RASSF9

Summary

RASSF9 (Ras association domain family member 9, HGNC:15739) is a protein-coding gene on chromosome 12q21.31, encoding Ras association domain-containing protein 9 (O75901). May play a role in regulating vesicuar trafficking in cells.

The protein encoded by this gene localizes to perinuclear endosomes. This protein associates with peptidylglycine alpha-amidating monooxygenase, and may be involved with the trafficking of this enzyme through secretory or endosomal pathways.

Source: NCBI Gene 9182 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 72 total
• MANE Select transcript: NM_005447

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15739
Approved symbol	RASSF9
Name	Ras association domain family member 9
Location	12q21.31
Locus type	gene with protein product
Status	Approved
Aliases	P-CIP1
Ensembl gene	ENSG00000198774
Ensembl biotype	protein_coding
OMIM	610383
Entrez	9182

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000361228

RefSeq mRNA: 1 — MANE Select: NM_005447 NM_005447

CCDS: CCDS44950

Canonical transcript exons

ENST00000361228 — 2 exons

Exon	Start	End
ENSE00001435606	85800703	85805962
ENSE00001641117	85836155	85836409

Expression profiles

Bgee: expression breadth ubiquitous, 176 present calls, max score 90.18.

FANTOM5 (CAGE): breadth broad, TPM avg 2.3432 / max 79.9141, expressed in 742 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
132365	1.3614	504
132364	0.2999	157
132366	0.2617	118
132363	0.2307	121
132367	0.1639	73
132368	0.0257	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of paranasal sinus	UBERON:0005030	90.18	gold quality
esophagus squamous epithelium	UBERON:0006920	88.21	silver quality
bronchial epithelial cell	CL:0002328	85.89	gold quality
germinal epithelium of ovary	UBERON:0001304	85.02	silver quality
epithelium of esophagus	UBERON:0001976	81.96	silver quality
olfactory segment of nasal mucosa	UBERON:0005386	81.53	gold quality
epithelium of bronchus	UBERON:0002031	81.50	gold quality
visceral pleura	UBERON:0002401	81.46	gold quality
bronchus	UBERON:0002185	80.37	gold quality
pleura	UBERON:0000977	79.55	silver quality
parietal pleura	UBERON:0002400	79.43	silver quality
palpebral conjunctiva	UBERON:0001812	78.75	gold quality
epithelium of nasopharynx	UBERON:0001951	78.63	silver quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	77.53	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	76.52	gold quality
oral cavity	UBERON:0000167	75.75	silver quality
frontal pole	UBERON:0002795	74.63	gold quality
skin of hip	UBERON:0001554	74.16	gold quality
paraflocculus	UBERON:0005351	74.05	gold quality
middle frontal gyrus	UBERON:0002702	73.85	gold quality
lower esophagus mucosa	UBERON:0035834	72.49	gold quality
esophagus mucosa	UBERON:0002469	71.96	gold quality
nasal cavity mucosa	UBERON:0001826	71.21	gold quality
penis	UBERON:0000989	70.81	gold quality
squamous epithelium	UBERON:0006914	70.81	silver quality
upper leg skin	UBERON:0004262	69.63	gold quality
calcaneal tendon	UBERON:0003701	69.62	gold quality
right uterine tube	UBERON:0001302	69.44	gold quality
smooth muscle tissue	UBERON:0001135	69.22	gold quality
hair follicle	UBERON:0002073	68.91	silver quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.02
E-MTAB-8060	no	319.22

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

16 targeting RASSF9, 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-574-5P	100.00	66.01	989
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-202-5P	99.78	67.65	991
HSA-MIR-4658	99.77	64.94	514
HSA-MIR-6790-5P	99.77	65.24	505
HSA-MIR-4517	99.76	69.19	1867
HSA-MIR-10393-3P	99.72	66.56	961
HSA-MIR-6801-5P	99.72	66.50	981
HSA-MIR-3659	99.70	67.97	694
HSA-MIR-1252-3P	99.55	67.71	2862
HSA-MIR-4477A	98.83	69.75	2952
HSA-MIR-337-3P	97.90	69.37	1052
HSA-MIR-516A-5P	93.40	64.96	90

Literature-anchored findings (GeneRIF, showing 3)

• Our analysis revealed 10 sun-exposure-dependent gene expression quantitative trait loci (se-eQTLs), including genes involved in skin pigmentation (SLC45A2) and epidermal differentiation (RASSF9). (PMID:27760139)
• RASSF9 is a direct target of miR-1254 in breast cancer. (PMID:30132526)
• RASSF effectors couple diverse RAS subfamily GTPases to the Hippo pathway. (PMID:33051258)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	rassf9	ENSDARG00000074721
mus_musculus	Rassf9	ENSMUSG00000044921
rattus_norvegicus	Rassf9	ENSRNOG00000038574
drosophila_melanogaster	meru	FBGN0052150

Paralogs (3): RASSF7 (ENSG00000099849), RASSF8 (ENSG00000123094), RASSF10 (ENSG00000189431)

Protein

Protein identifiers

Ras association domain-containing protein 9 — O75901 (reviewed: O75901)

Alternative names: PAM COOH-terminal interactor protein 1, Peptidylglycine alpha-amidating monooxygenase COOH-terminal interactor

All UniProt accessions (1): O75901

UniProt curated annotations — full annotation on UniProt →

Function. May play a role in regulating vesicuar trafficking in cells.

Subunit / interactions. Interacts with PAM.

Subcellular location. Endosome.

RefSeq proteins (1): NP_005438* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000159	RA_dom	Domain
IPR029071	Ubiquitin-like_domsf	Homologous_superfamily
IPR033593	N-RASSF	Family
IPR033633	RASSF9_RA	Domain

UniProt features (8 total): region of interest 2, chain 1, domain 1, coiled-coil region 1, compositionally biased region 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75901-F1	73.20	0.32

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 88 (showing top): GOBP_PROTEIN_TARGETING, GOBP_VESICLE_MEDIATED_TRANSPORT, NKX62_Q2, chr12q21, GOCC_COATED_VESICLE, DELYS_THYROID_CANCER_DN, GOCC_GOLGI_ASSOCIATED_VESICLE, CUI_TCF21_TARGETS_2_DN, GOCC_CLATHRIN_COATED_VESICLE, GOCC_TRANS_GOLGI_NETWORK_TRANSPORT_VESICLE_MEMBRANE, GOCC_GOLGI_ASSOCIATED_VESICLE_MEMBRANE, GOCC_CLATHRIN_COATED_VESICLE_MEMBRANE, GOCC_RECYCLING_ENDOSOME, GOCC_TRANSPORT_VESICLE_MEMBRANE, YOSHIMURA_MAPK8_TARGETS_UP

GO Biological Process (3): protein targeting (GO:0006605), signal transduction (GO:0007165), endosomal transport (GO:0016197)

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

GO Cellular Component (5): endosome (GO:0005768), cytosol (GO:0005829), trans-Golgi network transport vesicle membrane (GO:0012510), recycling endosome (GO:0055037), extracellular exosome (GO:0070062)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
establishment of protein localization	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
vesicle-mediated transport	1
intracellular transport	1
binding	1
endomembrane system	1
cytoplasmic vesicle	1
cytoplasm	1
cellular anatomical structure	1
trans-Golgi network transport vesicle	1
transport vesicle membrane	1
Golgi-associated vesicle membrane	1
clathrin-coated vesicle membrane	1
endosome	1
extracellular vesicle	1

Protein interactions and networks

STRING

458 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RASSF9	PAM	P19021	820
RASSF9	RAB11A	P24410	718
RASSF9	RASSF7	Q02833	690
RASSF9	RASSF6	Q6ZTQ3	507
RASSF9	RASSF2	P50749	482
RASSF9	RASSF3	Q86WH2	468
RASSF9	MTMR10	Q9NXD2	457
RASSF9	RASSF5	Q8WWW0	440
RASSF9	DVL1	O14640	432
RASSF9	SLC66A3	Q8N755	403
RASSF9	RGL4	Q8IZJ4	396
RASSF9	C7orf57	Q8NEG2	396
RASSF9	RSBN1	Q5VWQ0	395
RASSF9	WDR91	A4D1P6	389
RASSF9	RASSF1	Q9NS23	370

IntAct

6 interactions, top by confidence:

A	B	Type	Score
PPP1R13B	CCDC85C	psi-mi:“MI:0914”(association)	0.530
RASSF9	HSPB1	psi-mi:“MI:0915”(physical association)	0.370
Xpo1	IFT56	psi-mi:“MI:0914”(association)	0.350
TP53BP2	CCDC85C	psi-mi:“MI:0914”(association)	0.350
RASSF9	CCDC85C	psi-mi:“MI:0914”(association)	0.350

BioGRID (41): RASSF9 (Affinity Capture-RNA), RASSF9 (Affinity Capture-RNA), RASSF9 (Affinity Capture-MS), RASSF9 (Affinity Capture-MS), A2ML1 (Affinity Capture-MS), PPP1R13B (Affinity Capture-MS), TP53BP2 (Affinity Capture-MS), CTSD (Affinity Capture-MS), CCDC85B (Affinity Capture-MS), CCDC85C (Affinity Capture-MS), CSNK2B (Affinity Capture-MS), CSTA (Affinity Capture-MS), DDB1 (Affinity Capture-MS), DVL1 (Affinity Capture-MS), DVL2 (Affinity Capture-MS)

ESM2 similar proteins: A2RRS8, A4D1B5, A5PLK6, D3Z6S9, E7FA21, G3UYX5, O75747, O75901, O88480, O88869, Q2T9P0, Q3UMB5, Q3UPC7, Q3URV1, Q402B2, Q4R9E9, Q5SUS0, Q5T0N1, Q5XI56, Q5XX13, Q642P2, Q6DHV5, Q6INI0, Q6P2C0, Q7L0X2, Q80X60, Q86VV8, Q86WZ0, Q8CDN1, Q8IV33, Q8IXR9, Q8K342, Q8N7B9, Q8N7X0, Q8ND61, Q8NE09, Q8NG48, Q8R4Y8, Q8TDY2, Q8TEV9

Diamond homologs: A6NK89, B1A193, O75901, O88869, Q8BL43, Q8K342, Q02833, Q8CJ96, Q8NHQ8, Q9DD19

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
MAP3K7	“up-regulates activity”	RASSF9	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	67
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

489 predictions. Top by Δscore:

Variant	Effect	Δscore
12:85805958:GAGAT:G	acceptor_gain	1.0000
12:85805959:AGAT:A	acceptor_gain	1.0000
12:85805960:GAT:G	acceptor_gain	1.0000
12:85805961:AT:A	acceptor_gain	1.0000
12:85805962:TCT:T	acceptor_loss	1.0000
12:85805963:C:CC	acceptor_gain	1.0000
12:85805963:C:CG	acceptor_loss	1.0000
12:85836149:CTTTA:C	donor_loss	1.0000
12:85805960:GATCT:G	acceptor_gain	0.9900
12:85805961:ATCT:A	acceptor_gain	0.9900
12:85805962:TCTG:T	acceptor_gain	0.9900
12:85805975:C:CT	acceptor_gain	0.9900
12:85807840:T:A	donor_gain	0.9900
12:85836140:CACG:C	donor_gain	0.9900
12:85805959:AGATC:A	acceptor_gain	0.9800
12:85805963:C:A	acceptor_gain	0.9800
12:85805964:T:A	acceptor_gain	0.9800
12:85805976:A:T	acceptor_gain	0.9800
12:85836304:T:A	donor_gain	0.9800
12:85811977:G:C	acceptor_gain	0.9700
12:85834332:ACTT:A	acceptor_gain	0.9700
12:85834333:CTTG:C	acceptor_gain	0.9400
12:85836150:TTTA:T	donor_gain	0.9200
12:85836151:TTA:T	donor_gain	0.9200
12:85836153:A:AT	donor_gain	0.9200
12:85836152:TA:T	donor_gain	0.9100
12:85811633:T:C	acceptor_gain	0.9000
12:85836150:TTTAC:T	donor_gain	0.9000
12:85836152:TAC:T	donor_gain	0.9000
12:85836154:C:CG	donor_gain	0.9000

AlphaMissense

2904 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:85804762:A:C	S416R	0.999
12:85804762:A:T	S416R	0.999
12:85804764:T:G	S416R	0.999
12:85805891:A:T	V40D	0.999
12:85805918:A:T	V31D	0.999
12:85805528:A:T	V161D	0.998
12:85805675:A:G	F112S	0.998
12:85805703:A:G	W103R	0.998
12:85805703:A:T	W103R	0.998
12:85805763:A:G	W83R	0.998
12:85805763:A:T	W83R	0.998
12:85805855:A:T	V52D	0.998
12:85805444:A:G	L189P	0.997
12:85804750:A:C	S420R	0.996
12:85804750:A:T	S420R	0.996
12:85804752:T:G	S420R	0.996
12:85805513:C:G	R166P	0.995
12:85805515:G:C	F165L	0.995
12:85805515:G:T	F165L	0.995
12:85805517:A:G	F165L	0.995
12:85805761:C:A	W83C	0.995
12:85805761:C:G	W83C	0.995
12:85805411:T:G	Q200P	0.994
12:85805669:A:G	L114S	0.994
12:85805741:A:G	L90P	0.994
12:85804775:T:A	D412V	0.993
12:85804775:T:G	D412A	0.993
12:85805436:A:G	S192P	0.993
12:85805507:A:G	L168P	0.993
12:85805516:A:G	F165S	0.993

dbSNP variants (sampled 300 via entrez): RS1000007479 (12:85816701 T>A,C,G), RS1000086536 (12:85811864 C>T), RS1000142932 (12:85810411 A>G), RS1000183401 (12:85816683 A>T), RS1000338518 (12:85835813 C>A), RS1000749992 (12:85822996 C>A,G), RS1000803243 (12:85817076 T>A,G), RS1000804641 (12:85828288 T>C), RS1000888725 (12:85809444 C>T), RS1000989553 (12:85802737 C>A,T), RS1001132126 (12:85828137 A>G), RS1001138561 (12:85809142 C>G), RS1001151942 (12:85809788 C>A,T), RS1001290850 (12:85834366 A>T), RS1001325285 (12:85802233 C>A)

Disease associations

OMIM: gene MIM:610383 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST003999_14	Nose size	4.000000e-08
GCST006481_24	Lung function (FEV1)	4.000000e-08
GCST006483_56	Lung function (FVC)	1.000000e-08
GCST006483_57	Lung function (FVC)	8.000000e-08
GCST006483_7	Lung function (FVC)	2.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004314	forced expiratory volume
EFO:0004312	vital capacity

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Silicon Dioxide	decreases expression, increases expression	3
Acetaminophen	decreases expression	2
Benzo(a)pyrene	affects methylation, decreases methylation, increases expression	2
Nickel	decreases expression	2
FR900359	increases phosphorylation	1
sotorasib	decreases expression, affects cotreatment	1
trichostatin A	increases expression	1
butyraldehyde	decreases expression	1
abrine	increases expression	1
licochalcone B	decreases expression	1
jinfukang	decreases expression	1
trametinib	affects cotreatment, decreases expression	1
NVP-BKM120	affects cotreatment, decreases expression	1
Sunitinib	decreases expression	1
Estradiol	increases expression, decreases reaction	1
Formaldehyde	decreases expression	1
Progesterone	increases expression, decreases reaction	1
Tobacco Smoke Pollution	decreases expression	1
Okadaic Acid	decreases expression	1
Lactic Acid	decreases expression	1
S-Nitrosoglutathione	increases expression	1
Particulate Matter	decreases expression	1
Volatile Organic Compounds	affects expression	1

Clinical trials (associated diseases)

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