Griscelli syndrome

Summary

Griscelli syndrome (MONDO:0018306) is a disease with 1 cohort gene and 4 clinical trials. Top therapeutic interventions include fludarabine phosphate.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 1
• ClinVar variants: 1
• Phenotypes (HPO): 36
• Clinical trials: 4

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		150	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

36 HPO clinical features (Orphanet curated; top 36 by frequency):

HPO ID	Term	Frequency
HP:0001053	Hypopigmented skin patches	Very frequent (80-99%)
HP:0002216	Premature graying of hair	Very frequent (80-99%)
HP:0002218	Silver-gray hair	Very frequent (80-99%)
HP:0011364	White hair	Very frequent (80-99%)
HP:0001315	Reduced tendon reflexes	Frequent (30-79%)
HP:0001873	Thrombocytopenia	Frequent (30-79%)
HP:0001874	Abnormality of neutrophils	Frequent (30-79%)
HP:0001882	Leukopenia	Frequent (30-79%)
HP:0002716	Lymphadenopathy	Frequent (30-79%)
HP:0002721	Immunodeficiency	Frequent (30-79%)
HP:0003119	Abnormal circulating lipid concentration	Frequent (30-79%)
HP:0004313	Decreased circulating antibody level	Frequent (30-79%)
HP:0000238	Hydrocephalus	Occasional (5-29%)
HP:0000499	Abnormal eyelash morphology	Occasional (5-29%)
HP:0000534	Abnormal eyebrow morphology	Occasional (5-29%)
HP:0000639	Nystagmus	Occasional (5-29%)
HP:0000952	Jaundice	Occasional (5-29%)
HP:0001249	Intellectual disability	Occasional (5-29%)
HP:0001250	Seizure	Occasional (5-29%)
HP:0001251	Ataxia	Occasional (5-29%)
HP:0001252	Hypotonia	Occasional (5-29%)
HP:0001257	Spasticity	Occasional (5-29%)
HP:0001263	Global developmental delay	Occasional (5-29%)
HP:0001541	Ascites	Occasional (5-29%)
HP:0001744	Splenomegaly	Occasional (5-29%)
HP:0001945	Fever	Occasional (5-29%)
HP:0002021	Pyloric stenosis	Occasional (5-29%)
HP:0002084	Encephalocele	Occasional (5-29%)
HP:0002240	Hepatomegaly	Occasional (5-29%)
HP:0004322	Short stature	Occasional (5-29%)
HP:0005528	Bone marrow hypocellularity	Occasional (5-29%)
HP:0006824	Cranial nerve paralysis	Occasional (5-29%)
HP:0007730	Iris hypopigmentation	Occasional (5-29%)
HP:0010741	Pedal edema	Occasional (5-29%)
HP:0012115	Hepatitis	Occasional (5-29%)
HP:0100022	Abnormality of movement	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	Griscelli syndrome
Mondo ID	MONDO:0018306
OMIM	214450
Orphanet	381
DOID	DOID:0060831
SNOMED CT	37548006
UMLS	C0398794
MedGen	585090
GARD	0010913
Is cancer (heuristic)	no

Also known as: ChC)diak-Higashi-like syndrome · Chédiak-Higashi-like syndrome · Ch��diak-Higashi-like syndrome · Griscelli disease · Griscelli-PruniC)ras syndrome · Griscelli-Pruniéras syndrome · Griscelli-Pruni��ras syndrome · partial albinism-immunodeficiency syndrome

Data availability: 1 ClinVar variant.

Disease family

An umbrella term covering 3 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › syndromic disease › syndromic oculocutaneous albinism › Griscelli syndrome

Related subtypes (3): Chediak-Higashi syndrome, oculocerebral hypopigmentation syndrome, Cross type, Hermansky-Pudlak syndrome

Subtypes (3): Griscelli syndrome type 1, Griscelli syndrome type 2, Griscelli syndrome type 3

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

ClinVar germline variants

1 retrieved; paginated sample, class counts are floors:

1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
504894	NM_183235.3(RAB27A):c.149del (p.Arg50fs)	RAB27A	Pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
RAB27A	Orphanet:79477	Griscelli syndrome type 2

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
RAB27A	HGNC:9766	ENSG00000069974	P51159	Ras-related protein Rab-27A	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RAB27A	Ras-related protein Rab-27A	The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · 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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
RAB27A	Other/Unknown	no		Small_GTPase, Small_GTP-bd, P-loop_NTPase

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
lower lobe of lung	1
monocyte	1
trabecular bone tissue	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RAB27A	275	ubiquitous	marker	trabecular bone tissue, monocyte, lower lobe of lung

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
RAB27A	1,970

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
RAB27A	P51159	11

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 5. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways 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.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Insulin processing	1	456.8×	0.009	RAB27A
Regulation of MITF-M-dependent genes involved in pigmentation	1	265.6×	0.009	RAB27A
RAB geranylgeranylation	1	173.0×	0.010	RAB27A
RAB GEFs exchange GTP for GDP on RABs	1	124.1×	0.010	RAB27A
Neutrophil degranulation	1	23.1×	0.043	RAB27A

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
multivesicular body organization	1	16852.0×	4e-04	RAB27A
cytotoxic T cell degranulation	1	16852.0×	4e-04	RAB27A
positive regulation of constitutive secretory pathway	1	16852.0×	4e-04	RAB27A
complement-dependent cytotoxicity	1	8426.0×	6e-04	RAB27A
exosomal secretion	1	4213.0×	8e-04	RAB27A
melanosome localization	1	3370.4×	8e-04	RAB27A
positive regulation of regulated secretory pathway	1	3370.4×	8e-04	RAB27A
natural killer cell degranulation	1	2407.4×	0.001	RAB27A
positive regulation of reactive oxygen species biosynthetic process	1	1123.5×	0.002	RAB27A
synaptic vesicle transport	1	842.6×	0.002	RAB27A
melanocyte differentiation	1	802.5×	0.002	RAB27A
multivesicular body sorting pathway	1	802.5×	0.002	RAB27A
melanosome transport	1	766.0×	0.002	RAB27A
antigen processing and presentation	1	702.2×	0.002	RAB27A
positive regulation of exocytosis	1	601.9×	0.002	RAB27A
positive regulation of phagocytosis	1	318.0×	0.004	RAB27A
protein secretion	1	263.3×	0.004	RAB27A
blood coagulation	1	173.7×	0.006	RAB27A
exocytosis	1	151.8×	0.007	RAB27A
positive regulation of gene expression	1	38.7×	0.026	RAB27A

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
RAB27A	COPANLISIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
RAB27A	1	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
COPANLISIB	4	RAB27A

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
RAB27A	3	Binding:3

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

1 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.

Compound	Max phase	Cohort target (bioactivity)
COPANLISIB	4	RAB27A

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	RAB27A
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	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 4.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	2
PHASE2/PHASE3	1
PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00176826	PHASE2/PHASE3	TERMINATED	T-Cell Depletion and Stem Cell Transplant for Immune Deficiencies and Histiocytic Disorders
NCT00176865	PHASE2	COMPLETED	Stem Cell Transplant for Immunologic or Histiocytic Disorders
NCT01652092	Not specified	ACTIVE_NOT_RECRUITING	Allogeneic Hematopoietic Stem Cell Transplant for Patients With Primary Immune Deficiencies
NCT05687474	Not specified	COMPLETED	Baby Detect : Genomic Newborn Screening

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
FLUDARABINE PHOSPHATE	4	2