RASSF1

Summary

RASSF1 (Ras association domain family member 1, HGNC:9882) is a protein-coding gene on chromosome 3p21.31, encoding Ras association domain-containing protein 1 (Q9NS23). Potential tumor suppressor.

This gene encodes a protein similar to the RAS effector proteins. Loss or altered expression of this gene has been associated with the pathogenesis of a variety of cancers, which suggests the tumor suppressor function of this gene. The inactivation of this gene was found to be correlated with the hypermethylation of its CpG-island promoter region. The encoded protein was found to interact with DNA repair protein XPA. The protein was also shown to inhibit the accumulation of cyclin D1, and thus induce cell cycle arrest. Several alternatively spliced transcript variants of this gene encoding distinct isoforms have been reported.

Source: NCBI Gene 11186 — RefSeq curated summary.

At a glance

• GWAS associations: 12
• Clinical variants (ClinVar): 62 total — 1 likely-pathogenic
• MANE Select transcript: NM_007182

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9882
Approved symbol	RASSF1
Name	Ras association domain family member 1
Location	3p21.31
Locus type	gene with protein product
Status	Approved
Aliases	NORE2A, REH3P21, RDA32, 123F2
Ensembl gene	ENSG00000068028
Ensembl biotype	protein_coding
OMIM	605082
Entrez	11186

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 6 protein_coding, 2 nonsense_mediated_decay, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000327761, ENST00000357043, ENST00000359365, ENST00000395117, ENST00000395126, ENST00000478619, ENST00000482447, ENST00000488024, ENST00000494145, ENST00000616212, ENST00000954825

RefSeq mRNA: 5 — MANE Select: NM_007182 NM_001206957, NM_007182, NM_170712, NM_170713, NM_170714

CCDS: CCDS2820, CCDS2821, CCDS2822, CCDS43096

Canonical transcript exons

ENST00000359365 — 6 exons

Exon	Start	End
ENSE00003508136	50337905	50338011
ENSE00003508357	50331559	50331856
ENSE00003643771	50329788	50330727
ENSE00003666911	50331334	50331449
ENSE00003678464	50332050	50332154
ENSE00003918068	50340556	50340836

Expression profiles

Bgee: expression breadth ubiquitous, 203 present calls, max score 98.92.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 17.2327 / max 238.3430, expressed in 1802 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
42322	7.5990	1720
42331	3.1719	969
42323	2.5143	1245
42333	0.8280	175
42324	0.8145	183
42321	0.8104	506
42327	0.6651	221
42326	0.3338	158
42332	0.2916	102
42325	0.1465	67

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	98.92	gold quality
tibial nerve	UBERON:0001323	95.04	gold quality
upper lobe of left lung	UBERON:0008952	94.12	gold quality
right lung	UBERON:0002167	94.09	gold quality
omental fat pad	UBERON:0010414	93.79	gold quality
monocyte	CL:0000576	93.73	gold quality
peritoneum	UBERON:0002358	93.70	gold quality
spleen	UBERON:0002106	93.57	gold quality
endocervix	UBERON:0000458	93.45	gold quality
leukocyte	CL:0000738	93.40	gold quality
mononuclear cell	CL:0000842	93.39	gold quality
adipose tissue of abdominal region	UBERON:0007808	93.37	gold quality
left uterine tube	UBERON:0001303	93.16	gold quality
popliteal artery	UBERON:0002250	93.10	gold quality
tibial artery	UBERON:0007610	93.10	gold quality
right coronary artery	UBERON:0001625	93.03	gold quality
upper lobe of lung	UBERON:0008948	92.90	gold quality
ectocervix	UBERON:0012249	92.85	gold quality
skin of leg	UBERON:0001511	92.68	gold quality
body of uterus	UBERON:0009853	92.61	gold quality
aorta	UBERON:0000947	92.51	gold quality
stromal cell of endometrium	CL:0002255	92.40	gold quality
left coronary artery	UBERON:0001626	92.26	gold quality
ascending aorta	UBERON:0001496	92.25	gold quality
blood	UBERON:0000178	92.18	gold quality
thoracic aorta	UBERON:0001515	92.12	gold quality
apex of heart	UBERON:0002098	91.91	gold quality
small intestine Peyer’s patch	UBERON:0003454	91.78	gold quality
skin of abdomen	UBERON:0001416	91.71	gold quality
subcutaneous adipose tissue	UBERON:0002190	91.56	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-9801	yes	6.15
E-MTAB-6379	no	611.25
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CTCF, DLX6, DNMT1, DNMT3A, DNMT3B, E2F1, E4F1, EMX2, EZH2, FOXC1, GATA5, HIC1, HOXA9, HOXB5, MYC, MYCN, SP1, SP3, TBX15, TP53, ZHX2, ZNF699

miRNA regulators (miRDB)

46 targeting RASSF1, 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-5193	100.00	67.26	1744
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
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-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-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-3679-3P	99.64	69.88	1599
HSA-MIR-4437	99.52	65.29	1266
HSA-MIR-3612	99.45	66.02	1333
HSA-MIR-650	99.45	65.77	1309
HSA-MIR-5695	99.41	67.48	1047
HSA-MIR-4695-5P	99.06	64.87	1151
HSA-MIR-4324	99.04	70.14	1569
HSA-MIR-670-3P	99.03	68.88	2404
HSA-MIR-4297	98.77	66.95	2013
HSA-MIR-4763-5P	98.75	63.89	854
HSA-MIR-330-5P	98.73	67.63	1788
HSA-MIR-7851-3P	98.72	64.88	980
HSA-MIR-26B-3P	98.71	67.49	1102
HSA-MIR-4725-5P	98.67	65.42	628
HSA-MIR-504-5P	98.67	65.40	631
HSA-MIR-2117	98.48	67.97	1307
HSA-MIR-326	98.25	66.44	1565

Literature-anchored findings (GeneRIF, showing 40)

• The RASSF1A tumor suppressor blocks cell cycle progression and inhibits cyclin D1 accumulation (RASSF1A) (PMID:12024041)
• promoter methylation studied in 80 patients with head and neck squamous cell carcinoma (HNSCC) (PMID:12082610)
• RASSFIa protein. There is likely a causal relationship between SV40 infection, progressive RASSF1A methylation and its silencing, and the pathogenesis of mesothelioma. (PMID:12082623)
• Aberrant promoter methylation of RASSF1A may contribute to the pathogenesis of many different forms of pediatric tumors (PMID:12082624)
• Epigenetic inactivation of RASSF1A plays an important role in the progression of lung adenocarcinoma. (PMID:12114441)
• 3p loss is common in HNSCC and extensive 3p loss occurs even in early stage tumours. Furthermore, RASSF1A methylation is significantly higher in poorly differentiated then in moderate to well differentiated HNSCC (P=0.0048). (PMID:12142046)
• The high incidence of 3p loss and RASSF1A promoter hypermethylation detected may have implications for this tumor suppressor gene in the malignant progression of cholangiocarcinoma. (PMID:12399230)
• detection of aberrant promoter hypermethylation from smokers, lung cancer, and breast cancer patients (PMID:12527916)
• RASSF1A methylation was detected in four of 10 (40%) seminomas and 15 of 18 (83%) nonseminoma TGCT (NSTGCT) components (P=0.0346).These findings are consistent with a model for TGCT pathogenesis in which RASSF1A methylation occurs early in tumorigenesis (PMID:12545168)
• Frequent hypermethylation of promoter region of RASSF1A in tumor tissues and voided urine of urinary bladder cancer patients. (PMID:12594816)
• RASSF1A methylation could serve as a useful marker for the prognosis of cancer patients and could become important in early detection of cancer (PMID:12647816)
• The RASSF1A gene is turned off in a significant number of melanomas and that CpG promoter region hypermethylation may play a role in the transcriptional inactivation of the RASSF1A gene in malignant melanoma. (PMID:12670917)
• Hypermethylation of RASSF1A and Loss of heterozygosity at chromosome 3p21 is associated with cervical cancer (PMID:12673680)
• epigenetic silencing of RASSF1A gene expression by promoter hypermethylation could play an important role in primary esophageal squamous cell carcinogenesis (PMID:12684417)
• Epigenetic inactivation of RASSF1A may play an important role in the tumorigenesis of osteosarcomas (PMID:12792742)
• RASSF1 is a putative tumor suppressor in non-small cell lung cancer (PMID:12794755)
• There is a significant expression difference among the three RASSF1 transcripts in lung carcinoma. RASSF1A, closely associated with lymph metastasis and TNM stage of lung carcinoma, should be a new tumor suppressor gene. (PMID:12795841)
• Promoter hypermethylation of this gene is demonstrated in esophageal squamous cell carcinoma. (PMID:12839965)
• Hypermethylation of the promoter is associated with age of starting smoking and poor prognosis in NSLC. (PMID:12839968)
• epigenetic silencing of RASSF1A may play a role in the development of AC of the uterine cervix (PMID:12912945)
• RASSF1A promoter methylation has a role in abrogating the same pathway as HPV infection in head and neck tumorigenesis (PMID:14506151)
• there is an inverse relationship between Kras2 activation and RASSF1A promoter methylation in the majority of human lung adenocarcinomas and large cell carcinomas (PMID:14511407)
• hypermethylated in invasive and in in situ lobular breast cancer (PMID:14601057)
• Inactivation of RASSF1A by hypermethylation is associated with medulloblastoma pathogenesis (PMID:14688019)
• Specific inactivation of RASSF1A by short interfering RNA disrupts binding of RASSF1A to p120(E4F) in tumor cells (PMID:14729613)
• These findings implicate RASSF1A in the regulation of both APC-Cdc20 activity and mitotic progression. (PMID:14743218)
• epigenetic inactivation of RASSF1A may have a role in childhood neoplasm initiation (PMID:14871978)
• an important role for epigenetic silencing of RASSF1A in the pathogenesis of Hodgkin’s lymphoma (PMID:14961078)
• Reduced RASSF1A transcript levels are associated with malignant melanomas (PMID:14961576)
• RASSF1A is a target tumor suppressor from 3p21.3 in nasopharyngeal carcinoma (PMID:15027117)
• Data show that the connector enhancer of KSR 1 scaffold protein, through its binding of a RASSF1A/MST1 complex, participates in the proapoptotic signaling initiated by active Ras. (PMID:15075335)
• functional association with RASSF1 indicates a role for PMCA4b in the modulation of Ras-mediated signaling (PMID:15145946)
• Data identify a role for RASSF1A in the regulation of microtubules and cell cycle dynamics that could be part of the mechanism(s) by which RASSF1A exerts its growth inhibition on cancer cells. (PMID:15205320)
• The tumor suppressor gene, RASSF1A, is an independent prognostic parameter with poor outcome in breast cancer patients. (PMID:15251938)
• Hypermethylation of the RASSF1A tumor suppressor gene is associated with clear cell renal cell carcinoma (PMID:15375503)
• RASSF1A may mediate its tumor suppressive effects by inducing growth arrest in the G1 and G2/M phases (PMID:15378022)
• the RASSF1A but not p16INK4a methylated promoter region has a role in progression of non-small cell lung cancer (PMID:15447998)
• RASSF1A gene might play an important role in glioma carcinogenesis (PMID:15469871)
• RASSF1A is hypermethylated in early flat-type colorectal tumors (PMID:15480433)
• Smoking under age 18 is an independent risk for RASSF1A hypermethylation, thus identifying a molecular alteration related to the epidemiologic effect of teenage smoking as a lung cancer risk. (PMID:15540210)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	rassf1	ENSDARG00000004840
mus_musculus	Rassf1	ENSMUSG00000010067
rattus_norvegicus	Rassf1	ENSRNOG00000021548
drosophila_melanogaster	Rassf	FBGN0039055

Paralogs (5): RASSF2 (ENSG00000101265), RASSF4 (ENSG00000107551), RASSF3 (ENSG00000153179), RASSF6 (ENSG00000169435), RASSF5 (ENSG00000266094)

Protein

Protein identifiers

Ras association domain-containing protein 1 — Q9NS23 (reviewed: Q9NS23)

All UniProt accessions (1): Q9NS23

UniProt curated annotations — full annotation on UniProt →

Function. Potential tumor suppressor. Required for death receptor-dependent apoptosis. Mediates activation of STK3/MST2 and STK4/MST1 during Fas-induced apoptosis by preventing their dephosphorylation. When associated with MOAP1, promotes BAX conformational change and translocation to mitochondrial membranes in response to TNF and TNFSF10 stimulation. Isoform A interacts with CDC20, an activator of the anaphase-promoting complex, APC, resulting in the inhibition of APC activity and mitotic progression. Inhibits proliferation by negatively regulating cell cycle progression at the level of G1/S-phase transition by regulating accumulation of cyclin D1 protein. Isoform C has been shown not to perform these roles, no function has been identified for this isoform. Isoform A disrupts interactions among MDM2, DAXX and USP7, thus contributing to the efficient activation of TP53 by promoting MDM2 self-ubiquitination in cell-cycle checkpoint control in response to DNA damage.

Subunit / interactions. Interacts with MAP1S. Interacts with XPA. Binds to the N-terminal of CDC20 during prometaphase. Binds to STK3/MST2 and STK4/MST1. Recruited to the TNFRSF1A and TNFRSF10A complexes in response to their respective cognate ligand, after internalization. Can self-associate. Part of a complex with MDM2, DAXX, RASSF1 and USP7. Interacts with ECM2. Interacts with MOAP1. Interacts with E4F1. Interacts with RSSF5 and probably associates with HRAS via a RSSF1 isoform A-RSSF5 heterodimer. Interacts (via C-terminus) with DAXX (via N-terminus); the interaction is independent of MDM2 and TP53. Interacts (via N-terminus) with MDM2 (via C-terminus); the interaction is independent of TP53. Interacts with RAB39A. Interacts with RAB39B; the interaction is weak. Interacts (via N-terminus) with DAXX. Interacts with RAB39B; the interaction is strong. Does not interact with RAB39A. Interacts (via N-terminus) with DAXX.

Subcellular location. Cytoplasm. Cytoskeleton. Microtubule organizing center. Centrosome. Spindle. Spindle pole. Nucleus Nucleus.

Tissue specificity. Isoform A and isoform C are ubiquitously expressed in all tissues tested, however isoform A is absent in many corresponding cancer cell lines. Isoform B is mainly expressed in hematopoietic cells.

Miscellaneous. Produced by alternative promoter usage. Produced by alternative splicing of isoform D. Produced by alternative splicing of isoform D. Produced by alternative promoter usage. Produced by alternative splicing of isoform D. Produced by alternative splicing of isoform D. Produced by alternative splicing of isoform D. Produced by alternative splicing of isoform C.

Isoforms (8)

UniProt ID	Names	Canonical?
Q9NS23-1	D, RASSF1D, Cardiac-specific	yes
Q9NS23-2	A, RASSF1A
Q9NS23-3	B, RASSF1B
Q9NS23-4	C, RASSF1C
Q9NS23-5	E, RASSF1E, Pancreas-specific
Q9NS23-6	F, RASSF1F
Q9NS23-7	G, RASSF1G
Q9NS23-9	H

RefSeq proteins (5): NP_001193886, NP_009113, NP_733830, NP_733831, NP_733832 (=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
IPR033600	RASSF1_RA	Domain
IPR033614	RASSF1-6	Family
IPR046349	C1-like_sf	Homologous_superfamily

Pfam: PF00130, PF00788, PF16517

UniProt features (29 total): splice variant 9, sequence variant 7, modified residue 3, region of interest 3, domain 2, initiator methionine 1, chain 1, helix 1, zinc finger region 1, compositionally biased region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2KZU	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NS23-F1	72.56	0.27

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 (3): 2, 36, 2

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 196 (showing top): LI_PROSTATE_CANCER_EPIGENETIC, MORF_ATRX, GOBP_CELL_CYCLE_PHASE_TRANSITION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, TGACCTY_ERR1_Q2, MORF_ESR1, GOMF_GTPASE_BINDING, CAGCTG_AP4_Q5, HESSON_TUMOR_SUPPRESSOR_CLUSTER_3P21_3, GOCC_MICROTUBULE_ORGANIZING_CENTER, MONNIER_POSTRADIATION_TUMOR_ESCAPE_UP, OHM_METHYLATED_IN_ADULT_CANCERS, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN, KEGG_PATHWAYS_IN_CANCER

GO Biological Process (7): DNA damage response (GO:0006974), Ras protein signal transduction (GO:0007265), positive regulation of protein ubiquitination (GO:0031398), protein stabilization (GO:0050821), regulation of cell cycle (GO:0051726), regulation of cell cycle G1/S phase transition (GO:1902806), signal transduction (GO:0007165)

GO Molecular Function (5): zinc ion binding (GO:0008270), small GTPase binding (GO:0031267), identical protein binding (GO:0042802), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (8): spindle pole (GO:0000922), nucleus (GO:0005634), centrosome (GO:0005813), microtubule (GO:0005874), microtubule cytoskeleton (GO:0015630), cytoplasm (GO:0005737), spindle (GO:0005819), cytoskeleton (GO:0005856)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of cellular process	2
cellular anatomical structure	2
microtubule cytoskeleton	2
intracellular membraneless organelle	2
cellular response to stress	1
small GTPase-mediated signal transduction	1
protein ubiquitination	1
regulation of protein ubiquitination	1
positive regulation of protein modification by small protein conjugation or removal	1
regulation of protein stability	1
cell cycle	1
cell cycle G1/S phase transition	1
regulation of cell cycle phase transition	1
cell communication	1
cellular process	1
signaling	1
cellular response to stimulus	1
transition metal ion binding	1
GTPase binding	1
protein binding	1
binding	1
cation binding	1
spindle	1
intracellular membrane-bounded organelle	1
centriole	1
microtubule organizing center	1
polymeric cytoskeletal fiber	1
cytoskeleton	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1938 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RASSF1	MAP1S	Q66K74	954
RASSF1	XPA	P23025	937
RASSF1	MOAP1	Q96BY2	911
RASSF1	CDH13	P55290	906
RASSF1	CNKSR1	Q969H4	885
RASSF1	KRAS	P01116	880
RASSF1	CDKN2A	P42771	878
RASSF1	RASSF5	Q8WWW0	870
RASSF1	MGMT	P16455	868
RASSF1	SAV1	Q9H4B6	868
RASSF1	E4F1	Q66K89	842
RASSF1	GSTP1	P09211	811
RASSF1	DAPK1	P53355	811
RASSF1	RARB	P10826	789
RASSF1	LATS1	O95835	777

IntAct

84 interactions, top by confidence:

A	B	Type	Score
MDM2	USP7	psi-mi:“MI:0914”(association)	0.970
STK3	RASSF2	psi-mi:“MI:0914”(association)	0.950
MDM2	MDM4	psi-mi:“MI:0914”(association)	0.940
STK4	RASSF2	psi-mi:“MI:0914”(association)	0.930
DAXX	USP7	psi-mi:“MI:0914”(association)	0.840
STK4	MAP1B	psi-mi:“MI:0914”(association)	0.730
VAPB	FAM83G	psi-mi:“MI:0914”(association)	0.730
USP7	MDM4	psi-mi:“MI:0914”(association)	0.710
VAPA	FAM83G	psi-mi:“MI:0914”(association)	0.640
STK3	MAP1B	psi-mi:“MI:0914”(association)	0.640
RASSF1	DAXX	psi-mi:“MI:0915”(physical association)	0.630
DAXX	RASSF1	psi-mi:“MI:0915”(physical association)	0.630
DAXX	RASSF1	psi-mi:“MI:0403”(colocalization)	0.630
STK4	STRN	psi-mi:“MI:0914”(association)	0.610
STK4	STRN	psi-mi:“MI:2364”(proximity)	0.610
Rassf1	VAPB	psi-mi:“MI:0915”(physical association)	0.560
RASSF1	AKT1	psi-mi:“MI:0915”(physical association)	0.550
AKT1	RASSF1	psi-mi:“MI:2364”(proximity)	0.550
AKT1	RASSF1	psi-mi:“MI:0915”(physical association)	0.550
RASSF1	BTRC	psi-mi:“MI:0915”(physical association)	0.550
SUV39H2	RASSF1	psi-mi:“MI:0915”(physical association)	0.550
RASSF1	SUV39H2	psi-mi:“MI:0915”(physical association)	0.550
RASSF1	GABARAP	psi-mi:“MI:0407”(direct interaction)	0.540

BioGRID (216): RASSF1 (Affinity Capture-MS), E4F1 (Two-hybrid), E4F1 (Reconstituted Complex), E4F1 (Affinity Capture-Western), E4F1 (Phenotypic Enhancement), RASSF1 (Reconstituted Complex), MST1 (Two-hybrid), STK3 (Two-hybrid), RASSF1 (Affinity Capture-MS), NDUFV2 (Affinity Capture-MS), MAP1B (Affinity Capture-MS), STK3 (Affinity Capture-MS), STK4 (Affinity Capture-MS), MAP1S (Affinity Capture-MS), ITPRIP (Affinity Capture-MS)

ESM2 similar proteins: A0A075QQ08, A0A1D8EJF9, A0A2J6L8Y7, A0A3Q7FGP1, A4K436, A6NMX2, D3UW26, D4AB66, F1M5F3, F1N2W9, F1QWK4, O08908, O43272, O60336, O81481, O88984, O94851, P29557, P41111, P58797, Q0VGM9, Q28ET8, Q2KHI9, Q2T9Z1, Q3UTA9, Q496Y0, Q4V908, Q4VQY1, Q4VQY3, Q5R752, Q5RE34, Q5RJZ1, Q63788, Q66HY7, Q66UV4, Q6GR08, Q6H1L8, Q6NS57, Q6NU27, Q8BML1

Diamond homologs: O35141, Q22744, Q5EBH1, Q6ZTQ3, Q86WH2, Q8WWW0, Q99MK9, Q99P51, Q9NS23, Q9R1K8, Q9Z1S3, A0JNJ1, A4IJ06, A6N9I4, A8KBH6, A8XQD5, A8XWC4, O14795, O45818, O94806, O95267, P04409, P05126, P05128, P05129, P05130, P05696, P05771, P05772, P09215, P09216, P0C643, P10102, P10829, P10830, P13677, P13678, P15882, P16054, P17252

SIGNOR signaling

19 interactions.

A	Effect	B	Mechanism
AURKA	down-regulates	RASSF1	phosphorylation
CDK4	down-regulates	RASSF1	phosphorylation
ATM	up-regulates	RASSF1	phosphorylation
14-3-3	down-regulates	RASSF1	binding
RASSF1	up-regulates	STK3	binding
RASSF1	up-regulates	STK4	binding
AURKB	down-regulates	RASSF1	phosphorylation
CNKSR1	up-regulates	RASSF1	binding
FAS	up-regulates	RASSF1
CHEK1	unknown	RASSF1	phosphorylation
CyclinD/CDK4	down-regulates	RASSF1	phosphorylation
KRAS	“up-regulates activity”	RASSF1	binding
RASSF5	“up-regulates activity”	RASSF1	binding
RASSF1	“up-regulates activity”	STK3	binding
RASSF1	“down-regulates quantity by repression”	CCND1	“post transcriptional regulation”
RASSF1	up-regulates	STK3/4	binding
MOAP1	“up-regulates activity”	RASSF1	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 47 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
Regulation of TP53 Degradation	5	36.6×	9e-05
Macroautophagy	6	17.3×	2e-04

GO biological processes:

GO term	Partners	Fold	FDR
autophagosome maturation	6	51.4×	6e-07
mitophagy	6	46.5×	7e-07
autophagosome assembly	6	32.9×	4e-06
protein stabilization	6	9.8×	2e-03
regulation of cell cycle	5	9.1×	6e-03
protein ubiquitination	6	6.1×	8e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	52
Likely benign	1
Benign	2

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
3370459	NM_015896.4(ZMYND10):c.1024G>T (p.Glu342Ter)	Likely pathogenic

SpliceAI

923 predictions. Top by Δscore:

Variant	Effect	Δscore
3:50330723:TCCCA:T	acceptor_gain	1.0000
3:50330724:CCCA:C	acceptor_gain	1.0000
3:50330724:CCCAC:C	acceptor_gain	1.0000
3:50330725:CCA:C	acceptor_gain	1.0000
3:50330725:CCAC:C	acceptor_gain	1.0000
3:50330726:CA:C	acceptor_gain	1.0000
3:50330726:CAC:C	acceptor_gain	1.0000
3:50330727:AC:A	acceptor_loss	1.0000
3:50330728:C:CC	acceptor_gain	1.0000
3:50331328:A:AC	donor_gain	1.0000
3:50331329:C:CC	donor_gain	1.0000
3:50331332:A:AC	donor_gain	1.0000
3:50331333:C:CT	donor_gain	1.0000
3:50331333:CGTT:C	donor_gain	1.0000
3:50331374:AGGG:A	donor_gain	1.0000
3:50331445:GTACA:G	acceptor_gain	1.0000
3:50331446:TACA:T	acceptor_gain	1.0000
3:50331447:ACA:A	acceptor_gain	1.0000
3:50331448:CA:C	acceptor_gain	1.0000
3:50331448:CAC:C	acceptor_gain	1.0000
3:50331449:AC:A	acceptor_loss	1.0000
3:50331450:C:CA	acceptor_loss	1.0000
3:50331450:C:CC	acceptor_gain	1.0000
3:50331452:G:C	acceptor_gain	1.0000
3:50331452:G:GC	acceptor_gain	1.0000
3:50331554:CCCA:C	donor_loss	1.0000
3:50331556:CACCT:C	donor_loss	1.0000
3:50331558:CCT:C	donor_loss	1.0000
3:50331857:C:CC	acceptor_gain	1.0000
3:50332045:CTCA:C	donor_loss	1.0000

AlphaMissense

2197 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:50330692:G:C	F308L	1.000
3:50330692:G:T	F308L	1.000
3:50330693:A:G	F308S	1.000
3:50330694:A:G	F308L	1.000
3:50330702:A:G	L305P	1.000
3:50330716:G:C	F300L	1.000
3:50330716:G:T	F300L	1.000
3:50330717:A:G	F300S	1.000
3:50330718:A:G	F300L	1.000
3:50331593:A:C	F246L	1.000
3:50331593:A:T	F246L	1.000
3:50331595:A:G	F246L	1.000
3:50331830:G:C	F167L	1.000
3:50331830:G:T	F167L	1.000
3:50331832:A:G	F167L	1.000
3:50330681:A:G	L312P	0.999
3:50330717:A:C	F300C	0.999
3:50330725:C:A	W297C	0.999
3:50330725:C:G	W297C	0.999
3:50330727:A:G	W297R	0.999
3:50330727:A:T	W297R	0.999
3:50331588:A:T	L248H	0.999
3:50331594:A:G	F246S	0.999
3:50331620:G:C	F237L	0.999
3:50331620:G:T	F237L	0.999
3:50331622:A:G	F237L	0.999
3:50331676:G:C	H219D	0.999
3:50331798:A:T	V178D	0.999
3:50331834:C:T	G166D	0.999
3:50331835:C:G	G166R	0.999

dbSNP variants (sampled 300 via entrez): RS1000056347 (3:50333499 C>T), RS1000114251 (3:50333279 A>C), RS1000136650 (3:50333743 G>A), RS1001385515 (3:50340313 CTT>C), RS1001575032 (3:50329882 T>C), RS1002004757 (3:50330192 T>A), RS1002314413 (3:50341697 C>A,T), RS1002366879 (3:50341010 C>G), RS1002380667 (3:50335012 C>T), RS1002986684 (3:50331502 T>C), RS1003020047 (3:50337546 C>T), RS1003352879 (3:50336099 T>C), RS1004298559 (3:50341759 C>A), RS1004719414 (3:50337333 C>A,G,T), RS1005565439 (3:50332252 G>A)

Disease associations

OMIM: gene MIM:605082 | disease phenotypes: MIM:615444

GenCC curated gene-disease

Mondo (1): primary ciliary dyskinesia 22 (MONDO:0014192)

Orphanet (1): Primary ciliary dyskinesia (Orphanet:244)

HPO phenotypes

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

GWAS associations

12 associations (top):

Study	Trait	p-value
GCST004946_204	Schizophrenia	3.000000e-08
GCST007201_5	Schizophrenia	3.000000e-08
GCST007559_24	Sleep duration (short sleep)	3.000000e-08
GCST010698_80	Subcortical volume (min-P)	3.000000e-24
GCST010699_110	Brain morphology (min-P)	4.000000e-08
GCST010701_52	Cortical surface area (MOSTest)	1.000000e-16
GCST010702_36	Subcortical volume (MOSTest)	1.000000e-10
GCST010703_262	Brain morphology (MOSTest)	2.000000e-13
GCST90002380_139	Basophil percentage of white cells	3.000000e-11
GCST90002385_425	High light scatter reticulocyte count	2.000000e-48
GCST90002405_13	Reticulocyte count	1.000000e-42
GCST90002406_31	Reticulocyte fraction of red cells	4.000000e-39

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004346	neuroimaging measurement
EFO:0007992	basophil percentage of leukocytes
EFO:0007986	reticulocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs2236947	Efficacy	3	cetuximab	Colorectal Neoplasms

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2236947	RASSF1	3	2.75	1	cetuximab
rs2073498	RASSF1		0.00	0

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Decitabine	increases expression, decreases methylation, affects expression, decreases expression, decreases reaction (+4 more)	18
Cisplatin	affects expression, decreases expression, increases expression, increases reaction, increases response to substance (+1 more)	5
bisphenol A	decreases expression, affects cotreatment, increases expression	2
trichostatin A	affects cotreatment, affects expression, affects methylation	2
sodium arsenite	affects methylation, increases expression	2
Arsenic Trioxide	affects localization, increases expression, increases reaction, decreases methylation	2
Acetaminophen	increases expression	2
Arsenic	affects methylation, increases methylation	2
Smoke	affects expression, affects methylation, decreases expression	2
Tobacco Smoke Pollution	decreases expression, increases methylation	2
Cyclosporine	increases expression	2
Aflatoxin B1	increases methylation, increases expression	2
Asbestos, Crocidolite	affects expression, increases expression	2
Cadmium Chloride	decreases expression, increases expression, decreases reaction, increases methylation	2
aristolochic acid I	increases expression	1
GSK-J4	decreases expression	1
methylmercuric chloride	increases expression	1
zinc chromate	decreases expression, increases abundance	1
beta-methylcholine	affects expression	1
brequinar	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
chromium hexavalent ion	decreases expression, increases abundance	1
pentabromodiphenyl ether	increases expression	1
CGP 52608	affects binding, increases reaction	1
K 7174	increases expression	1
abrine	increases expression	1
ABT-737	increases reaction, increases response to substance	1
Grape Seed Proanthocyanidins	increases expression	1
jinfukang	increases reaction, decreases expression	1
picoxystrobin	decreases expression	1

Clinical trials (associated diseases)

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