HMGB2
high mobility group box 2, the group of Canonical high mobility group|SET complex
Basic information
Region (hg38): 4:173331376-173334432
Previous symbols: [ "HMG2" ]
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the HMGB2 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 | 9 | |||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 0 | |||||
| non coding | 0 | |||||
| Total | 0 | 0 | 9 | 0 | 0 |
Variants in HMGB2
This is a list of pathogenic ClinVar variants found in the HMGB2 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 4-173332109-C-T | not specified | Uncertain significance (Aug 17, 2022) | ||
| 4-173332119-T-A | not specified | Uncertain significance (Mar 20, 2024) | ||
| 4-173332143-A-C | not specified | Uncertain significance (Feb 10, 2023) | ||
| 4-173332154-C-T | not specified | Uncertain significance (Jan 23, 2023) | ||
| 4-173332217-T-C | not specified | Uncertain significance (Sep 16, 2021) | ||
| 4-173332919-T-C | not specified | Uncertain significance (Apr 19, 2024) | ||
| 4-173332948-C-T | not specified | Uncertain significance (Oct 04, 2024) | ||
| 4-173333149-G-T | not specified | Uncertain significance (Sep 20, 2024) | ||
| 4-173333197-C-A | not specified | Uncertain significance (Jan 23, 2024) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| HMGB2 | protein_coding | protein_coding | ENST00000296503 | 4 | 3431 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.951 | 0.0490 | 125718 | 0 | 2 | 125720 | 0.00000795 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 1.61 | 66 | 115 | 0.576 | 0.00000540 | 1406 |
| Missense in Polyphen | 12 | 23.66 | 0.50718 | 331 | ||
| Synonymous | -1.21 | 50 | 40.3 | 1.24 | 0.00000198 | 343 |
| Loss of Function | 2.85 | 0 | 9.48 | 0.00 | 4.67e-7 | 128 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00 | 0.00 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000176 | 0.0000176 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Multifunctional protein with various roles in different cellular compartments. May act in a redox sensitive manner. In the nucleus is an abundant chromatin-associated non-histone protein involved in transcription, chromatin remodeling and V(D)J recombination and probably other processes. Binds DNA with a preference to non-canonical DNA structures such as single-stranded DNA. Can bent DNA and enhance DNA flexibility by looping thus providing a mechanism to promote activities on various gene promoters by enhancing transcription factor binding and/or bringing distant regulatory sequences into close proximity (PubMed:7797075, PubMed:11909973, PubMed:19522541, PubMed:18413230, PubMed:19965638, PubMed:20123072). Involved in V(D)J recombination by acting as a cofactor of the RAG complex: acts by stimulating cleavage and RAG protein binding at the 23 bp spacer of conserved recombination signal sequences (RSS) (By similarity). Proposed to be involved in the innate immune response to nucleic acids by acting as a promiscuous immunogenic DNA/RNA sensor which cooperates with subsequent discriminative sensing by specific pattern recognition receptors (By similarity). In the extracellular compartment acts as a chemokine. Promotes proliferation and migration of endothelial cells implicating AGER/RAGE (PubMed:19811285). Has antimicrobial activity in gastrointestinal epithelial tissues (PubMed:23877675). Involved in inflammatory response to antigenic stimulus coupled with proinflammatory activity (By similarity). Involved in modulation of neurogenesis probably by regulation of neural stem proliferation (By similarity). Involved in articular cartilage surface maintenance implicating LEF1 and the Wnt/beta-catenin pathway (By similarity). {ECO:0000250|UniProtKB:P09429, ECO:0000250|UniProtKB:P30681, ECO:0000269|PubMed:11909973, ECO:0000269|PubMed:18413230, ECO:0000269|PubMed:19522541, ECO:0000269|PubMed:19811285, ECO:0000269|PubMed:19965638, ECO:0000269|PubMed:23877675, ECO:0000269|PubMed:7797075, ECO:0000305|PubMed:20123072}.;
- Pathway
- Retinoblastoma (RB) in Cancer;Ectoderm Differentiation;granzyme a mediated apoptosis pathway;apoptotic dna-fragmentation and tissue homeostasis;Activation of DNA fragmentation factor;Apoptosis induced DNA fragmentation;Apoptotic execution phase;Apoptosis;Programmed Cell Death
(Consensus)
Recessive Scores
- pRec
- 0.221
Intolerance Scores
- loftool
- 0.0678
- rvis_EVS
- -0.03
- rvis_percentile_EVS
- 51.04
Haploinsufficiency Scores
- pHI
- 0.940
- hipred
- Y
- hipred_score
- 0.728
- ghis
- 0.709
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.955
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Hmgb2
- Phenotype
- endocrine/exocrine gland phenotype; cellular phenotype; reproductive system phenotype;
Gene ontology
- Biological process
- positive regulation of endothelial cell proliferation;inflammatory response to antigenic stimulus;DNA topological change;apoptotic DNA fragmentation;DNA recombination;chromatin organization;nucleosome assembly;chromatin remodeling;regulation of transcription by RNA polymerase II;spermatid nucleus differentiation;male gonad development;positive regulation of nuclease activity;DNA geometric change;response to lipopolysaccharide;positive regulation of interferon-beta production;V(D)J recombination;response to drug;positive regulation of DNA binding;innate immune response;positive regulation of innate immune response;positive regulation of erythrocyte differentiation;positive regulation of megakaryocyte differentiation;negative regulation of transcription, DNA-templated;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;response to steroid hormone;regulation of neurogenesis;defense response to Gram-negative bacterium;defense response to Gram-positive bacterium;positive chemotaxis;DNA ligation involved in DNA repair;cell chemotaxis;cellular response to lipopolysaccharide;regulation of stem cell proliferation;negative regulation of extrinsic apoptotic signaling pathway via death domain receptors
- Cellular component
- nuclear chromatin;condensed chromosome;extracellular space;cell;nucleus;nucleoplasm;nucleolus;cytoplasm;protein-containing complex;perinuclear region of cytoplasm
- Molecular function
- four-way junction DNA binding;enhancer sequence-specific DNA binding;DNA binding;damaged DNA binding;double-stranded DNA binding;single-stranded DNA binding;transcription coactivator activity;RNA binding;protein binding;transcription factor binding;drug binding;DNA binding, bending;protein domain specific binding;chemoattractant activity;transcription regulatory region DNA binding;non-sequence-specific DNA binding, bending;RAGE receptor binding;supercoiled DNA binding