RASSF3

Summary

RASSF3 (Ras association domain family member 3, HGNC:14271) is a protein-coding gene on chromosome 12q14.2, encoding Ras association domain-containing protein 3 (Q86WH2).

The RAS oncogene (MIM 190020) is mutated in nearly one-third of all human cancers. Members of the RAS superfamily are plasma membrane GTP-binding proteins that modulate intracellular signal transduction pathways. A subfamily of RAS effectors, including RASSF3, share a RAS association (RA) domain.

Source: NCBI Gene 283349 — RefSeq curated summary.

At a glance

• GWAS associations: 17
• Clinical variants (ClinVar): 37 total
• MANE Select transcript: NM_178169

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14271
Approved symbol	RASSF3
Name	Ras association domain family member 3
Location	12q14.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000153179
Ensembl biotype	protein_coding
OMIM	607019
Entrez	283349

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 6 protein_coding, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000283172, ENST00000540088, ENST00000542104, ENST00000636333, ENST00000637125, ENST00000899845, ENST00000951679, ENST00000951680

RefSeq mRNA: 1 — MANE Select: NM_178169 NM_178169

CCDS: CCDS8969

Canonical transcript exons

ENST00000542104 — 5 exons

Exon	Start	End
ENSE00001009314	64688216	64688453
ENSE00001009318	64684787	64684894
ENSE00001606712	64694763	64697564
ENSE00003535739	64691470	64691579
ENSE00003844120	64610495	64610743

Expression profiles

Bgee: expression breadth ubiquitous, 257 present calls, max score 99.25.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 39.8311 / max 1465.4111, expressed in 1807 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
126453	22.4709	1785
126450	6.9508	1646
126452	6.8573	1672
126454	2.3253	1092
126455	0.6321	295
126451	0.5947	264

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
saphenous vein	UBERON:0007318	99.25	gold quality
left ventricle myocardium	UBERON:0006566	98.78	gold quality
cardiac muscle of right atrium	UBERON:0003379	98.64	gold quality
oocyte	CL:0000023	98.20	gold quality
myocardium	UBERON:0002349	98.20	gold quality
right coronary artery	UBERON:0001625	97.92	gold quality
popliteal artery	UBERON:0002250	97.77	gold quality
tibial artery	UBERON:0007610	97.76	gold quality
cauda epididymis	UBERON:0004360	97.52	gold quality
vena cava	UBERON:0004087	97.51	gold quality
seminal vesicle	UBERON:0000998	97.15	gold quality
colonic epithelium	UBERON:0000397	96.93	gold quality
aorta	UBERON:0000947	96.92	gold quality
heart right ventricle	UBERON:0002080	96.85	gold quality
lateral nuclear group of thalamus	UBERON:0002736	96.80	gold quality
urethra	UBERON:0000057	96.76	gold quality
monocyte	CL:0000576	96.74	gold quality
leukocyte	CL:0000738	96.72	gold quality
muscle layer of sigmoid colon	UBERON:0035805	96.67	gold quality
superficial temporal artery	UBERON:0001614	96.64	gold quality
cardia of stomach	UBERON:0001162	96.63	gold quality
descending thoracic aorta	UBERON:0002345	96.51	gold quality
oviduct epithelium	UBERON:0004804	96.36	gold quality
blood	UBERON:0000178	96.17	gold quality
coronary artery	UBERON:0001621	96.14	gold quality
ileal mucosa	UBERON:0000331	96.11	gold quality
buccal mucosa cell	CL:0002336	96.02	gold quality
left coronary artery	UBERON:0001626	95.93	gold quality
thoracic aorta	UBERON:0001515	95.77	gold quality
ascending aorta	UBERON:0001496	95.63	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-ENAD-21	yes	331.53
E-CURD-7	yes	326.79
E-ANND-3	yes	6.60
E-ENAD-27	yes	6.33
E-MTAB-6379	no	292.58
E-MTAB-4850	no	238.35
E-MTAB-5061	no	3.47

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NR1I2

miRNA regulators (miRDB)

188 targeting RASSF3, 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-6127	100.00	66.76	2188
HSA-MIR-6740-5P	100.00	65.64	932
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-196A-5P	100.00	68.16	684
HSA-MIR-196B-5P	100.00	68.16	681
HSA-MIR-3162-3P	100.00	65.37	363
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819

Literature-anchored findings (GeneRIF, showing 6)

• The presence of a Ras association domain common to NORE1,RASSF1, and RASSF3 suggests their possible involvement inRas-like signaling pathways. (PMID:11965544)
• Mammary tumor incidence in bi-transgenic mice is delayed, suggesting that transgenic Rassf3 may influence mammary tumor incidence in transgenic mice (PMID:19148488)
• tumor suppressor activity of RASSF3, which occurs through p53 stabilization and regulation of apoptosis and the cell cycle. (PMID:22593196)
• hypermethylation-induced RASSF3 silencing plays an important role in the tumorigenesis of pituitary somatotroph adenomas. (PMID:23555615)
• low expression is associated with malignant phenotypes in non-small cell lung cancer patients (PMID:24246507)
• Taken together, these findings indicate that the RASSF3 promoter rs6581580 T>G SNP is potentially functional, modulating susceptibility to SCCHN among non-Hispanic whites. (PMID:24295637)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	rassf3	ENSDARG00000059064
mus_musculus	Rassf3	ENSMUSG00000025795
rattus_norvegicus	Rassf3	ENSRNOG00000005388
drosophila_melanogaster	Rassf	FBGN0039055
caenorhabditis_elegans		WBGENE00011995

Paralogs (5): RASSF1 (ENSG00000068028), RASSF2 (ENSG00000101265), RASSF4 (ENSG00000107551), RASSF6 (ENSG00000169435), RASSF5 (ENSG00000266094)

Protein

Protein identifiers

Ras association domain-containing protein 3 — Q86WH2 (reviewed: Q86WH2)

All UniProt accessions (3): Q86WH2, A0A1B0GUG6, A0A1B0GWJ9

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Cytoplasm. Cytoskeleton.

Tissue specificity. Widely expressed.

Isoforms (2)

UniProt ID	Names	Canonical?
Q86WH2-1	1, A	yes
Q86WH2-2	2, B

RefSeq proteins (1): NP_835463* (*=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

Pfam: PF00788, PF16517

UniProt features (10 total): domain 2, splice variant 2, initiator methionine 1, chain 1, region of interest 1, compositionally biased region 1, modified residue 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86WH2-F1	79.66	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): 2

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 173 (showing top): GCM_MAP4K4, GCM_PTPRD, GAUSSMANN_MLL_AF4_FUSION_TARGETS_C_UP, PATIL_LIVER_CANCER, MARTINEZ_RB1_TARGETS_UP, MCBRYAN_PUBERTAL_BREAST_4_5WK_DN, MCBRYAN_PUBERTAL_BREAST_3_4WK_UP, INGRAM_SHH_TARGETS_UP, NIKOLSKY_BREAST_CANCER_12Q13_Q21_AMPLICON, MAF_Q6, MILI_PSEUDOPODIA_CHEMOTAXIS_UP, GCM_PTK2, MARSON_BOUND_BY_E2F4_UNSTIMULATED, PASQUALUCCI_LYMPHOMA_BY_GC_STAGE_DN, ZHENG_GLIOBLASTOMA_PLASTICITY_UP

GO Biological Process (1): signal transduction (GO:0007165)

GO Molecular Function (2): identical protein binding (GO:0042802), protein binding (GO:0005515)

GO Cellular Component (5): cytoplasm (GO:0005737), cytosol (GO:0005829), microtubule (GO:0005874), plasma membrane (GO:0005886), cytoskeleton (GO:0005856)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
protein binding	1
binding	1
intracellular anatomical structure	1
cytoplasm	1
microtubule cytoskeleton	1
polymeric cytoskeletal fiber	1
membrane	1
cell periphery	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

576 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RASSF3	RASSF7	Q02833	768
RASSF3	HRAS	P01112	656
RASSF3	RASSF6	Q6ZTQ3	647
RASSF3	RASSF10	A6NK89	610
RASSF3	RALGDS	Q12967	557
RASSF3	RGL2	O15211	550
RASSF3	RASSF2	P50749	537
RASSF3	ITPRIP	Q8IWB1	520
RASSF3	MOAP1	Q96BY2	514
RASSF3	KRAS	P01116	499
RASSF3	TBC1D30	Q9Y2I9	479
RASSF3	XPOT	O43592	472
RASSF3	RASSF9	O75901	468
RASSF3	RAP1A	P10113	458
RASSF3	RASSF8	Q8NHQ8	454

IntAct

85 interactions, top by confidence:

A	B	Type	Score
RASSF3	STK4	psi-mi:“MI:0915”(physical association)	0.820
STK4	RASSF3	psi-mi:“MI:0915”(physical association)	0.820
RASSF3	STK3	psi-mi:“MI:0915”(physical association)	0.790
LITAF	RASSF3	psi-mi:“MI:0915”(physical association)	0.740
RASSF3	LITAF	psi-mi:“MI:0915”(physical association)	0.740
VAPB	FAM83G	psi-mi:“MI:0914”(association)	0.730
STK4	MAP1B	psi-mi:“MI:0914”(association)	0.730
VAPA	FAM83G	psi-mi:“MI:0914”(association)	0.640
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
DAXX	RASSF3	psi-mi:“MI:0915”(physical association)	0.560
CBX8	RASSF3	psi-mi:“MI:0915”(physical association)	0.560
ITPRIP	RASSF3	psi-mi:“MI:0915”(physical association)	0.560
RPRD1B	RASSF3	psi-mi:“MI:0915”(physical association)	0.560
TFRC	RASSF3	psi-mi:“MI:0915”(physical association)	0.560
TRIM59	RASSF3	psi-mi:“MI:0915”(physical association)	0.560
FAM110A	RASSF3	psi-mi:“MI:0915”(physical association)	0.560
KDM1A	RASSF3	psi-mi:“MI:0915”(physical association)	0.560
RASSF3	RPRD1B	psi-mi:“MI:0915”(physical association)	0.560
RASSF3	DAXX	psi-mi:“MI:0915”(physical association)	0.560
KYNU	RASSF3	psi-mi:“MI:0915”(physical association)	0.560
RASSF3	PARD6B	psi-mi:“MI:0915”(physical association)	0.560
RASSF3	TENT5D	psi-mi:“MI:0915”(physical association)	0.560
RASSF3	CBX8	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (61): RASSF3 (Affinity Capture-MS), RASSF3 (Affinity Capture-MS), RASSF3 (Affinity Capture-Western), RASSF3 (Affinity Capture-Western), RASSF3 (Affinity Capture-MS), RASSF3 (Affinity Capture-MS), RASSF3 (Affinity Capture-MS), CDC37 (Affinity Capture-MS), FGFR1OP2 (Affinity Capture-MS), MAP1B (Affinity Capture-MS), MAP1S (Affinity Capture-MS), STK4 (Affinity Capture-MS), STK3 (Affinity Capture-MS), MOB4 (Affinity Capture-MS), SIKE1 (Affinity Capture-MS)

ESM2 similar proteins: A2A2Y4, A2AFR3, A2VDU2, A4IIM3, F1LXF1, G3V7Q0, O14795, O35141, O70585, P11274, P22681, P22682, P50749, Q14161, Q14CM0, Q3B7D5, Q4KUS2, Q566C5, Q5EBH1, Q5F3L9, Q5R803, Q5RDV5, Q62768, Q62769, Q66H91, Q6AYF1, Q6IQ26, Q6PAJ1, Q6PAL8, Q6QD73, Q6RFZ7, Q7ZYH1, Q80YA9, Q86WH2, Q8BHD4, Q8BKH7, Q8BMS9, Q8CB96, Q8WWW0, Q8WXI2

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

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
PIP3 activates AKT signaling	6	11.4×	5e-03

GO biological processes:

GO term	Partners	Fold	FDR
extrinsic apoptotic signaling pathway via death domain receptors	5	45.6×	5e-05
epidermal growth factor receptor signaling pathway	5	28.2×	1e-04
protein stabilization	6	9.1×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	29
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1779 predictions. Top by Δscore:

Variant	Effect	Δscore
12:64610708:A:T	donor_gain	1.0000
12:64610744:G:GG	donor_gain	1.0000
12:64663282:G:GT	donor_gain	1.0000
12:64684781:TTCTA:T	acceptor_loss	1.0000
12:64684782:TCTA:T	acceptor_loss	1.0000
12:64684784:TA:T	acceptor_loss	1.0000
12:64684785:A:AG	acceptor_gain	1.0000
12:64684785:A:T	acceptor_loss	1.0000
12:64684785:AG:A	acceptor_gain	1.0000
12:64684785:AGGAT:A	acceptor_gain	1.0000
12:64684786:G:GT	acceptor_gain	1.0000
12:64684786:GG:G	acceptor_gain	1.0000
12:64684786:GGA:G	acceptor_gain	1.0000
12:64684786:GGAT:G	acceptor_gain	1.0000
12:64684786:GGATG:G	acceptor_gain	1.0000
12:64684893:TGG:T	donor_loss	1.0000
12:64684894:GGTA:G	donor_loss	1.0000
12:64684895:G:GG	donor_gain	1.0000
12:64684895:G:T	donor_loss	1.0000
12:64684896:T:G	donor_loss	1.0000
12:64688363:G:GT	donor_gain	1.0000
12:64688363:G:T	donor_gain	1.0000
12:64688444:G:T	donor_gain	1.0000
12:64691464:A:AG	acceptor_gain	1.0000
12:64691465:C:G	acceptor_gain	1.0000
12:64691466:CCA:C	acceptor_loss	1.0000
12:64691467:CA:C	acceptor_loss	1.0000
12:64691468:A:AG	acceptor_gain	1.0000
12:64691468:A:G	acceptor_loss	1.0000
12:64691469:G:GA	acceptor_gain	1.0000

AlphaMissense

1589 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:64688240:T:C	F82L	1.000
12:64688242:C:A	F82L	1.000
12:64688242:C:G	F82L	1.000
12:64694788:T:C	L198P	1.000
12:64684856:T:G	Y61D	0.999
12:64684887:T:C	M71T	0.999
12:64688231:T:G	Y79D	0.999
12:64688237:G:C	G81R	0.999
12:64688238:G:A	G81D	0.999
12:64688244:T:A	I83N	0.999
12:64688336:C:G	H114D	0.999
12:64688379:T:C	L128P	0.999
12:64688424:T:A	L143H	0.999
12:64691503:C:A	P164Q	0.999
12:64691506:T:A	L165H	0.999
12:64691551:T:C	F180S	0.999
12:64694763:T:A	W190R	0.999
12:64694763:T:C	W190R	0.999
12:64694765:G:C	W190C	0.999
12:64694765:G:T	W190C	0.999
12:64694772:T:C	F193L	0.999
12:64694773:T:C	F193S	0.999
12:64694774:C:A	F193L	0.999
12:64694774:C:G	F193L	0.999
12:64694796:T:C	F201L	0.999
12:64694797:T:C	F201S	0.999
12:64694798:C:A	F201L	0.999
12:64694798:C:G	F201L	0.999
12:64684857:A:C	Y61S	0.998
12:64684887:T:G	M71R	0.998

dbSNP variants (sampled 300 via entrez): RS1000026938 (12:64520293 G>A), RS1000031977 (12:64568744 C>G), RS1000034848 (12:64604963 T>G), RS1000078182 (12:64558682 T>C,G), RS1000104227 (12:64678655 A>AAAAAC), RS1000111135 (12:64507457 AGGTATTCCACTT>A), RS1000111532 (12:64556683 C>T), RS1000138454 (12:64562608 T>C), RS1000154528 (12:64635635 G>C,T), RS1000170155 (12:64685508 G>A,T), RS1000170677 (12:64605202 T>G), RS1000171434 (12:64680021 A>G), RS1000195552 (12:64513938 G>A), RS1000210758 (12:64594553 G>A), RS1000211658 (12:64507584 C>T)

Disease associations

OMIM: gene MIM:607019 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

17 associations (top):

Study	Trait	p-value
GCST003818_85	Resting heart rate	5.000000e-19
GCST004599_192	Mean platelet volume	6.000000e-66
GCST004599_193	Mean platelet volume	2.000000e-44
GCST004603_111	Platelet count	2.000000e-28
GCST004603_112	Platelet count	3.000000e-21
GCST004744_41	Lung adenocarcinoma	6.000000e-07
GCST005789_23	Resting heart rate	2.000000e-07
GCST006085_56	Prostate cancer	3.000000e-12
GCST006101_7	Cardiometabolic and hematological traits	2.000000e-17
GCST007431_15	Lung function (FEV1/FVC)	6.000000e-10
GCST90002395_135	Mean platelet volume	1.000000e-78
GCST90002395_136	Mean platelet volume	9.000000e-26
GCST90002395_137	Mean platelet volume	1.000000e-22
GCST90002395_138	Mean platelet volume	4.000000e-41
GCST90002402_136	Platelet count	5.000000e-31
GCST90002402_137	Platelet count	1.000000e-15
GCST90002402_138	Platelet count	7.000000e-18

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004309	platelet count
EFO:0004713	FEV/FVC ratio

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, decreases expression	4
trichostatin A	affects cotreatment, increases expression	2
entinostat	increases expression, affects cotreatment	2
Particulate Matter	increases abundance, decreases expression	2
GSK-J4	increases expression	1
methyleugenol	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	increases methylation	1
titanium dioxide	decreases methylation, increases expression	1
kojic acid	increases expression	1
methylparaben	decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, 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, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
bisphenol S	decreases methylation	1
Sunitinib	decreases expression	1
Panobinostat	increases expression	1
Acetaminophen	affects expression	1
Air Pollutants	decreases expression, increases abundance	1
Benzo(a)pyrene	increases expression	1
Calcitriol	increases expression	1
Coumestrol	affects cotreatment, decreases expression	1
Smoke	decreases expression	1
Dihydrotestosterone	increases expression	1
Tretinoin	increases expression	1
Gold Compounds	increases expression	1
Lactic Acid	increases expression	1

Clinical trials (associated diseases)

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