HSPA1L

heat shock protein family A (Hsp70) member 1 like, the group of Heat shock 70kDa proteins|TIM23 complex

Basic information

Region (hg38): 6:31809618-31815283

Links

ENSG00000204390 ∙ NCBI:3305 ∙ OMIM:140559 ∙ HGNC:5234 ∙ Uniprot:P34931 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Abacavir, susceptibility to toxicity with	AD	Pharmacogenomic	Medication choice and administration may be affeted by the presence of variants	General	11943262; 11888582; 15024131

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the HSPA1L gene.

• Inborn genetic diseases (26 variants)
• not provided (11 variants)
• Inflammatory bowel disease 1 (2 variants)
• HSPA1L-related condition (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HSPA1L 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				1	3	4
missense			26	2	3	31
nonsense			1			1
start loss						0
frameshift				2		2
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	27	5	6

Variants in HSPA1L

This is a list of pathogenic ClinVar variants found in the HSPA1L region.

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

Position	Type	Phenotype	Significance	ClinVar
6-31810055-C-T		not specified	Uncertain significance (Oct 10, 2023)
6-31810064-T-C		not specified	Uncertain significance (Aug 24, 2023)
6-31810142-T-C		not specified	Uncertain significance (Apr 08, 2022)
6-31810169-C-T		HSPA1L-related disorder	Benign (Oct 18, 2019)
6-31810227-C-A		not specified	Uncertain significance (Sep 26, 2022)
6-31810255-A-G		not specified	Uncertain significance (Jun 24, 2022)
6-31810263-ATTTTT-A		HSPA1L-related disorder	Likely benign (Oct 06, 2020)
6-31810300-T-G		Inflammatory bowel disease 1 • HSPA1L-related disorder	Benign (Dec 23, 2019)
6-31810354-G-A		not specified	Uncertain significance (Apr 05, 2023)
6-31810385-C-T		not specified	Uncertain significance (Mar 07, 2024)
6-31810488-CTT-C			Likely benign (Dec 03, 2018)
6-31810495-G-A		HSPA1L-related disorder	Benign (Oct 21, 2019)
6-31810495-G-T		Chronic obstructive pulmonary disease	association (Aug 04, 2019)
6-31810507-T-C		not specified	Uncertain significance (Jan 04, 2022)
6-31810522-G-A		not specified	Uncertain significance (May 27, 2022)
6-31810530-G-A		HSPA1L-related disorder	Benign (Jan 01, 2024)
6-31810537-G-A		HSPA1L-related disorder	Benign (Sep 01, 2023)
6-31810543-T-A		not specified	Uncertain significance (Jan 24, 2023)
6-31810545-G-A		HSPA1L-related disorder	Benign (Dec 31, 2019)
6-31810658-C-T		not specified	Uncertain significance (Nov 15, 2021)
6-31810659-G-C		HSPA1L-related disorder	Likely benign (May 23, 2019)
6-31810660-G-A		not specified	Uncertain significance (Mar 04, 2024)
6-31810752-C-T		HSPA1L-related disorder	Benign (Oct 21, 2019)
6-31810864-G-A			Uncertain significance (Oct 01, 2022)
6-31810907-A-C		not specified	Uncertain significance (Apr 07, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HSPA1L	protein_coding	protein_coding	ENST00000375654	1	6042

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000106	0.570	125632	0	116	125748	0.000461

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.641	325	359	0.905	0.0000210	4189
Missense in Polyphen		184	205.11	0.89707		2436
Synonymous	0.727	135	146	0.923	0.00000898	1298
Loss of Function	0.908	11	14.8	0.745	8.80e-7	189

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00464	0.00465
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.000382	0.000381
Finnish	0.0000924	0.0000924
European (Non-Finnish)	0.000141	0.000141
Middle Eastern	0.000382	0.000381
South Asian	0.000359	0.000359
Other	0.000163	0.000163

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). Positive regulator of PRKN translocation to damaged mitochondria (PubMed:24270810). {ECO:0000269|PubMed:24270810, 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;HSF1 activation;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: 0.844
• rvis_EVS: -0.11
• rvis_percentile_EVS: 45.49

Haploinsufficiency Scores

• pHI: 0.527
• hipred: N
• hipred_score: 0.397
• ghis: 0.453

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.995

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Hspa1l

Gene ontology

• Biological process: response to unfolded protein;binding of sperm to zona pellucida;cellular response to heat;cellular response to unfolded protein;protein refolding;chaperone cofactor-dependent protein refolding;regulation of cellular response to heat;positive regulation of protein targeting to mitochondrion
• Cellular component: zona pellucida receptor complex;nucleoplasm;cytoplasm;cytosol;COP9 signalosome;cell body;blood microparticle
• Molecular function: protein binding;ATP binding;ATPase activity;heat shock protein binding;ubiquitin protein ligase binding;ATPase activity, coupled;protein folding chaperone;unfolded protein binding;misfolded protein binding