HSPA6

heat shock protein family A (Hsp70) member 6, the group of Heat shock 70kDa proteins

Basic information

Region (hg38): 1:161524540-161526894

Links

ENSG00000173110 ∙ NCBI:3310 ∙ OMIM:140555 ∙ HGNC:5239 ∙ Uniprot:P17066 ∙ 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 HSPA6 gene.

• not_specified (96 variants)
• not_provided (4 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HSPA6 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000002155.5. 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	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				3		3
missense			95	1		96
nonsense				1		1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	95	5	0

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HSPA6	protein_coding	protein_coding	ENST00000309758	1	2646

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000683	0.493	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.217	398	386	1.03	0.0000221	4169
Missense in Polyphen		163	166.14	0.98107		1894
Synonymous	-0.280	173	168	1.03	0.00000973	1348
Loss of Function	0.639	9	11.3	0.795	4.80e-7	158

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). {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;Cellular response to heat stress;MAPK Signaling Pathway;Neutrophil degranulation;HSF1 activation;Attenuation phase;HSF1-dependent transactivation;Regulation of HSF1-mediated heat shock response;Cellular responses to stress;Innate Immune System;Immune System;Cellular responses to external stimuli;Cellular response to heat stress (Consensus)

Intolerance Scores

• rvis_EVS: -0.02
• rvis_percentile_EVS: 52.25

Haploinsufficiency Scores

• pHI: 0.192
• hipred: N
• hipred_score: 0.418
• ghis: 0.452

Essentials

• essential_gene_CRISPR: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.861

Gene Damage Prediction

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

Gene ontology

• Biological process: response to unfolded protein;cellular response to heat;cellular response to unfolded protein;protein refolding;neutrophil degranulation;chaperone cofactor-dependent protein refolding;cellular heat acclimation
• Cellular component: extracellular region;nucleus;cytoplasm;centriole;cytosol;COP9 signalosome;protein-containing complex;secretory granule lumen;extracellular exosome;blood microparticle;ficolin-1-rich granule lumen
• Molecular function: protein binding;ATP binding;ATPase activity;enzyme binding;heat shock protein binding;ATPase activity, coupled;protein folding chaperone;unfolded protein binding;misfolded protein binding