REL

REL proto-oncogene, NF-kB subunit, the group of NF-kappa B complex subunits|IPT domain containing

Basic information

Region (hg38): 2:60881490-60931612

Links

ENSG00000162924 ∙ NCBI:5966 ∙ OMIM:164910 ∙ HGNC:9954 ∙ Uniprot:Q04864 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• immunodeficiency 92 (Strong), mode of inheritance: AR
• immunodeficiency 92 (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Immunodeficiency 92	AR	Allergy/Immunology/Infectious;	The condition involves increased risk of severe and early-onset infections, and awareness may allow preventative measures and early and aggressive treatment of infections; HSCT has been described	Allergy/Immunology/Infectious;	31103457; 34623332

ClinVar

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

• not provided (129 variants)
• Inborn genetic diseases (11 variants)
• not specified (2 variants)
• REL-related condition (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the REL 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			1	43	5	49
missense			46	4	2	52
nonsense	1					1
start loss						0
frameshift	1					1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			2	3	1	6
non coding			1	23	6	30
Total	2	0	48	70	13

Variants in REL

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

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

Position	Type	Phenotype	Significance	ClinVar
2-60881846-C-A			Likely benign (Aug 22, 2022)
2-60881858-T-C			Likely benign (Aug 01, 2023)
2-60881860-C-T		REL-related disorder	Likely benign (Jan 11, 2024)
2-60881861-A-T			Benign (Jan 31, 2024)
2-60881862-T-C			Likely benign (Jan 25, 2024)
2-60891604-A-G		not specified	Benign (Jan 24, 2024)
2-60891683-G-A			Uncertain significance (Sep 30, 2023)
2-60891696-G-A			Likely benign (Jan 10, 2024)
2-60891729-G-A			Likely benign (Nov 25, 2023)
2-60891800-A-G			Uncertain significance (Sep 26, 2022)
2-60891804-C-T			Likely benign (Jul 16, 2022)
2-60891805-C-A			Likely benign (Dec 23, 2023)
2-60891810-A-G			Likely benign (Jun 22, 2022)
2-60891842-C-T			Likely benign (Sep 27, 2022)
2-60894357-G-A		not specified	Benign (Jan 24, 2024)
2-60894383-C-T			Likely benign (Oct 15, 2023)
2-60894385-C-T			Likely benign (Oct 13, 2023)
2-60894387-C-G			Likely benign (Jul 10, 2023)
2-60894400-A-G		not specified	Uncertain significance (Mar 01, 2024)
2-60894414-A-G			Benign (Dec 19, 2023)
2-60894419-G-C		not specified	Uncertain significance (Sep 08, 2023)
2-60894426-G-A			Likely benign (Oct 05, 2022)
2-60894435-A-C			Likely benign (Sep 27, 2023)
2-60894435-A-G			Benign (Jan 29, 2024)
2-60894501-C-T			Likely benign (Oct 23, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
REL	protein_coding	protein_coding	ENST00000295025	11	50090

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.998	0.00164	125730	0	10	125740	0.0000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.76	243	333	0.729	0.0000170	4069
Missense in Polyphen		58	135.09	0.42935		1635
Synonymous	0.400	112	118	0.953	0.00000634	1172
Loss of Function	4.51	2	27.5	0.0727	0.00000149	357

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000124	0.000124
Ashkenazi Jewish	0.00	0.00
East Asian	0.000170	0.000163
Finnish	0.00	0.00
European (Non-Finnish)	0.0000265	0.0000264
Middle Eastern	0.000170	0.000163
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Proto-oncogene that may play a role in differentiation and lymphopoiesis. NF-kappa-B is a pleiotropic transcription factor which is present in almost all cell types and is involved in many biological processed such as inflammation, immunity, differentiation, cell growth, tumorigenesis and apoptosis. NF- kappa-B is a homo- or heterodimeric complex formed by the Rel-like domain-containing proteins RELA/p65, RELB, NFKB1/p105, NFKB1/p50, REL and NFKB2/p52. The dimers bind at kappa-B sites in the DNA of their target genes and the individual dimers have distinct preferences for different kappa-B sites that they can bind with distinguishable affinity and specificity. Different dimer combinations act as transcriptional activators or repressors, respectively. NF-kappa-B is controlled by various mechanisms of post-translational modification and subcellular compartmentalization as well as by interactions with other cofactors or corepressors. NF-kappa-B complexes are held in the cytoplasm in an inactive state complexed with members of the NF- kappa-B inhibitor (I-kappa-B) family. In a conventional activation pathway, I-kappa-B is phosphorylated by I-kappa-B kinases (IKKs) in response to different activators, subsequently degraded thus liberating the active NF-kappa-B complex which translocates to the nucleus. The NF-kappa-B heterodimer RELA/p65-c-Rel is a transcriptional activator.
• Pathway: Ras signaling pathway - Homo sapiens (human);Viral carcinogenesis - Homo sapiens (human);Transcriptional misregulation in cancer - Homo sapiens (human);Tacrolimus/Cyclosporine Pathway, Pharmacodynamics;IL-1 signaling pathway;Leptin signaling pathway;B Cell Receptor Signaling Pathway;TNF alpha Signaling Pathway;Photodynamic therapy-induced NF-kB survival signaling;Toll-like Receptor Signaling;Chromosomal and microsatellite instability in colorectal cancer;Ras Signaling;Interferon type I signaling pathways;T-Cell antigen Receptor (TCR) Signaling Pathway;Activation of NF-kappaB in B cells;Signaling by the B Cell Receptor (BCR);Immune System;Adaptive Immune System;Downstream signaling events of B Cell Receptor (BCR);IL1;TNFalpha;RANKL;Regulation of Androgen receptor activity;Atypical NF-kappaB pathway (Consensus)

Recessive Scores

• pRec: 0.362

Intolerance Scores

• loftool: 0.286
• rvis_EVS: -0.69
• rvis_percentile_EVS: 15.12

Haploinsufficiency Scores

• pHI: 0.853
• hipred: Y
• hipred_score: 0.682
• ghis: 0.603

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.567

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Rel
• Phenotype: cellular phenotype; homeostasis/metabolism 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); integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); normal phenotype; hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); growth/size/body region phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); digestive/alimentary phenotype; skeleton phenotype; immune system phenotype; respiratory system phenotype; liver/biliary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); embryo phenotype

Zebrafish Information Network

• Gene name: rel
• Affected structure: trunk
• Phenotype tag: abnormal
• Phenotype quality: curved

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;inflammatory response;I-kappaB kinase/NF-kappaB signaling;negative regulation of gene expression;negative regulation of interferon-beta production;response to cytokine;NIK/NF-kappaB signaling;positive regulation of I-kappaB kinase/NF-kappaB signaling;positive regulation of transcription by RNA polymerase II;negative regulation of neuron death
• Cellular component: nucleus;nucleoplasm;transcription factor complex;cytosol
• Molecular function: RNA polymerase II regulatory region sequence-specific DNA binding;RNA polymerase II distal enhancer sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription activator activity, RNA polymerase II-specific;chromatin binding;DNA-binding transcription factor activity;protein binding