HSPE1

Chr 2

heat shock protein family E (Hsp10) member 1

Also known as: CPN10, EPF, GROES, HSP10

NCBI Gene: 3336 ENSG00000115541 UniProt: P61604 OMIM: 600141

The protein functions as a mitochondrial co-chaperonin that works with Hsp60 to facilitate proper folding of imported proteins and prevent protein misfolding in the mitochondrial matrix. Mutations cause spastic paraplegia 13, an autosomal recessive disorder characterized by progressive spasticity primarily affecting the lower limbs. This gene is highly constrained against loss-of-function variants, reflecting its essential role in mitochondrial protein quality control.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a major heat shock protein which functions as a chaperonin. Its structure consists of a heptameric ring which binds to another heat shock protein in order to form a symmetric, functional heterodimer which enhances protein folding in an ATP-dependent manner. This gene and its co-chaperonin, HSPD1, are arranged in a head-to-head orientation on chromosome 2. Naturally occurring read-through transcription occurs between this locus and the neighboring locus MOBKL3.[provided by RefSeq, Feb 2011]

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.56

Clinical Summary— HSPE1

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Population Constraint (gnomAD)

Moderately constrained gene (pLI 0.80) — some intolerance to loss-of-function variants.

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ClinVar Variants

6 VUS of 7 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.56LOEUF

pLI 0.804

Z-score 2.15

OE 0.00 (0.00–0.56)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.45Z-score

OE missense 0.44 (0.31–0.62)

23 obs / 52.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.56)

0≤0.351.4

Missense OE?0.44 (0.31–0.62)

0≤0.61.4

Synonymous OE?1.35

0≤1.21.6

LoF obs/exp: 0 / 5.4Missense obs/exp: 23 / 52.6Syn Z: -1.20

This gene — mechanism propensity

0.4388th %ile

GOF

0.2398th %ile

LOF

0.77top 5%

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

LOFprediction above median

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

7 submitted variants in ClinVar

ClinVar

Classification Summary

VUS6

Likely Benign1

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	6	0	6
Likely Benign	0	1	1
Benign	0	0	0
Total	6	1	7

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

View in ClinVar →

36 pathogenic / likely-pathogenic (of 39) ClinVar copy-number / structural variants overlap HSPE1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →