Dorfman-Chanarin disease

Summary

Dorfman-Chanarin disease (MONDO:0010155) is a disease caused by ABHD5 (GenCC Definitive), with 2 cohort genes.

At a glance

• Prevalence: <1 / 1 000 000 (Europe)
• Causal gene: ABHD5 (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 132
• Phenotypes (HPO): 32

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	<1 / 1 000 000		Europe	Not yet validated

Signs & symptoms

Clinical features (HPO)

32 HPO clinical features (Orphanet curated; top 32 by frequency):

HPO ID	Term	Frequency
HP:0007479	Congenital nonbullous ichthyosiform erythroderma	Very frequent (80-99%)
HP:0009073	Progressive proximal muscle weakness	Very frequent (80-99%)
HP:0001288	Gait disturbance	Frequent (30-79%)
HP:0000385	Small earlobe	Frequent (30-79%)
HP:0000407	Sensorineural hearing impairment	Frequent (30-79%)
HP:0000486	Strabismus	Frequent (30-79%)
HP:0000508	Ptosis	Frequent (30-79%)
HP:0000523	Subcapsular cataract	Frequent (30-79%)
HP:0000639	Nystagmus	Frequent (30-79%)
HP:0000656	Ectropion	Frequent (30-79%)
HP:0001251	Ataxia	Frequent (30-79%)
HP:0001263	Global developmental delay	Frequent (30-79%)
HP:0001284	Areflexia	Frequent (30-79%)
HP:0001397	Hepatic steatosis	Frequent (30-79%)
HP:0001596	Alopecia	Frequent (30-79%)
HP:0001638	Cardiomyopathy	Frequent (30-79%)
HP:0001911	Abnormality of granulocytes	Frequent (30-79%)
HP:0002155	Hypertriglyceridemia	Frequent (30-79%)
HP:0002240	Hepatomegaly	Frequent (30-79%)
HP:0002910	Elevated circulating hepatic transaminase concentration	Frequent (30-79%)
HP:0002922	Increased CSF protein concentration	Frequent (30-79%)
HP:0003198	Myopathy	Frequent (30-79%)
HP:0003458	EMG: myopathic abnormalities	Frequent (30-79%)
HP:0003547	Shoulder girdle muscle weakness	Frequent (30-79%)
HP:0004322	Short stature	Frequent (30-79%)
HP:0012240	Increased intramyocellular lipid droplets	Frequent (30-79%)
HP:0012472	Eclabion	Frequent (30-79%)
HP:0040081	Abnormal circulating creatine kinase concentration	Frequent (30-79%)
HP:0001413	Micronodular cirrhosis	Occasional (5-29%)
HP:0007009	Central nervous system degeneration	Occasional (5-29%)
HP:0001513	Obesity	Excluded (0%)
HP:0001946	Ketosis	Excluded (0%)

Identifiers

Disease identifiers

Field	Value
Canonical name	Dorfman-Chanarin disease
Mondo ID	MONDO:0010155
OMIM	275630
Orphanet	98907
ICD-11	690728790
SNOMED CT	19604005
UMLS	C0268238
MedGen	82780
GARD	0003979
NORD	1283
Is cancer (heuristic)	no

Also known as: CDS · Chanarin-Dorfman Syndrome · Chanarin-Dorfman syndrome · DCs · disorder of cornification 12 (neutral lipid storage type) · Dorfman Chanarin syndrome · neutral lipid storage disease with ichthyosis · neutral lipid storage disease with ichthyotic · NLSDI

Data availability: 132 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › inborn errors of metabolism › inherited lipid metabolism disorder › disorder of phospholipids, sphingolipids and fatty acids biosynthesis › neutral lipid storage disease › Dorfman-Chanarin disease

Related subtypes (2): neutral lipid storage myopathy, triglyceride deposit cardiomyovasculopathy

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

132 retrieved; paginated sample, class counts are floors:

71 uncertain significance, 21 benign, 16 pathogenic, 10 conflicting classifications of pathogenicity, 4 likely pathogenic, 4 likely benign, 3 pathogenic/likely pathogenic, 3 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1323838	NM_016006.6(ABHD5):c.838C>T (p.Arg280Ter)	ABHD5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1693338	NM_016006.6(ABHD5):c.1006G>T (p.Glu336Ter)	ABHD5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2203346	NM_016006.6(ABHD5):c.700C>T (p.Arg234Ter)	ABHD5	Pathogenic	criteria provided, multiple submitters, no conflicts
2734489	NM_016006.6(ABHD5):c.507-1G>A	ABHD5	Pathogenic	criteria provided, single submitter
3236337	NM_016006.6(ABHD5):c.889C>T (p.Arg297Ter)	ABHD5	Pathogenic	no assertion criteria provided
3236338	ABHD5, ARG184TER	ABHD5	Pathogenic	no assertion criteria provided
5347	NM_016006.6(ABHD5):c.774-1G>A	ABHD5	Pathogenic	no assertion criteria provided
5348	NM_016006.6(ABHD5):c.98C>G (p.Ser33Ter)	ABHD5	Pathogenic	no assertion criteria provided
5349	NM_016006.6(ABHD5):c.134-2A>G	ABHD5	Pathogenic	no assertion criteria provided
5350	NM_016006.6(ABHD5):c.389A>C (p.Gln130Pro)	ABHD5	Pathogenic	no assertion criteria provided
5352	NM_016006.6(ABHD5):c.594dup (p.Arg199fs)	ABHD5	Pathogenic	no assertion criteria provided
5353	NM_016006.6(ABHD5):c.778G>A (p.Glu260Lys)	ABHD5	Pathogenic	no assertion criteria provided
5354	NM_016006.6(ABHD5):c.46_47del (p.Arg16fs)	ABHD5	Pathogenic	no assertion criteria provided
619125	NM_016006.6(ABHD5):c.934C>T (p.Arg312Ter)	ABHD5	Pathogenic	criteria provided, single submitter
812597	NM_016006.6(ABHD5):c.811G>A (p.Gly271Arg)	ABHD5	Pathogenic	criteria provided, single submitter
872540	NM_016006.6(ABHD5):c.730dup (p.Thr244fs)	ABHD5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
973467	NM_016006.6(ABHD5):c.550C>T (p.Arg184Ter)	ABHD5	Pathogenic	criteria provided, multiple submitters, no conflicts
977526	NM_016006.6(ABHD5):c.810T>A (p.Tyr270Ter)	ABHD5	Pathogenic	criteria provided, single submitter
996655	NM_016006.6(ABHD5):c.836del (p.Gln279fs)	ABHD5	Pathogenic	criteria provided, single submitter
2627677	NC_000003.12:g.43688574_43691430del	ABHD5	Likely pathogenic	criteria provided, single submitter
2627793	NC_000003.11:g.(?43743409)(43744194_?)del	ABHD5	Likely pathogenic	criteria provided, single submitter
3250431	NM_016006.6(ABHD5):c.683dup (p.Leu228fs)	ABHD5	Likely pathogenic	criteria provided, single submitter
3340145	NM_016006.6(ABHD5):c.345T>A (p.Ser115Arg)	ABHD5	Likely pathogenic	criteria provided, single submitter
1651331	NM_016006.6(ABHD5):c.258A>C (p.Gly86=)	ABHD5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
345217	NM_016006.6(ABHD5):c.228T>G (p.Thr76=)	ABHD5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
345219	NM_016006.6(ABHD5):c.430T>C (p.Leu144=)	ABHD5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
345221	NM_016006.6(ABHD5):c.662-10T>G	ABHD5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
345223	NM_016006.6(ABHD5):c.885C>T (p.Gly295=)	ABHD5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
748282	NM_016006.6(ABHD5):c.48-4C>G	ABHD5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
900235	NM_016006.6(ABHD5):c.444C>T (p.Ile148=)	ABHD5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · 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
ABHD5	Definitive	Autosomal recessive	Dorfman-Chanarin disease	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ABHD5	Orphanet:98907	Neutral lipid storage disease with ichthyosis
ANO10	Orphanet:284289	Adult-onset autosomal recessive cerebellar ataxia

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
ABHD5	HGNC:21396	ENSG00000011198	Q8WTS1	1-acylglycerol-3-phosphate O-acyltransferase ABHD5	gencc,clinvar
ANO10	HGNC:25519	ENSG00000160746	Q9NW15	Anoctamin-10	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ABHD5	1-acylglycerol-3-phosphate O-acyltransferase ABHD5	Coenzyme A-dependent lysophosphatidic acid acyltransferase that catalyzes the transfer of an acyl group on a lysophosphatidic acid.
ANO10	Anoctamin-10	Does not exhibit calcium-activated chloride channel (CaCC) activity.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · 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	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ABHD5	Other/Unknown	no		AB_hydrolase_1, AB_hydrolase_fold
ANO10	Other/Unknown	no		Anoctamin, Anoctamin_TM

Expression context

Cohort genes with no expression data: 0.

2 cohort genes 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
amniotic fluid	1
lower esophagus mucosa	1
upper leg skin	1
duodenum	1
mucosa of transverse colon	1
stromal cell of endometrium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ABHD5	276	ubiquitous	marker	amniotic fluid, lower esophagus mucosa, upper leg skin
ANO10	271	ubiquitous	marker	stromal cell of endometrium, mucosa of transverse colon, duodenum

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ABHD5	2,084
ANO10	766

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ANO10	Q9NW15	5

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ABHD5	Q8WTS1	87.62

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 14. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Induction of Cell-Cell Fusion	1	439.2×	0.020	ANO10
Triglyceride metabolism	1	335.9×	0.020	ABHD5
Triglyceride catabolism	1	237.9×	0.020	ABHD5
Late SARS-CoV-2 Infection Events	1	146.4×	0.024	ANO10
Stimuli-sensing channels	1	68.0×	0.041	ANO10
Ion channel transport	1	48.0×	0.048	ANO10
SARS-CoV-2 Infection	1	40.2×	0.049	ANO10
SARS-CoV Infections	1	27.7×	0.063	ANO10
Metabolism of lipids	1	15.8×	0.089	ABHD5
Viral Infection Pathways	1	15.4×	0.089	ANO10
Transport of small molecules	1	12.6×	0.092	ANO10
Infectious disease	1	12.4×	0.092	ANO10
Disease	1	6.5×	0.158	ANO10
Metabolism	1	5.8×	0.165	ABHD5

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
negative regulation of triglyceride storage	1	2808.7×	0.003	ABHD5
positive regulation of triglyceride catabolic process	1	1053.2×	0.004	ABHD5
phosphatidic acid biosynthetic process	1	255.3×	0.010	ABHD5
lipid homeostasis	1	168.5×	0.012	ABHD5
chloride transmembrane transport	1	118.7×	0.012	ANO10
monoatomic ion transmembrane transport	1	104.0×	0.012	ANO10
fatty acid metabolic process	1	96.8×	0.012	ABHD5
cell differentiation	1	14.6×	0.068	ABHD5

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 2 evidence-associated genes (50%) 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
ABHD5	NIFEDIPINE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ABHD5	8	4
ANO10	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
NIFEDIPINE	4	ABHD5
BENZBROMARONE	4	ABHD5
ETHACRYNIC ACID	4	ABHD5
MENADIONE	4	ABHD5
DISULFIRAM	4	ABHD5
INAMRINONE	4	ABHD5
CURCUMIN	3	ABHD5
EBSELEN	3	ABHD5

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
ABHD5	2	Binding:2

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

8 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)
NIFEDIPINE	4	ABHD5
BENZBROMARONE	4	ABHD5
ETHACRYNIC ACID	4	ABHD5
MENADIONE	4	ABHD5
DISULFIRAM	4	ABHD5
INAMRINONE	4	ABHD5
CURCUMIN	3	ABHD5
EBSELEN	3	ABHD5

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	ABHD5
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	ANO10

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)
ANO10	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.