HSPA2

protein-coding

heat shock protein family A (Hsp70) member 2, the group of Heat shock 70kDa proteins

Gene summary

Enables enzyme binding activity and unfolded protein binding activity. Involved in negative regulation of inclusion body assembly and protein refolding. Located in cytosol. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_021979.4

Inheritance

—

ClinVar variants

U:51B:3

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.32

Max pathogenic AF

—

Genomic locus

chr14:64,535,905-64,546,173

External References & Databases

Transcript & Mutation Effects

hg38 • Region Span ~10.3 kb
Loading mutation effect viewer...

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 HSPA2 variants in ClinVar

2 Conditions Cataloged
not specifiedTotal: 51
not providedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_021979.4. 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.

EffectPLPVUSLBBSum
synonymous
3
clinvar
3
missense
51
clinvar
51
nonsense
0
start loss
0
frameshift
0
splice donor/acceptor (+/-2bp)
0
Total00510354
Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 4 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_021979.4RefSeqNP_068814.21MANE Select
ENST00000247207.7EnsemblENSP00000247207.61MANE Select
NM_001387931.1RefSeqNP_001374860.11Standard
ENST00000394709.2EnsemblENSP00000378199.11Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Antigen processing and presentation - Homo sapiens (human)
  • Legionellosis - Homo sapiens (human)
  • Endocytosis - Homo sapiens (human)
  • Longevity regulating pathway - multiple species - Homo sapiens (human)
  • Influenza A - Homo sapiens (human)

Biological Process

  • positive regulation of protein phosphorylation
  • response to unfolded protein
  • male meiotic nuclear division
  • male meiosis I
  • spermatogenesis

Molecular Function

  • protein binding
  • ATP binding
  • ATPase activity
  • enzyme binding
  • heat shock protein binding

Cellular Component

  • synaptonemal complex
  • male germ cell nucleus
  • nucleus
  • cytoplasm
  • cytosol

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000247207
Coding exons
1
Length
7333
Individuals with no LoFs
0
Homozygous LoFs
0
Heterozygous LoFs
0
Defined
0
p
0.00
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense3.722194380.5000.00002854205
Missense (PolyPhen)84224.50.374162100
Synonymous2.141732130.8140.00001671325
Loss of Function2.50515.70.3197.79e-7182

Population LoF Frequency

PopulationCAFp-valueStatus
African00.0absent
Latino/Admixed American00.0absent
Ashkenazi Jewish00.0absent
East Asian00.0absent
Finnish00.0absent
European (Non-Finnish)00.0absent
South Asian00.0absent
Other00.0absent

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Molecular chaperone implicated in a wide variety of cellular processes, including protection of the proteome from stress, folding and transport of newly synthesized polypeptides, activation of proteolysis of misfolded proteins and the formation and dissociation of protein complexes. Plays a pivotal role in the protein quality control system, ensuring the correct folding of proteins, the re-folding of misfolded proteins and controlling the targeting of proteins for subsequent degradation. This is achieved through cycles of ATP binding, ATP hydrolysis and ADP release, mediated by co-chaperones. The affinity for polypeptides is regulated by its nucleotide bound state. In the ATP-bound form, it has a low affinity for substrate proteins. However, upon hydrolysis of the ATP to ADP, it undergoes a conformational change that increases its affinity for substrate proteins. It goes through repeated cycles of ATP hydrolysis and nucleotide exchange, which permits cycles of substrate binding and release (PubMed:26865365). Plays a role in spermatogenesis. In association with SHCBP1L may participate in the maintenance of spindle integrity during meiosis in male germ cells (By similarity). {ECO:0000250|UniProtKB:P17156, ECO:0000303|PubMed:26865365}.;

Intolerance Scores

LoFtool
0.463
RVIS EVS
0.13
RVIS percentile EVS
63.36

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Indispensability pred.
E
Indispensability score
0.989

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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