HSPA1L
protein-codingheat shock protein family A (Hsp70) member 1 like, the group of Heat shock 70kDa proteins|TIM23 complex
Gene summary
This gene encodes a 70kDa heat shock protein. In conjunction with other heat shock proteins, this protein stabilizes existing proteins against aggregation and mediates the folding of newly translated proteins in the cytosol and in organelles. The gene is located in the major histocompatibility complex class III region, in a cluster with two closely related genes which also encode isoforms of the 70kDa heat shock protein. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~5.7 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0005265
Submitter: PanelApp Australia
Clinical Genomic Database (CGD)
Manifestation: General
Intervention: Pharmacogenomic
Rationale: Medication choice and administration may be affeted by the presence of variants
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to HSPA1L variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_005527.4. 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 | 2 | 5 | 4 | 11 | ||
| missense | 98 | 3 | 3 | 104 | ||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 2 | 3 | |||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 102 | 10 | 7 | 119 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_005518.3 | 1 | MANE Select | |
| Ensembl | ENSP00000364805.4 | 1 | MANE Select | |
| Ensembl | ENSP00000549347.1 | 1 | Standard | |
| Ensembl | ENSP00000549347.1 | 1 | Standard |
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
- response to unfolded protein
- binding of sperm to zona pellucida
- cellular response to heat
- cellular response to unfolded protein
- protein refolding
Molecular Function
- protein binding
- ATP binding
- ATPase activity
- heat shock protein binding
- ubiquitin protein ligase binding
Cellular Component
- zona pellucida receptor complex
- nucleoplasm
- cytoplasm
- cytosol
- COP9 signalosome
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000375654
- Coding exons
- 1
- Length
- 6042
- Individuals with no LoFs
- 125632
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 116
- Defined
- 125748
- p
- 0.000461
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.641 | 325 | 359 | 0.905 | 0.0000210 | 4189 |
| Missense (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 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0044 | 0.0044 | notable |
| Latino/Admixed American | 0.00021 | 0.00017 | rare |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0.00038 | 0.00038 | rare |
| Finnish | 0.000092 | 0.000092 | rare |
| European (Non-Finnish) | 0.00014 | 0.00014 | rare |
| South Asian | 0.00036 | 0.00036 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- 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}.;
Intolerance Scores
- LoFtool
- 0.844
- RVIS EVS
- -0.11
- RVIS percentile EVS
- 45.49
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.995
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |