HSPA6

Chr 1

heat shock protein family A (Hsp70) member 6

Also known as: HSP70B'

NCBI Gene: 3310 ENSG00000173110 UniProt: P17066 OMIM: 140555

Enables several functions, including ATP hydrolysis activity; heat shock protein binding activity; and unfolded protein binding activity. Involved in cellular response to heat and protein refolding. Located in COP9 signalosome; centriole; and cytosol. [provided by Alliance of Genome Resources, Jul 2025]

OMIM Research

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 1.38

Clinical Summary— HSPA6

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

107 VUS of 113 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.38LOEUF

pLI 0.000

Z-score 0.64

OE 0.79 (0.48–1.38)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.22Z-score

OE missense 1.03 (0.95–1.12)

398 obs / 386.0 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.79 (0.48–1.38)

0≤0.351.4

Missense OE?1.03 (0.95–1.12)

0≤0.61.4

Synonymous OE?1.03

0≤1.21.6

LoF obs/exp: 9 / 11.3Missense obs/exp: 398 / 386.0Syn Z: -0.28

This gene — mechanism propensity

0.83top 10%

GOF

0.5562th %ile

LOF

0.2874th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

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

ClinVar Variant Classifications

113 submitted variants in ClinVar

ClinVar

Classification Summary

VUS107

Likely Benign5

Benign1

107

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	0	107	0	107
Likely Benign	1	1	3	5
Benign	0	1	0	1
Total	1	109	3	113

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

View in ClinVar →

11 pathogenic / likely-pathogenic (of 19) ClinVar copy-number / structural variants overlap HSPA6 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →