HSPB1

heat shock protein family B (small) member 1, the group of Small heat shock proteins

Basic information

Region (hg38): 7:76302672-76304295

Links

ENSG00000106211 ∙ NCBI:3315 ∙ OMIM:602195 ∙ HGNC:5246 ∙ Uniprot:P04792 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• neuronopathy, distal hereditary motor, type 2B (Moderate), mode of inheritance: AD
• Charcot-Marie-Tooth disease axonal type 2F (Supportive), mode of inheritance: AD
• distal hereditary motor neuropathy type 2 (Supportive), mode of inheritance: AD
• Charcot-Marie-Tooth disease axonal type 2F (Definitive), mode of inheritance: AD
• Charcot-Marie-Tooth disease axonal type 2F (Strong), mode of inheritance: AD
• Charcot-Marie-Tooth disease axonal type 2F (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neuronopathy, distal hereditary motor, autosomal dominant 3; Charcot-Marie-Tooth disease, axonal, type 2F	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	11528513; 15122254; 16087758; 18325928; 18832141; 18952241; 20301462; 20870250; 22176143

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the HSPB1 gene.

• Charcot-Marie-Tooth disease axonal type 2F (245 variants)
• not provided (90 variants)
• Inborn genetic diseases (55 variants)
• Charcot-Marie-Tooth disease (43 variants)
• Neuronopathy, distal hereditary motor, type 2B (38 variants)
• not specified (22 variants)
• HSPB1-related axonal neuropathies (2 variants)
• Charcot-Marie-Tooth disease axonal type 2F;Neuronopathy, distal hereditary motor, type 2B (2 variants)
• Hereditary peripheral neuropathy (1 variants)
• HSPB1-Related Disorder (1 variants)
• Charcot-Marie-Tooth disease type 4 (1 variants)
• HSPB1-Related Disorders (1 variants)
• Charcot-Marie-Tooth disease dominant intermediate C (1 variants)
• Charcot-Marie-Tooth disease type 2 (1 variants)
• Neuronopathy, distal hereditary motor (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HSPB1 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			4	52	1	57
missense	8	7	120	3	1	139
nonsense	1	3	3			7
start loss			3			3
frameshift	2	6	5			13
inframe indel			7			7
splice donor/acceptor (+/-2bp)						0
splice region			6	9	1	16
non coding	2	3	6	25	4	40
Total	13	19	148	80	6

Highest pathogenic variant AF is 0.00000704

Variants in HSPB1

This is a list of pathogenic ClinVar variants found in the HSPB1 region.

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

Position	Type	Phenotype	Significance	ClinVar
7-76302694-C-T		not specified • Neuronopathy, distal hereditary motor, type 2B • Charcot-Marie-Tooth disease axonal type 2F • Charcot-Marie-Tooth disease	Benign/Likely benign (Aug 01, 2023)
7-76302698-G-A		not specified • Charcot-Marie-Tooth disease • Inborn genetic diseases	Conflicting classifications of pathogenicity (Apr 06, 2023)
7-76302708-C-T		Charcot-Marie-Tooth disease	Likely benign (-)
7-76302709-C-T		Neuronopathy, distal hereditary motor, type 2B • Charcot-Marie-Tooth disease axonal type 2F • Charcot-Marie-Tooth disease	Conflicting classifications of pathogenicity (Jan 12, 2018)
7-76302713-A-C		Charcot-Marie-Tooth disease axonal type 2F	Uncertain significance (Oct 06, 2023)
7-76302714-TG-CA		Inborn genetic diseases	Uncertain significance (Feb 25, 2021)
7-76302715-G-A		Charcot-Marie-Tooth disease axonal type 2F • Inborn genetic diseases	Conflicting classifications of pathogenicity (May 23, 2023)
7-76302719-G-A		Charcot-Marie-Tooth disease axonal type 2F	Uncertain significance (Dec 10, 2020)
7-76302719-G-C		Inborn genetic diseases	Uncertain significance (Dec 12, 2019)
7-76302721-G-A		not specified • Charcot-Marie-Tooth disease axonal type 2F • Neuronopathy, distal hereditary motor, type 2B • Charcot-Marie-Tooth disease • Inborn genetic diseases • HSPB1-related disorder	Benign/Likely benign (Mar 01, 2024)
7-76302723-G-A		Charcot-Marie-Tooth disease axonal type 2F	Uncertain significance (Feb 13, 2023)
7-76302728-G-A		Charcot-Marie-Tooth disease axonal type 2F • Inborn genetic diseases	Conflicting classifications of pathogenicity (Jan 18, 2024)
7-76302728-G-T		Charcot-Marie-Tooth disease axonal type 2F	Uncertain significance (Dec 30, 2023)
7-76302729-T-C		Charcot-Marie-Tooth disease axonal type 2F • Inborn genetic diseases	Uncertain significance (Jun 04, 2022)
7-76302730-C-G		Charcot-Marie-Tooth disease axonal type 2F	Likely benign (Nov 22, 2023)
7-76302731-C-G			Uncertain significance (Jul 17, 2023)
7-76302731-C-T		Neuronopathy, distal hereditary motor, type 2B • Charcot-Marie-Tooth disease axonal type 2F	Conflicting classifications of pathogenicity (May 11, 2023)
7-76302732-C-G		Charcot-Marie-Tooth disease axonal type 2F	Likely pathogenic (Oct 24, 2020)
7-76302732-C-T			Uncertain significance (Jan 10, 2018)
7-76302733-C-T		Charcot-Marie-Tooth disease axonal type 2F	Likely benign (Aug 14, 2023)
7-76302736-C-T		not specified • Neuronopathy, distal hereditary motor, type 2B • Charcot-Marie-Tooth disease axonal type 2F • Inborn genetic diseases	Benign/Likely benign (Feb 01, 2024)
7-76302739-G-T		Charcot-Marie-Tooth disease axonal type 2F	Likely benign (Apr 05, 2019)
7-76302741-T-A		Charcot-Marie-Tooth disease axonal type 2F	Uncertain significance (Dec 25, 2023)
7-76302745-G-C		Charcot-Marie-Tooth disease axonal type 2F	Likely benign (Mar 14, 2021)
7-76302748-G-T		not specified • Neuronopathy, distal hereditary motor, type 2B • Inborn genetic diseases • Charcot-Marie-Tooth disease axonal type 2F	Benign/Likely benign (Jan 24, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HSPB1	protein_coding	protein_coding	ENST00000248553	3	1752

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.78e-7	0.0948	125520	0	27	125547	0.000108

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.515	136	120	1.13	0.00000590	1275
Missense in Polyphen		39	37.73	1.0337		420
Synonymous	-2.68	79	54.0	1.46	0.00000277	427
Loss of Function	-0.633	9	7.17	1.26	3.18e-7	71

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000269	0.000268
Ashkenazi Jewish	0.00	0.00
East Asian	0.000164	0.000163
Finnish	0.00	0.00
European (Non-Finnish)	0.000136	0.000132
Middle Eastern	0.000164	0.000163
South Asian	0.0000654	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Small heat shock protein which functions as a molecular chaperone probably maintaining denatured proteins in a folding- competent state (PubMed:10383393, PubMed:20178975). Plays a role in stress resistance and actin organization (PubMed:19166925). Through its molecular chaperone activity may regulate numerous biological processes including the phosphorylation and the axonal transport of neurofilament proteins (PubMed:23728742). {ECO:0000269|PubMed:10383393, ECO:0000269|PubMed:19166925, ECO:0000269|PubMed:20178975, ECO:0000269|PubMed:23728742}.
• Disease: DISEASE: Charcot-Marie-Tooth disease 2F (CMT2F) [MIM:606595]: A dominant axonal form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Neuropathies of the CMT2 group are characterized by signs of axonal degeneration in the absence of obvious myelin alterations, normal or slightly reduced nerve conduction velocities, and progressive distal muscle weakness and atrophy. Onset of Charcot-Marie-Tooth disease type 2F is between 15 and 25 years with muscle weakness and atrophy usually beginning in feet and legs (peroneal distribution). Upper limb involvement occurs later. {ECO:0000269|PubMed:15122254, ECO:0000269|PubMed:20178975, ECO:0000269|PubMed:22176143, ECO:0000269|PubMed:22206013, ECO:0000269|PubMed:23728742}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Neuronopathy, distal hereditary motor, 2B (HMN2B) [MIM:608634]: 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:15122254, ECO:0000269|PubMed:18832141, ECO:0000269|PubMed:18952241, ECO:0000269|PubMed:20178975, ECO:0000269|PubMed:20870250, ECO:0000269|PubMed:22176143, ECO:0000269|PubMed:23643870, ECO:0000269|PubMed:23728742, ECO:0000269|PubMed:23948568, ECO:0000269|PubMed:25965061, ECO:0000269|PubMed:28144995}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: VEGF signaling pathway - Homo sapiens (human);Amoebiasis - Homo sapiens (human);MAPK signaling pathway - Homo sapiens (human);Epstein-Barr virus infection - Homo sapiens (human);Apoptosis-related network due to altered Notch3 in ovarian cancer;Fas Ligand (FasL) pathway and Stress induction of Heat Shock Proteins (HSP) regulation;Cellular response to heat stress;MAPK Signaling Pathway;ATM Signaling Network in Development and Disease;VEGFA-VEGFR2 Signaling Pathway;p38 MAPK Signaling Pathway;Signal Transduction;HSF1 activation;Attenuation phase;HSF1-dependent transactivation;p38 mapk signaling pathway;downregulated of mta-3 in er-negative breast tumors;stress induction of hsp regulation;Regulation of HSF1-mediated heat shock response;MAPK6/MAPK4 signaling;Cellular responses to stress;AUF1 (hnRNP D0) binds and destabilizes mRNA;Metabolism of RNA;AndrogenReceptor;Cellular responses to external stimuli;MAPK family signaling cascades;Cellular response to heat stress;IL6;TNFalpha;Regulation of mRNA stability by proteins that bind AU-rich elements;Signaling mediated by p38-alpha and p38-beta;p38 signaling mediated by MAPKAP kinases (Consensus)

Recessive Scores

• pRec: 0.796

Haploinsufficiency Scores

• pHI: 0.498
• hipred: Y
• hipred_score: 0.728
• ghis: 0.468

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.992

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Hspb1
• Phenotype: 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); immune system phenotype; growth/size/body region phenotype; cellular phenotype; homeostasis/metabolism phenotype

Zebrafish Information Network

• Gene name: hspb1
• Affected structure: peripheral neuron
• Phenotype tag: abnormal
• Phenotype quality: branchiness

Gene ontology

• Biological process: retina homeostasis;regulation of protein phosphorylation;regulation of translational initiation;negative regulation of protein kinase activity;response to unfolded protein;response to virus;regulation of autophagy;positive regulation of interleukin-1 beta production;intracellular signal transduction;cellular response to vascular endothelial growth factor stimulus;positive regulation of endothelial cell chemotaxis by VEGF-activated vascular endothelial growth factor receptor signaling pathway;positive regulation of tumor necrosis factor biosynthetic process;negative regulation of apoptotic process;regulation of I-kappaB kinase/NF-kappaB signaling;regulation of mRNA stability;positive regulation of blood vessel endothelial cell migration;positive regulation of angiogenesis;chaperone-mediated protein folding;platelet aggregation;negative regulation of protein serine/threonine kinase activity;anterograde axonal protein transport;negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway;positive regulation of endothelial cell chemotaxis
• Cellular component: proteasome complex;extracellular space;nucleus;cytoplasm;spindle;cytosol;cytoskeleton;plasma membrane;focal adhesion;Z disc;extracellular exosome;axon cytoplasm
• Molecular function: RNA binding;protein kinase C binding;protein binding;protein kinase C inhibitor activity;protein kinase binding;identical protein binding;protein homodimerization activity;ubiquitin binding;protein folding chaperone