CREB3L4

Chr 1

cAMP responsive element binding protein 3 like 4

Also known as: AIBZIP, ATCE1, CREB3, CREB4, JAL, hJAL

NCBI Gene: 148327 ENSG00000143578 UniProt: Q8TEY5 OMIM: 607138

This gene encodes a CREB (cAMP responsive element binding) protein with a transmembrane domain which localizes it to the ER membrane. The encoded protein is a transcriptional activator which contains a dimerization domain, and this protein may function in a number of processing pathways including protein processing. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

OMIM Research

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 1.02

Clinical Summary— CREB3L4

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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

49 VUS of 72 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.02LOEUF

pLI 0.000

Z-score 1.50

OE 0.62 (0.39–1.02)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.01Z-score

OE missense 1.00 (0.89–1.12)

221 obs / 221.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.62 (0.39–1.02)

0≤0.351.4

Missense OE?1.00 (0.89–1.12)

0≤0.61.4

Synonymous OE?0.83

0≤1.21.6

LoF obs/exp: 11 / 17.9Missense obs/exp: 221 / 221.2Syn Z: 1.26

This gene — mechanism propensity

0.75top 25%

GOF

0.3987th %ile

LOF

0.3940th %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

72 submitted variants in ClinVar

ClinVar

Classification Summary

VUS49

Likely Benign6

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	49	49
Likely Benign	6	6
Benign	0	0
Total	55	55

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

View in ClinVar →

16 pathogenic / likely-pathogenic (of 22) ClinVar copy-number / structural variants overlap CREB3L4 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →