FAR1

fatty acyl-CoA reductase 1, the group of Short chain dehydrogenase/reductase superfamily

Basic information

Region (hg38): 11:13668659-13732346

Previous symbols: [ "MLSTD2" ]

Links

ENSG00000197601 ∙ NCBI:84188 ∙ OMIM:616107 ∙ HGNC:26222 ∙ Uniprot:Q8WVX9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• fatty acyl-CoA reductase 1 deficiency (Moderate), mode of inheritance: AR
• fatty acyl-CoA reductase 1 deficiency (Strong), mode of inheritance: AR
• fatty acyl-CoA reductase 1 deficiency (Supportive), mode of inheritance: AR
• hereditary spastic paraplegia 9A (Supportive), mode of inheritance: AD
• spastic paraparesis-cataracts-speech delay syndrome (Strong), mode of inheritance: AD
• fatty acyl-CoA reductase 1 upregulation (Moderate), mode of inheritance: AD
• fatty acyl-CoA reductase 1 deficiency (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cataracts, spastic paraparesis, and speech delay; Peroxisomal fatty acyl-CoA reductase 1 disorder	AD/AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Biochemical; Craniofacial; Neurologic; Ophthalmologic	26220973; 33239752

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the FAR1 gene.

• not provided (5 variants)
• CATARACTS, SPASTIC PARAPLEGIA, AND SPEECH DELAY (1 variants)
• CATARACTS, SPASTIC PARAPARESIS, AND SPEECH DELAY (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the FAR1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			4	84	2	90
missense	1	3	128	1		133
nonsense	3					3
start loss						0
frameshift	1		1			2
inframe indel		1	2			3
splice donor/acceptor (+/-2bp)						0
splice region			8	17	2	27
non coding			2	55	18	75
Total	5	4	137	140	20

Highest pathogenic variant AF is 0.0000132

Variants in FAR1

This is a list of pathogenic ClinVar variants found in the FAR1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
11-13694635-G-A			Benign (Jul 11, 2020)
11-13694777-C-T			Benign/Likely benign (Feb 01, 2024)
11-13694778-C-G			Uncertain significance (Jun 28, 2023)
11-13694789-T-C			Likely benign (Mar 04, 2022)
11-13694801-C-T			Likely benign (Oct 16, 2023)
11-13694802-G-A			Uncertain significance (Aug 24, 2023)
11-13694802-GTCC-G			Uncertain significance (Nov 24, 2023)
11-13694819-T-G			Likely benign (Dec 11, 2023)
11-13694822-C-T			Likely benign (May 20, 2023)
11-13694823-G-A		Fatty acyl-CoA reductase 1 deficiency	Uncertain significance (Oct 22, 2023)
11-13694829-C-G			Uncertain significance (Sep 15, 2021)
11-13694853-T-C			Likely benign (May 27, 2023)
11-13694867-T-C			Likely benign (Nov 29, 2022)
11-13694869-C-G			Uncertain significance (Oct 01, 2022)
11-13694876-G-A			Likely benign (Nov 12, 2021)
11-13694887-A-G			Uncertain significance (Apr 29, 2022)
11-13694900-G-A			Likely benign (Dec 18, 2023)
11-13694901-C-G			Uncertain significance (Jul 12, 2022)
11-13694909-T-G			Likely benign (Jul 12, 2022)
11-13694921-A-G			Likely benign (Mar 01, 2022)
11-13694925-G-C			Uncertain significance (Aug 10, 2022)
11-13694928-C-T			Pathogenic (Jan 01, 2022)
11-13694934-G-A			Uncertain significance (Mar 19, 2022)
11-13694940-G-A			Benign/Likely benign (Jan 30, 2024)
11-13694974-A-G			Likely benign (Dec 27, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
FAR1	protein_coding	protein_coding	ENST00000354817	11	63677

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.985	0.0150	125631	0	4	125635	0.0000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.30	124	279	0.444	0.0000145	3395
Missense in Polyphen		9	55.962	0.16082		714
Synonymous	0.534	89	95.6	0.931	0.00000496	958
Loss of Function	4.18	3	26.0	0.116	0.00000133	315

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000616	0.0000615
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000177	0.0000176
Middle Eastern	0.00	0.00
South Asian	0.0000341	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalyzes the reduction of saturated and unsaturated C16 or C18 fatty acyl-CoA to fatty alcohols (PubMed:15220348, PubMed:24108123). It plays an essential role in the production of ether lipids/plasmalogens which synthesis requires fatty alcohols (PubMed:20071337, PubMed:24108123). In parallel, it is also required for wax monoesters production since fatty alcohols also constitute a substrate for their synthesis (By similarity). {ECO:0000250|UniProtKB:Q922J9, ECO:0000269|PubMed:15220348, ECO:0000269|PubMed:20071337, ECO:0000269|PubMed:24108123}.
• Disease: DISEASE: Peroxisomal fatty acyl-CoA reductase 1 disorder (PFCRD) [MIM:616154]: An autosomal recessive metabolic disorder clinically characterized by severe intellectual disability, early-onset epilepsy, microcephaly, congenital cataracts, growth retardation, and spasticity. {ECO:0000269|PubMed:25439727}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Peroxisome - Homo sapiens (human);miR-targeted genes in epithelium - TarBase;miR-targeted genes in lymphocytes - TarBase;miR-targeted genes in muscle cell - TarBase;Metabolism of lipids;Metabolism;Wax biosynthesis (Consensus)

Recessive Scores

• pRec: 0.107

Intolerance Scores

• loftool: 0.345
• rvis_EVS: -0.21
• rvis_percentile_EVS: 38.58

Haploinsufficiency Scores

• pHI: 0.430
• hipred: Y
• hipred_score: 0.685
• ghis: 0.581

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: H
• gene_indispensability_pred: E
• gene_indispensability_score: 0.843

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Far1

Gene ontology

• Biological process: ether lipid biosynthetic process;wax biosynthetic process;long-chain fatty-acyl-CoA metabolic process;glycerophospholipid biosynthetic process;oxidation-reduction process
• Cellular component: peroxisome;peroxisomal membrane;integral component of peroxisomal membrane;peroxisomal matrix
• Molecular function: oxidoreductase activity;fatty-acyl-CoA reductase (alcohol-forming) activity;alcohol-forming fatty acyl-CoA reductase activity