HSPB3

protein-coding

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

Gene summary

This gene encodes a muscle-specific small heat shock protein. A mutation in this gene is the cause of autosomal dominant distal hereditary motor neuropathy type 2C.[provided by RefSeq, Sep 2010]

MANE transcript

NM_006308.3

Inheritance

ClinVar variants

P:1U:43B:23

Top phenotype

Neuronopathy, distal hereditary motor, autosomal dominant 4

gnomAD constraint

pLI —, LoF o/e 1.11

Max pathogenic AF

—

Genomic locus

chr5:54,455,699-54,456,377

External References & Databases

Ensembl (ENSG00000169271)

Transcript & Mutation Effects

hg38 • Region Span ~0.7 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

neuronopathy, distal hereditary motor, type 2CLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0013243

Submitter: Labcorp Genetics (formerly Invitae)

neuronopathy, distal hereditary motor, type 2CLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0013243

Submitter: PanelApp Australia

distal hereditary motor neuropathy type 2SUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0015352

Submitter: Orphanet

neuronopathy, distal hereditary motor, type 2CLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0013243

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Neuronopathy, distal hereditary motor, autosomal dominant 4AD

Manifestation: Neurologic

Intervention: General

Rationale: 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

Refs: 20142617

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to HSPB3 variants in ClinVar

5 Conditions Cataloged

Neuronopathy, distal hereditary motor, type 2CTotal: 52

not specifiedTotal: 20

not providedTotal: 8

HSPB3-related conditionTotal: 2

Charcot-Marie-Tooth disease type 2Total: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_006308.3. 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.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	13 clinvar		15
missense			36 clinvar	8 clinvar	1 clinvar	45
nonsense		1 clinvar	2 clinvar			3
start loss			2 clinvar			2
frameshift			1 clinvar	1 clinvar		2
splice donor/acceptor (+/-2bp)						0
Total	0	1	43	22	1	67

Highest pathogenic variant AF is 0.000002052138

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 2 of 2 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_006308.3	RefSeq	NP_006299.1	1	MANE Select
ENST00000302005.3	Ensembl	ENSP00000303394.1	1	MANE Select

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

response to unfolded protein

Cellular Component

nucleus
cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000302005
Coding exons: 1
Length: 763
Individuals with no LoFs: 0
Homozygous LoFs: 0
Heterozygous LoFs: 0
Defined: 0
p: 0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.0360	80	80.9	0.989	0.00000477	966
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0	0.0	absent
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

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

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.676

Gene Damage Prediction

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