HSPD1

Chr 2ARAD

heat shock protein family D (Hsp60) member 1

Also known as: CPN60, GROEL, HLD4, HSP-60, HSP60, HSP65, HuCHA60, SPG13

NCBI Gene: 3329 ENSG00000144381 UniProt: P10809 OMIM: 118190

This mitochondrial chaperonin is essential for folding and assembly of newly imported proteins in the mitochondria. Mutations cause autosomal recessive spastic paraplegia 13 and hypomyelinating leukodystrophy 4, with some cases showing autosomal dominant inheritance. The pathogenicity results from impaired mitochondrial protein folding, which disrupts cellular energy metabolism and protein homeostasis.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a member of the chaperonin family. The encoded mitochondrial protein may function as a signaling molecule in the innate immune system. This protein is essential for the folding and assembly of newly imported proteins in the mitochondria. This gene is adjacent to a related family member and the region between the 2 genes functions as a bidirectional promoter. Several pseudogenes have been associated with this gene. Two transcript variants encoding the same protein have been identified for this gene. Mutations associated with this gene cause autosomal recessive spastic paraplegia 13. [provided by RefSeq, Jun 2010]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismAR/ADLOEUF 0.272 OMIM phenotypes

Clinical Summary— HSPD1

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.99). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

8 unique Pathogenic / Likely Pathogenic· 183 VUS of 360 total submissions

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GeneReview available — HSPD1

Authoritative clinical overview · Recommended first read

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.27LOEUF

pLI 0.993

Z-score 4.11

OE 0.09 (0.03–0.27)

Highly constrained

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

Missense Constraint?

2.26Z-score

OE missense 0.64 (0.57–0.72)

195 obs / 306.1 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.09 (0.03–0.27)

0≤0.351.4

Missense OE?0.64 (0.57–0.72)

0≤0.61.4

Synonymous OE?1.00

0≤1.21.6

LoF obs/exp: 2 / 23.5Missense obs/exp: 195 / 306.1Syn Z: -0.01

ClinVar Variant Classifications

360 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic3

Likely Pathogenic5

VUS183

Likely Benign118

Benign25

Conflicting12

Pathogenic

Likely Pathogenic

183

VUS

118

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	3	0	0	3
Likely Pathogenic	0	5	0	0	5
VUS	5	152	20	6	183
Likely Benign	0	2	60	56	118
Benign	0	1	17	7	25
Conflicting	—				12
Total	5	163	97	69	346

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 HSPD1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →