RNASE8

Summary

RNASE8 (ribonuclease A family member 8, HGNC:19277) is a protein-coding gene on chromosome 14q11.2, encoding Ribonuclease 8 (Q8TDE3). Has a low ribonuclease activity.

The protein encoded by this gene belongs to the pancreatic ribonuclease family, a subset of the ribonuclease A superfamily. The protein is expressed prominently in the placenta and exhibits antimicrobial activity against pathogenic bacteria and fungi.

Source: NCBI Gene 122665 — RefSeq curated summary.

At a glance

• MANE Select transcript: NM_138331

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19277
Approved symbol	RNASE8
Name	ribonuclease A family member 8
Location	14q11.2
Locus type	gene with protein product
Status	Approved
Aliases	RAE2
Ensembl gene	ENSG00000173431
Ensembl biotype	protein_coding
OMIM	612485
Entrez	122665

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000308227

RefSeq mRNA: 1 — MANE Select: NM_138331 NM_138331

CCDS: CCDS9567

Canonical transcript exons

ENST00000308227 — 1 exons

Exon	Start	End
ENSE00001208085	21057822	21058455

Expression profiles

Bgee: expression breadth broad, 18 present calls, max score 54.37.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	54.37	gold quality
tonsil	UBERON:0002372	47.27	gold quality
saliva-secreting gland	UBERON:0001044	46.63	gold quality
calcaneal tendon	UBERON:0003701	43.97	silver quality
minor salivary gland	UBERON:0001830	41.95	gold quality
sural nerve	UBERON:0015488	40.93	gold quality
mucosa of transverse colon	UBERON:0004991	38.36	silver quality
colonic epithelium	UBERON:0000397	37.20	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
bone marrow cell	CL:0002092	36.16	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
skeletal muscle tissue	UBERON:0001134	33.38	gold quality
urinary bladder	UBERON:0001255	32.96	gold quality
right uterine tube	UBERON:0001302	32.61	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	32.32	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
monocyte	CL:0000576	31.96	gold quality
bone marrow	UBERON:0002371	31.74	gold quality
leukocyte	CL:0000738	31.56	gold quality
muscle tissue	UBERON:0002385	31.06	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
muscle of leg	UBERON:0001383	29.49	silver quality
lymph node	UBERON:0000029	29.26	silver quality
blood	UBERON:0000178	28.26	gold quality
gastrocnemius	UBERON:0001388	28.17	silver quality
duodenum	UBERON:0002114	28.14	gold quality
thoracic mammary gland	UBERON:0005200	28.07	silver quality
islet of Langerhans	UBERON:0000006	28.04	silver quality
pancreas	UBERON:0001264	26.96	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.31

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 3)

• RNase 8 was identified as a human antimicrobial protein with a broad spectrum activity against pathogenic organisms. (PMID:16940129)
• Study shows that both the loss and gain of the cysteines in human RNase 8 occurred in the common ancestor of African great apes (humans, chimps, and gorillas) 7-13 MYA. (PMID:17116644)
• Only two single-nucleotide polymorphisms and four unique alleles were identified within the RNase 8 coding sequence. (PMID:22272736)

Cross-species orthologs

0 orthologs

Paralogs (12): RNASE1 (ENSG00000129538), RNASE7 (ENSG00000165799), RNASE2 (ENSG00000169385), RNASE3 (ENSG00000169397), RNASE6 (ENSG00000169413), RNASE11 (ENSG00000173464), RNASE10 (ENSG00000182545), RNASE9 (ENSG00000188655), RNASE13 (ENSG00000206150), ANG (ENSG00000214274), RNASE12 (ENSG00000258436), RNASE4 (ENSG00000258818)

Protein

Protein identifiers

Ribonuclease 8 — Q8TDE3 (reviewed: Q8TDE3)

All UniProt accessions (1): Q8TDE3

UniProt curated annotations — full annotation on UniProt →

Function. Has a low ribonuclease activity.

Subcellular location. Secreted.

Tissue specificity. Expressed prominently in the placenta and is not detected in any other tissues examined.

Similarity. Belongs to the pancreatic ribonuclease family.

RefSeq proteins (1): NP_612204* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001427	RNaseA	Family
IPR023411	RNaseA_AS	Active_site
IPR023412	RNaseA_domain	Domain
IPR036816	RNaseA-like_dom_sf	Homologous_superfamily

Pfam: PF00074

UniProt features (11 total): disulfide bond 4, active site 2, binding site 2, signal peptide 1, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TDE3-F1	90.68	0.81

Functional residue map

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

Catalytic / active sites (2): 42 (proton acceptor); 149 (proton donor)

Ligand- & substrate-binding residues (2): 65–69; 90

Disulfide bonds (4): 50–93, 64–118, 82–133, 89–96

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-6803157	Antimicrobial peptides
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System

MSigDB gene sets: 21 (showing top): GOMF_ENDONUCLEASE_ACTIVITY, GOMF_RNA_NUCLEASE_ACTIVITY, REACTOME_INNATE_IMMUNE_SYSTEM, GOMF_NUCLEASE_ACTIVITY, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, GOMF_RNA_ENDONUCLEASE_ACTIVITY, GOBP_DEFENSE_RESPONSE_TO_GRAM_NEGATIVE_BACTERIUM, GOBP_DEFENSE_RESPONSE_TO_GRAM_POSITIVE_BACTERIUM, GOBP_RESPONSE_TO_FUNGUS, GOBP_DEFENSE_RESPONSE_TO_BACTERIUM, GOBP_RESPONSE_TO_BACTERIUM, GOBP_ANTIFUNGAL_INNATE_IMMUNE_RESPONSE, ZWANG_CLASS_1_TRANSIENTLY_INDUCED_BY_EGF, GOMF_PHOSPHORUS_OXYGEN_LYASE_ACTIVITY, GOMF_CATALYTIC_ACTIVITY_ACTING_ON_RNA

GO Biological Process (5): innate immune response (GO:0045087), defense response to Gram-negative bacterium (GO:0050829), defense response to Gram-positive bacterium (GO:0050830), defense response to fungus (GO:0050832), antifungal innate immune response (GO:0061760)

GO Molecular Function (6): nucleic acid binding (GO:0003676), ribonuclease A activity (GO:0004522), RNA nuclease activity (GO:0004540), hydrolase activity (GO:0016787), nuclease activity (GO:0004518), endonuclease activity (GO:0004519)

GO Cellular Component (2): obsolete extracellular space (GO:0005615), extracellular region (GO:0005576)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Innate Immune System	1
Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
defense response to bacterium	2
nuclease activity	2
immune response	1
defense response to symbiont	1
defense response	1
response to fungus	1
innate immune response	1
defense response to fungus	1
binding	1
RNA endonuclease activity	1
phosphorus-oxygen lyase activity	1
catalytic activity, acting on RNA	1
catalytic activity	1
catalytic activity, acting on a nucleic acid	1
cellular anatomical structure	1

Protein interactions and networks

STRING

134 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RNASE8	ANG	P03950	901
RNASE8	RNASE11	Q8TAA1	606
RNASE8	CATSPERH	E9PQX1	591
RNASE8	RNASE12	Q5GAN4	548
RNASE8	RNASE10	Q5GAN6	507
RNASE8	RNASE13	Q5GAN3	483
RNASE8	DEFB118	Q96PH6	413
RNASE8	THOC3	Q96J01	413
RNASE8	TMPRSS15	P98073	389
RNASE8	PAX6	P26367	370
RNASE8	ZNF275	Q9NSD4	366
RNASE8	RNF133	Q8WVZ7	353
RNASE8	RTL5	Q5HYW3	350
RNASE8	TOMM20L	Q6UXN7	348
RNASE8	RNASET2	O00584	334

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: A1YLB9, O46525, O46526, O46527, O46528, O46529, O46530, O46531, O46532, O46533, O46534, P00683, P00684, P08904, P39873, P61823, P81649, Q8SPN3, Q8SPN4, Q8SPZ4, Q8SPZ5, Q8SPZ6, Q8SPZ7, Q8SPZ8, Q8SQ04, Q8SQ05, Q8SQ06, Q8SQ08, Q8SQ11, Q8SQ12, Q8TDE3, Q8VD84, Q8VD87, Q8VD89, Q8VD93, Q93091, Q9D244, Q9H1E1, Q9QYX2, Q9QYX3

Diamond homologs: A1YLB9, B3EWJ0, O18937, O35290, O35291, O35292, O46525, O46526, O46527, O46528, O46529, O46530, O46531, O46532, O46533, O46534, O55004, P00657, P00680, P00682, P00685, P03950, P08904, P10153, P12724, P15466, P15467, P15468, P16414, P24717, P34096, P47778, P47779, P47780, P47781, P47782, P47783, P47784, P47785, P47786

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

160 predictions. Top by Δscore:

Variant	Effect	Δscore
14:21057912:G:GT	donor_gain	0.8200
14:21058065:A:AG	donor_gain	0.8100
14:21058065:A:G	donor_gain	0.7900
14:21058082:TGCA:T	donor_gain	0.7200
14:21058083:GCAA:G	donor_gain	0.6600
14:21057983:G:GT	donor_gain	0.6200
14:21058069:G:GG	donor_gain	0.6200
14:21058068:A:AG	donor_gain	0.6000
14:21058002:G:GA	donor_gain	0.5900
14:21058231:G:T	donor_gain	0.5700
14:21057960:TCC:T	donor_gain	0.5500
14:21057913:A:T	donor_gain	0.5400
14:21058167:GCT:G	donor_gain	0.5400
14:21058302:AACAG:A	acceptor_gain	0.5100
14:21058338:ACTTG:A	acceptor_gain	0.5100
14:21057952:G:GA	donor_gain	0.5000
14:21058231:G:GT	donor_gain	0.5000
14:21058122:G:GG	donor_gain	0.4900
14:21058121:A:AG	donor_gain	0.4800
14:21058076:GAACG:G	donor_gain	0.4600
14:21058071:ACAC:A	donor_gain	0.4500
14:21058075:AGAAC:A	donor_gain	0.4500
14:21058213:GG:G	donor_gain	0.4500
14:21058214:GG:G	donor_gain	0.4500
14:21058452:A:G	acceptor_gain	0.4400
14:21057961:CCT:C	donor_gain	0.4300
14:21058422:G:GG	donor_gain	0.4300
14:21058170:G:GG	donor_gain	0.4200
14:21058169:T:TG	donor_gain	0.4100
14:21058422:GTTC:G	acceptor_gain	0.4100

AlphaMissense

1008 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:21058100:T:C	F70L	0.768
14:21058102:C:A	F70L	0.768
14:21058102:C:G	F70L	0.768
14:21058004:T:C	F38L	0.703
14:21058006:T:A	F38L	0.703
14:21058006:T:G	F38L	0.703
14:21058115:T:C	F75L	0.690
14:21058117:C:A	F75L	0.690
14:21058117:C:G	F75L	0.690

dbSNP variants (sampled 300 via entrez): RS1003105398 (14:21058713 G>A), RS1006014096 (14:21056982 A>G), RS1006059215 (14:21056270 A>G), RS1007099327 (14:21057479 G>T), RS1007519818 (14:21057256 G>A), RS1009788045 (14:21056110 C>A,T), RS1010002271 (14:21055894 G>T), RS1011231163 (14:21057610 A>G), RS1011456159 (14:21055902 C>A), RS1011862167 (14:21056133 A>G,T), RS10133968 (14:21056111 A>G,T), RS10144810 (14:21056429 G>A,C,T), RS1015680347 (14:21056986 G>A), RS1016063459 (14:21056271 C>T), RS1016155958 (14:21056720 C>A,T)

Disease associations

OMIM: gene MIM:612485 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

3 total (human), top 3 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases methylation	1
8-Bromo Cyclic Adenosine Monophosphate	decreases expression	1
Aflatoxin B1	decreases methylation	1

Clinical trials (associated diseases)

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