EMG1

Chr 12AR

EMG1 N1-specific pseudouridine methyltransferase

Also known as: C2F, Grcc2f, NEP1

This gene encodes a methyltransferase that methylates pseudouridine in 18S ribosomal RNA and plays an essential role in 40S ribosomal subunit biogenesis. Mutations cause Bowen-Conradi syndrome, a severe autosomal recessive disorder characterized by growth restriction, microcephaly, and early lethality. The gene shows tolerance to loss-of-function variation in the general population (pLI 0.00001), but pathogenic mutations in both copies cause this devastating early-onset syndrome.

Summary from RefSeq, OMIM, UniProt
Research Assistant →

Primary Disease Associations & Inheritance

Bowen-Conradi syndromeMIM #211180
AR
0
Active trials
7
Pubs (1 yr)
47
P/LP submissions
2%
P/LP missense
1.25
LOEUF
DN
Mechanism· predicted
Clinical SummaryEMG1
🧬
Gene-Disease Validity (ClinGen)
Bowen-Conradi syndrome · ARStrong

Strong evidence — appropriate for clinical testing

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
46 unique Pathogenic / Likely Pathogenic· 54 VUS of 148 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.25LOEUF
pLI 0.000
Z-score 0.94
OE 0.71 (0.431.25)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.30Z-score
OE missense 1.07 (0.941.23)
147 obs / 137.0 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.71 (0.431.25)
00.351.4
Missense OE1.07 (0.941.23)
00.61.4
Synonymous OE1.28
01.21.6
LoF obs/exp: 9 / 12.6Missense obs/exp: 147 / 137.0Syn Z: -1.56
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongEMG1-related Bowen-Conradi syndromeOTHERAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.7327th %ile
GOF
0.3491th %ile
LOF
0.3357th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

148 submitted variants in ClinVar

Classification Summary

Pathogenic44
Likely Pathogenic2
VUS54
Likely Benign14
Benign8
44
Pathogenic
2
Likely Pathogenic
54
VUS
14
Likely Benign
8
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
1
43
0
44
Likely Pathogenic
0
0
2
0
2
VUS
0
42
12
0
54
Likely Benign
0
3
3
8
14
Benign
1
1
1
5
8
Total1476113122

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

EMG1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Key Publications
Landmark & review papers · by relevance
PubMed
Top 3 results · since 2015Search PubMed ↗