RASSF10

Summary

RASSF10 (Ras association domain family member 10, HGNC:33984) is a protein-coding gene on chromosome 11p15.2, encoding Ras association domain-containing protein 10 (A6NK89). Plays an important role in regulating embryonic neurogenesis.

Predicted to be involved in positive regulation of neural precursor cell proliferation and positive regulation of neurogenesis. Predicted to be located in centrosome; cytosol; and spindle pole.

Source: NCBI Gene 644943 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 98 total
• MANE Select transcript: NM_001080521

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:33984
Approved symbol	RASSF10
Name	Ras association domain family member 10
Location	11p15.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000189431
Ensembl biotype	protein_coding
OMIM	614713
Entrez	644943

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000529419

RefSeq mRNA: 1 — MANE Select: NM_001080521 NM_001080521

CCDS: CCDS44542

Canonical transcript exons

ENST00000529419 — 1 exons

Exon	Start	End
ENSE00003979581	13009316	13012119

Expression profiles

Bgee: expression breadth ubiquitous, 146 present calls, max score 84.25.

FANTOM5 (CAGE): breadth broad, TPM avg 0.9465 / max 95.5518, expressed in 311 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
113165	0.8497	294
113166	0.0968	39

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
esophagus squamous epithelium	UBERON:0006920	84.25	gold quality
kidney epithelium	UBERON:0004819	83.08	gold quality
bronchial epithelial cell	CL:0002328	77.90	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	77.74	silver quality
bronchus	UBERON:0002185	76.69	gold quality
oviduct epithelium	UBERON:0004804	76.09	gold quality
oral cavity	UBERON:0000167	74.42	gold quality
mammary duct	UBERON:0001765	74.16	gold quality
gingiva	UBERON:0001828	74.16	gold quality
epithelium of mammary gland	UBERON:0003244	74.05	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	74.01	gold quality
buccal mucosa cell	CL:0002336	73.97	gold quality
esophagus mucosa	UBERON:0002469	73.74	gold quality
nipple	UBERON:0002030	73.18	gold quality
pancreatic ductal cell	CL:0002079	73.02	silver quality
gingival epithelium	UBERON:0001949	72.97	gold quality
skin of leg	UBERON:0001511	72.95	gold quality
renal medulla	UBERON:0000362	72.67	gold quality
zone of skin	UBERON:0000014	72.20	gold quality
palpebral conjunctiva	UBERON:0001812	71.67	gold quality
skin of abdomen	UBERON:0001416	71.19	gold quality
pylorus	UBERON:0001166	70.20	gold quality
lower esophagus mucosa	UBERON:0035834	69.75	gold quality
ventricular zone	UBERON:0003053	68.47	gold quality
mammary gland	UBERON:0001911	67.71	gold quality
thoracic mammary gland	UBERON:0005200	67.61	gold quality
nasal cavity mucosa	UBERON:0001826	66.43	gold quality
upper arm skin	UBERON:0004263	66.15	gold quality
kidney	UBERON:0002113	65.74	gold quality
saliva-secreting gland	UBERON:0001044	65.20	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-7008	yes	66.81
E-ANND-3	yes	4.70

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, JUN, JUND

miRNA regulators (miRDB)

54 targeting RASSF10, 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-450A-1-3P	100.00	69.33	1837
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-552-5P	99.93	68.56	1583
HSA-MIR-22-3P	99.93	68.13	917
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-544A	99.84	68.66	1965
HSA-MIR-204-5P	99.79	71.62	2439
HSA-MIR-211-5P	99.79	71.65	2440
HSA-MIR-12130	99.75	65.47	452
HSA-MIR-212-3P	99.73	70.65	1424
HSA-MIR-6892-3P	99.68	66.40	1178
HSA-MIR-3158-5P	99.65	67.51	1763
HSA-MIR-543	99.52	69.03	2595
HSA-MIR-6832-3P	99.52	70.44	1726
HSA-MIR-642A-5P	99.51	65.10	1152
HSA-MIR-186-3P	99.51	66.24	1685
HSA-MIR-136-5P	99.50	67.26	1153
HSA-MIR-766-5P	99.47	67.91	2225
HSA-MIR-372-5P	99.41	69.11	2299
HSA-MIR-6839-3P	99.39	68.86	1301
HSA-MIR-19A-5P	99.36	66.93	1675
HSA-MIR-19B-1-5P	99.36	67.07	1669
HSA-MIR-19B-2-5P	99.36	67.07	1669

Literature-anchored findings (GeneRIF, showing 23)

• Sequencing revealed RASSF6 and RASSF10 were the only RASSF members with a high frequency of leukaemia-specific methylation. (PMID:19570220)
• RASSF10 may encode a novel epigenetically inactivated candidate tumor suppressor gene in thyroid carcinogenesis. (PMID:19934646)
• This is the first report demonstrating that RASSF10 can act as a tumor suppressor gene and is frequently methylated in gliomas (PMID:20956940)
• The RASSF10 promoter was hypermethylated in all malignant melanoma (MM) cell lines, 19/28 of the primary MM, 30/33 of the MM metastases, 2/18 of the dysplastic nevus cell nevi, and 0/29 of the non-dysplastic nevus cell nevi. (PMID:22113481)
• The study demonstrates the frequent epigenetic inactivation of RASSF10 in PCa and its implication in clinical symptoms of PCa. (PMID:22415519)
• the results of this study provide insight into the role of RASSF10 as a novel functional tumor suppressor in gastric cancer through inhibition of the Wnt/beta-catenin signaling pathway. (PMID:23428420)
• RASSF10 is an epigenetically silenced gene involved in tumor invasion and metastasis in gastric cancer (PMID:24573726)
• RASSF10 was frequently methylated in human esophageal squamous cell carcinoma and expression of RASSF10 was regulated by promoter region hypermethylation. RASSF10 may serve as a tumor suppressor of esophageal cancer (PMID:24759621)
• RASSF10 functions as a tumor suppressor by cooperating with GSTP1 to deregulate JNK/c-Jun/AP-1 pathway in gastric cancer (PMID:26279301)
• Since restoration of RASSF10 expression sensitized breast cancer cells to docetaxel, RASSF10 methylation is a potential docetaxel resistant marker. RASSF10 suppresses breast cancer growth by activating P53 signaling. (PMID:26645898)
• Loss of RASSF10 expression is associated with hepatocellular carcinoma. (PMID:26701853)
• serum RASSF10 promoter methylation levels can serve as a valuable indicator for the diagnosis and prognosis of gastric cancer in the clinic (PMID:26945573)
• Low expression of RASSF10 in colorectal carcinoma tissues is significantly correlated with poor survival after curative resection. (PMID:28041974)
• RASSF10 induces apoptosis in papillary thyroid carcinoma (PTC) cells by activating the p53 signaling pathway, indicating its role as a treatment target for PTC. (PMID:28268222)
• RASSF6 and RASSF10 were frequently hypermethylated in the samples at the time of diagnosis of adult acute lymphoblastic leukemia patients (PMID:28869817)
• Like a tumor suppressor gene, RASSF10 can inhibit the proliferation, invasion, and migration of hepatocellular carcinoma cells (PMID:28925496)
• RASSF10 overexpression inhibited the proliferation and invasion of lung cancer cells, which was the result of Wnt signaling suppression. RASSF10 bound to LRP6 via the coiled-coil domains and reduced p-LRP6 level, eventually prohibiting beta-catenin nuclear translocation. (PMID:30834575)
• High serum RASSF10 promoter methylation is associated with gastric cancer. (PMID:31119967)
• DNA methylation status of the RASSF6 and RASSF10 genes could be potential biomarkers for the assessment of residual disease in PB of patients with ALL. (PMID:31486880)
• RASSF10 is frequently epigenetically inactivated in kidney cancer and its knockout promotes neoplasia in cancer prone mice. (PMID:32047266)
• EBV as a high infection risk factor promotes RASSF10 methylation and induces cell proliferation in EBV-associated gastric cancer. (PMID:33588233)
• Molecular basis for RASSF10/NPM/RNF2 feedback cascade-mediated regulation of gastric cancer cell proliferation. (PMID:34224728)
• RASSF10 exhibits tumorsuppressing potential involving tumor proliferation, metastasis and epithelialmesenchymal transition in esophageal squamous cell carcinoma. (PMID:35211758)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	RASSF10	ENSDARG00000112859
mus_musculus	Rassf10	ENSMUSG00000098132
rattus_norvegicus	Rassf10	ENSRNOG00000073349
drosophila_melanogaster	meru	FBGN0052150

Paralogs (3): RASSF7 (ENSG00000099849), RASSF8 (ENSG00000123094), RASSF9 (ENSG00000198774)

Protein

Protein identifiers

Ras association domain-containing protein 10 — A6NK89 (reviewed: A6NK89)

All UniProt accessions (1): A6NK89

UniProt curated annotations — full annotation on UniProt →

Function. Plays an important role in regulating embryonic neurogenesis.

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

Tissue specificity. Expressed in brain. Tends to be down-regulated in astrocytic gliomas due to promoter methylation. Methylation occurs early in gliomagenesis and the extent of methylation parallels with higher glioma grades, so that methylation is observed in close to 70% WHO grade IV primary glioblastomas, but not in grade I astrocytomas.

RefSeq proteins (1): NP_001073990* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000159	RA_dom	Domain
IPR029071	Ubiquitin-like_domsf	Homologous_superfamily
IPR033593	N-RASSF	Family
IPR033634	RASSF10_RA	Domain
IPR048945	RASSF8/10_RA	Domain

Pfam: PF21712

UniProt features (12 total): compositionally biased region 4, region of interest 3, coiled-coil region 2, chain 1, domain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A6NK89-F1	73.51	0.38

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 64 (showing top): GOBP_NEUROGENESIS, GOBP_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT, GOBP_POSITIVE_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT, GOCC_MICROTUBULE_ORGANIZING_CENTER, BRUECKNER_TARGETS_OF_MIRLET7A3_DN, GOBP_NEURAL_PRECURSOR_CELL_PROLIFERATION, GOBP_POSITIVE_REGULATION_OF_CELL_DIFFERENTIATION, GOCC_CENTROSOME, GOBP_POSITIVE_REGULATION_OF_NEURAL_PRECURSOR_CELL_PROLIFERATION, CUI_TCF21_TARGETS_2_DN, GOBP_POSITIVE_REGULATION_OF_DEVELOPMENTAL_PROCESS, GOBP_POSITIVE_REGULATION_OF_CELL_DEVELOPMENT, VECCHI_GASTRIC_CANCER_EARLY_DN, GOBP_REGULATION_OF_NEURAL_PRECURSOR_CELL_PROLIFERATION, GOBP_REGULATION_OF_CELL_DEVELOPMENT

GO Biological Process (4): signal transduction (GO:0007165), nervous system development (GO:0007399), positive regulation of neurogenesis (GO:0050769), positive regulation of neural precursor cell proliferation (GO:2000179)

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

GO Cellular Component (5): spindle pole (GO:0000922), centrosome (GO:0005813), cytosol (GO:0005829), cytoplasm (GO:0005737), cytoskeleton (GO:0005856)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
system development	1
positive regulation of cell development	1
neurogenesis	1
regulation of neurogenesis	1
positive regulation of nervous system development	1
positive regulation of cell population proliferation	1
neural precursor cell proliferation	1
regulation of neural precursor cell proliferation	1
binding	1
spindle	1
centriole	1
microtubule organizing center	1
cytoplasm	1
intracellular anatomical structure	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

394 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RASSF10	RASSF7	Q02833	813
RASSF10	RASSF6	Q6ZTQ3	778
RASSF10	RASSF8	Q8NHQ8	691
RASSF10	RASSF1	Q9NS23	655
RASSF10	RASSF5	Q8WWW0	630
RASSF10	RASSF2	P50749	622
RASSF10	RASSF3	Q86WH2	610
RASSF10	FAM171A1	Q5VUB5	539
RASSF10	GNG13	Q9P2W3	500
RASSF10	TNNI3	P19429	468
RASSF10	TRIM3	O75382	404
RASSF10	ALKAL1	Q6UXT8	391
RASSF10	RAPH1	Q70E73	360
RASSF10	RGL4	Q8IZJ4	357
RASSF10	ARHGAP20	Q9P2F6	353

IntAct

76 interactions, top by confidence:

A	B	Type	Score
RASSF10	CBY1	psi-mi:“MI:0915”(physical association)	0.560
RASSF10	FAM171A1	psi-mi:“MI:0915”(physical association)	0.560
RASSF10	FAM110A	psi-mi:“MI:0915”(physical association)	0.560
RASSF10	TP53BP2	psi-mi:“MI:0915”(physical association)	0.560
RASSF10	LDOC1	psi-mi:“MI:0915”(physical association)	0.560
RASSF10	GNG13	psi-mi:“MI:0915”(physical association)	0.560
RASSF10	GADD45G	psi-mi:“MI:0915”(physical association)	0.560
RASSF10	MAGEA6	psi-mi:“MI:0915”(physical association)	0.560
RASSF10	SMU1	psi-mi:“MI:0915”(physical association)	0.560
RASSF10	NXT2	psi-mi:“MI:0915”(physical association)	0.560
GOLGA6L9	RASSF10	psi-mi:“MI:0915”(physical association)	0.560
RASSF10	TRIM54	psi-mi:“MI:0915”(physical association)	0.560
RASSF10	EIF1AD	psi-mi:“MI:0915”(physical association)	0.560
RASSF10	WNT11	psi-mi:“MI:0915”(physical association)	0.560
RASSF10	TEAD4	psi-mi:“MI:0915”(physical association)	0.560
RASSF10	SMG9	psi-mi:“MI:0915”(physical association)	0.560
RASSF10	CEP57	psi-mi:“MI:0915”(physical association)	0.560
RASSF10	ATP6V1E2	psi-mi:“MI:0915”(physical association)	0.560
RASSF10	CCDC183	psi-mi:“MI:0915”(physical association)	0.560
RASSF10	CCDC116	psi-mi:“MI:0915”(physical association)	0.560
RASSF10	CEP70	psi-mi:“MI:0915”(physical association)	0.560
RASSF10	TNNI3	psi-mi:“MI:0915”(physical association)	0.560
RASSF10	EGFL7	psi-mi:“MI:0915”(physical association)	0.560
rep	RASSF10	psi-mi:“MI:0915”(physical association)	0.490
M		psi-mi:“MI:0914”(association)	0.350
RASSF10	CCDC85C	psi-mi:“MI:0914”(association)	0.350
RASSF10	CBY1	psi-mi:“MI:0915”(physical association)	0.000
RASSF10	FAM171A1	psi-mi:“MI:0915”(physical association)	0.000
FAM110A	RASSF10	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (64): ANXA1 (Affinity Capture-MS), PPP1R13B (Affinity Capture-MS), TP53BP2 (Affinity Capture-MS), CTSD (Affinity Capture-MS), CCDC85C (Affinity Capture-MS), CPVL (Affinity Capture-MS), CSNK2A1 (Affinity Capture-MS), CSNK2B (Affinity Capture-MS), CSTA (Affinity Capture-MS), DDB1 (Affinity Capture-MS), DOCK7 (Affinity Capture-MS), DVL1 (Affinity Capture-MS), DVL2 (Affinity Capture-MS), DVL3 (Affinity Capture-MS), G3BP1 (Affinity Capture-MS)

ESM2 similar proteins: A0A8I3QA39, A2A6T1, A2A9T0, A2AEV7, A2AHG0, A4FUG8, A4IFI1, A5PKL7, A6NK89, A7MCY6, D3ZD05, E1U8D0, F1MRK3, G3V735, J3QNX5, O14529, O15049, O60299, O94964, O95153, P58660, Q1LZH7, Q2M3V2, Q3LUD3, Q3LUD4, Q5BJT1, Q5JTD0, Q5RCR6, Q63ZY3, Q6DG50, Q6NY19, Q6PDH0, Q7TNF8, Q86UU1, Q86X02, Q8BLS7, Q8C7U1, Q8K1Q4, Q8K371, Q8N137

Diamond homologs: A6NK89, B1A193, O75901, O88869, Q8BL43, Q8K342

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	97
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

7 predictions. Top by Δscore:

Variant	Effect	Δscore
11:13011039:GAC:G	donor_gain	0.4900
11:13011038:GGAC:G	donor_gain	0.4300
11:13011033:A:G	donor_gain	0.2500
11:13009619:G:GT	donor_gain	0.2400
11:13011081:T:G	donor_gain	0.2200
11:13011032:GA:G	donor_gain	0.2100
11:13011087:A:T	donor_gain	0.2000

AlphaMissense

3243 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:13009925:T:A	W117R	1.000
11:13009925:T:C	W117R	1.000
11:13009953:T:C	F126S	1.000
11:13009658:T:C	C28R	0.999
11:13009660:C:G	C28W	0.999
11:13009854:T:A	I93N	0.999
11:13009860:A:T	E95V	0.999
11:13009861:G:C	E95D	0.999
11:13009861:G:T	E95D	0.999
11:13009865:T:A	W97R	0.999
11:13009865:T:C	W97R	0.999
11:13009867:G:C	W97C	0.999
11:13009867:G:T	W97C	0.999
11:13009881:G:C	R102P	0.999
11:13009887:T:A	L104H	0.999
11:13009927:G:C	W117C	0.999
11:13009927:G:T	W117C	0.999
11:13009952:T:C	F126L	0.999
11:13009954:C:A	F126L	0.999
11:13009954:C:G	F126L	0.999
11:13009659:G:A	C28Y	0.998
11:13009880:C:A	R102S	0.998
11:13009887:T:C	L104P	0.998
11:13009905:T:A	I110N	0.998
11:13009905:T:C	I110T	0.998
11:13009914:T:C	L113P	0.998
11:13009953:T:G	F126C	0.998
11:13009959:T:C	L128P	0.998
11:13010117:T:C	F181L	0.998
11:13010119:T:A	F181L	0.998

dbSNP variants (sampled 300 via entrez): RS1000887892 (11:13009997 C>A,T), RS1001284909 (11:13008946 AG>A), RS1001318756 (11:13009756 C>T), RS1001925306 (11:13008575 C>T), RS1002295698 (11:13008821 G>A), RS1002754800 (11:13011409 A>C), RS1003132048 (11:13011723 A>G), RS1003392542 (11:13010707 T>C), RS1005641392 (11:13007619 C>G,T), RS1005844539 (11:13010347 G>T), RS1006170720 (11:13011831 G>A), RS1006855231 (11:13008016 G>C), RS1007142464 (11:13008339 A>T), RS1009193442 (11:13007739 T>C), RS1009250015 (11:13008122 T>C)

Disease associations

OMIM: gene MIM:614713 | 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
GCST001762_494	Obesity-related traits	8.000000e-06
GCST005751_8	Empathy quotient	4.000000e-07
GCST010479_19	Coronary artery disease	3.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0005109	energy expenditure
EFO:0009183	empathy measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression	5
trichostatin A	affects cotreatment, decreases expression	2
sodium arsenite	increases expression	2
Vorinostat	affects cotreatment, decreases expression	2
Panobinostat	decreases expression, affects cotreatment	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Tobacco Smoke Pollution	decreases expression	2
aristolochic acid I	increases expression	1
methylmercuric chloride	decreases expression	1
propionaldehyde	increases expression	1
2-methyl-4-isothiazolin-3-one	increases expression	1
butyraldehyde	increases expression	1
ferrous chloride	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment, decreases expression	1
pentanal	increases expression	1
avobenzone	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	affects cotreatment, increases expression	1
Aldehydes	increases expression	1
Benzo(a)pyrene	affects methylation	1
Cisplatin	affects cotreatment, increases expression	1
Estradiol	affects cotreatment, increases expression	1
Formaldehyde	decreases expression	1
Lipopolysaccharides	affects response to substance, increases expression, affects cotreatment, decreases expression	1
Niclosamide	decreases expression	1
Potassium Chloride	decreases expression, decreases response to substance	1
Smoke	decreases expression	1
Dronabinol	decreases response to substance, decreases expression	1

Clinical trials (associated diseases)

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