HSPH1

heat shock protein family H (Hsp110) member 1, the group of Heat shock 70kDa proteins

Basic information

Region (hg38): 13:31134972-31162388

Links

ENSG00000120694 ∙ NCBI:10808 ∙ OMIM:610703 ∙ HGNC:16969 ∙ Uniprot:Q92598 ∙ 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 HSPH1 gene.

• Inborn genetic diseases (16 variants)
• not provided (6 variants)
• not specified (3 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HSPH1 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	1	4
missense			17	1	2	20
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding						0
Total	0	0	17	4	3

Variants in HSPH1

This is a list of pathogenic ClinVar variants found in the HSPH1 region.

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

Position	Type	Phenotype	Significance	ClinVar
13-31137394-A-G		not specified	Uncertain significance (Dec 06, 2023)
13-31137439-G-A		not specified	Uncertain significance (Jun 29, 2023)
13-31137500-C-T		not specified	Uncertain significance (Jan 23, 2023)
13-31138435-C-T			Benign/Likely benign (Jan 01, 2024)
13-31138462-T-C		not specified	Uncertain significance (Jun 22, 2023)
13-31138511-T-C		not specified	Uncertain significance (Dec 13, 2023)
13-31138848-T-C		not specified	Uncertain significance (Jan 22, 2024)
13-31141184-T-C		not specified	Likely benign (Jul 26, 2022)
13-31141186-G-A		not specified	Uncertain significance (May 02, 2023)
13-31141251-T-C			Benign (Dec 31, 2019)
13-31143849-C-G		not specified	Uncertain significance (Feb 22, 2023)
13-31143860-G-C		not specified	Uncertain significance (May 04, 2023)
13-31143883-G-C		not specified	Uncertain significance (May 17, 2023)
13-31145646-C-G		not specified	Uncertain significance (Jan 04, 2022)
13-31148034-G-C			Benign (May 25, 2017)
13-31148091-C-T		not specified	Uncertain significance (Jul 13, 2022)
13-31148396-G-T		not specified	Uncertain significance (Dec 12, 2022)
13-31148455-T-C		not specified	Uncertain significance (Oct 13, 2023)
13-31148483-TA-T		not specified	Benign (Mar 29, 2016)
13-31150050-A-C		not specified	Uncertain significance (Aug 13, 2021)
13-31150061-C-A		not specified	Uncertain significance (Aug 25, 2015)
13-31150954-T-C		not specified	Uncertain significance (Jan 24, 2024)
13-31150958-T-C			Likely benign (Jul 01, 2022)
13-31151068-G-A		not specified	Uncertain significance (Dec 21, 2023)
13-31151101-A-G		not specified	Uncertain significance (Aug 25, 2015)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HSPH1	protein_coding	protein_coding	ENST00000320027	18	25764

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.998	0.00178	125735	0	10	125745	0.0000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.72	344	446	0.771	0.0000216	5695
Missense in Polyphen		110	185.48	0.59304		2393
Synonymous	-1.36	179	157	1.14	0.00000781	1557
Loss of Function	5.38	6	44.9	0.134	0.00000244	559

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000289	0.0000289
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000547	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000632	0.0000615
Middle Eastern	0.0000547	0.0000544
South Asian	0.00	0.00
Other	0.000164	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Acts as a nucleotide-exchange factor (NEF) for chaperone proteins HSPA1A and HSPA1B, promoting the release of ADP from HSPA1A/B thereby triggering client/substrate protein release (PubMed:24318877). Prevents the aggregation of denatured proteins in cells under severe stress, on which the ATP levels decrease markedly. Inhibits HSPA8/HSC70 ATPase and chaperone activities (By similarity). {ECO:0000250|UniProtKB:Q60446, ECO:0000250|UniProtKB:Q61699, ECO:0000269|PubMed:24318877}.
• Pathway: Protein processing in endoplasmic reticulum - Homo sapiens (human);Cellular response to heat stress;HSF1 activation;Attenuation phase;HSF1-dependent transactivation;Vesicle-mediated transport;Regulation of HSF1-mediated heat shock response;Cellular responses to stress;Cellular responses to external stimuli;Cellular response to heat stress;Binding and Uptake of Ligands by Scavenger Receptors;Scavenging by Class F Receptors (Consensus)

Recessive Scores

• pRec: 0.346

Intolerance Scores

• loftool: 0.503
• rvis_EVS: -0.57
• rvis_percentile_EVS: 18.96

Haploinsufficiency Scores

• pHI: 0.833
• hipred: Y
• hipred_score: 0.683
• ghis: 0.406

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: H
• gene_indispensability_pred: E
• gene_indispensability_score: 0.533

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Hsph1
• Phenotype: homeostasis/metabolism phenotype; cellular phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan)

Gene ontology

• Biological process: receptor-mediated endocytosis;response to unfolded protein;positive regulation of MHC class I biosynthetic process;regulation of catalytic activity;chaperone cofactor-dependent protein refolding;positive regulation of NK T cell activation;regulation of cellular response to heat
• Cellular component: extracellular region;nucleus;nucleoplasm;cytoplasm;cytosol;microtubule;protein-containing complex;extracellular exosome;endocytic vesicle lumen
• Molecular function: adenyl-nucleotide exchange factor activity;protein binding;ATP binding;alpha-tubulin binding