CELF1

Chr 11

CUGBP Elav-like family member 1

Also known as: BRUNOL2, CUG-BP, CUGBP, CUGBP1, EDEN-BP, NAB50, NAPOR, hNab50

NCBI Gene: 10658 ENSG00000149187 UniProt: Q92879 OMIM: 601074

CELF1 encodes an RNA-binding protein that regulates alternative splicing, mRNA translation, and stability across multiple tissues including heart and muscle. Mutations cause autosomal dominant myotonic dystrophy type 1, a multisystem disorder affecting skeletal muscle, cardiac conduction, and other organ systems with variable age of onset. The gene is highly constrained against loss-of-function variants, reflecting its essential role in RNA processing.

OMIM ResearchSummary from RefSeq, UniProt

Members of the CELF/BRUNOL protein family contain two N-terminal RNA recognition motif (RRM) domains, one C-terminal RRM domain, and a divergent segment of 160-230 aa between the second and third RRM domains. Members of this protein family regulate pre-mRNA alternative splicing and may also be involved in mRNA editing, and translation. This gene may play a role in myotonic dystrophy type 1 (DM1) via interactions with the dystrophia myotonica-protein kinase (DMPK) gene. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.17

LOEUF· LoF intol.

LOF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

0.17LOEUF

pLI 1.000

Z-score 4.71

OE 0.04 (0.01–0.17)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

3.34Z-score

OE missense 0.45 (0.39–0.52)

128 obs / 287.5 exp

Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?

LoF OE?0.04 (0.01–0.17)

0≤0.351.4

Missense OE?0.45 (0.39–0.52)

0≤0.61.4

Synonymous OE?0.86

0≤1.21.6

LoF obs/exp: 1 / 27.8Missense obs/exp: 128 / 287.5Syn Z: 1.14

Background carrier burden — how many people carry a rare variant somewhere in CELF1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 400

411 rare PASS variants

Rare truncating (LoF)

1 in 5,800

35 rare PASS variants

Rare synonymous (reference)

1 in 270

248 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CELF1. 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 430	1 in 11,000
South Asian	~43k	1 in 170	1 in 8,300
Remaining (unassigned)	~30k	1 in 340	1 in 3,300
European (Finnish)	~27k	1 in 2,100	none seen
Admixed American	~22k	1 in 320	≈ 1 in 8,900
African / African American	~21k	1 in 370	≈ 1 in 9,000
East Asian	~20k	1 in 310	1 in 1,100
Ashkenazi Jewish	~13k	1 in 540	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 320	none seen

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): 12 of 13 coding exons well covered in gnomAD exomes; exon 6 marginal. Genomes: all 13.? see exons ↓