EDC3

Summary

EDC3 (enhancer of mRNA decapping 3, HGNC:26114) is a protein-coding gene on chromosome 15q24.1, encoding Enhancer of mRNA-decapping protein 3 (Q96F86). Binds single-stranded RNA.

This gene encodes a protein that is important in mRNA degradation. The encoded protein is a component of a decapping complex that promotes efficient removal of the monomethylguanosine (m7G) cap from mRNAs, as part of the 5’ to 3’ mRNA decay pathway. Mutations in this gene have been identified in human patients with an autosomal recessive form of intellectual disability.

Source: NCBI Gene 80153 — RefSeq curated summary.

At a glance

• Gene–disease (curated): autosomal recessive non-syndromic intellectual disability (Supportive, GenCC) — +1 more curated relationship
• GWAS associations: 18
• Clinical variants (ClinVar): 71 total — 2 pathogenic
• Regional missense constraint (gnomAD): 1 of 3 regions constrained (≈5% of expected missense variation)
• GTEx eGene: eQTL in 8 tissues, sQTL in 0 (q < 0.05)
• Phenotypes (HPO): 6
• Constraint (gnomAD): pLI 0.04 (LoF-tolerant), LOEUF 0.66 (unconstrained)
• MANE Select transcript: NM_025083
• Notable: 71 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26114
Approved symbol	EDC3
Name	enhancer of mRNA decapping 3
Location	15q24.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ21128, hYjeF_N2-15q23, YJEFN2, LSM16
Ensembl gene	ENSG00000179151
Ensembl biotype	protein_coding
OMIM	609842
Entrez	80153

Gene structure

Transcript identifiers

Ensembl transcripts: 31 — 27 protein_coding, 2 retained_intron, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

MANE Select: ENST00000315127

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 3, TSL 2: 3, TSL 3: 5, TSL 4: 5, TSL 5: 2

ENST00000315127, ENST00000426797, ENST00000562047, ENST00000562174, ENST00000562974, ENST00000563009, ENST00000563292, ENST00000565602, ENST00000566119, ENST00000566219, ENST00000566243, ENST00000566828, ENST00000567813, ENST00000568176, ENST00000569007, ENST00000569561, ENST00000569606, ENST00000570138, ENST00000647659, ENST00000875246, ENST00000875247, ENST00000875248, ENST00000875249, ENST00000875250, ENST00000875251, ENST00000934283, ENST00000934284, ENST00000934285, ENST00001045871, ENST00001086112, ENST00001136057

RefSeq mRNA: 5 — MANE Select: NM_025083 NM_001142443, NM_001142444, NM_001351378, NM_001351379, NM_025083

CCDS: CCDS10267

Canonical transcript exons

ENST00000315127 — 7 exons

Exon	Start	End
ENSE00001253676	74671455	74671774
ENSE00001856853	74630558	74632946
ENSE00002583226	74695880	74696024
ENSE00003464012	74635409	74635626
ENSE00003599244	74655733	74656068
ENSE00003648252	74640466	74640619
ENSE00003793240	74674961	74675142

Expression profiles

Bgee: expression breadth ubiquitous, 204 present calls, max score 92.90.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 14.3690 / max 88.0971, expressed in 1802 samples.

Highest expression (Bgee): testis, cortical plate, stromal cell of endometrium, ganglionic eminence, ventricular zone.

Genetic regulation across tissues (GTEx eQTL / sQTL)

EDC3 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 8 tissues and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

8 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Adipose Subcutaneous	eqtl	8.3e-08	-0.19	15:74928674:C:T
Esophagus Gastroesophageal Junction	eqtl	2.2e-03	+0.21	15:73786096:A:G
Nerve Tibial	eqtl	1.1e-02	-0.24	15:73907831:CCTCA:C
Skin Sun Exposed Lower leg	eqtl	2.4e-02	+0.19	15:74078130:T:C
Liver	eqtl	2.5e-02	-0.21	15:73924264:C:T
Muscle Skeletal	eqtl	2.8e-02	+0.21	15:73958206:C:T
Adipose Visceral Omentum	eqtl	3.7e-02	-0.14	15:74303560:G:C
Cells Cultured fibroblasts	eqtl	4.9e-02	-0.08	15:74318059:G:A

FANTOM5 promoters

2 alternative TSS:

Promoter ID	TPM avg	Samples expressed
150925	13.7665	1801
207587	0.6025	322

Top tissues by expression

showing 100 of 270 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	92.90	gold quality
right testis	UBERON:0004534	92.89	gold quality
cortical plate	UBERON:0005343	91.34	gold quality
testis	UBERON:0000473	90.84	gold quality
stromal cell of endometrium	CL:0002255	90.74	gold quality
ganglionic eminence	UBERON:0004023	90.12	gold quality
ventricular zone	UBERON:0003053	89.25	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	88.84	gold quality
islet of Langerhans	UBERON:0000006	88.25	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.76	gold quality
granulocyte	CL:0000094	86.19	gold quality
right lobe of thyroid gland	UBERON:0001119	86.17	gold quality
apex of heart	UBERON:0002098	86.12	gold quality
embryo	UBERON:0000922	86.04	gold quality
right hemisphere of cerebellum	UBERON:0014890	85.79	gold quality
colonic epithelium	UBERON:0000397	85.70	gold quality
cerebellar hemisphere	UBERON:0002245	85.36	gold quality
cerebellar cortex	UBERON:0002129	85.31	gold quality
right ovary	UBERON:0002118	85.17	gold quality
rectum	UBERON:0001052	85.14	gold quality
lower esophagus mucosa	UBERON:0035834	85.11	gold quality
mucosa of transverse colon	UBERON:0004991	85.01	gold quality
left lobe of thyroid gland	UBERON:0001120	85.00	gold quality
body of uterus	UBERON:0009853	84.86	gold quality
monocyte	CL:0000576	84.82	gold quality
leukocyte	CL:0000738	84.74	gold quality
gastrocnemius	UBERON:0001388	84.73	gold quality
esophagus mucosa	UBERON:0002469	84.69	gold quality
mononuclear cell	CL:0000842	84.61	gold quality
left ovary	UBERON:0002119	84.55	gold quality
muscle of leg	UBERON:0001383	84.53	gold quality
hindlimb stylopod muscle	UBERON:0004252	84.42	gold quality
esophagus	UBERON:0001043	84.23	gold quality
popliteal artery	UBERON:0002250	84.19	gold quality
tibial artery	UBERON:0007610	84.17	gold quality
skin of leg	UBERON:0001511	84.16	gold quality
tonsil	UBERON:0002372	84.15	gold quality
transverse colon	UBERON:0001157	84.09	gold quality
pancreas	UBERON:0001264	84.04	gold quality
thyroid gland	UBERON:0002046	84.02	gold quality
right uterine tube	UBERON:0001302	83.98	gold quality
cerebellum	UBERON:0002037	83.93	gold quality
aorta	UBERON:0000947	83.92	gold quality
right frontal lobe	UBERON:0002810	83.87	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	83.84	gold quality
ectocervix	UBERON:0012249	83.83	gold quality
body of stomach	UBERON:0001161	83.82	gold quality
thoracic aorta	UBERON:0001515	83.73	gold quality
metanephros cortex	UBERON:0010533	83.69	gold quality
ascending aorta	UBERON:0001496	83.68	gold quality
lower esophagus	UBERON:0013473	83.65	gold quality
lower esophagus muscularis layer	UBERON:0035833	83.63	gold quality
descending thoracic aorta	UBERON:0002345	83.58	gold quality
muscle layer of sigmoid colon	UBERON:0035805	83.56	gold quality
small intestine Peyer’s patch	UBERON:0003454	83.55	gold quality
left uterine tube	UBERON:0001303	83.47	gold quality
endocervix	UBERON:0000458	83.44	gold quality
skin of abdomen	UBERON:0001416	83.40	gold quality
smooth muscle tissue	UBERON:0001135	83.22	gold quality
body of pancreas	UBERON:0001150	83.08	gold quality
adenohypophysis	UBERON:0002196	83.07	gold quality
stomach	UBERON:0000945	83.05	gold quality
left coronary artery	UBERON:0001626	82.82	gold quality
right coronary artery	UBERON:0001625	82.75	gold quality
small intestine	UBERON:0002108	82.74	gold quality
upper lobe of left lung	UBERON:0008952	82.67	gold quality
ovary	UBERON:0000992	82.62	gold quality
pituitary gland	UBERON:0000007	82.55	gold quality
coronary artery	UBERON:0001621	82.22	gold quality
spleen	UBERON:0002106	82.21	gold quality
minor salivary gland	UBERON:0001830	82.17	gold quality
lymph node	UBERON:0000029	82.13	gold quality
anterior cingulate cortex	UBERON:0009835	82.12	gold quality
cingulate cortex	UBERON:0003027	82.05	gold quality
omental fat pad	UBERON:0010414	82.05	gold quality
tibial nerve	UBERON:0001323	82.04	gold quality
peritoneum	UBERON:0002358	82.02	gold quality
gall bladder	UBERON:0002110	82.00	gold quality
right atrium auricular region	UBERON:0006631	81.98	gold quality
prefrontal cortex	UBERON:0000451	81.97	gold quality
zone of skin	UBERON:0000014	81.93	gold quality
heart left ventricle	UBERON:0002084	81.84	gold quality
adipose tissue of abdominal region	UBERON:0007808	81.68	gold quality
colon	UBERON:0001155	81.67	gold quality
right lobe of liver	UBERON:0001114	81.64	gold quality
upper lobe of lung	UBERON:0008948	81.60	gold quality
intestine	UBERON:0000160	81.58	gold quality
nucleus accumbens	UBERON:0001882	81.56	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	81.40	gold quality
mucosa of stomach	UBERON:0001199	81.38	gold quality
cardiac ventricle	UBERON:0002082	81.36	gold quality
left adrenal gland	UBERON:0001234	81.34	gold quality
large intestine	UBERON:0000059	81.31	gold quality
right adrenal gland cortex	UBERON:0035827	81.30	gold quality
right adrenal gland	UBERON:0001233	81.26	gold quality
prostate gland	UBERON:0002367	81.23	gold quality
left adrenal gland cortex	UBERON:0035825	81.15	gold quality
blood	UBERON:0000178	81.06	gold quality
subcutaneous adipose tissue	UBERON:0002190	81.02	gold quality
anatomical system	UBERON:0000467	80.92	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.65

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 79 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Testis	tissue	32.4	high
Choroid plexus	tissue	31.0
Nucleus accumbens	tissue	28.7
Hippocampus	tissue	26.1	medium
Locus coeruleus	tissue	24.1
Postcentral gyrus	tissue	23.0
Thymus	tissue	17.3
Tonsil	tissue	16.9	high
Ovary	tissue	16.5	low
Smooth muscle	tissue	15.9	medium
Fallopian tube	tissue	15.4	medium
Cerebellum	tissue	14.5	high
Skin 1	tissue	14.2	medium
Endometrium 1	tissue	14.2	medium
Lymph node	tissue	14.0	medium
Esophagus	tissue	14.0	high
Skeletal muscle	tissue	13.7	medium
Breast	tissue	12.9	medium
Rectum	tissue	12.9	high
Parathyroid gland	tissue	12.5
Cervix	tissue	12.2	medium
Urinary bladder	tissue	12.1	high
Adipose tissue	tissue	12.0	medium
Placenta	tissue	11.6	medium
Pituitary gland	tissue	11.4
Thyroid gland	tissue	11.4	medium
Prostate	tissue	11.2	medium
Colon	tissue	11.1	high
Appendix	tissue	11.1	medium
Small intestine	tissue	11.0	high
Retina	tissue	10.9
Tongue	tissue	10.7
Epididymis	tissue	10.4	medium
Seminal vesicle	tissue	10.2	medium
Spleen	tissue	10.1	low
Vagina	tissue	10.0	medium
Lung	tissue	9.9	medium
Duodenum	tissue	9.8	medium
Salivary gland	tissue	9.7	high
Putamen	tissue	9.6
Gallbladder	tissue	9.5	high
Stomach 1	tissue	9.3	high
Cerebral cortex	tissue	9.1	medium
Kidney	tissue	9.1	high
Corpus callosum	tissue	9.1
Somatosensory cortex	tissue	9.1
Occipital cortex	tissue	8.7
Pancreas	tissue	8.6	medium
Superior colliculi	tissue	8.5
Hippocampal formation	tissue	8.5
Motor cortex	tissue	8.4
Basal ganglia	tissue	8.4	high
Thalamus	tissue	8.4
Heart muscle	tissue	8.3	medium
Pons	tissue	8.3
Liver	tissue	8.3	medium
Midbrain	tissue	8.2
Spinal cord	tissue	8.2
Ventral forebrain	tissue	8.2
Medulla oblongata	tissue	8.1

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Flocculonodular lobe (35.7), Parieto-temporal junction (white matter) (35.5), Vermis (34.3), Temporal white matter (34.1), Cerebellar cortex (33.0).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting EDC3 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 92 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-22-3P	99.93	68.13	917
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-3151-5P	99.86	63.83	1069
HSA-MIR-6515-3P	99.82	68.19	1933
HSA-MIR-139-5P	99.80	69.50	1399
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-4524A-3P	99.72	66.85	2406
HSA-MIR-6752-3P	99.72	66.71	1587
HSA-MIR-3175	99.65	66.30	2031

Functional genomics

gnomAD constraint: pLI 0.0427, LOEUF 0.656, missense Z 3.22 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000315127 splits into 3 regions with different missense tolerance; 1 is missense-constrained (≈5% of the expected missense variation). Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
15:74,632,615–74,655,884	242 / 363.8	0.67	no
15:74,655,885–74,655,960	2 / 29.0	0.07	yes (p 5.3e-07)
15:74,655,961–74,675,124	200 / 244.0	0.82	no

Literature-anchored findings (GeneRIF, showing 5)

• The modular architecture enables EDC3 to interact with multiple components of the decapping machinery, including DCP1, DCP2, and Me31B. (PMID:17923697)
• The dimerization interface of Edc3 is highly conserved in eukaryotes despite the overall low sequence homology across species; structure-based site-directed mutagenesis revealed dimerization is required for efficient RNA binding, P-body formation (PMID:18678652)
• Structural basis for the mutually exclusive anchoring of P body components EDC3 and Tral to the DEAD box protein DDX6/Me31B. (PMID:19285948)
• In vitro decapping assays showed that altered EDC3 is unable to enhance DCP2 decapping at low concentrations and even inhibits DCP2 decapping at high concentration. (PMID:25701870)
• EDC3 might be preferentially involved in the degradation of long coding and non-coding RNAs (PMID:29685133)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	edc3	ENSDARG00000051931
mus_musculus	Edc3	ENSMUSG00000038957
rattus_norvegicus	Edc3	ENSRNOG00000019579
drosophila_melanogaster	Edc3	FBGN0036735
caenorhabditis_elegans	edc-3	WBGENE00011036

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:2142951) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 10 distinct phenotype terms.

Mouse phenotype (MP)	Records
enlarged lymph nodes	1
abnormal testis morphology	1
abnormal skin morphology	1
abnormal eye morphology	1
abnormal kidney morphology	1
increased mean platelet volume	1
increased circulating alkaline phosphatase level	1
enlarged kidney	1
single kidney	1
enlarged urinary bladder	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
Pongo abelii	Q5RDU9	99.4%	Diamond
Macaca fascicularis	Q4R8V9	98.0%	Diamond
Gallus gallus	Q5ZLS2	88.6%	Diamond
Xenopus laevis	Q5XH48	75.0%	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
ARID3B	protein-coding	10620
CLK3	protein-coding	1198
CYP1A1	protein-coding	1543
CLK3-AS1	protein-coding	102723750
MIR4513	ncRNA	100616183
CSK	protein-coding	1445
CYP1A2	protein-coding	1544
LMAN1L	protein-coding	79748

Protein

Protein identifiers

Enhancer of mRNA-decapping protein 3 — Q96F86 (reviewed: Q96F86)

Alternative names: LSM16 homolog, YjeF N-terminal domain-containing protein 2, YjeF domain-containing protein 1

All UniProt accessions (13): H3BMB8, H3BNJ7, H3BPN4, H3BPW9, H3BQ37, H3BQA1, H3BQP5, H3BSQ0, H3BTD6, H3BTF8, H3BTH0, H3BU87, Q96F86

UniProt curated annotations — full annotation on UniProt →

Function. Binds single-stranded RNA. Involved in the process of mRNA degradation and in the positive regulation of mRNA decapping. May play a role in spermiogenesis and oogenesis.

Subunit / interactions. Homodimer (via YjeF N-terminal domain). Forms a complex with DCP1A, DCP2, DDX6 and EDC4/HEDLS, within this complex directly interacts with DCP1A and DDX6. Interacts with ZFP36.

Subcellular location. Cytoplasm. P-body.

Tissue specificity. Expressed in theca and granulosa cells in ovary, and in spermatids of the meiotic division part II and apical membrane of Sertoli cells in testis (at protein level). Also expressed in brain and mammary gland.

Disease relevance. Intellectual developmental disorder, autosomal recessive 50 (MRT50) [MIM:616460] A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRT50 patients show mild intellectual disability and microcephaly. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The DFDF domain is unstructured by itself. It assumes a helical fold upon interaction with DDX6.

Similarity. Belongs to the EDC3 family.

RefSeq proteins (5): NP_001135915, NP_001135916, NP_001338307, NP_001338308, NP_079359* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004443	YjeF_N_dom	Domain
IPR019050	FDF_dom	Domain
IPR025609	Lsm14-like_N	Domain
IPR025762	DFDF	Domain
IPR034107	Lsm16_N	Domain
IPR036652	YjeF_N_dom_sf	Homologous_superfamily
IPR047575	Sm	Domain

Pfam: PF03853, PF09532, PF12701, PF16598

UniProt features (50 total): strand 15, helix 13, turn 5, modified residue 4, mutagenesis site 4, domain 3, region of interest 3, chain 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

6 structures by resolution:

PDB	Title	Method	Resolution (Å)
2VC8	Crystal structure of the LSm domain of human EDC3 (enhancer of decapping 3)	X-RAY DIFFRACTION	1.31
3D3K	Crystal structure of human Edc3p	X-RAY DIFFRACTION	2.2
6S8S	Extended structure of the human DDX6 C-terminal domain in complex with an EDC3 FDF peptide	X-RAY DIFFRACTION	2.21
2WAX	Structure of the human DDX6 C-terminal domain in complex with an EDC3- FDF peptide	X-RAY DIFFRACTION	2.3
2WAY	Structure of the human DDX6 C-terminal domain in complex with an EDC3- FDF peptide	X-RAY DIFFRACTION	2.3
3D3J	Crystal structure of human Edc3p	X-RAY DIFFRACTION	2.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96F86-F1	77.04	0.50

Human Protein Atlas

Protein class: Predicted intracellular proteins, Disease related genes, Human disease related genes, Mental and behavioural disorders

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): cytoplasmic bodies

Antibody reliability (HPA): IH uncertain · IF supported

Functional residue map

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

Post-translational modifications (4)

Type	Positions
Phosphoserine	161, 131, 138, 140

Mutagenesis-validated functional residues (4)

Position	Phenotype
204	abolishes interaction with ddx6; when associated with a-206.
206	abolishes interaction with ddx6; when associated with a-204.
306	abolishes homodimerization and rna binding; when associated with a-310.
310	abolishes homodimerization and rna binding; when associated with a-306.

Function

Pathways and Gene Ontology

Reactome pathways

1 curated (TAS) of 3; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

3 pathways:

ID	Pathway	Evidence
R-HSA-430039	mRNA decay by 5’ to 3’ exoribonuclease	curated
R-HSA-429914	Deadenylation-dependent mRNA decay	—
R-HSA-8953854	Metabolism of RNA	—

MSigDB gene sets: 124 (showing top): TGGTGCT_MIR29A_MIR29B_MIR29C, GOBP_P_BODY_ASSEMBLY, GOBP_REGULATION_OF_MRNA_CATABOLIC_PROCESS, XU_GH1_AUTOCRINE_TARGETS_UP, REACTOME_MRNA_DECAY_BY_5_TO_3_EXORIBONUCLEASE, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, GOBP_REGULATION_OF_CATABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_CATABOLIC_PROCESS, GOBP_ORGANELLE_ASSEMBLY, GOBP_NUCLEAR_TRANSCRIBED_MRNA_CATABOLIC_PROCESS_DEADENYLATION_DEPENDENT_DECAY, TGTTTAC_MIR30A5P_MIR30C_MIR30D_MIR30B_MIR30E5P, NRF2_01, REACTOME_METABOLISM_OF_RNA, GOCC_RIBONUCLEOPROTEIN_GRANULE

GO Biological Process (4): nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay (GO:0000288), deadenylation-dependent decapping of nuclear-transcribed mRNA (GO:0000290), deadenylation-independent decapping of nuclear-transcribed mRNA (GO:0031087), P-body assembly (GO:0033962)

GO Molecular Function (4): mRNA binding (GO:0003729), identical protein binding (GO:0042802), RNA binding (GO:0003723), protein binding (GO:0005515)

GO Cellular Component (4): P-body (GO:0000932), cytosol (GO:0005829), membrane (GO:0016020), cytoplasmic ribonucleoprotein granule (GO:0036464)

Reactome top-level categories

2 top-level categories:

Category	Pathways
Deadenylation-dependent mRNA decay	1
Metabolism of RNA	1

GO top-level categories

14 GO namespaces:

Category	Terms
nuclear-transcribed mRNA catabolic process	2
mRNA methylguanosine-cap decapping	2
cytoplasm	2
cellular anatomical structure	2
mRNA destabilization	1
nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay	1
nuclear-transcribed mRNA catabolic process, deadenylation-independent decay	1
membraneless organelle assembly	1
RNA binding	1
protein binding	1
nucleic acid binding	1
binding	1
cytoplasmic ribonucleoprotein granule	1
ribonucleoprotein granule	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 3 of 12 annotations. The rest are phylogenetic / computational / electronic (IEA).

3 experimentally-supported GO terms:

GO term	NS	Evidence
cytoplasmic ribonucleoprotein granule	CC	direct assay
membrane	CC	high-throughput assay
identical protein binding	MF	physical interaction

Protein interactions and networks

STRING

showing 15 of 1,518 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EDC3	DCP2	Q8IU60	986
EDC3	DDX6	P26196	981
EDC3	EDC4	Q6P2E9	978
EDC3	XRN1	Q8IZH2	972
EDC3	DCP1A	Q9NPI6	956
EDC3	LSM1	O15116	862
EDC3	UPF1	Q92900	844
EDC3	LSM14A	Q8ND56	810
EDC3	LSM4	Q9Y4Z0	804
EDC3	DCP1B	Q8IZD4	802
EDC3	PATL1	Q86TB9	765
EDC3	CNOT1	A5YKK6	688
EDC3	EIF4ENIF1	Q9NRA8	676
EDC3	VCX3A	Q9NNX9	647
EDC3	LSM14B	Q9BX40	641

IntAct

Human interaction partners of EDC3 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

showing 30 of 43 partners by confidence:

Partner	Interaction type	MIscore	Records
DDX6	association	0.960	15
DCP1A	colocalization	0.950	7
DCP1B	physical association	0.930	5
YWHAG	physical association	0.900	2
ANXA10	physical association	0.870	11
YWHAB	physical association	0.850	2
EFHC2	physical association	0.780	7
YWHAZ	physical association	0.750	2
BAG4	association	0.640	2
EDC4	association	0.640	1
PNLIPRP2	physical association	0.620	1
LNX1	physical association	0.560	3
PIAS2	physical association	0.560	3
QARS1	physical association	0.560	3
SFN	physical association	0.540	1
KLK10	association	0.530	1
ZFP36	physical association	0.500	1
NS	physical association	0.400	1
IGHG1	association	0.350	1
AGAP1	physical association	0.000	1
CBY1	physical association	0.000	1
CDC25B	physical association	0.000	1
CDK16	physical association	0.000	1
DCLK1	physical association	0.000	1
DENND1A	physical association	0.000	1
EIF4E2	physical association	0.000	1
GIGYF1	physical association	0.000	1
KCTD3	physical association	0.000	1
KIF13B	physical association	0.000	1
KSR1	physical association	0.000	1

BioGRID (310 interactions; top human partners by supporting records): DCP1A (Affinity Capture-MS; 21 records), DDX6 (Two-hybrid; 19 records), DCP1B (Two-hybrid; 15 records), EDC4 (Proximity Label-MS; 9 records), DCP2 (Affinity Capture-MS; 7 records), YWHAG (Affinity Capture-MS; 7 records), SNCA (Affinity Capture-MS; 5 records), YWHAB (Affinity Capture-MS; 5 records), YWHAH (Proximity Label-MS; 5 records), ANXA10 (Two-hybrid; 4 records), BAG4 (Affinity Capture-MS; 4 records), PIM1 (Affinity Capture-MS; 4 records), YWHAE (Proximity Label-MS; 4 records), EFHC2 (Two-hybrid; 3 records), KLK10 (Affinity Capture-MS; 3 records)

SIGNOR signaling

2 signaling interactions:

A	Effect	B	Mechanism
14-3-3	“down-regulates activity”	EDC3	binding
AKT	“down-regulates activity”	EDC3	phosphorylation

Protein complexes (CORUM) (1)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

1 complexes by size:

Complex	Subunits	Members
Decapping complex	5	EDC3, EDC4, DCP1A, DCP2, DDX6

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 43 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	126.9×	2e-08
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	5	112.0×	2e-08
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	5	112.0×	2e-08
Activation of BH3-only proteins	5	82.8×	9e-08
FOXO-mediated transcription	5	56.0×	6e-07
RHO GTPases activate PKNs	5	52.9×	7e-07
Intrinsic Pathway for Apoptosis	5	48.8×	9e-07
SARS-CoV-1-host interactions	5	29.3×	9e-06

GO biological processes:

GO term	Partners	Fold	FDR
protein targeting	5	45.8×	2e-05
intracellular protein localization	6	15.7×	2e-04

Disease & clinical

Genetic variants

Variant evidence for EDC3: 71 ClinVar records (2 pathogenic / likely pathogenic); 18 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	45
Likely benign	14
Benign	2

Top pathogenic / likely-pathogenic (2)

Showing all 2 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
3068515	NM_025083.5(EDC3):c.512del (p.Gln171fs)	Pathogenic	criteria provided, single submitter	1
372218	NM_025083.5(EDC3):c.161T>C (p.Phe54Ser)	Pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore EDC3’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 43 predictions of 930):

Position(s)	Effect	Δscore	Sites
15:74635627–74635628	acceptor_loss	1.0000	5
15:74655731–74655732	donor_loss	1.0000	5
15:74656069–74656070	acceptor_loss	1.0000	5
15:74671453–74671454	donor_loss	1.0000	5
15:74671775	acceptor_gain	1.0000
15:74671775–74671776	acceptor_loss	1.0000	5
15:74674959–74674960	donor_loss	1.0000	5
15:74632947–74632948	acceptor_loss	0.9900	6
15:74635407–74635408	donor_loss	0.9900	5
15:74635627	acceptor_loss	0.9900

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

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

4 prognostic cancer types:

Cancer	Prognostic	p-value
Liver Hepatocellular Carcinoma (TCGA)	unfavorable	2.27e-06
Liver Hepatocellular Carcinoma (validation)	unfavorable	1.24e-05
Lung Adenocarcinoma (validation)	unfavorable	2.62e-05
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	0.000259

Disease associations

OMIM: gene MIM:609842 | disease phenotypes: MIM:616460

GenCC curated gene-disease

2 curated gene-disease records:

Disease	Classification	Inheritance	Records
autosomal recessive non-syndromic intellectual disability	Supportive	Autosomal recessive
intellectual disability, autosomal recessive 50	Limited	Autosomal recessive	2

Mondo (2): intellectual disability, autosomal recessive 50 (MONDO:0014649), autosomal recessive non-syndromic intellectual disability (MONDO:0019502)

Orphanet (1): Autosomal recessive non-syndromic intellectual disability (Orphanet:88616)

HPO phenotypes

6 phenotypes (HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000252	Microcephaly
HP:0000407	Sensorineural hearing impairment
HP:0001100	Heterochromia iridis
HP:0001256	Mild intellectual disability
HP:0011463	Childhood onset

GWAS associations

18 associations:

Study	Trait	p-value
GCST004412_7	Craniofacial microsomia	1e-23
GCST003851_19	Caffeine metabolism (plasma 1,7-dimethylxanthine (paraxanthine) to 1,3,7-trimethylxanthine (caffeine) ratio)	9e-22
GCST003846_8	Caffeine metabolism (plasma 1,3,7-trimethylxanthine (caffeine) level)	1e-20
GCST003846_7	Caffeine metabolism (plasma 1,3,7-trimethylxanthine (caffeine) level)	5e-18
GCST003846_6	Caffeine metabolism (plasma 1,3,7-trimethylxanthine (caffeine) level)	2e-16
GCST003851_18	Caffeine metabolism (plasma 1,7-dimethylxanthine (paraxanthine) to 1,3,7-trimethylxanthine (caffeine) ratio)	4e-15
GCST90002395_518	Mean platelet volume	4e-15
GCST003851_16	Caffeine metabolism (plasma 1,7-dimethylxanthine (paraxanthine) to 1,3,7-trimethylxanthine (caffeine) ratio)	3e-14
GCST001032_7	Caffeine consumption	5e-14
GCST003846_5	Caffeine metabolism (plasma 1,3,7-trimethylxanthine (caffeine) level)	1e-11
GCST003851_17	Caffeine metabolism (plasma 1,7-dimethylxanthine (paraxanthine) to 1,3,7-trimethylxanthine (caffeine) ratio)	3e-11
GCST003846_11	Caffeine metabolism (plasma 1,3,7-trimethylxanthine (caffeine) level)	3e-9
GCST003848_2	Caffeine metabolism (plasma 1,3-dimethylxanthine (theophylline) level)	1e-8
GCST010108_21	Coffee consumption (cups per day)	2e-8
GCST003848_1	Caffeine metabolism (plasma 1,3-dimethylxanthine (theophylline) level)	1e-7
GCST003848_4	Caffeine metabolism (plasma 1,3-dimethylxanthine (theophylline) level)	1e-7
GCST003848_3	Caffeine metabolism (plasma 1,3-dimethylxanthine (theophylline) level)	2e-7
GCST003851_3	Caffeine metabolism (plasma 1,7-dimethylxanthine (paraxanthine) to 1,3,7-trimethylxanthine (caffeine) ratio)	3e-7

EFO canonical traits (from GWAS)

3 canonical traits:

EFO ID	Trait name
EFO:0004330	coffee consumption
EFO:0007872	caffeine metabolite measurement
EFO:0006782	cups of coffee per day measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Tetrachlorodibenzodioxin	affects cotreatment, increases expression	3
Estradiol	affects cotreatment, increases expression	2
Tobacco Smoke Pollution	increases expression	2
Cadmium Chloride	decreases expression, increases abundance, increases expression	2
FR900359	affects phosphorylation	1
bisphenol F	affects cotreatment, increases expression	1
chloroacetaldehyde	increases expression	1
triphenyl phosphate	affects expression	1
beta-lapachone	increases expression	1
sodium arsenite	increases expression	1
coumarin	decreases phosphorylation	1
di-n-butylphosphoric acid	affects expression	1
abrine	increases expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	decreases expression	1
3-(2-hydroxy-4-(2-methylnonan-2-yl)phenyl)cyclohexan-1-ol	decreases expression	1
Air Pollutants	affects expression, increases abundance	1
Benzo(a)pyrene	increases expression	1
Cadmium	increases abundance, increases expression	1
Caffeine	decreases phosphorylation	1
Dexamethasone	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Hydrogen Peroxide	affects expression	1
Indomethacin	affects cotreatment, increases expression	1
Ivermectin	decreases expression	1
Oxygen	affects expression	1
Ozone	affects expression, increases abundance	1
Quercetin	increases expression	1
Smoke	decreases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1

Clinical trials (associated diseases)

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