HSPA2

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

Basic information

Region (hg38): 14:64535905-64546173

Links

ENSG00000126803 ∙ NCBI:3306 ∙ OMIM:140560 ∙ HGNC:5235 ∙ Uniprot:P54652 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the HSPA2 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HSPA2 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					3	3
missense			24			24
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	24	0	3

Variants in HSPA2

This is a list of pathogenic ClinVar variants found in the HSPA2 region.

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

Position	Type	Phenotype	Significance	ClinVar
14-64540868-G-T		not specified	Uncertain significance (May 30, 2024)
14-64540979-G-A		not specified	Uncertain significance (Feb 16, 2023)
14-64541065-G-C		not specified	Uncertain significance (Dec 27, 2023)
14-64541153-C-T		not specified	Uncertain significance (Mar 31, 2023)
14-64541169-A-G		not specified	Uncertain significance (Dec 02, 2021)
14-64541183-A-T		not specified	Uncertain significance (Feb 14, 2023)
14-64541190-C-A		not specified	Uncertain significance (Feb 16, 2023)
14-64541274-G-A		not specified	Uncertain significance (Aug 02, 2021)
14-64541355-A-G		not specified	Uncertain significance (Oct 20, 2023)
14-64541565-G-T		not specified	Uncertain significance (Nov 22, 2023)
14-64541615-A-G		not specified	Uncertain significance (Oct 03, 2023)
14-64541742-C-T		not specified	Uncertain significance (Oct 12, 2023)
14-64541760-G-T		not specified	Uncertain significance (Apr 10, 2023)
14-64541764-C-A		not specified	Uncertain significance (May 26, 2022)
14-64541795-A-T		not specified	Uncertain significance (Feb 23, 2023)
14-64541930-G-A		not specified	Uncertain significance (Jan 23, 2024)
14-64541998-C-T			Benign (Dec 31, 2019)
14-64542028-C-G		not specified	Uncertain significance (Nov 21, 2022)
14-64542101-A-G		not specified	Uncertain significance (Mar 21, 2024)
14-64542203-A-T		not specified	Uncertain significance (Feb 05, 2024)
14-64542230-A-G		not specified	Uncertain significance (Jun 30, 2022)
14-64542257-G-T		not specified	Uncertain significance (Feb 28, 2023)
14-64542417-A-G		not specified	Uncertain significance (Jul 09, 2021)
14-64542508-G-A			Benign (Jun 05, 2018)
14-64542534-G-A		not specified	Uncertain significance (Oct 03, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HSPA2	protein_coding	protein_coding	ENST00000247207	1	7333

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0486	0.947	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.72	219	438	0.500	0.0000285	4205
Missense in Polyphen		84	224.5	0.37416		2100
Synonymous	2.14	173	213	0.814	0.0000167	1325
Loss of Function	2.50	5	15.7	0.319	7.79e-7	182

LoF frequencies by population

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

dbNSFP

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}.
• Pathway: 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);Protein processing in endoplasmic reticulum - Homo sapiens (human);Estrogen signaling pathway - Homo sapiens (human);MAPK signaling pathway - Homo sapiens (human);Toxoplasmosis - Homo sapiens (human);Spliceosome - Homo sapiens (human);Measles - Homo sapiens (human);Epstein-Barr virus infection - Homo sapiens (human);Parkin-Ubiquitin Proteasomal System pathway;MAPK Signaling Pathway;Attenuation phase;HSF1-dependent transactivation;Regulation of HSF1-mediated heat shock response;HSP90 chaperone cycle for steroid hormone receptors (SHR);Cellular responses to stress;Cellular responses to external stimuli;Cellular response to heat stress (Consensus)

Intolerance Scores

• loftool: 0.463
• rvis_EVS: 0.13
• rvis_percentile_EVS: 63.36

Haploinsufficiency Scores

• pHI: 0.639
• ghis: 0.389

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.989

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Hspa2
• Phenotype: reproductive system phenotype; endocrine/exocrine gland phenotype

Gene ontology

• Biological process: positive regulation of protein phosphorylation;response to unfolded protein;male meiotic nuclear division;male meiosis I;spermatogenesis;spermatid development;response to heat;response to cold;positive regulation of G2/M transition of mitotic cell cycle;vesicle-mediated transport;cellular response to heat;cellular response to unfolded protein;protein refolding;chaperone cofactor-dependent protein refolding;synaptonemal complex disassembly;negative regulation of inclusion body assembly;positive regulation of calcium-transporting ATPase activity
• Cellular component: synaptonemal complex;male germ cell nucleus;nucleus;cytoplasm;cytosol;plasma membrane;cell surface;membrane;CatSper complex;myelin sheath;extracellular exosome;blood microparticle;meiotic spindle
• Molecular function: protein binding;ATP binding;ATPase activity;enzyme binding;heat shock protein binding;ATPase activity, coupled;protein folding chaperone;tau protein binding;unfolded protein binding;chaperone binding;misfolded protein binding;glycolipid binding;disordered domain specific binding