CREB5

protein-coding

cAMP responsive element binding protein 5, the group of Basic leucine zipper proteins

Gene summary

The product of this gene belongs to the CRE (cAMP response element)-binding protein family. Members of this family contain zinc-finger and bZIP DNA-binding domains. The encoded protein specifically binds to CRE as a homodimer or a heterodimer with c-Jun or CRE-BP1, and functions as a CRE-dependent trans-activator. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

MANE transcript

NM_182898.4

Inheritance

—

ClinVar variants

U:62

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.24

Max pathogenic AF

—

Genomic locus

chr7:28,299,321-28,825,894

External References & Databases

Ensembl (ENSG00000146592)

Transcript & Mutation Effects

hg38 • Region Span ~526.6 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CREB5 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 60

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_182898.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar			1
missense			60 clinvar			60
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	62	0	0	62

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 27 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_182898.4	RefSeq	NP_878901.2	11	MANE Select
ENST00000357727.7	Ensembl	ENSP00000350359.2	11	MANE Select
NM_001011666.3	RefSeq	NP_001011666.1	7	Standard
NM_004904.4	RefSeq	NP_004895.2	10	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

PI3K-Akt signaling pathway - Homo sapiens (human)
Cortisol synthesis and secretion - Homo sapiens (human)
Relaxin signaling pathway - Homo sapiens (human)
Aldosterone synthesis and secretion - Homo sapiens (human)
Dopaminergic synapse - Homo sapiens (human)

Biological Process

regulation of transcription by RNA polymerase II
transcription by RNA polymerase II
positive regulation of transcription, DNA-templated

Molecular Function

DNA-binding transcription factor activity, RNA polymerase II-specific
DNA binding
DNA-binding transcription factor activity
protein binding
metal ion binding

Cellular Component

nucleus
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000357727
Coding exons: 11
Length: 526572
Individuals with no LoFs: 125737
Homozygous LoFs: 0
Heterozygous LoFs: 11
Defined: 125748
p: 0.0000437

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.61	230	310	0.742	0.0000177	3390
Missense (PolyPhen)		47	73.847	0.63645		825
Synonymous	0.181	112	114	0.979	0.00000716	955
Loss of Function	3.48	6	24.7	0.243	0.00000114	272

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000059	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.00014	0.00014	rare
European (Non-Finnish)	0.000036	0.000035	rare
South Asian	0.000065	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Binds to the cAMP response element and activates transcription. {ECO:0000269|PubMed:8378084}.;

Intolerance Scores

LoFtool: 0.217
RVIS EVS: -0.67
RVIS percentile EVS: 15.62

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.883

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium