EMG1

Chr 12AR

EMG1 N1-specific pseudouridine methyltransferase

Also known as: C2F, Grcc2f, NEP1

NCBI Gene: 10436 ENSG00000126749 UniProt: Q92979 OMIM: 611531

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.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Bowen-Conradi syndromeMIM #211180

Clinical highlights

Gene–disease validity (ClinGen)

Strong · Bowen-Conradi syndrome · AR · ClinGen 2025

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.25

LOEUF

Mechanism· predicted

📖

GeneReview available — EMG1

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.25LOEUF

pLI 0.000

Z-score 0.94

OE 0.71 (0.43–1.25)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.30Z-score

OE missense 1.07 (0.94–1.23)

147 obs / 137.0 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.71 (0.43–1.25)

0≤0.351.4

Missense OE?1.07 (0.94–1.23)

0≤0.61.4

Synonymous OE?1.28

0≤1.21.6

LoF obs/exp: 9 / 12.6Missense obs/exp: 147 / 137.0Syn Z: -1.56

Background carrier burden — how many people carry a rare variant somewhere in EMG1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 190

345 rare PASS variants

Rare truncating (LoF)

1 in 2,200

76 rare PASS variants

Rare synonymous (reference)

1 in 550

159 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for EMG1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 330	1 in 2,700
South Asian	~43k	1 in 180	1 in 3,100
Remaining (unassigned)	~30k	1 in 220	1 in 780
European (Finnish)	~27k	1 in 420	1 in 3,800
Admixed American	~22k	1 in 180	≈ 1 in 5,000
African / African American	~21k	1 in 120	1 in 1,200
East Asian	~20k	1 in 210	1 in 1,800
Ashkenazi Jewish	~13k	1 in 520	none seen
Middle Eastern	~2,884	1 in 240	≈ 1 in 2,900

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 5 of 6 coding exons well covered in gnomAD exomes; exon 6 marginal. Genomes: all 6.? see exons ↓