fatty acyl-CoA reductase 1 deficiency

Summary

fatty acyl-CoA reductase 1 deficiency (MONDO:0014510) is a disease caused by FAR1 (GenCC Definitive), with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: FAR1 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 10
• Phenotypes (HPO): 22

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		3	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

22 HPO clinical features (Orphanet curated; top 22 by frequency):

HPO ID	Term	Frequency
HP:0000253	Progressive microcephaly	Frequent (30-79%)
HP:0001118	Juvenile cataract	Frequent (30-79%)
HP:0001249	Intellectual disability	Frequent (30-79%)
HP:0001250	Seizure	Frequent (30-79%)
HP:0001263	Global developmental delay	Frequent (30-79%)
HP:0001285	Spastic tetraparesis	Frequent (30-79%)
HP:0001510	Growth delay	Frequent (30-79%)
HP:0001999	Abnormal facial shape	Frequent (30-79%)
HP:0004322	Short stature	Frequent (30-79%)
HP:0000219	Thin upper lip vermilion	Occasional (5-29%)
HP:0000316	Hypertelorism	Occasional (5-29%)
HP:0000319	Smooth philtrum	Occasional (5-29%)
HP:0000343	Long philtrum	Occasional (5-29%)
HP:0000400	Macrotia	Occasional (5-29%)
HP:0000508	Ptosis	Occasional (5-29%)
HP:0001272	Cerebellar atrophy	Occasional (5-29%)
HP:0001305	Dandy-Walker malformation	Occasional (5-29%)
HP:0002540	Inability to walk	Occasional (5-29%)
HP:0002553	Highly arched eyebrow	Occasional (5-29%)
HP:0003196	Short nose	Occasional (5-29%)
HP:0003698	Difficulty standing	Occasional (5-29%)
HP:0005280	Depressed nasal bridge	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	fatty acyl-CoA reductase 1 deficiency
Mondo ID	MONDO:0014510
OMIM	616154
Orphanet	438178
DOID	DOID:0081243
UMLS	C4015344
MedGen	863781
GARD	0013319
Is cancer (heuristic)	no

Also known as: FAR1 deficiency · fatty acyl-CoA reductase 1 deficiency · fatty acyl-CoA reductase 1 disorder · fatty acyl-CoA reductase 1 disorder or fatty acyl-CoA reductase 1 deficiency · peroxisomal fatty acyl-CoA reductase 1 disorder · PFCRD · rhizomelic chondrodysplasia punctata type 4 · severe intellectual disability-epilepsy-cataract syndrome due to FAR1 deficiency · severe intellectual disability-epilepsy-cataract syndrome due to fatty acyl-CoA reductase 1 deficiency · severe intellectual disability-epilepsy-cataract syndrome due to peroxisomal disorder

Data availability: 10 ClinVar variants · 5 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › disorder of orbital region › eye disorder › fatty acyl-CoA reductase 1 deficiency

Related subtypes (119): ptosis, eye accommodation disease, corneal disorder, asthenopia, lens disorder, keratomalacia, scleral disorder, ocular siderosis, coloboma, luxation of globe, mucopolysaccharidosis type 1, lacrimal apparatus disorder, Foster-Kennedy syndrome, anterior dislocation of lens, uveal disorder, eyelid disorder, ocular hypotension, scotoma, exophthalmos, ophthalmia nodosa, eye degenerative disorder, refractive error, glaucoma, retinal disorder, eye allergy, ocular vascular disorder, optic neuritis, conjunctival disorder, ocular hypertension, Tietz syndrome, Alagille syndrome, glaucoma-sleep apnea syndrome, Marshall syndrome, microcornea-glaucoma-absent frontal sinuses syndrome, nail-patella syndrome, oculodentodigital dysplasia, piebaldism, Sturge-Weber syndrome, cerebrotendinous xanthomatosis, ocular cystinosis, alpha-mannosidosis, megalocornea-intellectual disability syndrome, mucolipidosis type IV, mucopolysaccharidosis type 6, Netherton syndrome, galactosialidosis, Niemann-Pick disease type A, ocular motor apraxia, Cogan type, Peters plus syndrome, isolated Pierre-Robin syndrome, ectodermal dysplasia-blindness syndrome, Sandhoff disease, SHORT syndrome, Sjogren-Larsson syndrome, Smith-Lemli-Opitz syndrome, Tay-Sachs disease, tyrosinemia type II, Ito hypomelanosis, X-linked cone dysfunction syndrome with myopia, red color blindness, oculocerebrorenal syndrome, Lowry-MacLean syndrome, pigment dispersion syndrome, hereditary hyperferritinemia with congenital cataracts, dyssegmental dysplasia-glaucoma syndrome, mevalonic aciduria, familial cavitary optic disk anomaly, blindness - scoliosis - arachnodactyly syndrome, microcephaly-intellectual disability-sensorineural hearing loss-epilepsy-abnormal muscle tone syndrome, neurotrophic keratopathy, Cogan syndrome, atopic keratoconjunctivitis, rhizomelic chondrodysplasia punctata, Ehlers-Danlos syndrome, kyphoscoliotic type 1, IRVAN syndrome, Rothmund-Thomson syndrome type 2, microcornea-corectopia-macular hypoplasia syndrome, isolated anophthalmia-microphthalmia syndrome, Spasmus nutans, toxic maculopathy due to antimalarial drugs, syndromic recessive X-linked ichthyosis, acute zonal occult outer retinopathy, acute annular outer retinopathy, phakomatosis pigmentovascularis, lamellar ichthyosis, idiopathic linear interstitial keratitis, chondroectodermal dysplasia with night blindness, galactosemia, GM1 gangliosidosis, Gaucher disease, visual snow syndrome, extensive peripapillary myelinated nerve fibers, IgG4-related ophthalmic disorder, global developmental delay-visual anomalies-progressive cerebellar atrophy-truncal hypotonia syndrome, vernal keratoconjunctivitis, Gardner syndrome, anterior segment dysgenesis, isolated ankyloblepharon filiforme adnatum, hereditary optic neuropathy, essential strabismus, Axenfeld anomaly, eye neoplasm, isolated blepharochalasis, punctate inner choroidopathy, eye infectious disorder, vitreous body disorder, 9q33.3q34.11 microdeletion syndrome, autoimmune/inflammatory optic neuropathy, LTBP2-related ocular dysgenesis, ocular growth disorder, ocular dysgenesis caused by defects in PAX6 regulation, choroidal neovascularization, anterior segment developmental abnormality with extraocular manifestations, congenital optic disk excavation, neuroocular syndrome, isolated angioid streaks, multiple evanescent white dot syndrome, stellate multiform amelanotic choroidopathy, macular telangiectasia

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

10 retrieved; paginated sample, class counts are floors:

3 uncertain significance, 3 likely pathogenic, 2 pathogenic, 1 conflicting classifications of pathogenicity, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
162213	NM_032228.6(FAR1):c.787C>T (p.Arg263Ter)	FAR1	Pathogenic	no assertion criteria provided
162214	NM_032228.6(FAR1):c.1094A>G (p.Asp365Gly)	FAR1	Pathogenic	no assertion criteria provided
162212	NM_032228.6(FAR1):c.495_507delinsT (p.Glu165_Pro169delinsAsp)	FAR1	Likely pathogenic	criteria provided, single submitter
3891774	NM_032228.6(FAR1):c.1522C>T (p.Arg508Ter)	FAR1	Likely pathogenic	criteria provided, single submitter
800893	NM_032228.6(FAR1):c.772G>A (p.Gly258Arg)	FAR1	Likely pathogenic	no assertion criteria provided
719360	NM_032228.6(FAR1):c.286G>A (p.Glu96Lys)	FAR1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1333446	NM_032228.6(FAR1):c.58G>A (p.Gly20Ser)	FAR1	Uncertain significance	criteria provided, multiple submitters, no conflicts
3652753	NM_032228.6(FAR1):c.546-13A>G	FAR1	Uncertain significance	criteria provided, multiple submitters, no conflicts
973461	NM_032228.6(FAR1):c.1016A>G (p.Asn339Ser)	FAR1	Uncertain significance	criteria provided, multiple submitters, no conflicts
732045	NM_032228.6(FAR1):c.909T>C (p.Tyr303=)	FAR1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 8 · 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
FAR1	Definitive	Autosomal recessive	fatty acyl-CoA reductase 1 deficiency	8

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
FAR1	Orphanet:438178	Fatty acyl-CoA reductase 1 deficiency
FAR1	Orphanet:615938	Spastic paraparesis-cataracts-speech delay 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
FAR1	HGNC:26222	ENSG00000197601	Q8WVX9	Fatty acyl-CoA reductase 1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
FAR1	Fatty acyl-CoA reductase 1	Catalyzes the reduction of saturated and unsaturated C16 or C18 fatty acyl-CoA to fatty alcohols.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Enzyme (other)	1	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
FAR1	Enzyme (other)	yes	1.2.1.84	FAR_NAD-bd, FAR, FAR_C

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
corpus callosum	1
esophagus squamous epithelium	1
jejunal mucosa	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
FAR1	252	ubiquitous	marker	corpus callosum, esophagus squamous epithelium, jejunal mucosa

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
FAR1	1,666

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
FAR1	Q8WVX9	94.13

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. 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
Wax biosynthesis	1	2855.0×	4e-04	FAR1

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
wax biosynthetic process	1	4213.0×	5e-04	FAR1
long-chain fatty-acyl-CoA metabolic process	1	2407.4×	5e-04	FAR1
ether lipid biosynthetic process	1	1872.4×	5e-04	FAR1
glycerophospholipid biosynthetic process	1	1872.4×	5e-04	FAR1

Therapeutics

Drug target analysis

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

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

Top cohort targets by molecule count

Symbol	Molecules	Max phase
FAR1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
FAR1	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
FAR1	1.2.1.84	alcohol-forming fatty acyl-CoA reductase (NADPH)

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	1	FAR1
E	Difficult family or no structure, no drug	0

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)
FAR1	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.