Griscelli syndrome type 1

Summary

Griscelli syndrome type 1 (MONDO:0008962) is a disease caused by MYO5A (GenCC Definitive), with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: MYO5A (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 35
• Phenotypes (HPO): 16

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		20	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

16 HPO clinical features (Orphanet curated; top 16 by frequency):

HPO ID	Term	Frequency
HP:0000488	Retinopathy	Very frequent (80-99%)
HP:0000639	Nystagmus	Very frequent (80-99%)
HP:0000651	Diplopia	Very frequent (80-99%)
HP:0001250	Seizure	Very frequent (80-99%)
HP:0001251	Ataxia	Very frequent (80-99%)
HP:0001276	Hypertonia	Very frequent (80-99%)
HP:0001290	Generalized hypotonia	Very frequent (80-99%)
HP:0002216	Premature graying of hair	Very frequent (80-99%)
HP:0007443	Partial albinism	Very frequent (80-99%)
HP:0007730	Iris hypopigmentation	Very frequent (80-99%)
HP:0011364	White hair	Very frequent (80-99%)
HP:0100022	Abnormality of movement	Very frequent (80-99%)
HP:0001249	Intellectual disability	Frequent (30-79%)
HP:0001263	Global developmental delay	Frequent (30-79%)
HP:0003077	Hyperlipidemia	Frequent (30-79%)
HP:0002514	Cerebral calcification	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	Griscelli syndrome type 1
Mondo ID	MONDO:0008962
MeSH	C537301
OMIM	214450
Orphanet	79476
DOID	DOID:0060832
ICD-11	875700770
UMLS	C1859194
MedGen	347092
GARD	0002566
Is cancer (heuristic)	no

Also known as: Griscelli syndrome type 1 · Griscelli syndrome, type 1 · Griscelli-PruniC)ras syndrome type 1 · Griscelli-Pruniéras syndrome type 1 · GS1 · hypopigmentation-neurologic impairment syndrome · pigmentary dilution of the skin and hair, the presence of large clumps of pigment in hair shafts

Data availability: 35 ClinVar variants · 5 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › syndromic oculocutaneous albinism › Griscelli syndrome › Griscelli syndrome type 1

Related subtypes (2): 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

35 retrieved; paginated sample, class counts are floors:

14 uncertain significance, 10 benign, 5 pathogenic, 2 likely pathogenic, 2 conflicting classifications of pathogenicity, 1 benign/likely benign, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
14069	NM_001382347.1(MYO5A):c.2332C>T (p.Arg778Ter)	MYO5A	Pathogenic	no assertion criteria provided
14070	MYO5A, 47-BP INS, NT4634	MYO5A	Pathogenic	no assertion criteria provided
1686909	NM_001382347.1(MYO5A):c.2110C>T (p.Gln704Ter)	MYO5A	Pathogenic	no assertion criteria provided
1686910	NM_001382347.1(MYO5A):c.463C>T (p.Arg155Ter)	MYO5A	Pathogenic	no assertion criteria provided
561060	NM_001382347.1(MYO5A):c.2012+1G>T	MYO5A	Pathogenic	criteria provided, single submitter
1334000	NM_001382347.1(MYO5A):c.3043C>T (p.Arg1015Ter)	MYO5A	Likely pathogenic	criteria provided, single submitter
4277733	NM_001382347.1(MYO5A):c.655C>T (p.Arg219Cys)	MYO5A	Likely pathogenic	criteria provided, single submitter
435922	NM_001382347.1(MYO5A):c.3136G>A (p.Val1046Met)	MYO5A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
742942	NM_001382347.1(MYO5A):c.2477G>A (p.Arg826His)	MYO5A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1369212	NM_001382347.1(MYO5A):c.4555+2C>T	MYO5A	Uncertain significance	criteria provided, multiple submitters, no conflicts
1703722	NM_001382347.1(MYO5A):c.656G>A (p.Arg219His)	MYO5A	Uncertain significance	no assertion criteria provided
2003594	NM_001382347.1(MYO5A):c.3103A>C (p.Lys1035Gln)	MYO5A	Uncertain significance	criteria provided, single submitter
2433968	NM_001382347.1(MYO5A):c.1930C>T (p.His644Tyr)	MYO5A	Uncertain significance	criteria provided, single submitter
2433970	NM_001382347.1(MYO5A):c.2527G>A (p.Val843Ile)	MYO5A	Uncertain significance	criteria provided, single submitter
2556876	NM_001382347.1(MYO5A):c.1870C>T (p.Pro624Ser)	MYO5A	Uncertain significance	criteria provided, multiple submitters, no conflicts
2627586	NM_001382347.1(MYO5A):c.1958C>T (p.Thr653Ile)	MYO5A	Uncertain significance	criteria provided, single submitter
3063583	NM_001382347.1(MYO5A):c.2438G>A (p.Arg813His)	MYO5A	Uncertain significance	criteria provided, multiple submitters, no conflicts
3063584	NM_001382347.1(MYO5A):c.5034C>G (p.Ile1678Met)	MYO5A	Uncertain significance	criteria provided, single submitter
3165076	NM_001382347.1(MYO5A):c.4879C>G (p.Leu1627Val)	MYO5A	Uncertain significance	criteria provided, multiple submitters, no conflicts
3401567	NM_001382347.1(MYO5A):c.3520G>A (p.Asp1174Asn)	MYO5A	Uncertain significance	criteria provided, multiple submitters, no conflicts
3891792	NM_001382347.1(MYO5A):c.2522C>T (p.Thr841Ile)	MYO5A	Uncertain significance	criteria provided, single submitter
3891793	NM_001382347.1(MYO5A):c.4720G>A (p.Asp1574Asn)	MYO5A	Uncertain significance	criteria provided, single submitter
592085	NM_001382347.1(MYO5A):c.3098T>G (p.Leu1033Trp)	MYO5A	Uncertain significance	criteria provided, single submitter
1238192	NM_001382347.1(MYO5A):c.2012+27A>G	MYO5A	Benign	criteria provided, multiple submitters, no conflicts
1247578	NM_001382347.1(MYO5A):c.3858+12dup	MYO5A	Benign	criteria provided, multiple submitters, no conflicts
1264010	NM_001382347.1(MYO5A):c.613-26A>G	MYO5A	Benign	criteria provided, multiple submitters, no conflicts
1321830	NM_001382347.1(MYO5A):c.2526C>T (p.Ile842=)	MYO5A	Benign	criteria provided, multiple submitters, no conflicts
1321831	NM_001382347.1(MYO5A):c.1086A>C (p.Glu362Asp)	MYO5A	Benign	criteria provided, multiple submitters, no conflicts
211572	NM_001382347.1(MYO5A):c.5409+4G>A	MYO5A	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
2500061	NM_001382347.1(MYO5A):c.534A>C (p.Arg178=)	MYO5A	Likely benign	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · Orphanet: 3 · 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
MYO5A	Definitive	Autosomal recessive	Griscelli syndrome type 1	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MYO5A	Orphanet:33445	Neuroectodermal melanolysosomal disease
MYO5A	Orphanet:79476	Griscelli syndrome type 1
MYO5A	Orphanet:79478	Griscelli syndrome type 3

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
MYO5A	HGNC:7602	ENSG00000197535	Q9Y4I1	Unconventional myosin-Va	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MYO5A	Unconventional myosin-Va	Processive actin-based motor that can move in large steps approximating the 36-nm pseudo-repeat of the actin filament.

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)
MYO5A	Scaffold/PPI	no		IQ_motif_EF-hand-BS, Myosin_head_motor_dom-like, Dilute_dom

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
endothelial cell	1
lateral nuclear group of thalamus	1
substantia nigra pars compacta	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MYO5A	277	ubiquitous	marker	lateral nuclear group of thalamus, endothelial cell, substantia nigra pars compacta

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MYO5A	4,333

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MYO5A	Q9Y4I1	7

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 21. 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×	0.011	MYO5A
Parasite infection	1	346.1×	0.011	MYO5A
Leishmania phagocytosis	1	346.1×	0.011	MYO5A
Fcgamma receptor (FCGR) dependent phagocytosis	1	278.5×	0.011	MYO5A
Peptide hormone metabolism	1	271.9×	0.011	MYO5A
Regulation of MITF-M-dependent genes involved in pigmentation	1	265.6×	0.011	MYO5A
FCGR3A-mediated phagocytosis	1	187.2×	0.011	MYO5A
Regulation of actin dynamics for phagocytic cup formation	1	184.2×	0.011	MYO5A
MITF-M-dependent gene expression	1	181.3×	0.011	MYO5A
Leishmania infection	1	163.1×	0.011	MYO5A
Parasitic Infection Pathways	1	163.1×	0.011	MYO5A
Translocation of SLC2A4 (GLUT4) to the plasma membrane	1	154.3×	0.011	MYO5A
MITF-M-regulated melanocyte development	1	114.2×	0.014	MYO5A
Membrane Trafficking	1	37.1×	0.040	MYO5A
Vesicle-mediated transport	1	34.8×	0.040	MYO5A
Innate Immune System	1	25.5×	0.050	MYO5A
Infectious disease	1	24.8×	0.050	MYO5A
Developmental Biology	1	14.5×	0.081	MYO5A
Disease	1	13.1×	0.081	MYO5A
Immune System	1	13.0×	0.081	MYO5A
Metabolism of proteins	1	12.4×	0.081	MYO5A

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
vesicle transport along actin filament	1	2407.4×	0.003	MYO5A
post-Golgi vesicle-mediated transport	1	1053.2×	0.003	MYO5A
actin filament-based movement	1	802.5×	0.003	MYO5A
melanosome transport	1	766.0×	0.003	MYO5A
cellular response to insulin stimulus	1	170.2×	0.012	MYO5A
actin filament organization	1	118.7×	0.012	MYO5A
protein localization to plasma membrane	1	108.7×	0.012	MYO5A
vesicle-mediated transport	1	96.3×	0.012	MYO5A
endocytosis	1	95.2×	0.012	MYO5A
protein transport	1	43.9×	0.023	MYO5A

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
MYO5A	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	MYO5A

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)
MYO5A	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.