HSPB2

protein-coding

heat shock protein family B (small) member 2, the group of Small heat shock proteins

Gene summary

The protein encoded by this gene belongs to the superfamily of small heat-shock proteins containing a conservative alpha-crystallin domain at the C-terminal part of the molecule. The protein is expressed preferentially in the heart and skeletal muscle. This protein regulates Myotonic Dystrophy Protein Kinase, which plays an important role in maintenance of muscle structure and function. [provided by RefSeq, Dec 2012]

MANE transcript

NM_001541.4

Inheritance

—

ClinVar variants

U:24B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.76

Max pathogenic AF

—

Genomic locus

chr11:111,912,734-111,914,093

External References & Databases

Ensembl (ENSG00000170276)

Transcript & Mutation Effects

hg38 • Region Span ~1.4 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to HSPB2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 24

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001541.4. 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						0
missense			23 clinvar	2 clinvar		25
nonsense						0
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)						0
Total	0	0	24	2	0	26

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 6 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001541.4	RefSeq	NP_001532.1	2	MANE Select
ENST00000304298.4	Ensembl	ENSP00000302476.3	2	MANE Select
ENST00000941391.1	Ensembl	ENSP00000611450.1	2	Standard
ENST00001091865.1	Ensembl	ENSP00000761671.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Proteoglycans in cancer - Homo sapiens (human)
Epstein-Barr virus infection - Homo sapiens (human)
IL-1 signaling pathway
Cellular response to heat stress
HSF1 activation

Biological Process

response to unfolded protein
positive regulation of catalytic activity

Molecular Function

protein binding
enzyme activator activity

Cellular Component

nucleus
cytoplasm
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000304298
Coding exons: 2
Length: 6609
Individuals with no LoFs: 125736
Homozygous LoFs: 0
Heterozygous LoFs: 12
Defined: 125748
p: 0.0000477

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.517	103	119	0.867	0.00000751	1149
Missense (PolyPhen)		27	41.117	0.65667		366
Synonymous	-0.167	51	49.5	1.03	0.00000289	408
Loss of Function	0.626	6	7.90	0.760	6.80e-7	54

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.00012	0.00012	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00016	0.00016	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000027	0.000026	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May regulate the kinase DMPK. {ECO:0000269|PubMed:9490724}.;

Intolerance Scores

LoFtool: 0.258
RVIS EVS: 0.01
RVIS percentile EVS: 54.95

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.603

Gene Damage Prediction

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