RNASE9

Summary

RNASE9 (ribonuclease A family member 9 (inactive), HGNC:20673) is a protein-coding gene on chromosome 14q11.2, encoding Inactive ribonuclease-like protein 9 (P60153). Does not exhibit any ribonuclease activity.

Predicted to enable nucleic acid binding activity. Predicted to be involved in defense response to Gram-positive bacterium. Predicted to act upstream of or within positive regulation of flagellated sperm motility involved in capacitation. Predicted to be located in extracellular region.

Source: NCBI Gene 390443 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 31 total
• MANE Select transcript: NM_001110356

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20673
Approved symbol	RNASE9
Name	ribonuclease A family member 9 (inactive)
Location	14q11.2
Locus type	gene with protein product
Status	Approved
Aliases	h461, RAK1
Ensembl gene	ENSG00000188655
Ensembl biotype	protein_coding
OMIM	614014
Entrez	390443

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 11 protein_coding

ENST00000338904, ENST00000404716, ENST00000429244, ENST00000553541, ENST00000553706, ENST00000554964, ENST00000555230, ENST00000556208, ENST00000557068, ENST00000557209, ENST00000611135

RefSeq mRNA: 8 — MANE Select: NM_001110356 NM_001001673, NM_001110356, NM_001110357, NM_001110358, NM_001110359, NM_001110360, NM_001110361, NM_001289110

CCDS: CCDS32036, CCDS53883, CCDS55904

Canonical transcript exons

ENST00000554964 — 3 exons

Exon	Start	End
ENSE00001560931	20559582	20559633
ENSE00003533583	20556093	20557083
ENSE00004016208	20560874	20561047

Expression profiles

Bgee: expression breadth tissue_specific, 2 present calls, max score 41.58.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0485 / max 87.0734, expressed in 1 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
142037	0.0485	1

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
bone marrow cell	CL:0002092	41.58	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
sural nerve	UBERON:0015488	37.04	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
bone marrow	UBERON:0002371	35.63	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
granulocyte	CL:0000094	34.57	gold quality
skeletal muscle tissue	UBERON:0001134	33.38	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
muscle tissue	UBERON:0002385	31.06	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
prefrontal cortex	UBERON:0000451	29.04	gold quality
right uterine tube	UBERON:0001302	28.73	gold quality
duodenum	UBERON:0002114	28.14	gold quality
leukocyte	CL:0000738	28.07	gold quality
liver	UBERON:0002107	28.04	gold quality
monocyte	CL:0000576	27.58	gold quality
lymph node	UBERON:0000029	27.57	gold quality
placenta	UBERON:0001987	27.48	gold quality
tonsil	UBERON:0002372	27.05	gold quality
urinary bladder	UBERON:0001255	26.83	gold quality
islet of Langerhans	UBERON:0000006	26.55	gold quality
vermiform appendix	UBERON:0001154	26.42	gold quality
blood	UBERON:0000178	26.31	gold quality
gall bladder	UBERON:0002110	25.98	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	25.89	gold quality
muscle of leg	UBERON:0001383	24.99	gold quality
calcaneal tendon	UBERON:0003701	24.91	gold quality
primary visual cortex	UBERON:0002436	24.61	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.44

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

26 targeting RNASE9, 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-4425	100.00	67.59	1049
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-3140-3P	99.88	68.47	2069
HSA-MIR-6079	99.84	68.54	1170
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-3059-5P	99.70	69.93	2491
HSA-MIR-3153	99.55	67.59	2337
HSA-MIR-3609	99.52	69.89	2587
HSA-MIR-548AH-5P	99.52	69.73	2626
HSA-MIR-185-5P	99.35	68.60	2497
HSA-MIR-4644	99.35	69.12	2514
HSA-MIR-12113	99.32	67.54	1072
HSA-MIR-6828-5P	99.31	69.21	1433
HSA-MIR-18A-5P	99.29	71.05	806
HSA-MIR-18B-5P	99.29	71.05	806
HSA-MIR-6071	99.16	67.77	1780
HSA-MIR-4735-3P	99.14	69.85	777
HSA-MIR-4717-3P	99.06	66.34	1072
HSA-MIR-4711-3P	98.97	66.87	1020
HSA-MIR-1294	98.91	69.26	1030
HSA-MIR-9986	98.91	69.28	1024
HSA-MIR-4764-5P	98.88	65.53	894
HSA-MIR-93-3P	98.15	66.65	1309
HSA-MIR-6824-5P	97.41	68.43	583

Literature-anchored findings (GeneRIF, showing 1)

• may be involved in host defense (PMID:15974301)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Rnase9	ENSMUSG00000052382
rattus_norvegicus	Rnase9	ENSRNOG00000029516

Paralogs (12): RNASE1 (ENSG00000129538), RNASE7 (ENSG00000165799), RNASE2 (ENSG00000169385), RNASE3 (ENSG00000169397), RNASE6 (ENSG00000169413), RNASE8 (ENSG00000173431), RNASE11 (ENSG00000173464), RNASE10 (ENSG00000182545), RNASE13 (ENSG00000206150), ANG (ENSG00000214274), RNASE12 (ENSG00000258436), RNASE4 (ENSG00000258818)

Protein

Protein identifiers

Inactive ribonuclease-like protein 9 — P60153 (reviewed: P60153)

All UniProt accessions (3): A0AAG2RNW0, P60153, W0UV99

UniProt curated annotations — full annotation on UniProt →

Function. Does not exhibit any ribonuclease activity.

Subcellular location. Secreted.

Tissue specificity. At the mRNA level, widely expressed. At protein level, restricted to epididymis. Expressed in spermatozoa (sperm head and neck), with higher levels on ejaculated and epididymal sperm than on testicular sperm (at protein level). Expressed in the epithelial cells of the epididymal tubule (at protein level). Not detected in muscle.

Similarity. Belongs to the pancreatic ribonuclease family.

Isoforms (2)

UniProt ID	Names	Canonical?
P60153-1	1, alpha1, alpha2, alpha12, beta2, beta12	yes
P60153-2	2, alpha23, alpha123

RefSeq proteins (8): NP_001001673, NP_001103826, NP_001103827, NP_001103828, NP_001103829, NP_001103830, NP_001103831, NP_001276039 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001427	RNaseA	Family
IPR023412	RNaseA_domain	Domain
IPR036816	RNaseA-like_dom_sf	Homologous_superfamily

Pfam: PF00074

UniProt features (9 total): glycosylation site 2, disulfide bond 2, sequence variant 2, signal peptide 1, chain 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P60153-F1	80.96	0.53

Functional residue map

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

Disulfide bonds (2): 116–168, 123–130

Glycosylation sites (2): 131, 143

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 20 (showing top): GOMF_RNA_NUCLEASE_ACTIVITY, GOMF_NUCLEASE_ACTIVITY, ACEVEDO_LIVER_CANCER_WITH_H3K27ME3_UP, GOBP_DEFENSE_RESPONSE_TO_GRAM_POSITIVE_BACTERIUM, GOBP_DEFENSE_RESPONSE_TO_BACTERIUM, GOBP_RESPONSE_TO_BACTERIUM, GOMF_CATALYTIC_ACTIVITY_ACTING_ON_RNA, MIR4306, MIR3609, MIR548AH_5P, MIR6739_5P, MIR4425, MIR4717_3P, GOBP_BIOLOGICAL_PROCESS_INVOLVED_IN_INTERSPECIES_INTERACTION_BETWEEN_ORGANISMS, GOMF_CATALYTIC_ACTIVITY_ACTING_ON_A_NUCLEIC_ACID

GO Biological Process (1): defense response to Gram-positive bacterium (GO:0050830)

GO Molecular Function (1): nucleic acid binding (GO:0003676)

GO Cellular Component (1): extracellular region (GO:0005576)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
defense response to bacterium	1
binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

46 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RNASE9	PTK2	Q05397	417
RNASE9	TRAF6	Q9Y4K3	331
RNASE9	SUCLG2	Q96I99	325
RNASE9	RACK1	P25388	322
RNASE9	CDV3	Q9UKY7	247
RNASE9	CBLB	Q13191	220
RNASE9	SORD	Q00796	215
RNASE9	DGKE	P52429	210
RNASE9	GPHA2	Q96T91	203
RNASE9	CGA	P01215	185
RNASE9	DNAJA1	P31689	175
RNASE9	APRT	P07741	174
RNASE9	FRMD3	A2A2Y4	170
RNASE9	NPC2	P61916	170
RNASE9	ING5	Q8WYH8	164

IntAct

4 interactions, top by confidence:

A	B	Type	Score
RNASE9	MAP2K1	psi-mi:“MI:0915”(physical association)	0.400
RNASE9	CLYBL	psi-mi:“MI:0915”(physical association)	0.400
RNASE9	MAP2K1	psi-mi:“MI:0914”(association)	0.350

BioGRID (5): MAP2K1 (Affinity Capture-MS), PPME1 (Affinity Capture-MS), MAP2K1 (Affinity Capture-MS), CLYBL (Affinity Capture-MS), RNASE9 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A0A146B5A4, A6MFL7, A9XE49, B3EWZ2, E1ZVK1, F8RKW5, O73797, P02681, P03997, P03998, P15566, P17219, P20675, P25428, P34572, P48607, P60153, P60154, P85315, Q11070, Q22687, Q24155, Q3HXX5, Q3HXX7, Q3HXY1, Q3HXY2, Q3HXY3, Q3HXY4, Q3HXY5, Q3HXY6, Q3HXY7, Q3HXY8, Q566B1, Q5YF89, Q66Q82, Q7YRG7, Q7YRG8, Q7YRG9, Q7YRH0, Q7YRH1

Diamond homologs: P60153, P60154, Q7YRG7, Q7YRG8, Q7YRG9, Q7YRH0, Q7YRH1, Q7YRH2, Q7YRH3, Q7YRH4, Q863J7, Q863J8, Q863J9, Q863K0, Q863K1, P00678

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	29
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000050087 (14:20559295 A>G), RS1000513244 (14:20559190 G>A), RS1001045529 (14:20560719 C>G), RS1001139962 (14:20561212 G>T), RS1001400827 (14:20558321 G>A,C), RS1001572498 (14:20558740 G>C,T), RS1002154525 (14:20562500 T>C,G), RS1002354425 (14:20557442 G>A,C), RS1002940474 (14:20557977 G>C), RS1003359330 (14:20556089 G>A), RS1003845237 (14:20559865 G>T), RS1003875464 (14:20562151 A>C), RS1003947081 (14:20559162 C>T), RS1005253460 (14:20558555 C>T), RS1005719344 (14:20556016 G>A,C,T)

Disease associations

OMIM: gene MIM:614014 | 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
GCST002441_9	Immune response to measles-mumps-rubella vaccine	7.000000e-07
GCST005721_6	Food allergy (parent-of-origin effect)	1.000000e-06
GCST005726_2	Milk allergy (parent-of-origin effect)	5.000000e-06

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004645	response to vaccine
EFO:0005939	parental genotype effect measurement
EFO:0007016	food allergy measurement
EFO:0007019	milk allergy measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

6 total (human), top 6 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases expression	2
CGP 52608	affects binding, increases reaction	1
Arsenic	affects methylation	1
Cadmium	decreases expression, increases abundance	1
Aflatoxin B1	decreases methylation	1
Cadmium Chloride	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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