HSPA9

Chr 5q31.2

heat shock protein family A (Hsp70) member 9

Aliases:: GRP75, PBP74, mot-2, mthsp75
MANE:: ENST00000297185.9

OMIM: 600548 ↗NCBI: 3313 ↗Ensembl ↗

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Predicted protein structure

AlphaFold predicted structure

HSPA9 · P38646

v62025-08-01

Predicted Aligned Error matrix for HSPA9 — diagonal shows residue index, colour shows pairwise prediction confidence (lower is better) — Predicted Aligned Error

Mean pLDDT

85.9/ 100

Confident

679 residues

Confidence breakdown

Very high(≥ 90)60%
Confident(70–90)28%
Low(50–70)2%
Very low(< 50)10%

Open interactive 3D viewer

AlphaFold (Jumper et al., 2021) · CC BY 4.0

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

Deafness and congenital structural abnormalities
BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies
BIALLELIC, autosomal or pseudoautosomal
Likely inborn error of metabolism
BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorders
BIALLELIC, autosomal or pseudoautosomal
Possible mitochondrial disorder - nuclear genes
BIALLELIC, autosomal or pseudoautosomal
Rare anaemia
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Undiagnosed metabolic disorders
BIALLELIC, autosomal or pseudoautosomal

Disease associations (Open Targets)

even-plus syndrome
0.76
Constitutional sideroblastic anemia
0.69
autosomal dominant sideroblastic anemia
0.66
autosomal recessive sideroblastic anemia
0.37
sideroblastic anemia
0.37
atrial fibrillation
0.32
schizophrenia
0.26
neurodegenerative disease
0.25
hereditary disease
0.19
secondary malignant neoplasm
0.17

Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.

Protein function (UniProt)

Stress-70 protein, mitochondrial

Mitochondrial chaperone that plays a key role in mitochondrial protein import, folding, and assembly. Plays an essential role in the protein quality control system, the correct folding of proteins, the re-folding of misfolded proteins, and the targeting of proteins for subsequent degradation. These processes are achieved through cycles of ATP binding, ATP hydrolysis, and ADP release, mediated by co-chaperones (PubMed:18632665, PubMed:25615450, PubMed:28848044, PubMed:30933555, PubMed:31177526). In mitochondria, it associates with the TIM (translocase of the inner membrane) protein complex to assist in the import and folding of mitochondrial proteins (By similarity). Plays an important role in mitochondrial iron-sulfur cluster (ISC) biogenesis, interacts with and stabilizes ISC cluster assembly proteins FXN, NFU1, NFS1 and ISCU (PubMed:26702583). Regulates erythropoiesis via stabilization of ISC assembly (PubMed:21123823, PubMed:26702583). Regulates mitochondrial calcium-dependent apoptosis by coupling two calcium channels, ITPR1 and VDAC1, at the mitochondria-associated endoplasmic reticulum (ER) membrane to facilitate calcium transport from the ER lumen to the mitochondria intermembrane space, providing calcium for the downstream calcium channel MCU, which releases it into the mitochondrial matrix (By similarity). Although primarily located in the mitochondria, it is also found in other cellular compartments. In the cytosol, it associates with proteins involved in signaling, apoptosis, or senescence. It may play a role in cell cycle regulation via its interaction with and promotion of degradation of TP53 (PubMed:24625977, PubMed:26634371). May play a role in the control of cell proliferation and cellular aging (By similarity). Protects against reactive oxygen species (ROS) (By similarity). Extracellular HSPA9 plays a cytoprotective role by preventing cell lysis following immune attack by the membrane attack complex by disrupting formation of the complex (PubMed:16091382)