EMG1
protein-codingEMG1 N1-specific pseudouridine methyltransferase, the group of SPOUT methyltransferase domain containing|SSU processome
Gene summary
This gene encodes an essential, conserved eukaryotic protein that methylates pseudouridine in 18S rRNA. The related protein in yeast is a component of the small subunit processome and is essential for biogenesis of the ribosomal 40S subunit. A mutation in this gene has been associated with Bowen-Conradi syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~9.0 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0008879
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AR
Disease ID:MONDO:0008879
Submitter: Orphanet
Inheritance Pattern: AR
Disease ID:MONDO:0008879
Submitter: G2P
Inheritance Pattern: AR
Disease ID:MONDO:0008879
Submitter: ClinGen
*EMG1* (EMG1 N1-specific pseudouridine methyltransferase) is located on chromosome 12 at position 12p13.31. The protein is key in processing of pre-18S rRNA and small ribosomal subunit formation. *EMG1* was first reported in relation to autosomal recessive Bowen-Conradi Syndrome (BCS) in 2009 (Armistead et al., PMID: 19463982). This condition is characterized by facial anomalies such as micrognathia and prominent nose, joint contractures, congenital microcephaly, rocker bottom foot/clubbed foot, and digit anomalies including camptodactyly. BCS is often lethal within the first year of life due to complications linked to motor issues and poor growth. One variant (missense, p.(Asp86Gly)) that has been reported in 39 probands from 29 nuclear families in the highly consanguineous Hutteritte population, and in one publication, is included in this curation (PMID: 19463982). A founder effect is suspected. The mechanism of pathogenicity appears to be gain-of-function. This gene-disease relationship is also supported by experimental evidence including functional alteration, expression-level evidence, and mouse models (Liu & Thiele, 2001, PMID: 11694595; Eschrich et al., 2001, PMID: 11935223; Wu et al., 2010, PMID: 20858271; Armistead et al., 2015, PMID: 25708872). Functional alteration evidence shows that rRNA processing is inhibited when *EMG1* is mutated. The protein localized to the nucleus in a yeast cell analysis. Mouse models show that the mutants exhibited early embryonic lethality, abnormal expression of early cell lineage markers, increased apoptosis, and neural tube defects.The impact of other variants in *EMG1* is unknown; given the single position (p.Asp86Gly) involved to date, other variants would need very careful consideration. In summary, the classification of this gene-disease relationship was upgraded from moderate to strong based on the strength of evidence, particularly the evidence from the mouse models and the restrictions in scoring founder variants through the framework. This classification was approved by the ClinGen Syndromic Disorders GCEP on the meeting date May 16th, 2025 (SOP Version 11).
Inheritance Pattern: AR
Disease ID:MONDO:0008879
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0008879
Submitter: Ambry Genetics
Clinical Genomic Database (CGD)
Manifestation: Craniofacial; Musculoskeletal; 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
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to EMG1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_006331.8. 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 | 1 | 6 | 4 | 11 | ||
| missense | 1 | 11 | 3 | 15 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | 2 | |||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 1 | 0 | 13 | 9 | 5 | 28 |
Highest pathogenic variant AF is 0.0000043381797
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_006322.4 | 6 | MANE Select | |
| Ensembl | ENSP00000470560.1 | 6 | MANE Select | |
| RefSeq | NP_001306978.1 | 5 | Standard | |
| Ensembl | ENSP00000479546.1 | 5 | Standard |
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000261406
- Coding exons
- 7
- Length
- 33113
- Individuals with no LoFs
- 124615
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 22
- Defined
- 124637
- p
- 0.0000883
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.304 | 147 | 137 | 1.07 | 0.00000699 | 1565 |
| Missense (PolyPhen) | ||||||
| Synonymous | -1.56 | 64 | 49.9 | 1.28 | 0.00000232 | 488 |
| Loss of Function | 0.938 | 9 | 12.6 | 0.715 | 7.84e-7 | 125 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00026 | 0.00026 | rare |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00017 | 0.00017 | rare |
| Finnish | 0.00014 | 0.00014 | rare |
| European (Non-Finnish) | 0.000072 | 0.000071 | rare |
| South Asian | 0.00013 | 0.00013 | rare |
| Other | 0 | 0.0 | absent |