attenuated Chédiak-Higashi syndrome

Summary

attenuated Chédiak-Higashi syndrome (MONDO:0018133) is a disease with 1 cohort gene.

At a glance

• Prevalence: (Worldwide) [Orphanet-validated]
• Cohort genes: 1
• Phenotypes (HPO): 15

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		100	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Europe	Not yet validated

Signs & symptoms

Clinical features (HPO)

15 HPO clinical features (Orphanet curated; top 15 by frequency):

HPO ID	Term	Frequency
HP:0000225	Gingival bleeding	Very frequent (80-99%)
HP:0000421	Epistaxis	Very frequent (80-99%)
HP:0000978	Bruising susceptibility	Very frequent (80-99%)
HP:0001107	Ocular albinism	Very frequent (80-99%)
HP:0001249	Intellectual disability	Very frequent (80-99%)
HP:0001928	Abnormality of coagulation	Very frequent (80-99%)
HP:0002205	Recurrent respiratory infections	Very frequent (80-99%)
HP:0002721	Immunodeficiency	Very frequent (80-99%)
HP:0007513	Generalized hypopigmentation	Very frequent (80-99%)
HP:0009830	Peripheral neuropathy	Very frequent (80-99%)
HP:0200042	Skin ulcer	Very frequent (80-99%)
HP:0001276	Hypertonia	Occasional (5-29%)
HP:0002071	Abnormality of extrapyramidal motor function	Occasional (5-29%)
HP:0002311	Incoordination	Occasional (5-29%)
HP:0100022	Abnormality of movement	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	attenuated Chédiak-Higashi syndrome
Mondo ID	MONDO:0018133
Orphanet	352723
SNOMED CT	720520009
UMLS	C4304022
MedGen	929691
GARD	0021527
Is cancer (heuristic)	no

Also known as: attenuated Chediak-Higashi syndrome · atypical Chediak-Higashi syndrome · atypical Chédiak-Higashi syndrome

Data availability: 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › peripheral nervous system disorder › peripheral neuropathy › hereditary peripheral neuropathy › attenuated Chédiak-Higashi syndrome

Related subtypes (64): giant axonal neuropathy, Finnish type amyloidosis, familial amyloid neuropathy, carpal tunnel syndrome, congenital trigeminal anesthesia, familial recurrent peripheral facial palsy, meralgia paraesthetica, familial, amyotrophic neuralgia, hereditary neuropathy with liability to pressure palsies, abetalipoproteinemia, VPS13A-related neurodegenerative disease, mitochondrial DNA depletion syndrome 4a, oxoglutaricaciduria, cerebrotendinous xanthomatosis, Chediak-Higashi syndrome, homocystinuria due to methylene tetrahydrofolate reductase deficiency, Krabbe disease, beta-mannosidosis, biotinidase deficiency, Leigh syndrome, hereditary sensory and autonomic neuropathy with spastic paraplegia, ornithine aminotransferase deficiency, adult polyglucosan body disease, Sandhoff disease, Tay-Sachs disease, methylmalonic aciduria and homocystinuria type cblC, familial isolated deficiency of vitamin E, Kearns-Sayre syndrome, NARP syndrome, Charcot-Marie-Tooth disease type 5, hereditary motor and sensory neuropathy, Okinawa type, fumaric aciduria, spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 1, sensory ataxic neuropathy, dysarthria, and ophthalmoparesis, Niemann-Pick disease type B, long chain 3-hydroxyacyl-CoA dehydrogenase deficiency, primary CD59 deficiency, PHARC syndrome, progressive demyelinating neuropathy with bilateral striatal necrosis, cataract-growth hormone deficiency-sensory neuropathy-sensorineural hearing loss-skeletal dysplasia syndrome, ataxia - oculomotor apraxia type 4, adrenomyeloneuropathy, neuropathy with hearing impairment, hereditary motor and sensory neuropathy, hereditary sensory and autonomic neuropathy, Charcot-Marie-Tooth disease, infantile axonal neuropathy, mitochondrial neurogastrointestinal encephalomyopathy, coenzyme Q10 deficiency, familial episodic pain syndrome, non-progressive predominantly posterior cavitating leukoencephalopathy with peripheral neuropathy, metachromatic leukodystrophy, distal hereditary motor neuropathy, spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2, proximal spinal muscular atrophy, pyruvate dehydrogenase deficiency, peroxisome biogenesis disorder, neurodegeneration with brain iron accumulation 2A, neuropathy, congenital hypomelinating, optic atrophy-ataxia-peripheral neuropathy-global developmental delay syndrome, EMILIN-1-related connective tissue disease, PRPS1 deficiency disorder, neuropathy, hereditary sensory and autonomic, type IId, peripheral motor neuropathy, childhood-onset, biotin-responsive

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
LYST	Definitive	Autosomal recessive	Chediak-Higashi syndrome	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
LYST	Orphanet:167	Chédiak-Higashi syndrome
LYST	Orphanet:352723	Attenuated Chédiak-Higashi syndrome

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
LYST	HGNC:1968	ENSG00000143669	Q99698	Lysosomal-trafficking regulator	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
LYST	Lysosomal-trafficking regulator	Adapter protein that regulates and/or fission of intracellular vesicles such as lysosomes.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Scaffold/PPI	1	17.3×	0.058

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
LYST	Scaffold/PPI	no		BEACH_dom, WD40_rpt, PH-like_dom_sf

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
leukocyte	1
monocyte	1
mononuclear cell	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
LYST	278	ubiquitous	marker	monocyte, mononuclear cell, leukocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
LYST	1,556

Structural data

PDB: 0 · AlphaFold-only: 1 · No structure: 0

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
LYST	Q99698

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
mast cell secretory granule organization	1	8426.0×	0.001	LYST
endosome to lysosome transport via multivesicular body sorting pathway	1	2808.7×	0.002	LYST
leukocyte chemotaxis	1	1053.2×	0.003	LYST
pigmentation	1	702.2×	0.003	LYST
melanosome organization	1	648.1×	0.003	LYST
defense response to protozoan	1	601.9×	0.003	LYST
natural killer cell mediated cytotoxicity	1	432.1×	0.004	LYST
phagocytosis	1	240.7×	0.006	LYST
defense response to bacterium	1	108.0×	0.011	LYST
defense response to virus	1	69.3×	0.016	LYST
protein transport	1	43.9×	0.023	LYST

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
LYST	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	LYST

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
LYST	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.