HIKESHI

Summary

HIKESHI (heat shock protein nuclear import factor hikeshi, HGNC:26938) is a protein-coding gene on chromosome 11q14.2, encoding Protein Hikeshi (Q53FT3). 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. It is a selective cancer dependency (DepMap: 12.3% of cell lines).

This gene encodes an evolutionarily conserved nuclear transport receptor that mediates heat-shock-induced nuclear import of 70 kDa heat-shock proteins (Hsp70s) through interactions with FG-nucleoporins. The protein mediates transport of the ATP form but not the ADP form of Hsp70 proteins under conditions of heat shock stress. Structural analyses demonstrate that the protein forms an asymmetric homodimer and that the N-terminal domain consists of a jelly-roll/beta-sandwich fold structure that contains hydrophobic pockets involved in FG-nucleoporin recognition. Reduction of RNA expression levels in HeLa cells using small interfering RNAs results in inhibition of heat shock-induced nuclear accumulation of Hsp70s, indicating a role for this gene in regulation of Hsp70 nuclear import during heat shock stress.

Source: NCBI Gene 51501 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hypomyelinating leukodystrophy 13 (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 1
• Clinical variants (ClinVar): 70 total — 1 pathogenic, 4 likely-pathogenic
• Phenotypes (HPO): 25
• Cancer dependency (DepMap): dependent in 12.3% of screened cell lines
• MANE Select transcript: NM_016401

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26938
Approved symbol	HIKESHI
Name	heat shock protein nuclear import factor hikeshi
Location	11q14.2
Locus type	gene with protein product
Status	Approved
Aliases	HSPC138, HSPC179, OPI10
Ensembl gene	ENSG00000149196
Ensembl biotype	protein_coding
OMIM	614908
Entrez	51501

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 10 protein_coding, 3 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000278483, ENST00000528004, ENST00000529405, ENST00000530208, ENST00000531485, ENST00000532270, ENST00000533986, ENST00000909754, ENST00000932065, ENST00000932066, ENST00000932067, ENST00000932068, ENST00000932069, ENST00000932070, ENST00000932071

RefSeq mRNA: 4 — MANE Select: NM_016401 NM_001322404, NM_001322407, NM_001322409, NM_016401

CCDS: CCDS8275

Canonical transcript exons

ENST00000278483 — 5 exons

Exon	Start	End
ENSE00002165443	86302240	86302478
ENSE00003552301	86344603	86344721
ENSE00003579101	86337379	86337530
ENSE00003587354	86345584	86345943
ENSE00003690964	86306245	86306482

Expression profiles

Bgee: expression breadth ubiquitous, 254 present calls, max score 98.03.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 50.2899 / max 455.4540, expressed in 1819 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
116105	30.3284	1815
116104	18.4423	1809
116107	0.9016	360
116106	0.6176	325

Top tissues by expression

258 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
left ventricle myocardium	UBERON:0006566	98.03	gold quality
myocardium	UBERON:0002349	97.38	gold quality
tibialis anterior	UBERON:0001385	97.27	gold quality
cardiac muscle of right atrium	UBERON:0003379	97.15	gold quality
quadriceps femoris	UBERON:0001377	97.01	gold quality
vastus lateralis	UBERON:0001379	96.96	gold quality
deltoid	UBERON:0001476	96.65	gold quality
biceps brachii	UBERON:0001507	96.54	gold quality
upper arm skin	UBERON:0004263	96.33	gold quality
hindlimb stylopod muscle	UBERON:0004252	96.32	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	96.02	gold quality
cortical plate	UBERON:0005343	95.90	gold quality
ganglionic eminence	UBERON:0004023	95.77	gold quality
ventricular zone	UBERON:0003053	95.54	gold quality
heart right ventricle	UBERON:0002080	95.49	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	95.46	gold quality
skeletal muscle tissue	UBERON:0001134	95.43	gold quality
muscle tissue	UBERON:0002385	95.43	gold quality
popliteal artery	UBERON:0002250	94.93	gold quality
tibial artery	UBERON:0007610	94.93	gold quality
heart left ventricle	UBERON:0002084	94.90	gold quality
cardiac ventricle	UBERON:0002082	94.87	gold quality
left coronary artery	UBERON:0001626	94.84	gold quality
skeletal muscle organ	UBERON:0014892	94.84	gold quality
heart	UBERON:0000948	94.67	gold quality
aorta	UBERON:0000947	94.62	gold quality
coronary artery	UBERON:0001621	94.58	gold quality
right coronary artery	UBERON:0001625	94.54	gold quality
descending thoracic aorta	UBERON:0002345	94.50	gold quality
muscle of leg	UBERON:0001383	94.46	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.29
E-MTAB-6524	no	343.29

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

23 targeting HIKESHI, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6740-5P	100.00	65.64	932
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-7856-5P	99.75	69.99	2901
HSA-MIR-4328	99.57	71.06	4094
HSA-MIR-329-5P	99.27	68.11	1597
HSA-MIR-1264	99.25	66.81	1317
HSA-MIR-4464	98.95	67.73	820
HSA-MIR-4748	98.95	67.53	810
HSA-MIR-1-5P	98.70	68.66	1017
HSA-MIR-676-5P	98.49	68.87	1492
HSA-MIR-4662A-5P	98.48	67.18	1007
HSA-MIR-15B-3P	97.85	66.68	974
HSA-MIR-3198	97.84	65.64	579
HSA-MIR-4309	97.84	65.45	588
HSA-MIR-6783-5P	97.67	67.21	1528
HSA-MIR-4790-3P	96.63	67.08	806
HSA-MIR-431-5P	96.16	66.50	652
HSA-MIR-103B	95.51	66.85	441

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 12.3% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 9)

• identify a nuclear import pathway that operates during heat shock stress and is mediated by an evolutionarily conserved protein, Hikeshi (coded by the C11orf73 gene) binds to FG-Nups and translocates through nuclear pores on its own, showing characteristic features of nuclear transport carriers. (PMID:22541429)
• The crystal structure of Hikeshi explains how Hikeshi participates in the regulation of nuclear import through the recognition of FG-Nups and which part of Hikeshi affects its binding to Hsp70. (PMID:25760597)
• Leukoencephalopathy and early death associated with an Ashkenazi-Jewish founder mutation in the Hikeshi gene.P.V54L mutation in Hikeshi is associated with absence of nuclear HSP70 during heat shock stress. (PMID:26545878)
• A novel homozygous variant in HIKESHI was identified in a patient with hypomyelinating leukoencephalopathy with periventricular cysts and vermian atrophy. Modified interactions inside Hikeshi’s hydrophobic pockets induce mutant protein instability. (PMID:28000699)
• Our results suggest that HIKESHI is a marker of cancer progression and that the combination of HIKESHI inhibition and hyperthermia is a therapeutic tool for refractory gastric cancer (PMID:28731175)
• Depletion of Hikeshi renders HeLa cells proteotoxic stress-sensitive through the abrogation of the nuclear function of HSP70s required for HSF1 regulation. (PMID:28980748)
• HIKESHI silencing can enhance mild hyperthermia sensitivity in human oral squamous cell carcinoma HSC3 cells. (PMID:32377716)
• Further Delineation of the Clinical and Pathologic Features of HIKESHI-Related Hypomyelinating Leukodystrophy. (PMID:34111619)
• The interaction between the import carrier Hikeshi and HSP70 is modulated by heat, facilitating the nuclear import of HSP70 under heat stress conditions. (PMID:38987995)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	hikeshi	ENSDARG00000104071
mus_musculus	Hikeshi	ENSMUSG00000062797
rattus_norvegicus	Hikeshi	ENSRNOG00000017383
drosophila_melanogaster	CG13926	FBGN0035243
caenorhabditis_elegans		WBGENE00018328

Protein

Protein identifiers

Protein Hikeshi — Q53FT3 (reviewed: Q53FT3)

All UniProt accessions (3): Q53FT3, E9PJB2, E9PPG8

UniProt curated annotations — full annotation on UniProt →

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.

Subunit / interactions. Forms an asymmetric homodimer; required for binding and nuclear import of HSP70 proteins. Interacts with ATP-bound HSP70 proteins. Interacts with NUP62 and NUP153 (via F-X-F-G repeats). Interacts with HSPA8.

Subcellular location. Cytoplasm. Cytosol. Nucleus.

Disease relevance. 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. The disease is caused by variants affecting the gene represented in this entry.

Induction. Following heat-shock treatment.

Miscellaneous. ‘Hikeshi’ is a traditional Japanese compound word used for a firefighter, smokejumper, or troubleshooter.

Similarity. Belongs to the OPI10 family.

RefSeq proteins (4): NP_001309333, NP_001309336, NP_001309338, NP_057485* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008493	Hikeshi-like_N	Domain
IPR031318	OPI10	Family
IPR048364	Hikeshi-like_C	Domain

Pfam: PF05603, PF21057

UniProt features (30 total): strand 11, mutagenesis site 7, helix 5, region of interest 2, sequence variant 2, chain 1, sequence conflict 1, turn 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
3WVZ	X-RAY DIFFRACTION	1.88
3WW0	X-RAY DIFFRACTION	2.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q53FT3-F1	89.34	0.68

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Mutagenesis-validated functional residues (7):

Position	Phenotype
132–135	decreases nuclear import activity of hspa8. does not affect the dimer formation. markedly decreases binding to hspa8.
141	decreases nuclear import activity of hspa8. does not affect the dimer formation. decreases binding to hspa8.
18	impairs the nuclear migrating activity.
24	reduces the nuclear migrating activity.
55	reduces the nuclear migrating activity.
77	decreases nuclear import activity of hspa8. does not affect the dimer formation. impairs binding to hspa8.
97	increases the nuclear migrating activity.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-3371453	Regulation of HSF1-mediated heat shock response

MSigDB gene sets: 198 (showing top): GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_DN, CHIANG_LIVER_CANCER_SUBCLASS_UNANNOTATED_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_ORGANELLE, GOBP_NUCLEAR_TRANSPORT, MODULE_301, HNF4_01, GOBP_ENDOMEMBRANE_SYSTEM_ORGANIZATION, GOBP_CELLULAR_RESPONSE_TO_HEAT, GOBP_RESPONSE_TO_ABIOTIC_STIMULUS, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN, GOBP_PROTEIN_LOCALIZATION_TO_ORGANELLE, NIKOLSKY_BREAST_CANCER_11Q12_Q14_AMPLICON, BRACHAT_RESPONSE_TO_METHOTREXATE_DN

GO Biological Process (5): protein import into nucleus (GO:0006606), Golgi organization (GO:0007030), protein transport (GO:0015031), lung development (GO:0030324), cellular response to heat (GO:0034605)

GO Molecular Function (3): Hsp70 protein binding (GO:0030544), nuclear import signal receptor activity (GO:0061608), protein binding (GO:0005515)

GO Cellular Component (6): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytosol (GO:0005829), nuclear body (GO:0016604), nuclear speck (GO:0016607), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Cellular response to heat stress	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
import into nucleus	2
intracellular protein transport	1
protein localization to nucleus	1
establishment of protein localization to organelle	1
organelle organization	1
endomembrane system organization	1
transport	1
intracellular protein localization	1
establishment of protein localization	1
respiratory tube development	1
animal organ development	1
respiratory system development	1
response to heat	1
cellular response to stress	1
heat shock protein binding	1
protein-folding chaperone binding	1
nucleocytoplasmic carrier activity	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cytoplasm	1
nucleoplasm	1
intracellular membraneless organelle	1
nuclear ribonucleoprotein granule	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1312 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HIKESHI	HSPA4	P34932	660
HIKESHI	IPO13	O94829	488
HIKESHI	IPO5	O00410	475
HIKESHI	ATXN1	P54253	409
HIKESHI	TNPO1	Q92973	403
HIKESHI	NFYB	P25208	395
HIKESHI	NUTF2	P13662	392
HIKESHI	RCC1	P18754	389
HIKESHI	TNPO2	O14787	386
HIKESHI	TFDP2	Q14188	383
HIKESHI	TFB2M	Q9H5Q4	371
HIKESHI	XPO7	Q9UIA9	368
HIKESHI	RPS3	P23396	360
HIKESHI	HYCC1	Q9BYI3	359
HIKESHI	EDRF1	Q3B7T1	350

IntAct

35 interactions, top by confidence:

A	B	Type	Score
ABLIM3	HIKESHI	psi-mi:“MI:0915”(physical association)	0.560
OTX2	HIKESHI	psi-mi:“MI:0915”(physical association)	0.560
COMMD10	VPS26C	psi-mi:“MI:0914”(association)	0.530
HIKESHI	CLEC3A	psi-mi:“MI:0914”(association)	0.530
RCVRN	RAB9A	psi-mi:“MI:0914”(association)	0.530
ZNF581	DMWD	psi-mi:“MI:0914”(association)	0.530
SIRPD	HIKESHI	psi-mi:“MI:0914”(association)	0.530
LPAR1	TMEM223	psi-mi:“MI:0914”(association)	0.530
HIKESHI	NUP62	psi-mi:“MI:0407”(direct interaction)	0.440
Nup153	HIKESHI	psi-mi:“MI:0407”(direct interaction)	0.440
PHB1	HIKESHI	psi-mi:“MI:0915”(physical association)	0.400
RCAN1	CLEC3A	psi-mi:“MI:0914”(association)	0.350
IFNL3	HIKESHI	psi-mi:“MI:0914”(association)	0.350
SOCS2	HIKESHI	psi-mi:“MI:0914”(association)	0.350
ARMC6	DDX39A	psi-mi:“MI:0914”(association)	0.350
CHRM4	EXOC5	psi-mi:“MI:0914”(association)	0.350
DNAJC25	TUBAL3	psi-mi:“MI:0914”(association)	0.350
GSDME	DDX39A	psi-mi:“MI:0914”(association)	0.350
HPN	DDX39A	psi-mi:“MI:0914”(association)	0.350
PEX7	UBA6	psi-mi:“MI:0914”(association)	0.350
PPT1	CLGN	psi-mi:“MI:0914”(association)	0.350
		psi-mi:“MI:0914”(association)	0.350
HIKESHI	HSPA1A	psi-mi:“MI:0914”(association)	0.350
PTBP3		psi-mi:“MI:0914”(association)	0.350

BioGRID (28): CLEC3A (Affinity Capture-MS), C11orf73 (Affinity Capture-MS), C11orf73 (Affinity Capture-MS), C11orf73 (Affinity Capture-MS), TRMT61B (Affinity Capture-MS), C11orf73 (Affinity Capture-MS), C11orf73 (Affinity Capture-MS), OTX2 (Two-hybrid), ABLIM3 (Two-hybrid), C11orf73 (Positive Genetic), C11orf73 (Affinity Capture-RNA), C11orf73 (Affinity Capture-MS), TRMT61B (Affinity Capture-MS), C11orf73 (Affinity Capture-MS), C11orf73 (Affinity Capture-MS)

ESM2 similar proteins: A4IGP0, A4VY70, A4W4G5, A8H9H9, B0TPR8, I7GVL4, O76616, P05820, P08364, P0A382, P0CA97, P11077, P11078, P12397, P15480, P22047, P22351, P25219, P29802, P35259, P51737, P61825, P94594, Q04470, Q04916, Q06906, Q06VD5, Q09380, Q0PI70, Q16RI1, Q29E01, Q51887, Q53FT3, Q55385, Q568T4, Q56JY0, Q5M808, Q5RED5, Q5ZK09, Q6C3T0

Diamond homologs: A4IGP0, O60175, Q16RI1, Q29E01, Q53FT3, Q568T4, Q56JY0, Q5M808, Q5ZK09, Q6DCU7, Q7PRB5, Q9DD02, Q9W0C7

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

70 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	4
Uncertain significance	20
Likely benign	32
Benign	4

Top pathogenic / likely-pathogenic (5)

Variant ID	HGVS	Classification
1808656	GRCh37/hg19 11q14.1-14.3(chr11:80562738-88663067)x1	Pathogenic
2585407	NM_016401.4(HIKESHI):c.344del (p.Val115fs)	Likely pathogenic
3248553	NM_016401.4(HIKESHI):c.518C>T (p.Pro173Leu)	Likely pathogenic
376818	NM_016401.4(HIKESHI):c.31-1G>T	Likely pathogenic
4270825	NM_016401.4(HIKESHI):c.505G>T (p.Glu169Ter)	Likely pathogenic

SpliceAI

1299 predictions. Top by Δscore:

Variant	Effect	Δscore
11:86306241:CTA:C	acceptor_loss	1.0000
11:86306243:A:G	acceptor_loss	1.0000
11:86306482:GGTAA:G	donor_loss	1.0000
11:86306483:GTAA:G	donor_loss	1.0000
11:86306484:T:A	donor_loss	1.0000
11:86337373:TTGCA:T	acceptor_loss	1.0000
11:86337376:CA:C	acceptor_loss	1.0000
11:86337377:A:AG	acceptor_gain	1.0000
11:86337377:A:C	acceptor_loss	1.0000
11:86337378:G:GG	acceptor_gain	1.0000
11:86337378:GGA:G	acceptor_gain	1.0000
11:86337531:G:GC	donor_loss	1.0000
11:86337532:T:A	donor_loss	1.0000
11:86345578:TTCTA:T	acceptor_loss	1.0000
11:86345579:TCTAG:T	acceptor_loss	1.0000
11:86345580:CTAG:C	acceptor_loss	1.0000
11:86345581:TAG:T	acceptor_loss	1.0000
11:86306243:A:AG	acceptor_gain	0.9900
11:86306244:G:GG	acceptor_gain	0.9900
11:86306244:GGT:G	acceptor_gain	0.9900
11:86306483:G:GG	donor_gain	0.9900
11:86334744:GCC:G	donor_gain	0.9900
11:86337374:T:A	acceptor_gain	0.9900
11:86337377:AG:A	acceptor_gain	0.9900
11:86337378:GG:G	acceptor_gain	0.9900
11:86337378:GGAGA:G	acceptor_gain	0.9900
11:86344516:T:G	donor_gain	0.9900
11:86344601:A:AG	acceptor_gain	0.9900
11:86344602:G:GA	acceptor_gain	0.9900
11:86344602:GTT:G	acceptor_gain	0.9900

AlphaMissense

1287 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:86306321:T:A	V36D	0.999
11:86306327:T:A	V38D	0.999
11:86306369:G:A	G52E	0.999
11:86306375:T:A	V54D	0.999
11:86306425:G:A	G71R	0.999
11:86306425:G:C	G71R	0.999
11:86306426:G:A	G71E	0.999
11:86306449:A:C	S79R	0.999
11:86306451:T:A	S79R	0.999
11:86306451:T:G	S79R	0.999
11:86344720:T:A	W180R	0.999
11:86344720:T:C	W180R	0.999
11:86345627:T:A	W195R	0.999
11:86345627:T:C	W195R	0.999
11:86302456:G:A	G3D	0.998
11:86302470:G:T	G8W	0.998
11:86306329:T:C	F39L	0.998
11:86306331:T:A	F39L	0.998
11:86306331:T:G	F39L	0.998
11:86306413:T:A	W67R	0.998
11:86306413:T:C	W67R	0.998
11:86306426:G:T	G71V	0.998
11:86306432:T:A	V73D	0.998
11:86306458:T:C	F82L	0.998
11:86306459:T:C	F82S	0.998
11:86306460:C:A	F82L	0.998
11:86306460:C:G	F82L	0.998
11:86337445:G:A	G112E	0.998
11:86344640:C:A	A153D	0.998
11:86302455:G:C	G3R	0.997

dbSNP variants (sampled 300 via entrez): RS1000070503 (11:86323334 G>A,C), RS1000117490 (11:86335662 T>C,G), RS1000153503 (11:86313203 C>A), RS1000214254 (11:86340438 G>A), RS1000260739 (11:86305800 G>A), RS1000423540 (11:86323127 C>T), RS1000462158 (11:86313082 C>G,T), RS1000522962 (11:86327906 G>T), RS1000698952 (11:86327569 C>T), RS1000744574 (11:86315432 C>T), RS1000765269 (11:86321639 C>T), RS1000818611 (11:86318294 A>G,T), RS1000839197 (11:86334145 A>C,G), RS1000852695 (11:86312847 G>A,C), RS1000881745 (11:86322680 G>T)

Disease associations

OMIM: gene MIM:614908 | disease phenotypes: MIM:616881

GenCC curated gene-disease

Disease	Classification	Inheritance
hypomyelinating leukodystrophy 13	Strong	Autosomal recessive
c11orf73-related autosomal recessive hypomyelinating leukodystrophy	Moderate	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
hypomyelinating leukodystrophy 13	Definitive	AR

Mondo (2): hypomyelinating leukodystrophy 13 (MONDO:0014813), c11orf73-related autosomal recessive hypomyelinating leukodystrophy (MONDO:0044642)

Orphanet (0):

HPO phenotypes

25 total (25 of 25 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000505	Visual impairment
HP:0000639	Nystagmus
HP:0000648	Optic atrophy
HP:0000737	Irritability
HP:0001251	Ataxia
HP:0001257	Spasticity
HP:0001263	Global developmental delay
HP:0001276	Hypertonia
HP:0001344	Absent speech
HP:0001347	Hyperreflexia
HP:0001508	Failure to thrive
HP:0002013	Vomiting
HP:0002061	Lower limb spasticity
HP:0002169	Clonus
HP:0002188	Delayed CNS myelination
HP:0002267	Exaggerated startle response
HP:0002415	Leukodystrophy
HP:0002518	Abnormal periventricular white matter morphology
HP:0003593	Infantile onset
HP:0004466	Delayed brainstem auditory evoked response conduction time
HP:0005484	Secondary microcephaly
HP:0008936	Axial hypotonia
HP:0011968	Feeding difficulties
HP:0034392	Joint contracture

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST000477_41	Cognitive performance	2.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0003926	neuropsychological test

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

37 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases abundance, increases expression	2
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, decreases expression	2
dicrotophos	decreases expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
bisphenol A	increases methylation	1
beta-lapachone	increases expression	1
arsenite	affects binding, increases reaction	1
potassium chromate(VI)	decreases expression, affects cotreatment	1
methacrylaldehyde	increases oxidation, increases abundance, affects cotreatment	1
epigallocatechin gallate	decreases expression, affects cotreatment	1
di-n-butylphosphoric acid	affects expression	1
pyrimidifen	increases expression	1
Bortezomib	increases expression, increases response to substance	1
Resveratrol	affects cotreatment, increases expression	1
Vorinostat	increases expression	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Arsenic	increases abundance, increases expression	1
Diethylstilbestrol	increases expression	1
Doxorubicin	increases expression	1
Gallic Acid	increases expression	1
Ivermectin	decreases expression	1
Lead	affects splicing	1
Ozone	affects cotreatment, increases oxidation, increases abundance	1
Plant Extracts	affects cotreatment, increases expression	1
Silver	increases expression	1
Testosterone	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	decreases expression	1
Valproic Acid	decreases methylation	1
Cyclosporine	increases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.