HMGB3

high mobility group box 3, the group of Canonical high mobility group

Basic information

Region (hg38): X:150980509-150990771

Previous symbols: [ "HMG4" ]

Links

ENSG00000029993 ∙ NCBI:3149 ∙ OMIM:300193 ∙ HGNC:5004 ∙ Uniprot:O15347 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• X-linked colobomatous microphthalmia-microcephaly-intellectual disability-short stature syndrome (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Microphthalmia, syndromic 13	XL	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Dental; Musculoskeletal; Neurologic; Ophthalmologic	4998085; 24993872

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the HMGB3 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HMGB3 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	1	3
missense			3			3
nonsense						0
start loss						0
frameshift			2			2
inframe indel			1	1	1	3
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding				1		1
Total	0	0	6	4	2

Variants in HMGB3

This is a list of pathogenic ClinVar variants found in the HMGB3 region.

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

Position	Type	Phenotype	Significance	ClinVar
X-150985685-A-G		not specified	Uncertain significance (Dec 28, 2023)
X-150985686-GA-G			Uncertain significance (Jan 20, 2017)
X-150985715-C-T		not specified	Uncertain significance (Feb 10, 2022)
X-150986060-G-A		not specified	Uncertain significance (Apr 04, 2024)
X-150987788-C-CTA		X-linked colobomatous microphthalmia-microcephaly-intellectual disability-short stature syndrome	Uncertain significance (Jun 24, 2023)
X-150987797-G-A			Likely benign (Aug 29, 2023)
X-150987804-A-C		not specified	Uncertain significance (Jan 26, 2022)
X-150987866-A-G			Benign (Jan 19, 2024)
X-150987884-AGAG-A		HMGB3-related disorder	Benign (Aug 08, 2019)
X-150987884-AGAGGAG-A		HMGB3-related disorder	Likely benign (Nov 02, 2022)
X-150987884-A-AGAG			Uncertain significance (Apr 16, 2023)
X-150987887-G-A		HMGB3-related disorder	Likely benign (Jun 18, 2019)
X-150987913-AAAG-A		HMGB3-related disorder	Likely benign (Apr 01, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HMGB3	protein_coding	protein_coding	ENST00000325307	4	10267

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.798	0.197	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.78	32	75.4	0.424	0.00000596	1340
Missense in Polyphen		0	12.781	0		328
Synonymous	-1.86	39	26.8	1.46	0.00000213	331
Loss of Function	2.13	0	5.29	0.00	3.98e-7	118

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)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Multifunctional protein with various roles in different cellular compartments. May act in a redox sensitive manner. Associates with chromatin and 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 similarity). Proposed to be involved in the innate immune response to nucleic acids by acting as a cytoplasmic promiscuous immunogenic DNA/RNA sensor (By similarity). Negatively regulates B-cell and myeloid cell differentiation. In hematopoietic stem cells may regulate the balance between self-renewal and differentiation. Involved in negative regulation of canonical Wnt signaling (By similarity). {ECO:0000250|UniProtKB:O54879, ECO:0000250|UniProtKB:P09429, ECO:0000250|UniProtKB:P40618}.
• Disease: DISEASE: Microphthalmia, syndromic, 13 (MCOPS13) [MIM:300915]: A form of microphthalmia, a disorder of eye formation, ranging from small size of a single eye to complete bilateral absence of ocular tissues (anophthalmia). In many cases, microphthalmia/anophthalmia occurs in association with syndromes that include non-ocular abnormalities. MCOPS13 patients exhibit colobomatous microphthalmia with microcephaly, short stature, and psychomotor retardation. {ECO:0000269|PubMed:24993872}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.142

Intolerance Scores

• loftool: 0.172
• rvis_EVS: -0.03
• rvis_percentile_EVS: 51.04

Haploinsufficiency Scores

• pHI: 0.935
• hipred: Y
• hipred_score: 0.549
• ghis: 0.488

Essentials

• essential_gene_CRISPR: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.307

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Hmgb3
• Phenotype: normal phenotype; hematopoietic system phenotype; immune system phenotype

Gene ontology

• Biological process: DNA recombination;chromatin remodeling;regulation of transcription by RNA polymerase II;multicellular organism development;DNA geometric change;innate immune response;positive regulation of innate immune response;positive regulation of transcription by RNA polymerase II
• Cellular component: nuclear chromatin;cytoplasm
• Molecular function: four-way junction DNA binding;double-stranded DNA binding;RNA binding;protein binding;transcription factor binding;DNA binding, bending