain	1.0000
8:143381592:A:AG	acceptor_gain	1.0000
8:143381593:G:GG	acceptor_gain	1.0000
8:143381705:G:GT	donor_gain	1.0000
8:143381716:GCG:G	donor_gain	1.0000
8:143381719:G:GG	donor_gain	1.0000
8:143381964:GCTTG:G	donor_gain	1.0000

AlphaMissense

4295 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:143381835:T:A	I555N	0.995
8:143381587:T:C	F502L	0.992
8:143381589:C:A	F502L	0.992
8:143381589:C:G	F502L	0.992
8:143381681:T:A	V533D	0.989
8:143381678:C:A	P532H	0.987
8:143377419:G:C	K115N	0.985
8:143377419:G:T	K115N	0.985
8:143381663:T:A	L527H	0.985
8:143381835:T:G	I555S	0.984
8:143381588:T:C	F502S	0.983
8:143378984:C:A	N219K	0.982
8:143378984:C:G	N219K	0.982
8:143381334:T:C	F493S	0.982
8:143378963:G:C	E212D	0.981
8:143378963:G:T	E212D	0.981
8:143380601:T:C	L410P	0.981
8:143380609:G:C	A413P	0.981
8:143379356:A:C	S265R	0.980
8:143379358:C:A	S265R	0.980
8:143379358:C:G	S265R	0.980
8:143379924:G:C	K347N	0.980
8:143379924:G:T	K347N	0.980
8:143381572:G:A	G497R	0.979
8:143381572:G:C	G497R	0.979
8:143378970:A:C	S215R	0.977
8:143378972:C:A	S215R	0.977
8:143378972:C:G	S215R	0.977
8:143381573:G:A	G497E	0.977
8:143381333:T:C	F493L	0.972

dbSNP variants (sampled 300 via entrez): RS1000058899 (8:143374556 G>A), RS1000312030 (8:143381917 C>A,G,T), RS1000359334 (8:143381758 G>A), RS1000402579 (8:143384089 C>T), RS1000410340 (8:143374403 A>C,G), RS1000417255 (8:143384225 A>C), RS1000595745 (8:143375521 T>A,G), RS1000736896 (8:143383380 G>A), RS1000768252 (8:143383549 C>T), RS1000829922 (8:143368763 C>T), RS1000944052 (8:143368616 C>A,T), RS1000983908 (8:143366356 G>A), RS1001052762 (8:143372917 T>A,C,G), RS1001154340 (8:143363905 T>C), RS1001280599 (8:143383966 C>T)

Disease associations

OMIM: gene MIM:601031 | 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)

CTD chemical–gene interactions

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	increases abundance, increases expression, decreases expression	2
Smoke	decreases expression, increases abundance	2
Valproic Acid	affects expression, increases methylation	2
bufotalin	decreases expression	1
methyleugenol	increases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1
sulforaphane	decreases expression	1
sodium arsenite	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
(+)-JQ1 compound	decreases expression	1
Sunitinib	increases expression	1
Cisplatin	affects cotreatment, increases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Estradiol	affects cotreatment, decreases expression	1
Lipopolysaccharides	affects expression, affects response to substance	1
Rotenone	decreases expression	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
1-Methyl-4-phenylpyridinium	increases expression	1
Cyclosporine	decreases methylation	1
Antirheumatic Agents	decreases expression	1
Okadaic Acid	increases expression	1
Acrylamide	decreases expression	1
Particulate Matter	increases abundance, increases expression	1

Clinical trials (associated diseases)

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