CREB3L3

cAMP responsive element binding protein 3 like 3, the group of CREB3 transcription factor family

Basic information

Region (hg38): 19:4153631-4173054

Links

ENSG00000060566 ∙ NCBI:84699 ∙ OMIM:611998 ∙ HGNC:18855 ∙ Uniprot:Q68CJ9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hypertriglyceridemia (Strong), mode of inheritance: AD
• hypertriglyceridemia 2 (Limited), mode of inheritance: AD
• hypertriglyceridemia 2 (Strong), mode of inheritance: AD
• hypertriglyceridemia 1 (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hypertriglyceridemia 2	AD	Cardiovascular	The condition can involve hypertriglyceridemia, and management via diet and omega-3 fatty acid therapy has been described as beneficial	Cardiovascular	26427795; 29954705

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CREB3L3 gene.

• not provided (6 variants)
• Hypertriglyceridemia 2 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CREB3L3 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	27	8	37
missense			78	14	3	95
nonsense	3	2		1	1	7
start loss						0
frameshift	3		2			5
inframe indel			2			2
splice donor/acceptor (+/-2bp)		4				4
splice region			5	5		10
non coding				12	23	35
Total	6	6	84	54	35

Highest pathogenic variant AF is 0.0000131

Variants in CREB3L3

This is a list of pathogenic ClinVar variants found in the CREB3L3 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
19-4153662-G-A			Benign (May 10, 2021)
19-4153755-C-T		not specified	Likely benign (Aug 30, 2021)
19-4153756-G-A			Likely benign (Dec 21, 2023)
19-4153776-T-C		not specified	Conflicting classifications of pathogenicity (Apr 29, 2024)
19-4153791-C-A			Likely benign (Feb 18, 2023)
19-4153859-T-C			Benign (May 10, 2021)
19-4154849-G-A			Benign (May 11, 2021)
19-4154890-G-A			Benign (Jan 25, 2024)
19-4154891-C-T			Likely benign (Nov 14, 2023)
19-4154892-G-A			Likely benign (Sep 29, 2021)
19-4154895-C-G			Likely benign (Jan 08, 2024)
19-4154903-C-T		not specified	Uncertain significance (Oct 16, 2024)
19-4154906-C-T			Uncertain significance (Mar 03, 2023)
19-4154913-C-T			Benign (Feb 01, 2024)
19-4154920-A-G		not specified	Uncertain significance (Feb 07, 2023)
19-4154926-C-T			Uncertain significance (Nov 16, 2022)
19-4154931-C-T			Likely benign (Sep 15, 2022)
19-4154935-A-C		not specified	Uncertain significance (Jun 24, 2022)
19-4154948-T-C		not specified	Uncertain significance (Oct 21, 2024)
19-4154954-T-G			Uncertain significance (Jan 02, 2023)
19-4154974-G-A		not specified	Uncertain significance (Sep 27, 2021)
19-4154989-G-A			Uncertain significance (Aug 17, 2023)
19-4154998-G-T		CREB3L3-related disorder	Uncertain significance (Nov 08, 2023)
19-4155001-G-T			Pathogenic (Mar 02, 2022)
19-4155002-A-G			Uncertain significance (Nov 07, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CREB3L3	protein_coding	protein_coding	ENST00000078445	10	19454

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
8.06e-14	0.0187	125569	0	179	125748	0.000712

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.249	258	270	0.957	0.0000168	2950
Missense in Polyphen		74	81.201	0.91132		955
Synonymous	-1.81	149	123	1.21	0.00000868	990
Loss of Function	-0.0484	20	19.8	1.01	0.00000109	210

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00194	0.00194
Ashkenazi Jewish	0.000198	0.000198
East Asian	0.000218	0.000217
Finnish	0.000231	0.000231
European (Non-Finnish)	0.000795	0.000791
Middle Eastern	0.000218	0.000217
South Asian	0.000196	0.000196
Other	0.00213	0.00212

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Transcription factor that may act during endoplasmic reticulum stress by activating unfolded protein response target genes. Activated in response to cAMP stimulation. In vitro, binds to the cAMP response element (CRE) and box-B element. Activates transcription through box-B element. Activates transcription through CRE (By similarity). Seems to function synergistically with ATF6. In acute inflammatory response, may activate expression of acute phase response (APR) genes. May be involved in growth suppression. {ECO:0000250, ECO:0000269|PubMed:11353085, ECO:0000269|PubMed:15800215, ECO:0000269|PubMed:16469704}.
• Pathway: 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);Insulin resistance - Homo sapiens (human);Cushing,s syndrome - Homo sapiens (human);Thyroid hormone synthesis - Homo sapiens (human);Vasopressin-regulated water reabsorption - Homo sapiens (human);Huntington,s disease - Homo sapiens (human);TNF signaling pathway - Homo sapiens (human);AMPK signaling pathway - Homo sapiens (human);Thermogenesis - Homo sapiens (human);Glucagon signaling pathway - Homo sapiens (human);Adrenergic signaling in cardiomyocytes - Homo sapiens (human);Prostate cancer - Homo sapiens (human);Longevity regulating pathway - Homo sapiens (human);cAMP signaling pathway - Homo sapiens (human);Estrogen signaling pathway - Homo sapiens (human);Amphetamine addiction - Homo sapiens (human);Viral carcinogenesis - Homo sapiens (human);Hepatitis B - Homo sapiens (human);cGMP-PKG signaling pathway - Homo sapiens (human);Cholinergic synapse - Homo sapiens (human);Alcoholism - Homo sapiens (human);Cocaine addiction - Homo sapiens (human);Insulin secretion - Homo sapiens (human);Melanogenesis - Homo sapiens (human);Human papillomavirus infection - Homo sapiens (human);Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;PI3K-Akt Signaling Pathway;G1 to S cell cycle control;Unfolded Protein Response (UPR);Metabolism of proteins;CREB3 factors activate genes;Transport of small molecules;Assembly of active LPL and LIPC lipase complexes;Plasma lipoprotein assembly, remodeling, and clearance;Plasma lipoprotein remodeling (Consensus)

Recessive Scores

• pRec: 0.134

Intolerance Scores

• loftool: 0.262
• rvis_EVS: -0.71
• rvis_percentile_EVS: 14.67

Haploinsufficiency Scores

• pHI: 0.0814
• hipred: N
• hipred_score: 0.170
• ghis: 0.427

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.433

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Creb3l3
• Phenotype: mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype; immune system phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: positive regulation of acute inflammatory response;endoplasmic reticulum unfolded protein response;positive regulation of transcription by RNA polymerase II;positive regulation of transcription from RNA polymerase II promoter in response to endoplasmic reticulum stress
• Cellular component: Golgi membrane;nucleus;nucleoplasm;endoplasmic reticulum;endoplasmic reticulum membrane;cytosol;membrane;integral component of membrane
• Molecular function: transcription regulatory region sequence-specific DNA binding;RNA polymerase II regulatory region sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription activator activity, RNA polymerase II-specific;protein binding;cAMP response element binding;protein homodimerization activity;protein heterodimerization activity