CELF2

Chr 10

CUGBP Elav-like family member 2

Also known as: BRUNOL3, CELF-2, CUG-BP2, CUGBP2, DEE97, ETR-3, ETR3, NAPOR

NCBI Gene: 10659 ENSG00000048740 UniProt: O95319

CELF2 encodes an RNA-binding protein that regulates pre-mRNA alternative splicing, mRNA stability, and translation through binding to UG-rich sequences and other RNA motifs. Mutations cause developmental and epileptic encephalopathy 97, inherited in an autosomal dominant pattern. The gene is highly constrained against loss-of-function variants (pLI = 1.00, LOEUF = 0.174), consistent with its critical role in neurodevelopment.

ResearchSummary from RefSeq, OMIM, 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. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.17

Clinical Summary— CELF2

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

17 unique Pathogenic / Likely Pathogenic· 65 VUS of 113 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

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 4.66

OE 0.04 (0.01–0.17)

Highly constrained

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

Missense Constraint?

4.34Z-score

OE missense 0.29 (0.25–0.35)

88 obs / 298.9 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?0.29 (0.25–0.35)

0≤0.61.4

Synonymous OE?1.05

0≤1.21.6

LoF obs/exp: 1 / 27.2Missense obs/exp: 88 / 298.9Syn Z: -0.45

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

strongCELF2-related neurodevelopmental disorderLOFAD

This gene — mechanism propensity

0.4190th %ile

GOF

0.4283th %ile

LOF

0.84top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · 65% of P/LP variants are LoF · LOEUF 0.17

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

113 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic8

Likely Pathogenic9

VUS65

Likely Benign11

Benign2

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	4	4	0	0	8
Likely Pathogenic	7	2	0	0	9
VUS	9	52	3	1	65
Likely Benign	0	5	5	1	11
Benign	0	1	1	0	2
Total	20	64	9	2	95

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

View in ClinVar →

21 pathogenic / likely-pathogenic (of 37) ClinVar copy-number / structural variants overlap CELF2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →