HIKESHI

Chr 11AR

heat shock protein nuclear import factor hikeshi

Also known as: C11orf73, HLD13, HSPC138, HSPC179, L7RN6, OPI10

The protein functions as a nuclear transport receptor that specifically imports ATP-bound HSP70 heat shock proteins into the nucleus during cellular stress responses. Mutations cause hypomyelinating leukodystrophy 13, an autosomal recessive disorder affecting white matter development in the brain. This gene shows moderate constraint against loss-of-function variants (LOEUF 0.59), suggesting some tolerance to functional disruption.

OMIMResearchSummary from RefSeq, OMIM, UniProt
DNmechanismARLOEUF 0.591 OMIM phenotype
Clinical SummaryHIKESHI
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Gene-Disease Validity (ClinGen)
hypomyelinating leukodystrophy 13 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.52) — some intolerance to loss-of-function variants.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.59LOEUF
pLI 0.525
Z-score 2.46
OE 0.19 (0.080.59)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
0.93Z-score
OE missense 0.74 (0.610.90)
75 obs / 101.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.19 (0.080.59)
00.351.4
Missense OE0.74 (0.610.90)
00.61.4
Synonymous OE0.91
01.21.6
LoF obs/exp: 2 / 10.7Missense obs/exp: 75 / 101.5Syn Z: 0.43
DN
0.6357th %ile
GOF
0.5954th %ile
LOF
0.4332th %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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

HIKESHI · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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