FAR1

Chr 11ADAR

fatty acyl-CoA reductase 1

Also known as: CSPSD, MLSTD2, PFCRD, SDR10E1

The protein encoded by this gene is required for the reduction of fatty acids to fatty alcohols, a process that is required for the synthesis of monoesters and ether lipids. NADPH is required as a cofactor in this reaction, and 16-18 carbon saturated and unsaturated fatty acids are the preferred substrate. This is a peroxisomal membrane protein, and studies suggest that the N-terminus contains a large catalytic domain located on the outside of the peroxisome, while the C-terminus is exposed to the matrix of the peroxisome. Studies indicate that the regulation of this protein is dependent on plasmalogen levels. Mutations in this gene have been associated with individuals affected by severe intellectual disability, early-onset epilepsy, microcephaly, congenital cataracts, growth retardation, and spasticity (PMID: 25439727). A pseudogene of this gene is located on chromosome 13. [provided by RefSeq, Jan 2015]

Primary Disease Associations & Inheritance

Cataracts, spastic paraparesis, and speech delayMIM #619338
AD
Peroxisomal fatty acyl-CoA reductase 1 disorderMIM #616154
AR
0
Active trials
27
Pathogenic / LP
434
ClinVar variants
24
Pubs (1 yr)
3.3
Missense Z· constrained
0.30
LOEUF· LoF intolerant
Clinical SummaryFAR1
🧬
Gene-Disease Validity (ClinGen)
fatty acyl-CoA reductase 1 upregulation · ADModerate

Moderate evidence — consider for supplementary testing

2 total gene-disease associations curated

Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.99). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
27 Pathogenic / Likely Pathogenic· 194 VUS of 434 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Dual constrained — LoF & missense intolerant
LoF Constraint
0.30LOEUF
pLI 0.985
Z-score 4.18
OE 0.12 (0.050.30)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
3.30Z-score
OE missense 0.44 (0.380.52)
124 obs / 279.4 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.12 (0.050.30)
00.351.4
Missense OE0.44 (0.380.52)
00.61.4
Synonymous OE0.93
01.21.6
LoF obs/exp: 3 / 26.0Missense obs/exp: 124 / 279.4Syn Z: 0.53

ClinVar Variant Classifications

434 submitted variants in ClinVar

Classification Summary

Pathogenic20
Likely Pathogenic7
VUS194
Likely Benign188
Benign22
Conflicting3
20
Pathogenic
7
Likely Pathogenic
194
VUS
188
Likely Benign
22
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
2
17
0
20
Likely Pathogenic
1
4
2
0
7
VUS
2
171
14
7
194
Likely Benign
0
2
86
100
188
Benign
0
0
20
2
22
Conflicting
3
Total4179139109434

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

FAR1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

FAR1-related severe intellectual disability, epilepsy, and cataracts

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. DisordersEye
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Landmark / reviewRecent case evidence