GeneBe

HMGB2

protein-coding

high mobility group box 2, the group of Canonical high mobility group|SET complex

Gene summary

This gene encodes a member of the non-histone chromosomal high mobility group protein family. The proteins of this family are chromatin-associated and ubiquitously distributed in the nucleus of higher eukaryotic cells. In vitro studies have demonstrated that this protein is able to efficiently bend DNA and form DNA circles. These studies suggest a role in facilitating cooperative interactions between cis-acting proteins by promoting DNA flexibility. This protein was also reported to be involved in the final ligation step in DNA end-joining processes of DNA double-strand breaks repair and V(D)J recombination. [provided by RefSeq, Jul 2008]

Previous symbols:
  • HMG2

MANE transcript

NM_002129.4

Inheritance

—

ClinVar variants

U:13

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chr4:173,331,376-173,334,432

External References & Databases

Ensembl (ENSG00000164104)NCBI Gene (3148)OMIM (163906)HGNC:5000GenCCUniProt (P26583)AlphaFoldClinVar (HMGB2)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~3.1 kb
Loading mutation effect viewer...

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 HMGB2 variants in ClinVar

1 Conditions Cataloged
not specifiedTotal: 10

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002129.4. 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.

EffectPLPVUSLBBSum
synonymous
1
clinvar
 1
missense
10
clinvar
 10
nonsense
0
start loss
0
frameshift
0
splice donor/acceptor (+/-2bp)
2
clinvar
 2
Total00130013
Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 42 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_002129.4RefSeqNP_002120.14MANE Select
ENST00000296503.10EnsemblENSP00000296503.54MANE Select
NM_001130688.1RefSeqNP_001124160.14Standard
NM_001130689.1RefSeqNP_001124161.14Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Retinoblastoma (RB) in Cancer
  • Ectoderm Differentiation
  • granzyme a mediated apoptosis pathway
  • apoptotic dna-fragmentation and tissue homeostasis
  • Activation of DNA fragmentation factor

Biological Process

  • positive regulation of endothelial cell proliferation
  • inflammatory response to antigenic stimulus
  • DNA topological change
  • apoptotic DNA fragmentation
  • DNA recombination

Molecular Function

  • four-way junction DNA binding
  • enhancer sequence-specific DNA binding
  • DNA binding
  • damaged DNA binding
  • double-stranded DNA binding

Cellular Component

  • nuclear chromatin
  • condensed chromosome
  • extracellular space
  • cell
  • nucleus

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000296503
Coding exons
4
Length
3431
Individuals with no LoFs
125718
Homozygous LoFs
0
Heterozygous LoFs
2
Defined
125720
p
0.00000795
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense1.61661150.5760.000005401406
Missense (PolyPhen)1223.660.50718331
Synonymous-1.215040.31.240.00000198343
Loss of Function2.8509.480.004.67e-7128

Population LoF Frequency

PopulationCAFp-valueStatus
African00.0absent
Latino/Admixed American00.0absent
Ashkenazi Jewish00.0absent
East Asian00.0absent
Finnish00.0absent
European (Non-Finnish)0.0000180.000018rare
South Asian00.0absent
Other00.0absent

dbNSFP Gene Annotations

Source: dbNSFP

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}.;

Recessive Scores

pRec
0.221

Intolerance Scores

LoFtool
0.0678
RVIS EVS
-0.03
RVIS percentile EVS
51.04

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.955

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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