CREG1

Chr 1

cellular repressor of E1A stimulated genes 1

Also known as: CREG

NCBI Gene: 8804 ENSG00000143162 UniProt: O75629

The protein encoded by CREG1 contributes to transcriptional control of cell growth and differentiation by antagonizing cellular transformation and interacting with IGF2R. Mutations cause autosomal recessive developmental and epileptic encephalopathy with onset in infancy, characterized by severe intellectual disability, seizures, and brain malformations. This gene shows tolerance to loss-of-function variants in the general population.

ResearchSummary from RefSeq, UniProt

The adenovirus E1A protein both activates and represses gene expression to promote cellular proliferation and inhibit differentiation. The protein encoded by this gene antagonizes transcriptional activation and cellular transformation by E1A. This protein shares limited sequence similarity with E1A and binds both the general transcription factor TBP and the tumor suppressor pRb in vitro. This gene may contribute to the transcriptional control of cell growth and differentiation. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…

DNmechanismLOEUF 1.51

Clinical Summary— CREG1

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

39 VUS of 45 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

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.51LOEUF

pLI 0.001

Z-score 0.64

OE 0.73 (0.38–1.51)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.42Z-score

OE missense 0.86 (0.71–1.06)

67 obs / 77.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.73 (0.38–1.51)

0≤0.351.4

Missense OE?0.86 (0.71–1.06)

0≤0.61.4

Synonymous OE?0.85

0≤1.21.6

LoF obs/exp: 5 / 6.8Missense obs/exp: 67 / 77.5Syn Z: 0.64

This gene — mechanism propensity

0.6649th %ile

GOF

0.6346th %ile

LOF

0.3162th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

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

ClinVar Variant Classifications

45 submitted variants in ClinVar

ClinVar

Classification Summary

VUS39

Likely Benign2

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	39	0	39
Likely Benign	0	2	2
Benign	0	0	0
Total	39	2	41

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

View in ClinVar →

18 pathogenic / likely-pathogenic (of 21) ClinVar copy-number / structural variants overlap CREG1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →