CREB3L2

cAMP responsive element binding protein 3 like 2, the group of CREB3 transcription factor family

Basic information

Region (hg38): 7:137874978-138002086

Links

ENSG00000182158 ∙ NCBI:64764 ∙ OMIM:608834 ∙ HGNC:23720 ∙ Uniprot:Q70SY1 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CREB3L2 gene.

• Inborn genetic diseases (19 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CREB3L2 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						0
missense			18	1		19
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	18	1	0

Variants in CREB3L2

This is a list of pathogenic ClinVar variants found in the CREB3L2 region.

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

Position	Type	Phenotype	Significance	ClinVar
7-137880547-T-C		not specified	Uncertain significance (Sep 22, 2023)
7-137880549-A-T		not specified	Uncertain significance (Dec 19, 2022)
7-137882458-C-T		not specified	Uncertain significance (Nov 13, 2023)
7-137882493-G-A		not specified	Uncertain significance (Jan 03, 2024)
7-137882545-C-T		not specified	Uncertain significance (Mar 23, 2023)
7-137882568-G-A		not specified	Uncertain significance (May 30, 2023)
7-137882586-G-A		not specified	Likely benign (Apr 22, 2022)
7-137882587-G-T		not specified	Uncertain significance (Apr 06, 2022)
7-137882595-T-C		not specified	Uncertain significance (Aug 11, 2022)
7-137884998-C-T		not specified	Uncertain significance (Jul 12, 2023)
7-137885072-T-C		not specified	Uncertain significance (Jul 08, 2022)
7-137885100-C-T		not specified	Uncertain significance (Feb 17, 2022)
7-137885443-G-A		not specified	Uncertain significance (Oct 14, 2021)
7-137885479-T-C		not specified	Uncertain significance (Sep 20, 2023)
7-137885502-C-G		not specified	Uncertain significance (May 16, 2023)
7-137908262-G-A		not specified	Uncertain significance (Jan 31, 2024)
7-137908298-C-T		not specified	Uncertain significance (Apr 18, 2023)
7-137908313-G-C		not specified	Uncertain significance (Sep 28, 2021)
7-137908400-G-A		not specified	Uncertain significance (Nov 12, 2021)
7-137915880-G-T		not specified	Uncertain significance (Aug 10, 2021)
7-137915917-C-T		not specified	Uncertain significance (Jun 11, 2021)
7-137916007-C-T		not specified	Uncertain significance (Jan 31, 2024)
7-137928179-T-C		not specified	Uncertain significance (Oct 30, 2023)
7-137928191-G-C		not specified	Uncertain significance (Jan 24, 2023)
7-137928200-C-T		not specified	Uncertain significance (Apr 14, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CREB3L2	protein_coding	protein_coding	ENST00000330387	12	127089

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00153	0.997	125708	0	40	125748	0.000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.0304	260	261	0.995	0.0000140	3339
Missense in Polyphen		125	127.74	0.97853		1675
Synonymous	0.401	112	118	0.953	0.00000731	1067
Loss of Function	2.83	9	23.9	0.376	0.00000108	312

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000362	0.000362
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000586	0.0000544
Finnish	0.0000465	0.0000462
European (Non-Finnish)	0.000106	0.000105
Middle Eastern	0.0000586	0.0000544
South Asian	0.000555	0.000555
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Transcription factor involved in unfolded protein response (UPR). In the absence of endoplasmic reticulum (ER) stress, inserted into ER membranes, with N-terminal DNA-binding and transcription activation domains oriented toward the cytosolic face of the membrane. In response to ER stress, transported to the Golgi, where it is cleaved in a site-specific manner by resident proteases S1P/MBTPS1 and S2P/MBTPS2. The released N-terminal cytosolic domain is translocated to the nucleus to effect transcription of specific target genes. Plays a critical role in chondrogenesis by activating the transcription of SEC23A, which promotes the transport and secretion of cartilage matrix proteins, and possibly that of ER biogenesis-related genes (By similarity). In a neuroblastoma cell line, protects cells from ER stress- induced death (PubMed:17178827). In vitro activates transcription of target genes via direct binding to the CRE site (PubMed:17178827). {ECO:0000250|UniProtKB:Q8BH52, ECO:0000269|PubMed:17178827}.
• Disease: DISEASE: Note=A chromosomal aberration involving CREB3L2 is found in low grade fibromyxoid sarcoma (LGFMS). Translocation t(7;16)(q33;p11) with FUS.
• 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;TYROBP Causal Network;PI3K-Akt Signaling Pathway;Unfolded Protein Response (UPR);Metabolism of proteins;CREB3 factors activate genes (Consensus)

Recessive Scores

• pRec: 0.136

Intolerance Scores

• loftool: 0.640
• rvis_EVS: -0.69
• rvis_percentile_EVS: 15.2

Haploinsufficiency Scores

• pHI: 0.272
• hipred: Y
• hipred_score: 0.609
• ghis: 0.576

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.831

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Creb3l2
• Phenotype: craniofacial phenotype; growth/size/body region phenotype; skeleton phenotype; digestive/alimentary phenotype; limbs/digits/tail 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)

Zebrafish Information Network

• Gene name: creb3l2
• Affected structure: melanocyte
• Phenotype tag: abnormal
• Phenotype quality: immature

Gene ontology

• Biological process: chondrocyte differentiation;endoplasmic reticulum to Golgi vesicle-mediated transport;response to wounding;positive regulation of neuron projection development;endoplasmic reticulum unfolded protein response;response to endoplasmic reticulum stress;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;cartilage development
• Cellular component: chromatin;nucleus;nucleoplasm;endoplasmic reticulum;endoplasmic reticulum membrane;integral component of membrane;perinuclear endoplasmic reticulum
• Molecular function: DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription activator activity, RNA polymerase II-specific;cAMP response element binding;transcription regulatory region DNA binding