HSPB3

heat shock protein family B (small) member 3, the group of Small heat shock proteins

Basic information

Region (hg38): 5:54455698-54456377

Links

ENSG00000169271 ∙ NCBI:8988 ∙ OMIM:604624 ∙ HGNC:5248 ∙ Uniprot:Q12988 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• neuronopathy, distal hereditary motor, type 2C (Limited), mode of inheritance: AD
• distal hereditary motor neuropathy type 2 (Supportive), mode of inheritance: AD
• neuronopathy, distal hereditary motor, type 2C (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neuronopathy, distal hereditary motor, autosomal dominant 4	AD	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	Neurologic	20142617

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the HSPB3 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HSPB3 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	11	2	14
missense			22	4	1	27
nonsense			2			2
start loss			2			2
frameshift			2			2
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			6	2		8
Total	0	0	35	17	3

Variants in HSPB3

This is a list of pathogenic ClinVar variants found in the HSPB3 region.

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

Position	Type	Phenotype	Significance	ClinVar
5-54455701-T-C		Neuronopathy, distal hereditary motor, type 2C	Uncertain significance (Jan 13, 2018)
5-54455723-C-T		Neuronopathy, distal hereditary motor, type 2C	Uncertain significance (Apr 27, 2017)
5-54455773-C-A		Neuronopathy, distal hereditary motor, type 2C	Likely benign (Jan 13, 2018)
5-54455790-A-G			Uncertain significance (Aug 21, 2015)
5-54455791-T-C		Neuronopathy, distal hereditary motor, type 2C	Uncertain significance (Nov 20, 2023)
5-54455810-G-T		Neuronopathy, distal hereditary motor, type 2C	Likely benign (Jan 11, 2024)
5-54455814-C-T		Neuronopathy, distal hereditary motor, type 2C	Uncertain significance (Dec 17, 2021)
5-54455826-C-T		Neuronopathy, distal hereditary motor, type 2C	Uncertain significance (Feb 10, 2023)
5-54455832-C-T			Uncertain significance (Jan 04, 2021)
5-54455856-C-T		Neuronopathy, distal hereditary motor, type 2C	Uncertain significance (May 25, 2023)
5-54455857-G-A		Neuronopathy, distal hereditary motor, type 2C	Uncertain significance (Jan 20, 2024)
5-54455879-G-T		Neuronopathy, distal hereditary motor, type 2C	Likely benign (May 15, 2020)
5-54455881-A-G		Neuronopathy, distal hereditary motor, type 2C	Uncertain significance (Jul 12, 2023)
5-54455886-G-GC		Neuronopathy, distal hereditary motor, type 2C	Uncertain significance (Aug 23, 2023)
5-54455895-G-T		not specified	Uncertain significance (Nov 06, 2023)
5-54455916-G-A		Neuronopathy, distal hereditary motor, type 2C	Uncertain significance (Jun 29, 2022)
5-54455933-C-A		Neuronopathy, distal hereditary motor, type 2C	Likely benign (Jun 04, 2022)
5-54455947-C-A		Neuronopathy, distal hereditary motor, type 2C	Uncertain significance (Jan 12, 2018)
5-54455953-C-T		not specified	Uncertain significance (Jan 17, 2024)
5-54455959-A-T		not specified	Uncertain significance (May 11, 2022)
5-54455965-C-T		Neuronopathy, distal hereditary motor, type 2C	Uncertain significance (Jun 19, 2023)
5-54455966-G-A		Neuronopathy, distal hereditary motor, type 2C	Likely benign (Jul 13, 2022)
5-54455972-G-A		Neuronopathy, distal hereditary motor, type 2C	Likely benign (Jul 31, 2020)
5-54455974-C-T		Neuronopathy, distal hereditary motor, type 2C	Uncertain significance (Feb 06, 2023)
5-54455983-G-A		Neuronopathy, distal hereditary motor, type 2C	Uncertain significance (Jul 20, 2017)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HSPB3	protein_coding	protein_coding	ENST00000302005	1	763

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000609	0.288	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.0360	80	80.9	0.989	0.00000477	966
Missense in Polyphen		32	35.276	0.90713		422
Synonymous	-0.495	37	33.4	1.11	0.00000223	315
Loss of Function	-0.246	6	5.38	1.11	4.83e-7	44

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: Inhibitor of actin polymerization.
• Disease: DISEASE: Neuronopathy, distal hereditary motor, 2C (HMN2C) [MIM:613376]: A neuromuscular disorder. Distal hereditary motor neuronopathies constitute a heterogeneous group of neuromuscular disorders caused by selective degeneration of motor neurons in the anterior horn of the spinal cord, without sensory deficit in the posterior horn. The overall clinical picture consists of a classical distal muscular atrophy syndrome in the legs without clinical sensory loss. The disease starts with weakness and wasting of distal muscles of the anterior tibial and peroneal compartments of the legs. Later on, weakness and atrophy may expand to the proximal muscles of the lower limbs and/or to the distal upper limbs. {ECO:0000269|PubMed:20142617}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.103

Intolerance Scores

• loftool: 0.478
• rvis_EVS: -0.12
• rvis_percentile_EVS: 44.89

Haploinsufficiency Scores

• pHI: 0.179
• hipred: N
• hipred_score: 0.251
• ghis: 0.496

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.676

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Hspb3
• Phenotype: homeostasis/metabolism phenotype

Gene ontology

• Biological process: response to unfolded protein
• Cellular component: nucleus;cytoplasm