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

The protein functions as a mitochondrial chaperone essential for protein import, folding and assembly, and plays a critical role in iron-sulfur cluster biogenesis and erythropoiesis. Mutations cause sideroblastic anemia 4 and Even-plus syndrome through both autosomal dominant and autosomal recessive inheritance patterns. The pathogenic mechanism involves disruption of mitochondrial protein quality control and iron-sulfur cluster assembly, leading to defective erythropoiesis and cellular dysfunction.

Summary from RefSeq, OMIM, UniProt
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Primary Disease Associations & Inheritance

Anemia, sideroblastic, 4MIM #182170
AD
Even-plus syndromeMIM #616854
AR
1
Active trials
39
Pubs (1 yr)
0
P/LP submissions
P/LP missense
0.32
LOEUF· LoF intol.
LOF
Mechanism· predicted
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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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 OE0.16 (0.090.32)
00.351.4
Missense OE0.85 (0.770.93)
00.61.4
Synonymous OE1.03
01.21.6
LoF obs/exp: 6 / 37.2Missense obs/exp: 312 / 368.0Syn Z: -0.27
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 · 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.PMID:21123823

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

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

HSPA9 · protein map & ClinVar variants

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

Clinical Literature
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