HIKESHI

heat shock protein nuclear import factor hikeshi

Basic information

Region (hg38): 11:86302211-86345943

Previous symbols: [ "C11orf73" ]

Links

ENSG00000149196 ∙ NCBI:51501 ∙ OMIM:614908 ∙ HGNC:26938 ∙ Uniprot:Q53FT3 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• c11orf73-related autosomal recessive hypomyelinating leukodystrophy (Moderate), mode of inheritance: AR
• hypomyelinating leukodystrophy 13 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Leukodystrophy, hypomyelinating, 13	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Cardiovascular; Neurologic	26545878

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the HIKESHI gene.

• HIKESHI-related disorder (1 variants)
• not provided (1 variants)
• Hypomyelinating leukodystrophy 13 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HIKESHI gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				13	2	15
missense	1		14	1		16
nonsense			1			1
start loss						0
frameshift		1				1
inframe indel						0
splice donor/acceptor (+/-2bp)		1				1
splice region			1	3		4
non coding				8	3	11
Total	1	2	15	22	5

Highest pathogenic variant AF is 0.0000920

Variants in HIKESHI

This is a list of pathogenic ClinVar variants found in the HIKESHI region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
11-86306229-G-A			Benign (Jan 22, 2024)
11-86306230-T-A			Likely benign (Jan 11, 2024)
11-86306241-C-T			Likely benign (Jan 13, 2024)
11-86306244-G-T			Likely pathogenic (Sep 08, 2016)
11-86306266-G-A			Uncertain significance (Aug 16, 2022)
11-86306279-A-C		Inborn genetic diseases	Uncertain significance (Aug 09, 2022)
11-86306313-C-T			Likely benign (Jan 24, 2024)
11-86306344-A-G			Likely benign (Jan 22, 2024)
11-86306346-C-T			Likely benign (Dec 01, 2022)
11-86306353-C-T			Uncertain significance (Dec 06, 2022)
11-86306362-A-G			Uncertain significance (Jun 22, 2022)
11-86306374-G-C		Hypomyelinating leukodystrophy 13 • HIKESHI-related disorder	Pathogenic (Aug 12, 2024)
11-86306378-A-G		Inborn genetic diseases	Conflicting classifications of pathogenicity (Nov 27, 2023)
11-86306388-T-C			Likely benign (Jun 12, 2022)
11-86306414-G-A			Uncertain significance (Dec 13, 2021)
11-86306414-G-T			Uncertain significance (Oct 03, 2022)
11-86306418-A-G			Benign (Jan 22, 2024)
11-86306446-C-T			Uncertain significance (Mar 01, 2019)
11-86306450-G-T			Uncertain significance (Dec 19, 2021)
11-86306489-A-G			Likely benign (Sep 16, 2022)
11-86306492-A-G			Likely benign (Dec 27, 2021)
11-86306496-A-T			Likely benign (Dec 04, 2023)
11-86337359-C-G			Likely benign (Jan 22, 2024)
11-86337359-C-T			Benign (Jan 26, 2024)
11-86337360-A-G			Likely benign (Mar 01, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HIKESHI	protein_coding	protein_coding	ENST00000278483	5	43717

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.525	0.472	125725	0	12	125737	0.0000477

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.933	75	101	0.739	0.00000462	1286
Missense in Polyphen		24	32.706	0.7338		439
Synonymous	0.425	32	35.2	0.909	0.00000167	377
Loss of Function	2.46	2	10.7	0.188	5.38e-7	122

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000579	0.0000579
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000926	0.0000924
European (Non-Finnish)	0.0000711	0.0000703
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Acts as a specific nuclear import carrier for HSP70 proteins following heat-shock stress: acts by mediating the nucleoporin-dependent translocation of ATP-bound HSP70 proteins into the nucleus. HSP70 proteins import is required to protect cells from heat shock damages. Does not translocate ADP-bound HSP70 proteins into the nucleus. {ECO:0000269|PubMed:22541429}.
• Disease: DISEASE: Leukodystrophy, hypomyelinating, 13 (HLD13) [MIM:616881]: An autosomal recessive neurodegenerative disorder with infantile onset, affecting mainly the central white matter. Clinical features include early feeding difficulties, global developmental delay, postnatal progressive microcephaly, truncal hypotonia, spasticity, and variable neurologic deficits, such as visual impairment. {ECO:0000269|PubMed:26545878}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Regulation of HSF1-mediated heat shock response;Cellular responses to stress;Cellular responses to external stimuli;Cellular response to heat stress (Consensus)

Recessive Scores

• pRec: 0.113

Intolerance Scores

• rvis_EVS: 0.04
• rvis_percentile_EVS: 56.64

Haploinsufficiency Scores

• pHI: 0.813
• hipred: Y
• hipred_score: 0.530
• ghis: 0.610

Essentials

• essential_gene_gene_trap: N

Mouse Genome Informatics

• Gene name: Hikeshi
• Phenotype: homeostasis/metabolism phenotype; respiratory system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span)

Gene ontology

• Biological process: protein import into nucleus;Golgi organization;protein transport;lung development;cellular response to heat;regulation of cellular response to heat
• Cellular component: nucleus;nucleoplasm;cytosol
• Molecular function: protein transporter activity;Hsp70 protein binding