RASSF2

Summary

RASSF2 (Ras association domain family member 2, HGNC:9883) is a protein-coding gene on chromosome 20p13, encoding Ras association domain-containing protein 2 (P50749). Potential tumor suppressor.

This gene encodes a protein that contains a Ras association domain. Similar to its cattle and sheep counterparts, this gene is located near the prion gene. Two alternatively spliced transcripts encoding the same isoform have been reported.

Source: NCBI Gene 9770 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 57 total
• Druggable target: yes
• MANE Select transcript: NM_014737

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9883
Approved symbol	RASSF2
Name	Ras association domain family member 2
Location	20p13
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0168, CENP-34
Ensembl gene	ENSG00000101265
Ensembl biotype	protein_coding
OMIM	609492
Entrez	9770

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 17 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000379376, ENST00000379400, ENST00000478553, ENST00000872643, ENST00000872644, ENST00000872645, ENST00000872646, ENST00000872647, ENST00000872648, ENST00000872649, ENST00000872650, ENST00000872651, ENST00000872652, ENST00000937949, ENST00000969800, ENST00000969801, ENST00000969802, ENST00000969803

RefSeq mRNA: 2 — MANE Select: NM_014737 NM_014737, NM_170774

CCDS: CCDS13083

Canonical transcript exons

ENST00000379400 — 12 exons

Exon	Start	End
ENSE00001364105	4822329	4822403
ENSE00001376536	4823557	4823608
ENSE00003104669	4795815	4795966
ENSE00003106816	4798010	4798085
ENSE00003128587	4787633	4787754
ENSE00003191248	4800972	4801062
ENSE00003486551	4792539	4792627
ENSE00003539322	4786231	4786328
ENSE00003544015	4780023	4784342
ENSE00003569457	4789596	4789697
ENSE00003648935	4788217	4788268
ENSE00003681565	4790451	4790611

Expression profiles

Bgee: expression breadth ubiquitous, 266 present calls, max score 99.44.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 30.1393 / max 2807.0975, expressed in 1250 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
186240	14.7655	920
186239	7.9386	985
186238	6.4763	789
186237	0.4854	111
186230	0.2079	89
186229	0.0998	52
186241	0.0833	42
186228	0.0824	45

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
inferior vagus X ganglion	UBERON:0005363	99.44	gold quality
subthalamic nucleus	UBERON:0001906	99.10	gold quality
spinal cord	UBERON:0002240	99.06	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	99.06	gold quality
lateral globus pallidus	UBERON:0002476	98.83	gold quality
medulla oblongata	UBERON:0001896	98.70	gold quality
corpus callosum	UBERON:0002336	98.64	gold quality
substantia nigra pars reticulata	UBERON:0001966	98.59	gold quality
superior vestibular nucleus	UBERON:0007227	98.49	gold quality
globus pallidus	UBERON:0001875	98.37	gold quality
medial globus pallidus	UBERON:0002477	98.22	gold quality
middle frontal gyrus	UBERON:0002702	98.20	gold quality
inferior olivary complex	UBERON:0002127	98.10	gold quality
substantia nigra pars compacta	UBERON:0001965	98.04	gold quality
dorsal plus ventral thalamus	UBERON:0001897	97.83	gold quality
midbrain	UBERON:0001891	97.72	gold quality
substantia nigra	UBERON:0002038	97.68	gold quality
pons	UBERON:0000988	97.67	gold quality
blood	UBERON:0000178	97.64	gold quality
ventral tegmental area	UBERON:0002691	97.58	gold quality
monocyte	CL:0000576	97.20	gold quality
mononuclear cell	CL:0000842	97.15	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	97.13	gold quality
leukocyte	CL:0000738	97.12	gold quality
cranial nerve II	UBERON:0000941	96.96	gold quality
lateral nuclear group of thalamus	UBERON:0002736	96.95	gold quality
ganglionic eminence	UBERON:0004023	95.71	gold quality
amygdala	UBERON:0001876	95.15	gold quality
bone marrow	UBERON:0002371	95.07	gold quality
Ammon’s horn	UBERON:0001954	95.02	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	13.98

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

157 targeting RASSF2, 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-8485	100.00	77.57	4731
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-5195-3P	99.92	70.92	1877

Literature-anchored findings (GeneRIF, showing 39)

• RASSF2 is a new member of the RASSF1 family of Ras effectors/tumor suppressors that exhibits a specificity for interacting with K-Ras (PMID:12732644)
• In colonic neoplsms epigenetic (RASSF2A) and genetic (K-ras) changes are mutually exclusive and provide alternative pathways for affecting Ras signalling. (PMID:15806169)
• RASSF2 is a novel tumor suppressor gene that regulates Ras signaling and plays a pivotal role in the early stages of colorectal tumorigenesis. (PMID:16012945)
• RASSF2 is silenced by hypermethylation near the transcription start site in gastric cancer (PMID:16265349)
• Inactivation of RASSF2A by promoter methylation correlates with lymph node metastasis in nasopharyngeal carcinoma (PMID:17013896)
• Hypermethylation of the RASSF2A promoter and K-ras/BRAF mutations is associated with microsatellite-stable colorectal cancers (PMID:17013898)
• Transport of Ras effector superfamily proteins into the nucleus/nucleolus may play a vital role in modulating Ras-mediated cell proliferation during tumorigenesis. (PMID:17320110)
• Aberrant methylation of the RASSF2 gene with the subsequent loss of RASSF2 expression plays an important role in the pathogenesis of lung cancers. (PMID:17549418)
• A novel methylation marker for multiple malignancies; suppresses breast tumor cell growth in vitro and in vivo. (PMID:17891178)
• epigenetic inactivation of RASSF2 plays an important role in oral squamous cell carcinoma tumorigenesis (PMID:18294275)
• The epigenetic silencing of tumor suppressor genes involved in the Ras/PI3K/AKT pathway plays an important role in oral squamous cell carcinoma radioresistance (PMID:19509163)
• Aberrant methylation of the RASSF2A gene with the subsequent loss of RASSF2A expression plays an important role in the pathogenesis of hepatocellular carcinoma. (PMID:19513612)
• MST2 and RASSF2 form an active complex in vivo, in which RASSF2 is maintained in a phosphorylated state and protects MST2 from degradation and turnover (PMID:19525978)
• Data provide evidence that MAPK/ERK-2 mediated phosphorylation regulates nucleo-cytoplasmic transport and cell growth arrest activity of RASSF2. (PMID:19555684)
• Tumor-specific methylation of APC, MGMT, RASSF2A, and Wif-1 genes might be a valuable biomarker in plasma for the early detection of colorectal cancer. (PMID:19773381)
• these findings indicate that MST1 is a major determinant of RASSF2 protein stability, and suggest that RASSF2 acts in a complex manner that extends beyond simple protein-protein association to play an important role in MST1 regulation. (PMID:19962960)
• Data show that RASSF2 forms a direct and endogenous complex with prostate apoptosis response protein 4 (PAR-4) and that this interaction is regulated by K-Ras and is essential for the full apoptotic effects of PAR-4. (PMID:20368356)
• Sp1-mediated RASSF2A gene transcription is activated by p300 through histone acetylation, and this activation plays an important role in inducing late apoptosis. (PMID:20716062)
• Results suggest that RASSF2 encodes a novel epigenetically inactivated candidate tumor suppressor gene in thyroid carcinogenesis. (PMID:20920251)
• Hypermethylation of RASSF2 gene is associated with advanced gastric cancer. (PMID:21409489)
• Promoter hypermethylation of RASSF2A is observed in pancreatic ductal adenocarcinoma, while not in normal pancreatic tissue. (PMID:21792082)
• our results suggest that RASSF2 potentially functions as a new tumor-suppressor gene that is inactivated through hypermethylation in cervical cancer (PMID:23542458)
• results suggest that both RASSF1A and RASSF2 are novel epigenetically inactivated tumor suppressor genes in Ewing sarcoma and RASSF2 methylation may have prognostic implications for ES patients (PMID:23887284)
• Promoter hypermethylation of RASSF2A is observed in cervical cancer, while not in normal cervical tissues. (PMID:24605823)
• Epigenetic inactivation of RASSF2A through aberrant promoter methylation may play an important role in the pathogenesis of epithelial ovarian cancer. (PMID:24606436)
• We conclude that EPB41L3, RASSF2 and TSP-1 genes are involved in the pathogenesis of diffuse gliomas (PMID:25621889)
• RASSF2 gene is differently methylated in luminal and non-luminal tumors and is a promising suppressor gene with clinical involvement in breast cancer (PMID:26284587)
• Results suggest that down-regulation of RASSF2, and RASSF6 is a tumor-specific phenomenon and their inactivation through CpG island methylation may play important roles in gastric cardia carcinogenesis. (PMID:26456015)
• RASSF2 may be an important molecular marker for carcinogenesis, prognosis and progression in gastric cancer (PMID:26459248)
• our results suggest that RASSF2 may function as a tumor suppressor gene (PMID:26482475)
• The statistically most significant association rs4813720 correlates with RASSF2 expression and may play a significant role in childhood ALL etiology. (PMID:27861356)
• we confirmed that the RASSF2-PAR-4 axis was mainly responsible for miR-7 functions in CAFs using bioinformatics methods. Overexpression of miR-7 in CAFs led to down-regulation of RASSF2, which dramatically decreased the secretion of PAR-4 from CAFs and then enhanced the proliferation and migration of the co-cultured cancer cells. (PMID:27901488)
• Results showed that in the endometrial adenocarcinoma (OEA group) and ovarian clear cell carcinoma (OCC group) groups, the methylation degrees of the RASSF2A promoter were obviously higher than that of the other two groups. The expression level of RASSF2A mRNA in the OEA and OCC groups was lower than that of the other two groups. (PMID:29504361)
• suggest that circRASSF2 is a central component linking circRNAs to progression of LSCC via an miR-302b-3p/IGF-1R axis (PMID:30992382)
• RASSF2 methylation was significantly higher in gastric cancer than in noncancerous tissues; RASSF2 gene methylation was not associated with gender and was not associated with lymph node metastasis. (PMID:31453724)
• The RUNX1-ETO target gene RASSF2 suppresses t(8;21) AML development and regulates Rac GTPase signaling. (PMID:32029705)
• RASSF effectors couple diverse RAS subfamily GTPases to the Hippo pathway. (PMID:33051258)
• Hyperhomocysteinemia may aggravate abdominal aortic aneurysm formation by up-regulating RASSF2. (PMID:38036076)
• Diagnostic Value of GSTP1, RASSF1, AND RASSF2 Methylation in Serum of Prostate Cancer Patients. (PMID:38493315)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	rassf2a	ENSDARG00000029865
danio_rerio	rassf2b	ENSDARG00000044044
mus_musculus	Rassf2	ENSMUSG00000027339
rattus_norvegicus	Rassf2	ENSRNOG00000021261
drosophila_melanogaster	Rassf	FBGN0039055

Paralogs (5): RASSF1 (ENSG00000068028), RASSF4 (ENSG00000107551), RASSF3 (ENSG00000153179), RASSF6 (ENSG00000169435), RASSF5 (ENSG00000266094)

Protein

Protein identifiers

Ras association domain-containing protein 2 — P50749 (reviewed: P50749)

All UniProt accessions (1): P50749

UniProt curated annotations — full annotation on UniProt →

Function. Potential tumor suppressor. Acts as a KRAS-specific effector protein. May promote apoptosis and cell cycle arrest. Stabilizes STK3/MST2 by protecting it from proteasomal degradation.

Subunit / interactions. Interacts directly with activated KRAS in a GTP-dependent manner. Interacts (via SARAH domain) with STK3/MST2 and STK4/MST1.

Subcellular location. Nucleus. Cytoplasm. Chromosome. Centromere. Kinetochore.

Tissue specificity. Widely expressed with highest levels in brain, placenta, peripheral blood and lung. Frequently down-regulated in lung tumor cell lines.

Post-translational modifications. Phosphorylated by STK3/MST2 and STK4/MST1.

Isoforms (2)

UniProt ID	Names	Canonical?
P50749-1	1	yes
P50749-2	2

RefSeq proteins (2): NP_055552, NP_739580 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000159	RA_dom	Domain
IPR011524	SARAH_dom	Domain
IPR029071	Ubiquitin-like_domsf	Homologous_superfamily
IPR033614	RASSF1-6	Family
IPR033618	RASSF2_RA	Domain

Pfam: PF00788, PF16517

UniProt features (9 total): domain 2, splice variant 2, sequence conflict 2, chain 1, region of interest 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P50749-F1	78.73	0.60

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 353 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, CREL_01, RRAGTTGT_UNKNOWN, HORIUCHI_WTAP_TARGETS_DN, GOBP_REGULATION_OF_OSTEOCLAST_DIFFERENTIATION, GOBP_REGULATION_OF_PHOSPHORYLATION, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, SCHWAB_TARGETS_OF_BMYB_POLYMORPHIC_VARIANTS_DN, GCANCTGNY_MYOD_Q6, MODULE_45, GOBP_PEPTIDYL_SERINE_MODIFICATION, GOBP_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, GOBP_POSITIVE_REGULATION_OF_MAPK_CASCADE, GOBP_OSTEOBLAST_DIFFERENTIATION, MITSIADES_RESPONSE_TO_APLIDIN_DN

GO Biological Process (17): skeletal system development (GO:0001501), ossification (GO:0001503), signal transduction (GO:0007165), epidermal growth factor receptor signaling pathway (GO:0007173), canonical NF-kappaB signal transduction (GO:0007249), positive regulation of protein autophosphorylation (GO:0031954), negative regulation of peptidyl-serine phosphorylation (GO:0033137), positive regulation of apoptotic process (GO:0043065), regulation of osteoblast differentiation (GO:0045667), regulation of osteoclast differentiation (GO:0045670), positive regulation of protein kinase activity (GO:0045860), positive regulation of JNK cascade (GO:0046330), bone remodeling (GO:0046849), homeostasis of number of cells (GO:0048872), protein stabilization (GO:0050821), regulation of non-canonical NF-kappaB signal transduction (GO:1901222), negative regulation of non-canonical NF-kappaB signal transduction (GO:1901223)

GO Molecular Function (2): protein kinase activity (GO:0004672), protein binding (GO:0005515)

GO Cellular Component (10): kinetochore (GO:0000776), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), Golgi apparatus (GO:0005794), cytosol (GO:0005829), plasma membrane (GO:0005886), protein-containing complex (GO:0032991), chromosome, centromeric region (GO:0000775), chromosome (GO:0005694)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
positive regulation of protein phosphorylation	2
non-canonical NF-kappaB signal transduction	2
intracellular membraneless organelle	2
intracellular membrane-bounded organelle	2
cytoplasm	2
system development	1
multicellular organismal process	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
ERBB signaling pathway	1
intracellular signaling cassette	1
regulation of protein autophosphorylation	1
positive regulation of protein kinase activity	1
protein autophosphorylation	1
negative regulation of protein phosphorylation	1
peptidyl-serine phosphorylation	1
regulation of peptidyl-serine phosphorylation	1
apoptotic process	1
regulation of apoptotic process	1
positive regulation of programmed cell death	1
osteoblast differentiation	1
regulation of cell differentiation	1
regulation of myeloid leukocyte differentiation	1
osteoclast differentiation	1
protein kinase activity	1
positive regulation of kinase activity	1
regulation of protein kinase activity	1
JNK cascade	1
positive regulation of MAPK cascade	1
regulation of JNK cascade	1
tissue remodeling	1
multicellular organismal-level homeostasis	1
regulation of protein stability	1
regulation of intracellular signal transduction	1
regulation of non-canonical NF-kappaB signal transduction	1
negative regulation of intracellular signal transduction	1

Protein interactions and networks

STRING

1006 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RASSF2	RASSF7	Q02833	776
RASSF2	KRAS	P01116	748
RASSF2	RASSF10	A6NK89	622
RASSF2	RASSF5	Q8WWW0	619
RASSF2	STK4	Q13043	600
RASSF2	MOAP1	Q96BY2	563
RASSF2	RASSF3	Q86WH2	537
RASSF2	STK24	Q9Y6E0	523
RASSF2	HRAS	P01112	520
RASSF2	RASSF9	O75901	482
RASSF2	RASSF8	Q8NHQ8	480
RASSF2	FLNC	Q14315	475
RASSF2	RASSF1	Q9NS23	467
RASSF2	SCG3	Q8WXD2	464
RASSF2	ENDOG	Q14249	443

IntAct

86 interactions, top by confidence:

A	B	Type	Score
STK3	RASSF2	psi-mi:“MI:0915”(physical association)	0.950
RASSF2	STK3	psi-mi:“MI:0915”(physical association)	0.950
STK3	RASSF2	psi-mi:“MI:0914”(association)	0.950
STK4	RASSF2	psi-mi:“MI:0914”(association)	0.930
STK4	RASSF2	psi-mi:“MI:0915”(physical association)	0.930
RASSF2	STK4	psi-mi:“MI:0914”(association)	0.930
RASSF2	YWHAG	psi-mi:“MI:0914”(association)	0.730
STK4	MAP1B	psi-mi:“MI:0914”(association)	0.730
MOB1A	LATS1	psi-mi:“MI:0914”(association)	0.670
YWHAG	BLTP3B	psi-mi:“MI:0914”(association)	0.640
STK3	MAP1B	psi-mi:“MI:0914”(association)	0.640
RASSF2	YWHAH	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
YWHAE	PIK3C2A	psi-mi:“MI:0914”(association)	0.570
YWHAH	BLTP3B	psi-mi:“MI:0914”(association)	0.570
RASSF5	RASSF2	psi-mi:“MI:0915”(physical association)	0.560
RASSF2	S100Z	psi-mi:“MI:0915”(physical association)	0.560
CALR	RASSF2	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (92): RASSF2 (Two-hybrid), RASSF5 (Two-hybrid), STK3 (Affinity Capture-MS), STK4 (Affinity Capture-MS), PPP1R9A (Affinity Capture-MS), PPP3CA (Affinity Capture-MS), PPP3CB (Affinity Capture-MS), RASSF2 (Affinity Capture-MS), RASSF2 (Affinity Capture-MS), YWHAH (Affinity Capture-MS), YWHAG (Affinity Capture-MS), CALML3 (Affinity Capture-MS), STK4 (Affinity Capture-MS), STK3 (Affinity Capture-MS), SPRR2E (Affinity Capture-MS)

ESM2 similar proteins: A1A5B6, A4D2P6, A7UA95, B2DCZ9, E1BBQ2, O08773, O35141, O43566, O75808, P49796, P50749, P51509, P52734, P97492, P98174, Q05AA6, Q0QWG9, Q13474, Q2KJ58, Q3B7D5, Q3ZCA1, Q496Y0, Q566C5, Q5EBH1, Q5T848, Q69Z89, Q69ZK0, Q80U62, Q8BMS9, Q8C4S8, Q8CB96, Q8HXH0, Q8IYL2, Q8TCU6, Q8WWW0, Q92974, Q96KN4, Q99MK9, Q99NH3, Q9BST9

Diamond homologs: P50749, Q3B7D5, Q4QR82, Q566C5, Q5EBH1, Q6ZTQ3, Q80UQ2, Q8BMS9, Q8CB96, Q9H2L5, Q99MK9, Q9NS23, O35141, Q22744, Q86WH2, Q8WWW0, Q99P51, Q9R1K8, Q9Z1S3

SIGNOR signaling

0 interactions.

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
Activation of BAD and translocation to mitochondria	6	120.2×	1e-09
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	5	88.4×	8e-08
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	5	88.4×	8e-08
Signaling by Hippo	6	85.9×	7e-09
Activation of BH3-only proteins	6	78.4×	9e-09
RHO GTPases activate PKNs	6	50.1×	8e-08
Intrinsic Pathway for Apoptosis	6	46.2×	9e-08
Apoptosis	7	30.9×	8e-08

GO biological processes:

GO term	Partners	Fold	FDR
hippo signaling	5	81.4×	2e-06
intracellular protein localization	6	14.0×	7e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	47
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2277 predictions. Top by Δscore:

Variant	Effect	Δscore
20:4784207:AGCTT:A	donor_gain	1.0000
20:4784208:G:C	donor_gain	1.0000
20:4784211:T:TA	donor_gain	1.0000
20:4786227:TTAC:T	donor_loss	1.0000
20:4786228:TACTT:T	donor_loss	1.0000
20:4786229:A:AC	donor_gain	1.0000
20:4786229:AC:A	donor_loss	1.0000
20:4786229:ACTTG:A	donor_gain	1.0000
20:4786230:C:CA	donor_gain	1.0000
20:4786230:C:G	donor_loss	1.0000
20:4786230:CT:C	donor_gain	1.0000
20:4786230:CTT:C	donor_gain	1.0000
20:4786230:CTTG:C	donor_gain	1.0000
20:4786230:CTTGC:C	donor_gain	1.0000
20:4786252:T:TA	donor_gain	1.0000
20:4786253:C:A	donor_gain	1.0000
20:4786324:GCCAC:G	acceptor_gain	1.0000
20:4786325:CCAC:C	acceptor_gain	1.0000
20:4786325:CCACC:C	acceptor_gain	1.0000
20:4786326:CAC:C	acceptor_gain	1.0000
20:4786326:CACC:C	acceptor_gain	1.0000
20:4786327:AC:A	acceptor_gain	1.0000
20:4786327:ACCT:A	acceptor_gain	1.0000
20:4786328:CC:C	acceptor_gain	1.0000
20:4786329:C:CA	acceptor_loss	1.0000
20:4786329:C:CC	acceptor_gain	1.0000
20:4787631:A:AC	donor_gain	1.0000
20:4787632:C:CC	donor_gain	1.0000
20:4787646:T:TA	donor_gain	1.0000
20:4787753:CT:C	acceptor_gain	1.0000

AlphaMissense

2132 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:4786273:A:G	L290P	1.000
20:4786294:A:G	L283P	1.000
20:4787724:G:T	P241Q	1.000
20:4788245:A:C	F221L	1.000
20:4788245:A:T	F221L	1.000
20:4788247:A:G	F221L	1.000
20:4789599:A:C	F212L	1.000
20:4789599:A:T	F212L	1.000
20:4789600:A:G	F212S	1.000
20:4789601:A:C	F212V	1.000
20:4789601:A:G	F212L	1.000
20:4789601:A:T	F212I	1.000
20:4789602:T:A	K211N	1.000
20:4789602:T:G	K211N	1.000
20:4789603:T:A	K211I	1.000
20:4789604:T:C	K211E	1.000
20:4789609:A:G	L209P	1.000
20:4789612:A:G	L208P	1.000
20:4789644:G:C	S197R	1.000
20:4789644:G:T	S197R	1.000
20:4789646:T:G	S197R	1.000
20:4789657:A:T	V193D	1.000
20:4789681:G:T	P185Q	1.000
20:4789682:G:A	P185S	1.000
20:4789686:G:C	F183L	1.000
20:4789686:G:T	F183L	1.000
20:4789687:A:C	F183C	1.000
20:4789687:A:G	F183S	1.000
20:4789688:A:C	F183V	1.000
20:4789688:A:G	F183L	1.000

dbSNP variants (sampled 300 via entrez): RS1000001972 (20:4780974 A>T), RS1000050122 (20:4803053 G>A,C,T), RS1000144710 (20:4818948 GTCTTT>G,GTCTTTTCTTT), RS1000153425 (20:4822273 T>C), RS1000200779 (20:4790304 T>A,C), RS1000462931 (20:4781279 T>C), RS1000560839 (20:4808856 T>C), RS1000565083 (20:4824809 C>T), RS1000618875 (20:4824522 G>A), RS1000682662 (20:4797756 C>T), RS1000689620 (20:4792954 C>T), RS1000795142 (20:4782789 G>C), RS1000801171 (20:4791610 A>C), RS1000814786 (20:4819551 C>T), RS1000844924 (20:4782997 T>C)

Disease associations

OMIM: gene MIM:609492 | 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
GCST002463_24	Systemic lupus erythematosus	2.000000e-06
GCST010002_60	Refractive error	9.000000e-11
GCST012279_15	Suicide attempt severity in mood disorders	3.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0006882	suicide behaviour measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066878 (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
7.82	Kd	15.26	nM	CHEMBL3752910
7.78	ED50	16.43	nM	CHEMBL3752910
5.50	Kd	3188	nM	CHEMBL5653589
5.46	ED50	3431	nM	CHEMBL5653589

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-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149196: Binding affinity to human RASSF2 incubated for 45 mins by Kinobead based pull down assay	kd	0.0153	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149196: Binding affinity to human RASSF2 incubated for 45 mins by Kinobead based pull down assay	kd	3.1876	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases expression, increases methylation, increases mutagenesis	4
Valproic Acid	increases expression, increases methylation, decreases expression	4
trichostatin A	affects cotreatment, decreases expression, increases expression	3
Tretinoin	decreases expression, increases expression	3
bisphenol A	decreases methylation, decreases expression	2
(+)-JQ1 compound	decreases expression, increases expression	2
Estradiol	decreases expression	2
Tobacco Smoke Pollution	decreases expression, increases methylation	2
Aflatoxin B1	decreases methylation, increases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	decreases expression	1
FR900359	decreases phosphorylation	1
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1
2,5,2’,5’-tetrachlorobiphenyl	decreases expression	1
arsenite	decreases reaction, affects binding	1
sulforaphane	decreases expression	1
sodium arsenite	increases expression	1
benzo(e)pyrene	decreases methylation	1
aflatoxin B2	affects methylation	1
pentanal	increases expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
ICG 001	decreases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
licochalcone B	decreases expression	1
NSC668394	increases expression	1
Dasatinib	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
CHEMBL5652238	Binding	Binding affinity to human RASSF2 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_1518	NCI-H2052	Cancer cell line	Male

Clinical trials (associated diseases)

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