HSPB8

heat shock protein family B (small) member 8, the group of Small heat shock proteins

Basic information

Region (hg38): 12:119171555-119224855

Links

ENSG00000152137

∙ NCBI:26353 ∙ OMIM:608014 ∙ HGNC:30171 ∙ Uniprot:Q9UJY1 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

Charcot-Marie-Tooth disease axonal type 2L (Supportive), mode of inheritance: AD
distal hereditary motor neuropathy type 2 (Supportive), mode of inheritance: AD
autosomal dominant distal axonal motor neuropathy-myofibrillar myopathy syndrome (Supportive), mode of inheritance: AD
neuronopathy, distal hereditary motor, type 2A (Strong), mode of inheritance: AD
Charcot-Marie-Tooth disease axonal type 2L (Strong), mode of inheritance: AD
neuronopathy, distal hereditary motor, autosomal dominant (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Charcot-Marie-Tooth disease, axonal, type 2L; Neuronopathy, distal hereditary motor, autosomal dominant 2; Myopathy, myofibrillar, 13, with rimmed vacuoles	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	Musculoskeletal; Neurologic	1517763; 15122253; 15021985; 15565283; 18325928; 20538880; 21985219; 26718575; 28501893; 31403083; 32165108; 33744911; 36854646; 39548192

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the HSPB8 gene.

Charcot-Marie-Tooth_disease_axonal_type_2L (183 variants)
not_provided (48 variants)
Inborn_genetic_diseases (36 variants)
Neuronopathy,_distal_hereditary_motor,_type_2A (18 variants)
not_specified (12 variants)
Myopathy,_myofibrillar,_13,_with_rimmed_vacuoles (8 variants)
HSPB8-related_disorder (4 variants)
Charcot-Marie-Tooth_disease (4 variants)
Peripheral_neuropathy (1 variants)
Distal_myopathy (1 variants)
See_cases (1 variants)
. (1 variants)
HSPB8-related_neuromuscular_disorder (1 variants)
Myopathy,_autophagic_vacuolar,_infantile-onset (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HSPB8 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000014365.3. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	43 clinvar	4 clinvar	48
missense	5 clinvar	3 clinvar	119 clinvar	8 clinvar	1 clinvar	136
nonsense			4 clinvar			4
start loss						0
frameshift	6 clinvar	4 clinvar	8 clinvar			18
splice donor/acceptor (+/-2bp)						0
Total	11	7	132	51	5

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HSPB8	protein_coding	protein_coding	ENST00000281938	3	42490

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0431	0.858	125743	0	5	125748	0.0000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.0269	110	111	0.993	0.00000612	1270
Missense in Polyphen		32	37.2	0.86021		464
Synonymous	-0.464	47	43.1	1.09	0.00000239	404
Loss of Function	1.35	3	6.78	0.442	3.45e-7	70

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000289	0.0000289
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000354	0.0000352
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

Function: FUNCTION: Displays temperature-dependent chaperone activity.;
Disease: DISEASE: Neuronopathy, distal hereditary motor, 2A (HMN2A) [MIM:158590]: 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:15122253, ECO:0000269|PubMed:28144995}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Charcot-Marie-Tooth disease 2L (CMT2L) [MIM:608673]: An 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. {ECO:0000269|PubMed:15565283}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.221

Intolerance Scores

loftool: 0.229
rvis_EVS: 0.22
rvis_percentile_EVS: 67.92

Haploinsufficiency Scores

pHI: 0.556
hipred: Y
hipred_score: 0.706
ghis: 0.505

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.980

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Hspb8
Phenotype: homeostasis/metabolism phenotype; cellular phenotype; muscle 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); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); respiratory system phenotype; immune system phenotype;

Gene ontology

Biological process: protein phosphorylation;cellular response to unfolded protein;regulation of cellular response to heat;positive regulation of aggrephagy
Cellular component: nucleus;nucleoplasm;cytoplasm;cytosol;chaperone complex
Molecular function: protein kinase activity;protein binding;identical protein binding;protein homodimerization activity