HSPBP1

protein-coding

HSPA (Hsp70) binding protein 1, the group of Armadillo like helical domain containing

Gene summary

Enables molecular sequestering activity and ubiquitin protein ligase binding activity. Involved in positive regulation of proteasomal ubiquitin-dependent protein catabolic process and positive regulation of protein ubiquitination. Is active in obsolete extracellular space. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_012267.5

Inheritance

—

ClinVar variants

U:65B:6

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.31

Max pathogenic AF

—

Genomic locus

chr19:55,262,223-55,280,381

External References & Databases

Ensembl (ENSG00000133265)

Transcript & Mutation Effects

hg38 • Region Span ~18.2 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to HSPBP1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 58

not providedTotal: 6

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_012267.5. 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 clinvar	4 clinvar	1 clinvar	7
missense			61 clinvar	1 clinvar		62
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	65	5	1	71

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 63 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_012267.5	RefSeq	NP_036399.3	7	MANE Select
ENST00000433386.7	Ensembl	ENSP00000398244.1	7	MANE Select
NM_001130106.2	RefSeq	NP_001123578.1	7	Standard
NM_001297600.2	RefSeq	NP_001284529.1	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Protein processing in endoplasmic reticulum - Homo sapiens (human)

Biological Process

protein folding
positive regulation of protein ubiquitination
positive regulation of proteasomal ubiquitin-dependent protein catabolic process
negative regulation of catalytic activity

Molecular Function

adenyl-nucleotide exchange factor activity
enzyme inhibitor activity
protein binding
ubiquitin protein ligase binding

Cellular Component

cytoplasm
endoplasmic reticulum

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000255631
Coding exons: 7
Length: 18151
Individuals with no LoFs: 125695
Homozygous LoFs: 0
Heterozygous LoFs: 27
Defined: 125722
p: 0.000107

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.04	182	226	0.805	0.0000142	2250
Missense (PolyPhen)		54	66.364	0.81369		635
Synonymous	0.135	100	102	0.983	0.00000647	757
Loss of Function	2.57	5	16.1	0.310	8.35e-7	169

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00014	0.00012	rare
Latino/Admixed American	0.00015	0.00014	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.00018	0.00017	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Inhibits HSPA1A chaperone activity by changing the conformation of the ATP-binding domain of HSPA1A and interfering with ATP binding. Interferes with ubiquitination mediated by STUB1 and inhibits chaperone-assisted degradation of immature CFTR. {ECO:0000269|PubMed:10786638, ECO:0000269|PubMed:12651857, ECO:0000269|PubMed:15215316, ECO:0000269|PubMed:9830037}.;

Recessive Scores

pRec: 0.131

Intolerance Scores

LoFtool: 0.649
RVIS EVS: -0.18
RVIS percentile EVS: 40.16

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.801

Gene Damage Prediction

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