RASSF5

Summary

RASSF5 (Ras association domain family member 5, HGNC:17609) is a protein-coding gene on chromosome 1q32.1, encoding Ras association domain-containing protein 5 (Q8WWW0). Potential tumor suppressor.

This gene is a member of the Ras association domain family. It functions as a tumor suppressor, and is inactivated in a variety of cancers. The encoded protein localizes to centrosomes and microtubules, and associates with the GTP-activated forms of Ras, Rap1, and several other Ras-like small GTPases. The protein regulates lymphocyte adhesion and suppresses cell growth in response to activated Rap1 or Ras. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 83593 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 20 total
• Druggable target: yes
• MANE Select transcript: NM_182663

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17609
Approved symbol	RASSF5
Name	Ras association domain family member 5
Location	1q32.1
Locus type	gene with protein product
Status	Approved
Aliases	Maxp1, NORE1, RAPL
Ensembl gene	ENSG00000266094
Ensembl biotype	protein_coding
OMIM	607020
Entrez	83593

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 7 protein_coding, 3 retained_intron

ENST00000577571, ENST00000579436, ENST00000579942, ENST00000580449, ENST00000581503, ENST00000581888, ENST00000605120, ENST00000605653, ENST00000636182, ENST00000931405

RefSeq mRNA: 3 — MANE Select: NM_182663 NM_182663, NM_182664, NM_182665

CCDS: CCDS1463, CCDS1464, CCDS30998

Canonical transcript exons

ENST00000579436 — 6 exons

Exon	Start	End
ENSE00002699683	206538172	206538293
ENSE00002705403	206585180	206585295
ENSE00002711467	206583269	206583379
ENSE00003527477	206584387	206584684
ENSE00003630537	206507531	206508059
ENSE00003796489	206586826	206589448

Expression profiles

Bgee: expression breadth ubiquitous, 250 present calls, max score 97.96.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 34.6862 / max 4506.8685, expressed in 1423 samples.

FANTOM5 promoters (14 alternative TSS)

Promoter ID	TPM avg	Samples expressed
8086	10.5169	1144
8093	8.3518	541
8091	7.5697	537
8092	2.8273	413
8094	2.8146	329
8095	1.2635	298
8087	0.4746	251
8115	0.2715	55
8096	0.2300	80
8118	0.2051	105

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
upper arm skin	UBERON:0004263	97.96	gold quality
granulocyte	CL:0000094	97.67	gold quality
blood	UBERON:0000178	97.67	gold quality
thymus	UBERON:0002370	97.48	gold quality
leukocyte	CL:0000738	96.46	gold quality
ileal mucosa	UBERON:0000331	96.32	gold quality
lymph node	UBERON:0000029	96.31	gold quality
monocyte	CL:0000576	96.29	gold quality
bone marrow	UBERON:0002371	96.24	gold quality
vermiform appendix	UBERON:0001154	96.17	gold quality
nasal cavity epithelium	UBERON:0005384	95.96	gold quality
amniotic fluid	UBERON:0000173	95.94	gold quality
epithelium of nasopharynx	UBERON:0001951	95.37	gold quality
pharyngeal mucosa	UBERON:0000355	95.17	gold quality
spleen	UBERON:0002106	95.16	gold quality
bone marrow cell	CL:0002092	94.87	gold quality
tonsil	UBERON:0002372	94.60	gold quality
esophagus squamous epithelium	UBERON:0006920	94.06	gold quality
palpebral conjunctiva	UBERON:0001812	93.91	gold quality
cardiac muscle of right atrium	UBERON:0003379	93.72	silver quality
caecum	UBERON:0001153	93.43	gold quality
lower esophagus mucosa	UBERON:0035834	93.25	gold quality
oral cavity	UBERON:0000167	93.19	gold quality
pancreatic ductal cell	CL:0002079	93.03	gold quality
trabecular bone tissue	UBERON:0002483	92.58	gold quality
gingiva	UBERON:0001828	92.13	gold quality
esophagus mucosa	UBERON:0002469	92.12	gold quality
trachea	UBERON:0003126	92.06	gold quality
epithelial cell of pancreas	CL:0000083	91.74	gold quality
gingival epithelium	UBERON:0001949	91.72	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	12.94
E-CURD-89	no	494.90
E-HCAD-29	no	245.24

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 40)

• Nore1 is a member of a family of Ras effector/tumor suppressors that includes RASSF1 (PMID:12676952)
• the epigenetic alteration of NORE1A is confined to lung tumors with a wild-type K-ras: 88% (15 of 17) of the tumors with NORE1 hypermethylation did not harbor a K-ras mutation (P=0.008, Fisher’s exact test) (PMID:15378027)
• Rap1 activation contributes to directional vascular endothelial cell migration accompanied by extension of microtubules on which RAPL localizes (PMID:15569673)
• results indicate that RASSF1A epigenetic changes are an early event in thyroid tumor pathogenesis and progression (PMID:15980887)
• Suppression of NORE1A, a known Ras effector, in PAX8-PPARgamma fusion-carrying follicular thyroid cancer. (PMID:16352687)
• association of NORE1A with cytoskeletal elements is essential for NORE1A-induced growth suppression and that the ERK pathway is a target for NORE1A growth-suppressive activities (PMID:16421102)
• The candidate tumor suppressor gene NORE1B is epigenetically down-regulated in hepatocellular carcinoma. (PMID:16516329)
• These findings suggest that endogenous Nore1B recruits active Ras to the APC-T cell interface and mediates the interaction between Ras and Carma1. (PMID:16520020)
• The NORE1A gene was never found epigenetically methylated in hepatitic or non-hepatitic liver. (PMID:16606445)
• Nuclear localization of RASSF5 is critical for its cell growth control activity. (PMID:17320110)
• interaction surfaces in RAPL-Rap1 and RAPL-Rap2 complexes are different and that a single residue in the switch I region of Rap proteins (residue 39) contributes considerably to the different kinetics of these protein-protein interactions. (PMID:17716979)
• nuclear export of NORE1A via nuclear export signal is involved in the NORE1A-mediated induction of apoptosis (PMID:18211824)
• NORE1A promoter methylation is a rare event in neuroblastoma cells and primary tumors. Other mechanisms are likely to account for the frequent reduction of NORE1A mRNA expression. Also, antitumorigenic role of NORE1A in human neuroblastoma is evident. (PMID:18452173)
• Study describes the crystal structure of Ras in complex with the Ras binding domain (RBD) of NORE1A; the contact area of NORE1A is extended as compared with other Ras effectors & provides a rationale for an exceptionally long lifetime of the complex. (PMID:18596699)
• findings showed that only 4% of the glioma tumors revealed a methylated promoter for NORE1A (PMID:18616639)
• Data show that degradation by calpains is a novel mechanism for downregulation of NORE1A and RASSF1A proteins and might be the mechanism allowing cancer cells to escape growth suppression. (PMID:19098985)
• NORE1B suppresses replication and transformation of cells as effectively as RASSF1A and is a putative tumor suppressor gene. NORE1B interacts with RASSF1A and loss of one of these may lead to uncontrolled growth and transformation of hepatocytes. (PMID:19118008)
• NORE1A activates p21(CIP1) via promoting p53 nuclear localization. (PMID:19435914)
• The present investigation provided evidence that Lck-mediated phosphorylation regulates the nucleocytoplasmic shuttling and cell growth control activities of RASSF5. (PMID:20064523)
• a novel regulatory network composed of the tumor suppressor NORE1A, the mitotic kinase Aurora A, the small GTPase Ras, and the microtubule cytoskeleton. (PMID:20339001)
• findings define a T cell receptor “inside-out” pathway via N-SKAP1-C-RapL that regulates T cell adhesion, motility, and arrest times with dendritic cells in lymph nodes. (PMID:20346707)
• NORE1A has activity that suppresses the centrosome amplification induced by HU and that NORE1A mRNA down-regulation is one of the common gene abnormalities in NSCLCs, both of which imply a key preventive role of NORE1A against the carcinogenesis of NSCLC. (PMID:20434789)
• epigenetic inactivation of NORE1 due to aberrant promoter hypermethylation is a frequent event in colorectal tumorigenesis and might be implicated in the malignant progression of colorectal tumors (PMID:20969767)
• N-terminal myr-tagged SKAP1 for membrane binding facilitated constitutive RapL membrane and Rap1 binding and effectively substituted for PI3K and TCR ligation in the activation of LFA-1 in T cells. (PMID:21669874)
• These findings indicate that the control of HIPK1 stability by Mdm2-NORE1 has a major effect on cell behaviour, and epigenetic inactivation of NORE1 enables adenocarcinoma formation in vivo through HIPK1 stabilization. (PMID:22173032)
• The RASSF gene family members RASSF5, RASSF6 and RASSF7 show frequent DNA methylation in neuroblastoma. (PMID:22695170)
• crystal of NORE1 diffracted to 2.7 A resolution and belonged to space group P6(1)22, with unit-cell parameters a = b = 73.041, c = 66.092 A, alpha = beta = 90, gamma = 120 degrees (PMID:22750872)
• Ubiquitin ligase Itch is a unique negative regulator of RASSF5. (PMID:23538446)
• RASSF5 can act as an inhibitor or a potential positive regulator of Mst2, depending on whether it binds to Mst2 before or after activation-loop phosphorylation. (PMID:23972470)
• RASSF5 expression is negatively correlated with distant metastasis of osteosarcoma, and RASSF5 may function as a tumor suppressor in OS cells through activation of the MST1/LATS1 pathway. (PMID:25109282)
• NORE1A has a role in Ras regulation of SCF(beta-TrCP) protein activity and specificity (PMID:25217643)
• Down-regulation of RASSF5A and RASSF5C expression is a tumor-specific phenomenon. (PMID:25420558)
• the inactivation of RASSF5A through CpG island 1 methylation may play an important role in esophageal squamous cell carcinoma (ESCC) carcinogenesis, RASSF5A may be a functional tumor suppressor and may serve as a prognostic biomarker for ESCC. (PMID:25579665)
• NORE1A allows Ras to qualitatively modify p53 function to promote senescence. (PMID:25778922)
• Ras induces the formation of a complex between NORE1A and the phosphatase PP1A, promoting the activation of the Rb tumor suppressor by dephosphorylation (PMID:26677227)
• mCD40L-induced cell death mediated by NORE1A expression appeared to be independent of mCD40L-induced cell death mediated by sustained JNK activation since NORE1A inhibition did not affect JNK phosphorylation and vice versa (PMID:26986513)
• Hepatitis C virus uses NS5B to specifically suppress NORE1A, facilitating viral replication and elevated Ras signaling. (PMID:28090674)
• Our study demonstrated that miR-214 expression was elevated and RASSF5 was down regulated in oral cancer. Moreover, miR-214 suppressed KB cell apoptosis through down regulation of RASSF5 expression (PMID:28290615)
• REVIEW: elucidate the acknowledged structure, progress in the verified functions and research advances of RASSF5 and the probably relevant signaling pathways (PMID:28356010)
• Ubc9 is an essential regulator of ADAP where it is required for TCR-induced membrane recruitment of the small GTPase Rap1 and its effector protein RapL. (PMID:29127148)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	rassf5	ENSDARG00000070601
mus_musculus	Rassf5	ENSMUSG00000026430
rattus_norvegicus	Rassf5	ENSRNOG00000005342
drosophila_melanogaster	Rassf	FBGN0039055
caenorhabditis_elegans		WBGENE00011995

Paralogs (5): RASSF1 (ENSG00000068028), RASSF2 (ENSG00000101265), RASSF4 (ENSG00000107551), RASSF3 (ENSG00000153179), RASSF6 (ENSG00000169435)

Protein

Protein identifiers

Ras association domain-containing protein 5 — Q8WWW0 (reviewed: Q8WWW0)

Alternative names: New ras effector 1, Regulator for cell adhesion and polarization enriched in lymphoid tissues

All UniProt accessions (4): A0A075B763, A0A1B0GTG4, Q8WWW0, Q8TEK8

UniProt curated annotations — full annotation on UniProt →

Function. Potential tumor suppressor. Seems to be involved in lymphocyte adhesion by linking RAP1A activation upon T-cell receptor or chemokine stimulation to integrin activation. Isoform 2 stimulates lymphocyte polarization and the patch-like distribution of ITGAL/LFA-1, resulting in an enhanced adhesion to ICAM1. Together with RAP1A may participate in regulation of microtubule growth. The association of isoform 2 with activated RAP1A is required for directional movement of endothelial cells during wound healing. May be involved in regulation of Ras apoptotic function. The RASSF5-STK4/MST1 complex may mediate HRAS and KRAS induced apoptosis.

Subunit / interactions. Interacts directly with activated HRAS; a RASSF5-STK4/MST1 complex probably associates with activated HRAS. Interacts with KRAS. Probably interacts with Ras-like GTPases RRAS, MRAS, RAP1B, RAP2A and RALA. Interacts with RRAS2. Can self-associate. Interacts with RSSF1 isoform A. The RSSF1 isoform A-RSSF5 heterodimer probably mediates the association of RSSF1 with HRAS. Isoform 2 interacts with activated RAP1A and ITGAL/LFA-1. Binds STK4/MST1, inhibiting STK4/MST1 autoactivation.

Subcellular location. Cytoplasm. Cytoskeleton.

Tissue specificity. Widely expressed. Frequently down-regulated in lung tumor cell lines and primary lung tumors.

Isoforms (3)

UniProt ID	Names	Canonical?
Q8WWW0-1	1, A, NORE1A	yes
Q8WWW0-2	2, B
Q8WWW0-3	3, C, NORE1B

RefSeq proteins (3): NP_872604, NP_872605, NP_872606 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000159	RA_dom	Domain
IPR002219	PKC_DAG/PE	Domain
IPR011524	SARAH_dom	Domain
IPR029071	Ubiquitin-like_domsf	Homologous_superfamily
IPR033614	RASSF1-6	Family
IPR033623	RASSF5_RA	Domain
IPR046349	C1-like_sf	Homologous_superfamily

Pfam: PF00130, PF00788, PF16517

UniProt features (17 total): splice variant 4, modified residue 4, domain 2, helix 2, chain 1, initiator methionine 1, zinc finger region 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
4OH8	X-RAY DIFFRACTION	2.28
4LGD	X-RAY DIFFRACTION	3.05

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8WWW0-F1	68.03	0.24

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 (4): 2, 182, 279, 352

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 248 (showing top): BENPORATH_ES_WITH_H3K27ME3, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, PEREZ_TP63_TARGETS, GOZGIT_ESR1_TARGETS_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, SCHLESINGER_METHYLATED_DE_NOVO_IN_CANCER, BONCI_TARGETS_OF_MIR15A_AND_MIR16_1, NIKOLSKY_BREAST_CANCER_1Q32_AMPLICON, GTGCCTT_MIR506, RICKMAN_METASTASIS_DN, KEGG_PATHWAYS_IN_CANCER, GOBP_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, GATA1_03, NEMETH_INFLAMMATORY_RESPONSE_LPS_DN

GO Biological Process (6): apoptotic process (GO:0006915), signal transduction (GO:0007165), positive regulation of protein ubiquitination (GO:0031398), lymphocyte proliferation (GO:0046651), negative regulation of lymphocyte proliferation (GO:0050672), regulation of protein localization to nucleus (GO:1900180)

GO Molecular Function (4): zinc ion binding (GO:0008270), identical protein binding (GO:0042802), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (4): nucleus (GO:0005634), cytoplasm (GO:0005737), microtubule (GO:0005874), cytoskeleton (GO:0005856)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
protein ubiquitination	1
regulation of protein ubiquitination	1
positive regulation of protein modification by small protein conjugation or removal	1
mononuclear cell proliferation	1
lymphocyte activation	1
negative regulation of mononuclear cell proliferation	1
lymphocyte proliferation	1
regulation of lymphocyte proliferation	1
negative regulation of lymphocyte activation	1
regulation of protein localization	1
protein localization to nucleus	1
transition metal ion binding	1
protein binding	1
binding	1
cation binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cellular anatomical structure	1
microtubule cytoskeleton	1
polymeric cytoskeletal fiber	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

1042 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RASSF5	RASSF1	Q9NS23	870
RASSF5	RAP1A	P10113	852
RASSF5	HRAS	P01112	829
RASSF5	SKAP1	Q86WV1	825
RASSF5	MOAP1	Q96BY2	811
RASSF5	RASSF7	Q02833	781
RASSF5	KRAS	P01116	752
RASSF5	RALGDS	Q12967	736
RASSF5	FYB1	O15117	719
RASSF5	APBB1IP	Q7Z5R6	715
RASSF5	SAV1	Q9H4B6	712
RASSF5	STK4	Q13043	679
RASSF5	RAP1B	P09526	666
RASSF5	RAP2A	P10114	632
RASSF5	CNKSR1	Q969H4	630
RASSF5	RASSF10	A6NK89	630

IntAct

114 interactions, top by confidence:

A	B	Type	Score
STK3	RASSF2	psi-mi:“MI:0914”(association)	0.950
STK4	RASSF2	psi-mi:“MI:0914”(association)	0.930
STK3	RASSF5	psi-mi:“MI:0915”(physical association)	0.890
RASSF5	STK4	psi-mi:“MI:0915”(physical association)	0.880
SMAD4	RASSF5	psi-mi:“MI:0915”(physical association)	0.800
RASSF5	SMAD4	psi-mi:“MI:0915”(physical association)	0.800
RASSF5	SMAD4	psi-mi:“MI:2364”(proximity)	0.800
SMAD4	RASSF5	psi-mi:“MI:2364”(proximity)	0.800
STK4	MAP1B	psi-mi:“MI:0914”(association)	0.730
MYLIP	RASSF5	psi-mi:“MI:0915”(physical association)	0.670
BTRC	RASSF5	psi-mi:“MI:0915”(physical association)	0.670
RASSF5	MYLIP	psi-mi:“MI:0915”(physical association)	0.670
RASSF5	BTRC	psi-mi:“MI:0915”(physical association)	0.670
STK3	MAP1B	psi-mi:“MI:0914”(association)	0.640
STK4	STRN	psi-mi:“MI:0914”(association)	0.610
STK4	STRN	psi-mi:“MI:2364”(proximity)	0.610
RASSF5	MAP1LC3B	psi-mi:“MI:0407”(direct interaction)	0.590
RASSF5	MAP1LC3B	psi-mi:“MI:0915”(physical association)	0.590
RASSF5	HRAS	psi-mi:“MI:0915”(physical association)	0.590

BioGRID (100): BTRC (Affinity Capture-Western), RASSF5 (Affinity Capture-Western), RASSF5 (Two-hybrid), RASSF5 (Two-hybrid), RASSF5 (Two-hybrid), RASSF5 (Two-hybrid), RASSF5 (Two-hybrid), RASSF5 (Two-hybrid), RASSF5 (Two-hybrid), RASSF5 (Two-hybrid), RASSF5 (Two-hybrid), RASSF5 (Two-hybrid), RASSF5 (Two-hybrid), RASSF5 (Two-hybrid), RASSF5 (Two-hybrid)

ESM2 similar proteins: A1L3C1, A2AWP8, A2RRU4, A6QM06, A6QNS9, E1BBQ2, F1LQY6, G3V9M2, O43189, O94827, P29372, P29590, P41155, P97260, Q01113, Q02833, Q04841, Q0P5I0, Q12770, Q13387, Q13505, Q29RM4, Q32L49, Q3V1H9, Q5MNU5, Q5R5M3, Q66T02, Q69Z89, Q6GQT6, Q6IPT2, Q6RFZ7, Q6ZN54, Q70EL4, Q7Z6G3, Q8BQB4, Q8C4U2, Q8N1F8, Q8N554, Q8WWW0, Q8WXF8

Diamond homologs: O35141, Q22744, Q5EBH1, Q6ZTQ3, Q86WH2, Q8WWW0, Q99MK9, Q99P51, Q9NS23, Q9R1K8, Q9Z1S3, A4IJ06, A5PJM7, A8KBH6, A8XQD5, A8XWC4, B2RTY4, D3ZEY4, E7EZG2, O45818, O95267, P04409, P05126, P05128, P05129, P05130, P05696, P05771, P05772, P09215, P09216, P10102, P10829, P10830, P13677, P13678, P15882, P16054, P17252, P20444

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
RASSF5	“up-regulates activity”	KRAS	binding
RASSF5	“up-regulates activity”	RASSF1	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 48 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
Signaling by Hippo	5	60.4×	7e-06
Signaling by BRAF and RAF1 fusions	5	18.9×	1e-03
Macroautophagy	7	17.9×	2e-05
Diseases of signal transduction by growth factor receptors and second messengers	6	7.6×	6e-03

GO biological processes:

GO term	Partners	Fold	FDR
hippo signaling	5	76.3×	8e-07
mitophagy	9	59.6×	9e-12
autophagosome maturation	7	51.2×	1e-08
autophagosome assembly	8	37.5×	9e-09
macroautophagy	6	30.1×	6e-06
epidermal growth factor receptor signaling pathway	5	25.8×	1e-04
cellular response to starvation	5	20.2×	3e-04
positive regulation of ERK1 and ERK2 cascade	7	12.4×	1e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	18
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1388 predictions. Top by Δscore:

Variant	Effect	Δscore
1:206508055:CACTA:C	donor_gain	1.0000
1:206508056:ACTA:A	donor_gain	1.0000
1:206508057:CTA:C	donor_gain	1.0000
1:206508058:TA:T	donor_gain	1.0000
1:206508059:AGT:A	donor_loss	1.0000
1:206508060:G:GG	donor_gain	1.0000
1:206508061:T:A	donor_loss	1.0000
1:206538164:A:AG	acceptor_gain	1.0000
1:206538165:C:G	acceptor_gain	1.0000
1:206538169:CAGAC:C	acceptor_loss	1.0000
1:206538170:A:AG	acceptor_gain	1.0000
1:206538170:AGACT:A	acceptor_gain	1.0000
1:206538171:G:A	acceptor_loss	1.0000
1:206538171:G:GA	acceptor_gain	1.0000
1:206538171:GA:G	acceptor_gain	1.0000
1:206538171:GACT:G	acceptor_gain	1.0000
1:206538171:GACTG:G	acceptor_gain	1.0000
1:206538289:GCCAG:G	donor_gain	1.0000
1:206538290:CCAGG:C	donor_loss	1.0000
1:206538294:G:T	donor_loss	1.0000
1:206538295:T:A	donor_loss	1.0000
1:206583257:T:TA	acceptor_gain	1.0000
1:206583265:CCAG:C	acceptor_loss	1.0000
1:206583266:CA:C	acceptor_loss	1.0000
1:206583267:A:AG	acceptor_gain	1.0000
1:206583267:AGAAT:A	acceptor_gain	1.0000
1:206583268:G:GG	acceptor_gain	1.0000
1:206583268:GA:G	acceptor_gain	1.0000
1:206583268:GAA:G	acceptor_gain	1.0000
1:206583268:GAAT:G	acceptor_gain	1.0000

AlphaMissense

2687 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:206584534:T:C	F280L	1.000
1:206584536:C:A	F280L	1.000
1:206584536:C:G	F280L	1.000
1:206584613:T:C	L306P	1.000
1:206584648:T:C	F318L	1.000
1:206584650:T:A	F318L	1.000
1:206584650:T:G	F318L	1.000
1:206585267:T:C	L359P	1.000
1:206586826:T:A	W369R	1.000
1:206586826:T:C	W369R	1.000
1:206586828:G:C	W369C	1.000
1:206586828:G:T	W369C	1.000
1:206586851:T:C	L377P	1.000
1:206586859:T:C	F380L	1.000
1:206586861:C:A	F380L	1.000
1:206586861:C:G	F380L	1.000
1:206584408:G:C	G238R	0.999
1:206584409:G:A	G238D	0.999
1:206584411:T:C	F239L	0.999
1:206584413:C:A	F239L	0.999
1:206584413:C:G	F239L	0.999
1:206584415:T:A	I240N	0.999
1:206584427:T:C	L244P	0.999
1:206584433:T:C	L246P	0.999
1:206584445:T:A	V250E	0.999
1:206584565:T:C	L290P	0.999
1:206584567:C:G	H291D	0.999
1:206584610:T:C	L305P	0.999
1:206584621:T:C	F309L	0.999
1:206584622:T:C	F309S	0.999

dbSNP variants (sampled 300 via entrez): RS1000062517 (1:206534424 C>T), RS1000085991 (1:206577586 C>T), RS1000090108 (1:206534112 G>T), RS1000146813 (1:206576059 G>A), RS1000184971 (1:206570988 T>A), RS1000361001 (1:206564685 G>T), RS1000362944 (1:206540148 A>G), RS1000402830 (1:206520146 G>T), RS1000541046 (1:206577378 T>C), RS1000661488 (1:206521894 G>A), RS1000668751 (1:206527910 C>T), RS1000732877 (1:206521582 C>G,T), RS1000784504 (1:206559632 C>G), RS1000837013 (1:206559342 A>T), RS1000863432 (1:206515799 A>G,T)

Disease associations

OMIM: gene MIM:607020 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST001725_40	Inflammatory bowel disease	7.000000e-42
GCST002594_19	Neurofibrillary tangles	9.000000e-06
GCST003815_67	Late-onset Alzheimer’s disease	6.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0006797	neurofibrillary tangles measurement
EFO:1001870	late-onset Alzheimers disease

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066286 (SINGLE PROTEIN)

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

ChEMBL bioactivities

4 potent at pChembl≥5 of 4 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.33	Kd	4663	nM	CHEMBL5653589
5.32	ED50	4742	nM	CHEMBL5653589
5.20	Kd	6302	nM	CHEMBL3752910
5.19	ED50	6410	nM	CHEMBL3752910

PubChem BioAssay actives

2 with measured affinity, of 4 total; 2 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
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149197: Binding affinity to human RASSF5 incubated for 45 mins by Kinobead based pull down assay	kd	4.6628	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149197: Binding affinity to human RASSF5 incubated for 45 mins by Kinobead based pull down assay	kd	6.3021	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases expression, decreases methylation	3
Valproic Acid	increases expression	3
(+)-JQ1 compound	decreases expression	2
Nickel	increases expression	2
Silicon Dioxide	decreases expression, increases expression	2
Tretinoin	increases expression	2
Cadmium Chloride	decreases expression, increases expression	2
daidzein	affects expression, affects cotreatment	1
triphenyl phosphate	affects expression	1
bis(tri-n-butyltin)oxide	increases expression	1
tributyltin	increases expression	1
trichostatin A	affects expression	1
daidzin	affects cotreatment, affects expression	1
sulforaphane	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	affects cotreatment, increases abundance, increases expression	1
cobaltous chloride	increases expression	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
ochratoxin A	increases expression	1
methylmercury II	increases expression	1
hydroquinone	affects cotreatment, affects expression, affects reaction	1
genistin	affects cotreatment, affects expression	1
di-n-butylphosphoric acid	affects expression	1
benzyloxycarbonylleucyl-leucyl-leucine aldehyde	decreases expression, decreases reaction	1
perfluorooctane sulfonic acid	decreases expression	1
glycitein	affects cotreatment, affects expression	1
CGP 52608	affects binding, increases reaction	1
entinostat	affects cotreatment, increases expression	1
glycitin	affects cotreatment, affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652239	Binding	Binding affinity to human RASSF5 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_TI55	HAP1 RASSF5 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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