RASSF8

Summary

RASSF8 (Ras association domain family member 8, HGNC:13232) is a protein-coding gene on chromosome 12p12.1, encoding Ras association domain-containing protein 8 (Q8NHQ8).

This gene encodes a member of the Ras-assocation domain family (RASSF) of tumor suppressor proteins. This gene is essential for maintaining adherens junction function in epithelial cells and has a role in epithelial cell migration. It is a lung tumor suppressor gene candidate. A chromosomal translocation t(12;22)(p11.2;q13.3) leading to the fusion of this gene and the FBLN1 gene is found in a complex type of synpolydactyly. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 11228 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 67 total
• MANE Select transcript: NM_001394098

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13232
Approved symbol	RASSF8
Name	Ras association domain family member 8
Location	12p12.1
Locus type	gene with protein product
Status	Approved
Aliases	HoJ-1
Ensembl gene	ENSG00000123094
Ensembl biotype	protein_coding
OMIM	608231
Entrez	11228

Gene structure

Transcript identifiers

Ensembl transcripts: 28 — 25 protein_coding, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000282884, ENST00000381352, ENST00000405154, ENST00000535907, ENST00000537946, ENST00000538081, ENST00000538365, ENST00000539545, ENST00000541218, ENST00000541490, ENST00000542004, ENST00000542315, ENST00000542865, ENST00000545413, ENST00000615708, ENST00000688511, ENST00000689434, ENST00000689635, ENST00000866628, ENST00000916362, ENST00000916363, ENST00000953804, ENST00000953805, ENST00000953806, ENST00000953807, ENST00000953808, ENST00000953809, ENST00000953810

RefSeq mRNA: 13 — MANE Select: NM_001394098 NM_001164746, NM_001164747, NM_001164748, NM_001394094, NM_001394095, NM_001394096, NM_001394097, NM_001394098, NM_001394099, NM_001394100, NM_001394101, NM_001394102, NM_007211

CCDS: CCDS53765, CCDS8705

Canonical transcript exons

ENST00000689635 — 6 exons

Exon	Start	End
ENSE00001007933	26064498	26065387
ENSE00001098633	26067569	26067713
ENSE00001315354	26055236	26055446
ENSE00001488370	26068697	26072869
ENSE00001523418	25995037	25995130
ENSE00003938276	25958682	25959148

Expression profiles

Bgee: expression breadth ubiquitous, 256 present calls, max score 97.10.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 14.7210 / max 636.3947, expressed in 1556 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
124799	9.9413	1482
124804	1.3022	781
124798	0.8781	601
124800	0.6244	395
124801	0.6157	384
124803	0.5477	338
124802	0.3968	203
124797	0.2334	87
124806	0.1333	2
124807	0.0170	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	97.10	gold quality
calcaneal tendon	UBERON:0003701	97.06	gold quality
stromal cell of endometrium	CL:0002255	95.50	gold quality
left testis	UBERON:0004533	95.20	gold quality
right testis	UBERON:0004534	94.93	gold quality
testis	UBERON:0000473	93.45	gold quality
male germ cell	CL:0000015	93.00	gold quality
pigmented layer of retina	UBERON:0001782	92.68	gold quality
colonic epithelium	UBERON:0000397	92.23	gold quality
tendon	UBERON:0000043	91.88	gold quality
sural nerve	UBERON:0015488	90.85	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	90.45	gold quality
secondary oocyte	CL:0000655	89.97	gold quality
germinal epithelium of ovary	UBERON:0001304	89.78	gold quality
parietal pleura	UBERON:0002400	89.60	gold quality
cauda epididymis	UBERON:0004360	88.79	gold quality
gall bladder	UBERON:0002110	87.10	gold quality
cartilage tissue	UBERON:0002418	86.76	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	86.73	gold quality
mucosa of stomach	UBERON:0001199	86.39	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	86.38	gold quality
biceps brachii	UBERON:0001507	86.16	gold quality
tibial artery	UBERON:0007610	86.04	gold quality
popliteal artery	UBERON:0002250	86.03	gold quality
pleura	UBERON:0000977	86.00	gold quality
body of uterus	UBERON:0009853	85.76	gold quality
right lung	UBERON:0002167	85.71	gold quality
hindlimb stylopod muscle	UBERON:0004252	85.61	gold quality
artery	UBERON:0001637	85.51	gold quality
spinal cord	UBERON:0002240	85.33	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-137537	yes	6.11
E-MTAB-4850	no	7.83
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F1, GLI1

miRNA regulators (miRDB)

40 targeting RASSF8, 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-150-5P	99.99	66.69	1976
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-8075	99.97	67.20	962
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-9718	99.94	68.91	918
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-629-3P	99.85	67.99	1875
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-4713-5P	99.78	67.80	1794
HSA-MIR-3156-3P	99.76	66.72	939
HSA-MIR-12130	99.75	65.47	452
HSA-MIR-6134	99.63	65.68	1537
HSA-MIR-1260A	99.61	66.67	1098
HSA-MIR-1260B	99.61	66.67	1098
HSA-MIR-5004-3P	99.54	68.27	1371
HSA-MIR-4677-3P	99.49	67.91	1246
HSA-MIR-6740-3P	99.48	68.49	1392
HSA-MIR-4687-3P	99.48	66.41	968
HSA-MIR-6839-3P	99.39	68.86	1301
HSA-MIR-6853-3P	99.36	70.79	1558
HSA-MIR-148A-5P	99.30	68.27	1141
HSA-MIR-504-3P	99.30	67.18	1745
HSA-MIR-1206	99.30	69.32	1016
HSA-MIR-488-5P	99.28	68.12	821
HSA-MIR-3978	99.24	68.39	2201
HSA-MIR-3940-5P	99.14	65.26	493

Literature-anchored findings (GeneRIF, showing 11)

• Expression of RASSF8 protein by transfected lung cancer cells led to inhibition of anchorage-independent growth in soft agar in A549 cells and reduction of clonogenic activity in NCI-H520 cells (PMID:16462760)
• RASSF8 as a tumor suppressor gene that is essential for maintaining AJs function in epithelial cells and have a role in epithelial cell migration. (PMID:20514026)
• RASSF8 plays a significant role in suppressing the progression of cutaneous melanoma. (PMID:26334503)
• RASSF8 knockdown by specific RNAi showed similar effects in cervical cancer cells transfected with miR-224 mimic. Our findings suggest that miR-224 directly targets RASSF8 and thereby acts as a tumor promoter in cervical cancer progression (PMID:27626930)
• These results indicate that hypoxia-inducible miR-224 promotes gastric cancer cell growth, migration and invasion by downregulating RASSF8 and acts as an oncogene, implying that inhibition of miR-224 may have potential as a therapeutic target for patients with hypoxic gastric tumors. (PMID:28173803)
• The miR-224 played an oncogenic role in the proliferation of NSCLC by direct targeting RASSF8. (PMID:28770961)
• data provide evidence that E4BP4 attenuates RASSF8-mediated anti-proliferation and apoptosis, shedding mechanistic insights into RASSF8 down-regulation in breast cancers. (PMID:29467226)
• MiR-505 mediated MTX resistance, propagation, cell cycle and metastasis by targeting RASSF8 in colorectal cancer (PMID:29726011)
• CircCERS6 Suppresses the Development of Epithelial Ovarian Cancer Through Mediating miR-630/RASSF8. (PMID:35676548)
• RASSF8-AS1 displays low expression in colorectal cancer and up-regulates RASSF8 to suppress cell invasion and migration. (PMID:35839610)
• Tailored modulation of S100A1 and RASSF8 expression by butanediamide augments healing of rotator cuff tears. (PMID:37601265)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	rassf8b	ENSDARG00000045485
danio_rerio	rassf8a	ENSDARG00000045596
mus_musculus	Rassf8	ENSMUSG00000030259
rattus_norvegicus	Rassf8	ENSRNOG00000015986
drosophila_melanogaster	RASSF8	FBGN0261986
caenorhabditis_elegans		WBGENE00019403

Paralogs (3): RASSF7 (ENSG00000099849), RASSF10 (ENSG00000189431), RASSF9 (ENSG00000198774)

Protein

Protein identifiers

Ras association domain-containing protein 8 — Q8NHQ8 (reviewed: Q8NHQ8)

Alternative names: Carcinoma-associated protein HOJ-1

All UniProt accessions (8): Q8NHQ8, F5GYP8, F5H0S5, F5H343, F5H7J1, F5H8B9, F5H8C5, H0YG85

UniProt curated annotations — full annotation on UniProt →

Tissue specificity. Widely expressed as a 6.2 kb transcript. A 2.2 kb alternatively spliced transcript is expressed exclusively in testis.

Disease relevance. A chromosomal aberration involving RASSF8 is found in a complex type of synpolydactyly referred to as 3/3-prime/4 synpolydactyly associated with metacarpal and metatarsal synostoses. Reciprocal translocation t(12;22)(p11.2;q13.3) with FBLN1.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8NHQ8-1	1	yes
Q8NHQ8-2	2

RefSeq proteins (13): NP_001158218, NP_001158219, NP_001158220, NP_001381023, NP_001381024, NP_001381025, NP_001381026, NP_001381027, NP_001381028, NP_001381029, NP_001381030, NP_001381031, NP_009142 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000159	RA_dom	Domain
IPR029071	Ubiquitin-like_domsf	Homologous_superfamily
IPR033593	N-RASSF	Family
IPR048944	RASSF8_RA	Domain
IPR048945	RASSF8/10_RA	Domain

Pfam: PF21712

UniProt features (19 total): strand 8, modified residue 4, helix 3, chain 1, domain 1, splice variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2CS4	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NHQ8-F1	76.65	0.52

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (4): 105, 129, 131, 387

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 224 (showing top): GSE45365_NK_CELL_VS_CD8_TCELL_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, KORKOLA_CHORIOCARCINOMA_DN, LINDGREN_BLADDER_CANCER_CLUSTER_2A_DN, YORDY_RECIPROCAL_REGULATION_BY_ETS1_AND_SP100_DN, WANG_LMO4_TARGETS_DN, KORKOLA_EMBRYONAL_CARCINOMA_DN, INGRAM_SHH_TARGETS_UP, TGANTCA_AP1_C, SENESE_HDAC1_TARGETS_UP, LIU_BREAST_CANCER, TGGAAA_NFAT_Q4_01, GEORGES_TARGETS_OF_MIR192_AND_MIR215, chr12p12, HEB_Q6

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

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

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
binding	1

Protein interactions and networks

STRING

738 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RASSF8	FBLN1	P23142	926
RASSF8	RASSF10	A6NK89	691
RASSF8	TP53BP2	Q13625	623
RASSF8	RASSF6	Q6ZTQ3	609
RASSF8	FRMD6	Q96NE9	569
RASSF8	PPP1R13B	Q96KQ4	537
RASSF8	PTPN14	Q15678	537
RASSF8	RASSF1	Q9NS23	497
RASSF8	RASSF2	P50749	480
RASSF8	LMNTD1	Q8N9Z9	471
RASSF8	WBP2	Q969T9	466
RASSF8	RASSF5	Q8WWW0	455
RASSF8	RASSF3	Q86WH2	454
RASSF8	CABP7	Q86V35	438
RASSF8	AMOT	Q4VCS5	434

IntAct

94 interactions, top by confidence:

A	B	Type	Score
YWHAG	RASSF8	psi-mi:“MI:0915”(physical association)	0.830
YWHAH	ABLIM1	psi-mi:“MI:0914”(association)	0.800
PPP1CC	CCDC85C	psi-mi:“MI:0914”(association)	0.740
PPP1CA	CCDC85C	psi-mi:“MI:0914”(association)	0.670
PPP1CA	CCDC85C	psi-mi:“MI:2364”(proximity)	0.670
RASSF8	FRMD6	psi-mi:“MI:0915”(physical association)	0.660
YWHAG	BLTP3B	psi-mi:“MI:2364”(proximity)	0.640
RASSF8	PPP1CC	psi-mi:“MI:0914”(association)	0.640
PARD3	PRKCI	psi-mi:“MI:0914”(association)	0.620
YWHAH	PLEKHG3	psi-mi:“MI:0914”(association)	0.610
YWHAB	BLTP3B	psi-mi:“MI:2364”(proximity)	0.610
MPDZ	SMCHD1	psi-mi:“MI:0914”(association)	0.590
YWHAH	BLTP3B	psi-mi:“MI:2364”(proximity)	0.570
YWHAG	SHTN1	psi-mi:“MI:0914”(association)	0.560
RASSF8	SMAD4	psi-mi:“MI:0915”(physical association)	0.550
SMAD4	RASSF8	psi-mi:“MI:2364”(proximity)	0.550
YWHAB	SHTN1	psi-mi:“MI:0914”(association)	0.530
YWHAE	SHTN1	psi-mi:“MI:0914”(association)	0.530
YWHAZ	SHTN1	psi-mi:“MI:0914”(association)	0.530
YWHAZ	BLTP3B	psi-mi:“MI:0914”(association)	0.530
RASSF8	CORO1A	psi-mi:“MI:0914”(association)	0.530
YWHAB	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
YWHAQ	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
ERC1	RASSF8	psi-mi:“MI:0915”(physical association)	0.400
RASSF8	Klc1	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (165): RASSF8 (Affinity Capture-MS), RASSF8 (Affinity Capture-MS), RASSF8 (Affinity Capture-MS), RASSF8 (Affinity Capture-MS), RASSF8 (Affinity Capture-MS), PPP1R13B (Affinity Capture-MS), TP53BP2 (Affinity Capture-MS), PARD3 (Affinity Capture-MS), GOLGA2 (Affinity Capture-MS), PRKCI (Affinity Capture-MS), ZBTB2 (Affinity Capture-MS), PCM1 (Affinity Capture-MS), ZNF639 (Affinity Capture-MS), POC1A (Affinity Capture-MS), C17orf70 (Affinity Capture-MS)

ESM2 similar proteins: A0MZ67, A1L260, A2AMM0, A2VDA9, A4IGC3, A5PJI6, A9C3W3, B1PRL5, B9EKI3, O35711, O35867, O54724, O76878, O94876, O95810, P34609, P55326, P70302, P83093, P84903, P85125, Q0IIE0, Q13586, Q29EP6, Q32PN7, Q58CP9, Q5BKX8, Q5FWS6, Q63918, Q66H98, Q674X7, Q69ZS8, Q69ZZ6, Q6NZI2, Q6P0R8, Q6P402, Q7T019, Q8CJ96, Q8K2Q9, Q8MJK1

Diamond homologs: Q02833, Q8CJ96, Q8NHQ8, Q9DD19, O75901, O88869, Q8K342

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 71 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	8	110.7×	1e-13
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	9	109.9×	5e-15
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	7	85.5×	5e-11
Activation of BH3-only proteins	9	81.2×	1e-13
RHO GTPases activate PKNs	9	51.9×	6e-12
Intrinsic Pathway for Apoptosis	9	47.9×	1e-11
FOXO-mediated transcription	7	42.8×	9e-09
Apoptosis	9	27.5×	2e-09

GO biological processes:

GO term	Partners	Fold	FDR
protein targeting	5	28.2×	4e-04
intracellular protein localization	12	19.3×	9e-10
epidermal growth factor receptor signaling pathway	5	19.1×	1e-03
axonogenesis	5	12.3×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	59
Likely benign	3
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1717 predictions. Top by Δscore:

Variant	Effect	Δscore
12:25959144:ACTGA:A	donor_gain	1.0000
12:25959145:CTGA:C	donor_gain	1.0000
12:25959146:TGA:T	donor_gain	1.0000
12:25959147:GA:G	donor_gain	1.0000
12:25959147:GAG:G	donor_gain	1.0000
12:25959148:AG:A	donor_loss	1.0000
12:25959149:G:GG	donor_gain	1.0000
12:26055416:G:GT	donor_gain	1.0000
12:26067565:CTA:C	acceptor_loss	1.0000
12:26067566:TA:T	acceptor_loss	1.0000
12:26067567:AG:A	acceptor_gain	1.0000
12:26067568:GG:G	acceptor_gain	1.0000
12:26067711:GGG:G	donor_gain	1.0000
12:26067712:GG:G	donor_gain	1.0000
12:26067712:GGG:G	donor_gain	1.0000
12:26067713:GG:G	donor_gain	1.0000
12:26067714:G:GG	donor_gain	1.0000
12:26067715:T:A	donor_loss	1.0000
12:25959150:T:G	donor_loss	0.9900
12:25977309:GACT:G	donor_gain	0.9900
12:25977312:T:G	donor_gain	0.9900
12:25977312:T:TG	donor_gain	0.9900
12:26055234:A:AG	acceptor_gain	0.9900
12:26055235:G:GG	acceptor_gain	0.9900
12:26055235:GCT:G	acceptor_gain	0.9900
12:26055444:TAGG:T	donor_loss	0.9900
12:26055445:AGG:A	donor_loss	0.9900
12:26055447:G:GA	donor_loss	0.9900
12:26055448:T:A	donor_loss	0.9900
12:26055449:GAGT:G	donor_loss	0.9900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000058218 (12:26016737 TTTC>T), RS1000144332 (12:26011012 C>G), RS1000163028 (12:25972932 A>G), RS1000178752 (12:26075155 C>T), RS1000218681 (12:26050204 C>G), RS1000322290 (12:25978067 C>G,T), RS1000350565 (12:26056169 C>T), RS1000401723 (12:26069360 G>A), RS1000412263 (12:26022985 G>A), RS1000468143 (12:26057469 A>G), RS1000488369 (12:26061863 G>A), RS1000502791 (12:26009848 G>A), RS1000508666 (12:26074179 C>A,T), RS1000554804 (12:25971253 T>C), RS1000611109 (12:25977018 C>A)

Disease associations

OMIM: gene MIM:608231 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST005956_3	Waist-to-hip ratio adjusted for BMI	4.000000e-14
GCST005958_7	Waist-to-hip ratio adjusted for BMI (age >50)	4.000000e-10
GCST005962_18	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	3.000000e-13
GCST006979_892	Heel bone mineral density	4.000000e-11
GCST007844_17	Ankylosing spondylitis	4.000000e-06
GCST008486_2	Atrial fibrillation	9.000000e-09

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement
EFO:0009270	heel bone mineral density

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
trichostatin A	decreases expression	2
sodium arsenite	affects cotreatment, increases abundance, decreases expression	2
Acetaminophen	increases expression	2
Valproic Acid	decreases expression, increases methylation	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
TL8-506	affects cotreatment, increases expression	1
dicrotophos	decreases expression	1
geldanamycin	increases expression	1
bisphenol A	increases expression	1
beta-lapachone	decreases expression	1
arsenite	decreases reaction, affects binding	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
coumarin	increases phosphorylation	1
epigallocatechin gallate	decreases expression, affects cotreatment	1
jinfukang	affects cotreatment, decreases expression	1
Arsenic Trioxide	increases expression	1
Vorinostat	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Arsenic	increases abundance, affects cotreatment, decreases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Cisplatin	affects cotreatment, decreases expression	1
Coal	increases abundance, increases expression	1
Endosulfan	decreases expression	1
Estradiol	affects expression	1
Manganese	affects cotreatment, decreases expression, increases abundance	1
Poly I-C	affects cotreatment, increases expression	1
Smoke	increases abundance, increases expression	1
Thimerosal	decreases expression	1

Clinical trials (associated diseases)

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