ENDOU

Summary

ENDOU (endonuclease, poly(U) specific, HGNC:14369) is a protein-coding gene on chromosome 12q13.11, encoding Uridylate-specific endoribonuclease (P21128). Endoribonuclease that cleaves single-stranded RNAs at 5’ of uridylates and releases a product with a 2’,3’-cyclic phosphate at the 3’-end.

This gene encodes a protein with endoribonuclease activity that binds polyuridine-enriched single-stranded RNA. This gene was initially characterized based on its high expression in placenta but was mischaracterized as a serine protease. In mouse, this gene promotes tolerance to self-antigens by regulating B cell activation-induced cell death (AICD). The protein may be useful as a tumor marker. Multiple alternatively spliced transcript variants encoding distinct protein isoforms have been found for this gene.

Source: NCBI Gene 8909 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 61 total
• GTEx eGene: eQTL in 21 tissues, sQTL in 1 (q < 0.05)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.09 (unconstrained)
• MANE Select transcript: NM_001172439
• Notable: 61 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14369
Approved symbol	ENDOU
Name	endonuclease, poly(U) specific
Location	12q13.11
Locus type	gene with protein product
Status	Approved
Aliases	PP11, P11, PRSS26
Ensembl gene	ENSG00000111405
Ensembl biotype	protein_coding
OMIM	606720
Entrez	8909

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 4 protein_coding, 1 retained_intron

MANE Select: ENST00000422538

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 2: 2

ENST00000422538, ENST00000229003, ENST00000545824, ENST00000551186, ENST00001134221

RefSeq mRNA: 3 — MANE Select: NM_001172439 NM_001172439, NM_001172440, NM_006025

CCDS: CCDS53784, CCDS53785, CCDS8754

Canonical transcript exons

ENST00000422538 — 10 exons

Exon	Start	End
ENSE00000737756	47717518	47717655
ENSE00000737760	47713275	47713388
ENSE00000737762	47712516	47712622
ENSE00000737765	47711633	47711775
ENSE00000888022	47718129	47718194
ENSE00001787867	47720753	47720875
ENSE00002388121	47725359	47725490
ENSE00002403545	47709734	47710919
ENSE00003469373	47716890	47717058
ENSE00003639144	47716300	47716499

Expression profiles

Bgee: expression breadth ubiquitous, 187 present calls, max score 98.30.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.4167 / max 154.2665, expressed in 48 samples.

Highest expression (Bgee): lower esophagus mucosa, tongue squamous epithelium, gingival epithelium, gingiva, esophagus mucosa.

Genetic regulation across tissues (GTEx eQTL / sQTL)

ENDOU is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 21 tissues and its splicing (sQTL) in 1 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 22 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Thyroid	eqtl	1.1e-13	-0.34	12:47728106:C:T
Esophagus Mucosa	eqtl	1.5e-09	+0.13	12:47707418:T:TTC
Adipose Subcutaneous	eqtl	9.0e-09	-0.21	12:47735779:A:G
Nerve Tibial	eqtl	1.7e-08	-0.20	12:47735561:A:G
Cells Cultured fibroblasts	eqtl	4.3e-06	+0.23	12:47722214:G:C
Spleen	eqtl	4.0e-05	+0.34	12:47571196:A:G
Heart Left Ventricle	eqtl	7.6e-05	-0.27	12:47738931:G:A
Breast Mammary Tissue	eqtl	1.1e-04	-0.18	12:47738376:A:T
Lung	eqtl	4.3e-04	-0.17	12:47735779:A:G
Skin Sun Exposed Lower leg	eqtl	9.3e-04	+0.12	12:47657673:A:G
Adipose Visceral Omentum	eqtl	1.1e-03	-0.14	12:47738376:A:T
Artery Aorta	eqtl	1.3e-03	+0.16	12:47604521:A:G
Colon Transverse	eqtl	1.7e-03	-0.18	12:47713860:A:G
Skin Not Sun Exposed Suprapubic	eqtl	1.9e-03	+0.15	12:47713698:A:G
Colon Sigmoid	eqtl	8.0e-03	-0.75	12:46760412:T:C
Kidney Cortex	eqtl	1.5e-02	-0.51	12:47758822:G:C
Liver	eqtl	2.4e-02	-0.38	12:47750737:G:C
Muscle Skeletal	eqtl	2.9e-02	-0.14	12:47713860:A:G
Artery Tibial	eqtl	3.2e-02	+0.37	12:48476712:TGCACCCAATACAGGA:T
Cells EBV-transformed lymphocytes	eqtl	3.7e-02	+0.34	12:47722472:A:G

FANTOM5 promoters

5 alternative TSS:

Promoter ID	TPM avg	Samples expressed
130682	0.2164	26
130683	0.1218	20
130681	0.0397	10
130684	0.0250	6
130680	0.0138	7

Top tissues by expression

showing 100 of 290 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	98.30	gold quality
tongue squamous epithelium	UBERON:0006919	98.20	gold quality
gingival epithelium	UBERON:0001949	95.83	gold quality
gingiva	UBERON:0001828	95.57	gold quality
esophagus mucosa	UBERON:0002469	93.91	gold quality
cervix squamous epithelium	UBERON:0006922	93.38	gold quality
oral cavity	UBERON:0000167	92.81	gold quality
squamous epithelium	UBERON:0006914	92.70	gold quality
epithelium of esophagus	UBERON:0001976	91.22	gold quality
esophagus squamous epithelium	UBERON:0006920	90.80	gold quality
cervix epithelium	UBERON:0004801	90.73	gold quality
pharyngeal mucosa	UBERON:0000355	90.66	gold quality
penis	UBERON:0000989	89.86	gold quality
body of tongue	UBERON:0011876	87.31	gold quality
skin of abdomen	UBERON:0001416	86.53	gold quality
mammalian vulva	UBERON:0000997	85.79	gold quality
upper arm skin	UBERON:0004263	85.62	gold quality
skin of leg	UBERON:0001511	85.28	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.07	silver quality
zone of skin	UBERON:0000014	84.84	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	84.16	gold quality
vagina	UBERON:0000996	81.16	gold quality
placenta	UBERON:0001987	79.60	gold quality
esophagus	UBERON:0001043	79.06	gold quality
tongue	UBERON:0001723	78.39	gold quality
upper leg skin	UBERON:0004262	77.14	gold quality
skin of hip	UBERON:0001554	74.68	gold quality
uterine cervix	UBERON:0000002	73.58	gold quality
oviduct epithelium	UBERON:0004804	73.03	gold quality
ectocervix	UBERON:0012249	69.93	gold quality
medial globus pallidus	UBERON:0002477	69.35	silver quality
buccal mucosa cell	CL:0002336	69.09	gold quality
tonsil	UBERON:0002372	69.03	gold quality
mouth mucosa	UBERON:0003729	68.94	gold quality
superior surface of tongue	UBERON:0007371	68.89	gold quality
caudate nucleus	UBERON:0001873	68.61	gold quality
amygdala	UBERON:0001876	68.44	gold quality
putamen	UBERON:0001874	67.92	gold quality
mucosa of stomach	UBERON:0001199	67.62	gold quality
left ovary	UBERON:0002119	67.31	gold quality
hair follicle	UBERON:0002073	67.13	gold quality
right ovary	UBERON:0002118	66.89	gold quality
fallopian tube	UBERON:0003889	66.65	gold quality
right frontal lobe	UBERON:0002810	65.88	gold quality
cingulate cortex	UBERON:0003027	65.73	gold quality
anterior cingulate cortex	UBERON:0009835	65.44	gold quality
prefrontal cortex	UBERON:0000451	65.18	gold quality
descending thoracic aorta	UBERON:0002345	65.04	gold quality
minor salivary gland	UBERON:0001830	64.84	gold quality
hindlimb stylopod muscle	UBERON:0004252	64.07	gold quality
calcaneal tendon	UBERON:0003701	63.99	gold quality
right uterine tube	UBERON:0001302	63.30	gold quality
globus pallidus	UBERON:0001875	63.26	silver quality
left uterine tube	UBERON:0001303	63.17	gold quality
metanephros cortex	UBERON:0010533	62.73	gold quality
nucleus accumbens	UBERON:0001882	62.57	gold quality
subcutaneous adipose tissue	UBERON:0002190	62.51	gold quality
ovary	UBERON:0000992	62.45	gold quality
omental fat pad	UBERON:0010414	62.43	gold quality
peritoneum	UBERON:0002358	62.37	gold quality
Brodmann (1909) area 9	UBERON:0013540	62.14	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	61.90	gold quality
female reproductive system	UBERON:0000474	61.87	gold quality
apex of heart	UBERON:0002098	61.66	gold quality
tendon	UBERON:0000043	61.52	gold quality
lower esophagus	UBERON:0013473	61.42	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	61.39	gold quality
adipose tissue of abdominal region	UBERON:0007808	61.24	gold quality
lower esophagus muscularis layer	UBERON:0035833	61.24	gold quality
nipple	UBERON:0002030	61.20	gold quality
saliva-secreting gland	UBERON:0001044	61.05	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	60.96	gold quality
neocortex	UBERON:0001950	60.79	gold quality
frontal cortex	UBERON:0001870	60.73	gold quality
telencephalon	UBERON:0001893	60.51	gold quality
amniotic fluid	UBERON:0000173	59.88	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	59.80	gold quality
thoracic aorta	UBERON:0001515	59.75	gold quality
tibial artery	UBERON:0007610	59.50	gold quality
ascending aorta	UBERON:0001496	59.44	gold quality
aorta	UBERON:0000947	59.43	gold quality
popliteal artery	UBERON:0002250	59.39	gold quality
frontal pole	UBERON:0002795	59.33	gold quality
middle frontal gyrus	UBERON:0002702	59.11	gold quality
paraflocculus	UBERON:0005351	59.07	gold quality
forebrain	UBERON:0001890	59.06	gold quality
cerebral cortex	UBERON:0000956	58.74	gold quality
left lobe of thyroid gland	UBERON:0001120	58.59	gold quality
right atrium auricular region	UBERON:0006631	58.11	gold quality
spinal cord	UBERON:0002240	57.96	gold quality
tendon of biceps brachii	UBERON:0008188	57.75	gold quality
muscle of leg	UBERON:0001383	57.72	gold quality
thyroid gland	UBERON:0002046	57.69	gold quality
temporal lobe	UBERON:0001871	57.68	gold quality
hypothalamus	UBERON:0001898	57.61	gold quality
adipose tissue	UBERON:0001013	57.58	gold quality
gastrocnemius	UBERON:0001388	57.51	gold quality
anatomical system	UBERON:0000467	57.50	gold quality
cardiac atrium	UBERON:0002081	57.41	gold quality
Ammon’s horn	UBERON:0001954	57.38	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.66

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 73 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Esophagus	tissue	60.6	medium
Vagina	tissue	29.9	medium
Skin 1	tissue	19.9	high
Tonsil	tissue	8.2	low
Frontal cortex	tissue	2.4
Placenta	tissue	2.4	high
Postcentral gyrus	tissue	2.4
Nucleus accumbens	tissue	1.8
Spinal cord	tissue	1.8
Hippocampus	tissue	1.8	not detected
Cerebral cortex	tissue	1.7	not detected
Medulla oblongata	tissue	1.7
Somatosensory cortex	tissue	1.7
Breast	tissue	1.6	not detected
Thalamus	tissue	1.6
Substantia nigra	tissue	1.6
Periaqueductal gray	tissue	1.6
Pons	tissue	1.5
Midbrain	tissue	1.5
Superior colliculi	tissue	1.5
Septum	tissue	1.5
Temporal cortex	tissue	1.5
Amygdala	tissue	1.4
Locus coeruleus	tissue	1.4
Hippocampal formation	tissue	1.4
Ventral forebrain	tissue	1.4
Retrosplenial cortex	tissue	1.4
Motor cortex	tissue	1.3
Basal ganglia	tissue	1.3	not detected
Hypothalamus	tissue	1.3
Corpus callosum	tissue	1.3
Occipital cortex	tissue	1.3
Insular cortex	tissue	1.3
Prefrontal cortex	tissue	1.2
Putamen	tissue	1.2
Entorhinal cortex	tissue	1.2
Choroid plexus	tissue	1.1
Retrosplenial and cingulate cortex	tissue	1.1
Epididymis	tissue	1.0	not detected
Ovary	tissue	0.9	not detected
Adipose tissue	tissue	0.8	not detected
Cervix	tissue	0.7	high
Olfactory bulb	tissue	0.7
Fallopian tube	tissue	0.7	not detected
Heart muscle	tissue	0.6	not detected
Pituitary gland	tissue	0.5
Thyroid gland	tissue	0.5	not detected
Gallbladder	tissue	0.5	not detected
Caudate putamen	tissue	0.5
Salivary gland	tissue	0.4	not detected
Smooth muscle	tissue	0.4	not detected
Endometrium 1	tissue	0.4	not detected
Lymph node	tissue	0.3	not detected
Skeletal muscle	tissue	0.3	not detected
Cerebellum	tissue	0.3
Seminal vesicle	tissue	0.2	not detected
Lung	tissue	0.2	not detected
Bone marrow	tissue	0.2	not detected
Testis	tissue	0.1	low
Stomach 1	tissue	0.1	not detected

Brain sub-regions (HPA Brain Atlas): detected in 189; highest nTPM — Globus pallidus, externus (3.1), Dorsal cochlear nucleus (3.0), Posterior thalamic nucleus (3.0), Cerebellar nuclei (2.8), Lateral vestibular nucleus (2.7).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYC

Functional genomics

gnomAD constraint: pLI 1.94e-12, LOEUF 1.09, missense Z 1.05 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000422538 — one region, missense o/e 0.90.

Literature-anchored findings (GeneRIF, showing 4)

• human placental protein 11 is an endoribonuclease (PMID:18936097)
• Connecting the dots on vertical transmission of SARS-CoV-2 using protein-protein interaction network analysis - Potential roles of placental ACE2 and ENDOU. (PMID:33197855)
• Poly(U)-specific endoribonuclease ENDOU promotes translation of human CHOP mRNA by releasing uORF element-mediated inhibition. (PMID:33511665)
• [1]H, [13]C and [15]N backbone resonance assignment of the calcium-activated EndoU endoribonuclease. (PMID:39249657)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	endou	ENSDARG00000044204
mus_musculus	Endou	ENSMUSG00000022468
rattus_norvegicus	Endou	ENSRNOG00000056446
drosophila_melanogaster	CG2145	FBGN0030251
drosophila_melanogaster	EndoU	FBGN0038381
caenorhabditis_elegans	endu-1	WBGENE00010488
caenorhabditis_elegans		WBGENE00019779

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:97746) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 1 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal retina morphology	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Xenopus laevis	B1WBB4	94.2%	Diamond
Xenopus tropicalis	B1H3D5	90.8%	Diamond
Bos taurus	A6QLQ8	85.0%	Diamond
Paralichthys olivaceus	Q9PTU6	69.2%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
RPAP3-DT	ncRNA	105369748
LINC02156	ncRNA	111082992
RPAP3	protein-coding	79657
LINC02354	ncRNA	107984503
HDAC7	protein-coding	51564
SLC48A1	protein-coding	55652
RAPGEF3	protein-coding	10411
VDR	protein-coding	7421

Protein

Protein identifiers

Uridylate-specific endoribonuclease — P21128 (reviewed: P21128)

Alternative names: Placental protein 11, Protein endoU

All UniProt accessions (1): P21128

UniProt curated annotations — full annotation on UniProt →

Function. Endoribonuclease that cleaves single-stranded RNAs at 5’ of uridylates and releases a product with a 2’,3’-cyclic phosphate at the 3’-end. The UU and GU sites are more efficiently cleaved than CU and AU sites. Targets mRNAs to regulate their expression.

Subunit / interactions. Monomer.

Subcellular location. Secreted.

Tissue specificity. Placental-specific, but also associated with various malignant neoplasms.

Post-translational modifications. It has been suggested that the active SMB domain may be permitted considerable disulfide bond heterogeneity or variability, thus two alternate disulfide patterns based on 3D structures are described with 1 disulfide bond conserved in both.

Similarity. Belongs to the ENDOU family.

Isoforms (3)

UniProt ID	Names	Canonical?
P21128-1	1	yes
P21128-2	2
P21128-3	3

RefSeq proteins (3): NP_001165910, NP_001165911, NP_006016 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001212	Somatomedin_B_dom	Domain
IPR018998	EndoU_C	Domain
IPR020436	SMB_chordata	Domain
IPR036024	Somatomedin_B-like_dom_sf	Homologous_superfamily
IPR037227	EndoU-like	Homologous_superfamily
IPR039787	ENDOU	Family

Pfam: PF01033, PF09412

Catalyzed reactions (Rhea)

• ribonucleotidyl-uridine-RNA = a 5’-end dephospho-uridine-RNA + a 3’-end 2’,3’-cyclophospho-ribonucleotide-RNA (RHEA:67792)

UniProt features (55 total): disulfide bond 14, helix 12, strand 11, mutagenesis site 5, domain 3, active site 3, splice variant 2, sequence conflict 2, signal peptide 1, chain 1, turn 1

Structure

Experimental structures (PDB)

1 structures by resolution:

PDB	Title	Method	Resolution (Å)
9FTW	Crystal structure of calcium-activated EndoU	X-RAY DIFFRACTION	1.65

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P21128-F1	85.91	0.64

Human Protein Atlas

Protein class: Predicted secreted proteins

Protein evidence: Evidence at protein level

Antibody reliability (HPA): IH enhanced

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 (3)

Position	Role
285
300
343

Disulfide bonds (14)

Type	Positions
Alternate	28–58, 38–51, 38–40, 51–58, 90–106, 90–94, 94–124, 104–117, 104–106, 117–124, 24–40, 24–28
Disulfide bond	44–50, 110–116

Mutagenesis-validated functional residues (5)

Position	Phenotype
284	abolishes endoribonuclease activity and increases rna-binding activity.
285	abolishes endoribonuclease activity without affecting rna-binding activity.
290	abolishes endoribonuclease activity without affecting rna-binding activity.
300	abolishes endoribonuclease activity without affecting rna-binding activity.
343	strongly impairs endoribonuclease activity without affecting rna-binding activity.

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 0; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

MSigDB gene sets: 137 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_UP, GOMF_ENDONUCLEASE_ACTIVITY, GOMF_RNA_NUCLEASE_ACTIVITY, GOBP_NEGATIVE_REGULATION_OF_LIPID_METABOLIC_PROCESS, GOMF_NUCLEASE_ACTIVITY, KYNG_DNA_DAMAGE_DN, GOMF_GROWTH_FACTOR_ACTIVITY, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, GOBP_REGULATION_OF_LIPID_METABOLIC_PROCESS, GOMF_RNA_ENDONUCLEASE_ACTIVITY, GOBP_REGULATION_OF_CATABOLIC_PROCESS, GOBP_LIPID_METABOLIC_PROCESS, GOBP_MULTI_MULTICELLULAR_ORGANISM_PROCESS, GOBP_NEGATIVE_REGULATION_OF_LIPID_CATABOLIC_PROCESS

GO Biological Process (7): proteolysis (GO:0006508), immune response (GO:0006955), female pregnancy (GO:0007565), post-transcriptional gene silencing (GO:0016441), negative regulation of lipid catabolic process (GO:0050995), signal transduction (GO:0007165), vesicle-mediated transport (GO:0016192)

GO Molecular Function (13): RNA binding (GO:0003723), RNA endonuclease activity (GO:0004521), scavenger receptor activity (GO:0005044), growth factor activity (GO:0008083), serine-type peptidase activity (GO:0008236), lyase activity (GO:0016829), manganese ion binding (GO:0030145), polysaccharide binding (GO:0030247), nuclease activity (GO:0004518), endonuclease activity (GO:0004519), RNA nuclease activity (GO:0004540), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)

GO Cellular Component (3): extracellular region (GO:0005576), cytoplasm (GO:0005737), plasma membrane (GO:0005886)

GO top-level categories

35 GO namespaces:

Category	Terms
cellular process	2
catalytic activity	2
nuclease activity	2
cellular anatomical structure	2
protein metabolic process	1
immune system process	1
response to stimulus	1
multi-organism reproductive process	1
multi-multicellular organism process	1
post-transcriptional regulation of gene expression	1
negative regulation of gene expression	1
negative regulation of catabolic process	1
lipid catabolic process	1
negative regulation of lipid metabolic process	1
regulation of lipid catabolic process	1
cell communication	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
transport	1
nucleic acid binding	1
endonuclease activity	1
RNA nuclease activity	1
cargo receptor activity	1
receptor ligand activity	1
peptidase activity	1
serine hydrolase activity	1
transition metal ion binding	1
carbohydrate binding	1
catalytic activity, acting on a nucleic acid	1
catalytic activity, acting on RNA	1
cation binding	1
intracellular anatomical structure	1
membrane	1
cell periphery	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 8 of 24 annotations. The rest are phylogenetic / computational / electronic (IEA).

8 experimentally-supported GO terms:

GO term	NS	Evidence
female pregnancy	BP	expression pattern
negative regulation of lipid catabolic process	BP	genetic interaction
post-transcriptional gene silencing	BP	genetic interaction
proteolysis	BP	direct assay
cytoplasm	CC	direct assay
RNA binding	MF	direct assay
RNA endonuclease activity	MF	direct assay
serine-type peptidase activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 414 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ENDOU	LGALS13	Q9UHV8	569
ENDOU	PPEF1	O14829	549
ENDOU	PPP1CA	P08129	544
ENDOU	SH2D3A	Q9BRG2	500
ENDOU	RNASEL	Q05823	473
ENDOU	RNGTT	O60942	462
ENDOU	CTRL	P40313	460
ENDOU	IGFBP1	P08833	441
ENDOU	SH2D3C	Q8N5H7	441
ENDOU	IFIH1	Q9BYX4	441
ENDOU	NUTF2	P13662	440
ENDOU	DEDD	O75618	439
ENDOU	PPP6C	O00743	436
ENDOU	PAEP	P09466	406
ENDOU	PRSS57	Q6UWY2	391

IntAct

BioGRID (25 interactions; top human partners by supporting records): FCF1 (Affinity Capture-MS; 2 records), AGPAT1 (Affinity Capture-MS), C18orf21 (Affinity Capture-MS), CCR1 (Affinity Capture-MS), CDK15 (Affinity Capture-MS), FAM213A (Affinity Capture-MS), FNDC5 (Affinity Capture-MS), GOT1 (Affinity Capture-MS), KLHL11 (Affinity Capture-MS), MBNL1 (Affinity Capture-MS), NRSN1 (Affinity Capture-MS), OR2A4 (Affinity Capture-MS), PHF11 (Affinity Capture-MS), PIGT (Affinity Capture-MS), PINK1 (Affinity Capture-MS)

Disease & clinical

Genetic variants

Variant evidence for ENDOU: 61 ClinVar records (0 pathogenic / likely pathogenic); 2 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	48
Likely benign	3
Benign	3

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 33 predictions of 781):

Position(s)	Effect	Δscore	Sites
12:47711681	donor_gain	1.0000
12:47711776–47711777	acceptor_loss	1.0000	6
12:47711778	acceptor_gain	1.0000
12:47712514–47712515	donor_loss	1.0000	3
12:47713273–47713274	donor_loss	1.0000	5
12:47713389–47713390	acceptor_loss	1.0000	5
12:47716298–47716299	donor_loss	1.0000	4
12:47716501	acceptor_loss	1.0000
12:47718095	donor_gain	1.0000
12:47710920–47710921	acceptor_loss	0.9900	6

AlphaMissense

592 missense substitutions predicted likely pathogenic (of 2,739 scored), across 154 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
F268	8	0.914	0.976
F283	8	0.912	0.984
F287	8	0.876	0.969
H300	8	0.866	0.962
H285	8	0.850	0.941
D152	8	0.834	0.948
W302	7	0.954	0.991
W267	7	0.948	0.994
C90	7	0.932	0.966
C106	7	0.906	0.958
S353	7	0.895	0.991
C364	7	0.891	0.976
C110	7	0.889	0.952
C117	7	0.887	0.946
C373	7	0.886	0.942
F336	7	0.871	0.958
F186	7	0.855	0.952
C104	7	0.832	0.930
F259	7	0.827	0.931
W338	7	0.824	0.918

HPA cancer prognostics

RNA cancer specificity: Cancer enhanced (Head and Neck Squamous Cell Carcinoma)

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

1 prognostic cancer types:

Cancer	Prognostic	p-value
Head and Neck Squamous Cell Carcinoma (TCGA)	favorable	0.000886

Disease associations

OMIM: gene MIM:606720 | disease phenotypes:

GWAS associations

2 associations:

Study	Trait	p-value
GCST007611_6	Chronic obstructive pulmonary disease or high blood pressure (pleiotropy)	7e-11
GCST006585_1202	Blood protein levels	4e-10

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

13 total (human), top 13 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
bisphenol A	decreases methylation, affects cotreatment, increases methylation	1
perfluorooctanoic acid	increases expression	1
CGP 52608	affects binding, increases reaction	1
2,3,5-trichloro-6-phenyl-(1,4)benzoquinone	decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Acetaminophen	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Cadmium	decreases expression, increases abundance	1
Silicon Dioxide	increases expression	1
Aflatoxin B1	increases methylation	1
Cadmium Chloride	decreases expression, increases abundance	1
Lactic Acid	decreases expression	1

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.