RASSF7

Summary

RASSF7 (Ras association domain family member 7, HGNC:1166) is a protein-coding gene on chromosome 11p15.5, encoding Ras association domain-containing protein 7 (Q02833). Negatively regulates stress-induced JNK activation and apoptosis by promoting MAP2K7 phosphorylation and inhibiting its ability to activate JNK.

Predicted to be involved in apoptotic process and signal transduction. Located in centriolar satellite.

Source: NCBI Gene 8045 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 104 total
• MANE Select transcript: NM_003475

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1166
Approved symbol	RASSF7
Name	Ras association domain family member 7
Location	11p15.5
Locus type	gene with protein product
Status	Approved
Aliases	HRC1, HRAS1, FAP88, CFAP88
Ensembl gene	ENSG00000099849
Ensembl biotype	protein_coding
OMIM	143023
Entrez	8045

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 12 protein_coding, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000397582, ENST00000397583, ENST00000414138, ENST00000431809, ENST00000454668, ENST00000524468, ENST00000528736, ENST00000531112, ENST00000886265, ENST00000886266, ENST00000886267, ENST00000971581, ENST00000971582, ENST00000971583, ENST00000971584

RefSeq mRNA: 3 — MANE Select: NM_003475 NM_001143993, NM_001143994, NM_003475

CCDS: CCDS44505, CCDS44506, CCDS7702

Canonical transcript exons

ENST00000397583 — 6 exons

Exon	Start	End
ENSE00000655976	563396	563478
ENSE00000655978	562079	562776
ENSE00000892597	563189	563317
ENSE00001694199	561762	561892
ENSE00001872425	560970	561477
ENSE00002168084	563558	564025

Expression profiles

Bgee: expression breadth ubiquitous, 132 present calls, max score 98.83.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 5.1404 / max 59.4163, expressed in 1384 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
112216	5.1404	1384

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	98.83	gold quality
mucosa of transverse colon	UBERON:0004991	97.72	gold quality
metanephros cortex	UBERON:0010533	97.56	gold quality
lower esophagus mucosa	UBERON:0035834	96.65	gold quality
right lobe of liver	UBERON:0001114	94.44	gold quality
right lung	UBERON:0002167	94.35	gold quality
body of pancreas	UBERON:0001150	93.96	gold quality
right hemisphere of cerebellum	UBERON:0014890	93.86	gold quality
adult mammalian kidney	UBERON:0000082	93.78	gold quality
cerebellar hemisphere	UBERON:0002245	93.55	gold quality
cerebellar cortex	UBERON:0002129	93.54	gold quality
cerebellum	UBERON:0002037	93.50	gold quality
cortex of kidney	UBERON:0001225	93.22	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	93.17	gold quality
skin of leg	UBERON:0001511	92.92	gold quality
zone of skin	UBERON:0000014	92.61	gold quality
skin of abdomen	UBERON:0001416	92.60	gold quality
upper lobe of left lung	UBERON:0008952	92.34	gold quality
duodenum	UBERON:0002114	92.26	gold quality
granulocyte	CL:0000094	91.92	gold quality
esophagus mucosa	UBERON:0002469	91.82	gold quality
minor salivary gland	UBERON:0001830	90.80	gold quality
saliva-secreting gland	UBERON:0001044	90.63	gold quality
body of stomach	UBERON:0001161	90.45	gold quality
transverse colon	UBERON:0001157	90.35	gold quality
kidney	UBERON:0002113	90.27	gold quality
fallopian tube	UBERON:0003889	90.05	gold quality
liver	UBERON:0002107	90.00	gold quality
small intestine Peyer’s patch	UBERON:0003454	89.74	gold quality
small intestine	UBERON:0002108	89.04	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-HCAD-10	yes	19.77
E-ANND-3	yes	10.01

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

13 targeting RASSF7, 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-6721-5P	99.93	68.92	2981
HSA-MIR-8073	99.86	65.21	1118
HSA-MIR-221-5P	99.86	65.45	1052
HSA-MIR-3941	99.86	70.54	2735
HSA-MIR-7112-5P	99.59	65.76	104
HSA-MIR-6809-5P	99.13	68.45	1223
HSA-MIR-4260	98.78	65.37	848
HSA-MIR-1227-5P	98.65	65.32	1549
HSA-MIR-5572	98.55	65.84	970
HSA-MIR-891A-3P	98.05	67.99	970
HSA-MIR-6793-3P	97.66	65.78	1084
HSA-MIR-1204	89.50	65.56	109

Literature-anchored findings (GeneRIF, showing 8)

• “rare” alleles of HRas1 minisatellite are associated with increased risk of papillary thyroid cancer formation in children and adolescents after Chernobyl accident (PMID:15098441)
• RASSF7 regulates the microtubule cytoskeleton and is required for spindle formation, Aurora B activation and chromosomal congression during mitosis. (PMID:20629633)
• RASSF7 acts in concert with N-Ras to constitute a stress-sensitive temporary mechanism of apoptotic regulation. (PMID:21278800)
• The RASSF gene family members RASSF5, RASSF6 and RASSF7 show frequent DNA methylation in neuroblastoma. (PMID:22695170)
• truncated RASSF7 could act as an oncogene in a small subset of tumours where it is mutated in this way. (PMID:26569555)
• Suggest that loss of RASSF7 expression results in apoptosis in nucleus pulposus cells in human intervertebral disc degeneration. (PMID:26884887)
• RASSF7 promotes cell proliferation through activating MEK1/MEK2-ERK1/ERK2 signaling pathway in hepatocellular carcinoma. (PMID:29729697)
• RASSF7 competed with MAX in the formation of a heterodimeric complex with c-Myc and attenuated its occupancy on target gene promoters to regulate transcription. (PMID:30139745)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	rassf7b	ENSDARG00000003193
danio_rerio	rassf7a	ENSDARG00000079917
mus_musculus	Rassf7	ENSMUSG00000038618
rattus_norvegicus	Rassf7	ENSRNOG00000017109
drosophila_melanogaster	RASSF8	FBGN0261986
caenorhabditis_elegans		WBGENE00019403

Paralogs (3): RASSF8 (ENSG00000123094), RASSF10 (ENSG00000189431), RASSF9 (ENSG00000198774)

Protein

Protein identifiers

Ras association domain-containing protein 7 — Q02833 (reviewed: Q02833)

Alternative names: HRAS1-related cluster protein 1

All UniProt accessions (4): Q02833, E9PM39, F8W7Q0, H0YEI0

UniProt curated annotations — full annotation on UniProt →

Function. Negatively regulates stress-induced JNK activation and apoptosis by promoting MAP2K7 phosphorylation and inhibiting its ability to activate JNK. Following prolonged stress, anti-apoptotic effect stops because of degradation of RASSF7 protein via the ubiquitin-proteasome pathway. Required for the activation of AURKB and chromosomal congression during mitosis where it stimulates microtubule polymerization.

Subunit / interactions. Interacts with MAP2K7 and GTP-bound NRAS.

Subcellular location. Cytoplasm. Cytoskeleton. Microtubule organizing center. Centrosome.

Post-translational modifications. Polyubiquitinated and degraded by the proteasome upon prolonged stress stimuli.

Isoforms (3)

UniProt ID	Names	Canonical?
Q02833-1	1	yes
Q02833-2	2
Q02833-3	3

RefSeq proteins (3): NP_001137465, NP_001137466, NP_003466* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000159	RA_dom	Domain
IPR029071	Ubiquitin-like_domsf	Homologous_superfamily
IPR033593	N-RASSF	Family
IPR033631	RASSF7_RA	Domain

Pfam: PF00788

UniProt features (11 total): splice variant 3, sequence variant 2, region of interest 2, coiled-coil region 2, chain 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q02833-F1	75.00	0.50

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 101 (showing top): RNGTGGGC_UNKNOWN, MULLIGHAN_NPM1_SIGNATURE_3_UP, AREB6_03, HNF1_Q6, GOCC_MICROTUBULE_ORGANIZING_CENTER, GOCC_CENTROSOME, MORF_IKBKG, EGR1_01, KIM_WT1_TARGETS_12HR_UP, GINESTIER_BREAST_CANCER_ZNF217_AMPLIFIED_DN, LIU_SOX4_TARGETS_DN, MORF_MYST2, GOCC_CENTRIOLAR_SATELLITE, MULLIGHAN_MLL_SIGNATURE_1_UP, MODULE_13

GO Biological Process (2): apoptotic process (GO:0006915), signal transduction (GO:0007165)

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

GO Cellular Component (4): centriolar satellite (GO:0034451), cytoplasm (GO:0005737), centrosome (GO:0005813), cytoskeleton (GO:0005856)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
binding	1
centrosome	1
intracellular anatomical structure	1
centriole	1
microtubule organizing center	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

636 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RASSF7	RASSF6	Q6ZTQ3	842
RASSF7	RASSF10	A6NK89	813
RASSF7	DISC1	Q9NRI5	798
RASSF7	RASSF5	Q8WWW0	781
RASSF7	RASSF2	P50749	776
RASSF7	RASSF3	Q86WH2	768
RASSF7	RASSF1	Q9NS23	766
RASSF7	RASSF9	O75901	690
RASSF7	PPP1R13B	Q96KQ4	635
RASSF7	MOAP1	Q96BY2	629
RASSF7	TP53BP2	Q13625	611
RASSF7	NRAS	P01111	599
RASSF7	YAP1	P46937	508
RASSF7	UBXN2B	Q14CS0	455
RASSF7	RASSF4	Q9H2L5	434

IntAct

56 interactions, top by confidence:

A	B	Type	Score
NCK2	RASSF7	psi-mi:“MI:0915”(physical association)	0.740
RASSF7	NCK2	psi-mi:“MI:0915”(physical association)	0.740
PPP1CC	CCDC85C	psi-mi:“MI:0914”(association)	0.740
PPP1CC	CCDC85C	psi-mi:“MI:2364”(proximity)	0.740
PPP1CA	CCDC85C	psi-mi:“MI:0914”(association)	0.670
PPP1CA	CCDC85C	psi-mi:“MI:2364”(proximity)	0.670
SNAP29	RASSF7	psi-mi:“MI:0915”(physical association)	0.660
RASSF7	SNAP29	psi-mi:“MI:0914”(association)	0.660
YWHAH	BLTP3B	psi-mi:“MI:0914”(association)	0.570
YWHAG	SHTN1	psi-mi:“MI:0914”(association)	0.560
PPP1R13B	CCDC85C	psi-mi:“MI:0914”(association)	0.530
CENPH	PSMD11	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
ALK	PIK3R2	psi-mi:“MI:0914”(association)	0.420
RASSF7		psi-mi:“MI:0915”(physical association)	0.370
RASSF7	CHMP1B	psi-mi:“MI:0915”(physical association)	0.370
RASSF7	TSC1	psi-mi:“MI:0915”(physical association)	0.370
NPAS2	RASSF7	psi-mi:“MI:0915”(physical association)	0.370
RASSF7	N	psi-mi:“MI:0915”(physical association)	0.370
RASSF7	rep	psi-mi:“MI:0915”(physical association)	0.370
DISC1	RASSF7	psi-mi:“MI:0915”(physical association)	0.370
Pard6b	PARD3	psi-mi:“MI:0914”(association)	0.350
Xpo1	IFT56	psi-mi:“MI:0914”(association)	0.350

BioGRID (91): NCK2 (Two-hybrid), RASSF7 (Affinity Capture-MS), RASSF7 (Affinity Capture-MS), RASSF7 (Affinity Capture-MS), PPP1R13B (Affinity Capture-MS), TP53BP2 (Affinity Capture-MS), CEP97 (Affinity Capture-MS), NCK2 (Affinity Capture-MS), PSMC3 (Affinity Capture-MS), GNPTAB (Affinity Capture-MS), TARSL2 (Affinity Capture-MS), CCDC6 (Affinity Capture-MS), PCM1 (Affinity Capture-MS), CENPH (Affinity Capture-MS), PICK1 (Affinity Capture-MS)

ESM2 similar proteins: A1L3C1, A2AWP8, A2RRU4, A6QM06, A6QNS9, E1BBQ2, F1LQY6, G3V9M2, O43189, O94827, P29372, P29590, P41155, P97260, Q01113, Q02833, Q04841, Q0P5I0, Q12770, Q13387, Q13505, Q29RM4, Q32L49, Q3V1H9, Q5MNU5, Q5R5M3, Q66T02, Q69Z89, Q6GQT6, Q6IPT2, Q6RFZ7, Q6ZN54, Q70EL4, Q7Z6G3, Q8BQB4, Q8C4U2, Q8N1F8, Q8N554, Q8WWW0, Q8WXF8

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 44 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	5	119.0×	4e-08
Activation of BH3-only proteins	7	108.6×	8e-11
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	5	105.0×	6e-08
Intrinsic Pathway for Apoptosis	7	64.0×	2e-09
FOXO-mediated transcription	5	52.5×	2e-06
Apoptosis	7	36.7×	5e-08
Programmed Cell Death	7	32.0×	1e-07
Translocation of SLC2A4 (GLUT4) to the plasma membrane	6	28.9×	2e-06

GO biological processes:

GO term	Partners	Fold	FDR
epidermal growth factor receptor signaling pathway	5	32.6×	3e-04
intracellular protein localization	5	13.8×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	89
Likely benign	6
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

909 predictions. Top by Δscore:

Variant	Effect	Δscore
11:561111:A:T	donor_gain	1.0000
11:561890:TAGGT:T	donor_loss	1.0000
11:561891:AGG:A	donor_loss	1.0000
11:561893:G:GC	donor_loss	1.0000
11:561894:T:A	donor_loss	1.0000
11:562074:CCCAG:C	acceptor_loss	1.0000
11:562076:CAG:C	acceptor_loss	1.0000
11:562077:A:AG	acceptor_gain	1.0000
11:562077:A:T	acceptor_loss	1.0000
11:562078:G:GT	acceptor_gain	1.0000
11:562078:GGCC:G	acceptor_gain	1.0000
11:562078:GGCCA:G	acceptor_gain	1.0000
11:560677:ACCT:A	donor_loss	0.9900
11:560678:CCTA:C	donor_loss	0.9900
11:560679:CTACC:C	donor_loss	0.9900
11:560680:TA:T	donor_loss	0.9900
11:560681:A:AC	donor_gain	0.9900
11:560681:A:C	donor_loss	0.9900
11:560681:AC:A	donor_gain	0.9900
11:560681:ACC:A	donor_gain	0.9900
11:560682:C:CC	donor_gain	0.9900
11:560682:CC:C	donor_gain	0.9900
11:560682:CCC:C	donor_gain	0.9900
11:561109:G:GT	donor_gain	0.9900
11:561109:G:T	donor_gain	0.9900
11:561131:G:GT	donor_gain	0.9900
11:561136:A:T	donor_gain	0.9900
11:561180:G:GT	donor_gain	0.9900
11:561180:G:T	donor_gain	0.9900
11:561200:GC:G	donor_gain	0.9900

AlphaMissense

2335 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:562093:T:C	F47L	0.998
11:562095:T:A	F47L	0.998
11:562095:T:G	F47L	0.998
11:561830:T:A	V21D	0.997
11:562100:T:A	L49H	0.997
11:561869:T:A	V34D	0.996
11:562094:T:C	F47S	0.996
11:562199:T:C	F82S	0.996
11:563249:T:C	F295L	0.996
11:563251:C:A	F295L	0.996
11:563251:C:G	F295L	0.996
11:561797:T:C	L10P	0.995
11:561881:C:A	A38D	0.995
11:561823:C:A	R19S	0.994
11:561878:T:C	L37P	0.994
11:561886:G:C	A40P	0.994
11:562094:T:G	F47C	0.994
11:561857:G:A	C30Y	0.993
11:561858:C:G	C30W	0.993
11:562100:T:C	L49P	0.993
11:562205:T:C	L84P	0.993
11:563250:T:C	F295S	0.993
11:561856:T:C	C30R	0.992
11:562193:T:A	V80D	0.992
11:563253:T:C	I296T	0.992
11:563226:T:C	L287P	0.991
11:561839:T:A	V24D	0.990
11:561878:T:A	L37Q	0.990
11:562199:T:G	F82C	0.990
11:562205:T:A	L84Q	0.990

dbSNP variants (sampled 300 via entrez): RS1000012138 (11:564435 T>C), RS1000856296 (11:562111 C>T), RS1001244556 (11:564401 C>G,T), RS1001296929 (11:564187 C>T), RS1001576130 (11:559692 G>A), RS1001759149 (11:561199 G>A,C,T), RS1002969970 (11:561597 C>A), RS1003025996 (11:560003 C>T), RS1003877969 (11:559723 G>A,T), RS1004052863 (11:562446 G>A,C), RS1005815228 (11:561239 A>G), RS1005896735 (11:564404 A>G), RS1005968018 (11:561012 C>T), RS1006898925 (11:563580 C>T), RS1007286122 (11:562387 G>A,T)

Disease associations

OMIM: gene MIM:143023 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST003155_11	Systemic lupus erythematosus	9.000000e-10

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Tobacco Smoke Pollution	affects expression, increases expression	2
Valproic Acid	decreases expression, increases methylation	2
beta-lapachone	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
ICG 001	increases expression	1
abrine	decreases expression	1
(4-amino-1,4-dihydro-3-(2-pyridyl)-5-thioxo-1,2,4-triazole)copper(II)	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Zoledronic Acid	decreases expression	1
Arsenic Trioxide	decreases response to substance	1
Lycopene	increases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	increases abundance, decreases expression	1
Caffeine	affects phosphorylation	1
Cisplatin	increases expression	1
Lead	affects expression	1
Lipopolysaccharides	increases expression, decreases expression, affects response to substance	1
Phenobarbital	affects expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Selenium	increases expression, affects cotreatment	1
Silicon Dioxide	decreases expression	1
Smoke	decreases expression	1
Tetrachlorodibenzodioxin	affects expression	1
Triclosan	increases expression	1
Urethane	decreases expression	1
Vitamin E	affects cotreatment, increases expression	1

Clinical trials (associated diseases)

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