EDC3

protein-coding

enhancer of mRNA decapping 3

Gene summary

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. [provided by RefSeq, May 2017]

Previous symbols:

YJDC

MANE transcript

NM_025083.5

Inheritance

ClinVar variants

P:2U:47B:17

Top phenotype

Intellectual developmental disorder, autosomal recessive 50

gnomAD constraint

pLI —, LoF o/e 0.33

Max pathogenic AF

—

Genomic locus

chr15:74,630,558-74,696,292

External References & Databases

Ensembl (ENSG00000179151)

Transcript & Mutation Effects

hg38 • Region Span ~65.7 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

autosomal recessive non-syndromic intellectual disabilitySUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0019502

Submitter: Orphanet

intellectual developmental disorder, autosomal recessive 50LIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0014649

Submitter: Labcorp Genetics (formerly Invitae)

intellectual developmental disorder, autosomal recessive 50LIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0014649

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Intellectual developmental disorder, autosomal recessive 50AR

Manifestation: Neurologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 25701870

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to EDC3 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 45

not providedTotal: 15

EDC3-related disorderTotal: 4

Intellectual disability, autosomal recessive 50Total: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_025083.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				13 clinvar	1 clinvar	14
missense	1 clinvar		44 clinvar	3 clinvar		48
nonsense						0
start loss						0
frameshift	1 clinvar					1
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	2	0	47	16	1	66

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 49 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_025083.5	RefSeq	NP_079359.2	6	MANE Select
ENST00000315127.9	Ensembl	ENSP00000320503.4	6	MANE Select
NM_001142443.3	RefSeq	NP_001135915.1	6	Standard
NM_001142444.3	RefSeq	NP_001135916.1	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

RNA degradation - Homo sapiens (human)
Metabolism of RNA
mRNA decay by 5, to 3, exoribonuclease
Deadenylation-dependent mRNA decay

Biological Process

deadenylation-independent decapping of nuclear-transcribed mRNA
cytoplasmic mRNA processing body assembly
exonucleolytic nuclear-transcribed mRNA catabolic process involved in deadenylation-dependent decay
RNA phosphodiester bond hydrolysis, endonucleolytic

Molecular Function

mRNA binding
protein binding
identical protein binding
phosphodiesterase decapping endonuclease activity

Cellular Component

P-body
cytosol
membrane
cytoplasmic ribonucleoprotein granule

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000315127
Coding exons: 6
Length: 65735
Individuals with no LoFs: 125733
Homozygous LoFs: 0
Heterozygous LoFs: 15
Defined: 125748
p: 0.0000596

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.05	191	289	0.661	0.0000164	3356
Missense (PolyPhen)		46	91.944	0.5003		1111
Synonymous	0.948	101	114	0.887	0.00000649	1023
Loss of Function	2.67	6	18.3	0.327	8.53e-7	218

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00018	0.00012	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.000055	0.000054	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000089	0.000088	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: 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. {ECO:0000269|PubMed:16364915, ECO:0000269|PubMed:17533573, ECO:0000269|PubMed:18678652, ECO:0000269|PubMed:25701870}.;
Disease: DISEASE: Mental retardation, autosomal recessive 50 (MRT50) [MIM:616460]: A form of mental retardation, 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. {ECO:0000269|PubMed:25701870}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.124

Intolerance Scores

LoFtool: 0.138
RVIS EVS: -0.07
RVIS percentile EVS: 48.35

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.843

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium