HSPA9

Chr 5ADAR

heat shock protein family A (Hsp70) member 9

Also known as: CRP40, CSA, EVPLS, GRP-75, GRP75, HEL-S-124m, HSPA9B, MOT

This gene encodes a member of the heat shock protein 70 gene family. The encoded protein is primarily localized to the mitochondria but is also found in the endoplasmic reticulum, plasma membrane and cytoplasmic vesicles. This protein is a heat-shock cognate protein. This protein plays a role in cell proliferation, stress response and maintenance of the mitochondria. A pseudogene of this gene is found on chromosome 2.[provided by RefSeq, May 2010]

OMIMResearchGenerating clinical summary…
LOFmechanismAD/ARLOEUF 0.322 OMIM phenotypes
Clinical SummaryHSPA9
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.97). One damaged copy is likely sufficient to cause disease.
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ClinVar Variants
6 unique Pathogenic / Likely Pathogenic· 75 VUS of 129 total submissions
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint?
0.32LOEUF
pLI 0.969
Z-score 4.74
OE 0.16 (0.090.32)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?
1.04Z-score
OE missense 0.85 (0.770.93)
312 obs / 368.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.16 (0.090.32)
00.351.4
Missense OE?0.85 (0.770.93)
00.61.4
Synonymous OE?1.03
01.21.6
LoF obs/exp: 6 / 37.2Missense obs/exp: 312 / 368.0Syn Z: -0.27

This gene — mechanism propensity

DN
0.5771th %ile
GOF
0.5071th %ile
LOF
0.60top 25%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOF1 literature citation · 50% of P/LP variants are LoF · LOEUF 0.32

Literature Evidence

LOFChen et al. (2011) concluded that haploinsufficiency for HSPA9 may contribute to abnormal hematopoiesis in myelodysplastic syndromes with deletions spanning chromosome 5q31.2.1

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

References

  1. 1.PMID 21123823

ClinVar Variant Classifications

129 submitted variants in ClinVar

Classification Summary

Pathogenic4
Likely Pathogenic2
VUS75
Likely Benign24
Benign5
Conflicting3
4
Pathogenic
2
Likely Pathogenic
75
VUS
24
Likely Benign
5
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
2
0
0
4
Likely Pathogenic
1
1
0
0
2
VUS
0
74
1
0
75
Likely Benign
0
3
4
17
24
Benign
1
1
2
1
5
Conflicting
3
Total481718113

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

12 pathogenic / likely-pathogenic (of 19) ClinVar copy-number / structural variants overlap HSPA9 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

HSPA9 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.