FAR1

Summary

FAR1 (fatty acyl-CoA reductase 1, HGNC:26222) is a protein-coding gene on chromosome 11p15.3, encoding Fatty acyl-CoA reductase 1 (Q8WVX9). Catalyzes the reduction of saturated and unsaturated C16 or C18 fatty acyl-CoA to fatty alcohols.

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.

Source: NCBI Gene 84188 — RefSeq curated summary.

At a glance

• Gene–disease (curated): fatty acyl-CoA reductase 1 deficiency (Definitive, GenCC) — +3 more curated relationships
• GWAS associations: 8
• Clinical variants (ClinVar): 429 total — 8 pathogenic, 5 likely-pathogenic
• Phenotypes (HPO): 47
• Druggable target: yes
• MANE Select transcript: NM_032228

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26222
Approved symbol	FAR1
Name	fatty acyl-CoA reductase 1
Location	11p15.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ22728, SDR10E1
Ensembl gene	ENSG00000197601
Ensembl biotype	protein_coding
OMIM	616107
Entrez	84188

Gene structure

Transcript identifiers

Ensembl transcripts: 27 — 16 protein_coding, 7 nonsense_mediated_decay, 3 retained_intron, 1 non_stop_decay

ENST00000354817, ENST00000524933, ENST00000532502, ENST00000532701, ENST00000532769, ENST00000703358, ENST00000714146, ENST00000714147, ENST00000714153, ENST00000714154, ENST00000714155, ENST00000714156, ENST00000714157, ENST00000714158, ENST00000714159, ENST00000907330, ENST00000907331, ENST00000907332, ENST00000929686, ENST00000929687, ENST00000929688, ENST00000929689, ENST00000969261, ENST00000969262, ENST00000969263, ENST00000969264, ENST00000969265

RefSeq mRNA: 1 — MANE Select: NM_032228 NM_032228

CCDS: CCDS7813

Canonical transcript exons

ENST00000354817 — 12 exons

Exon	Start	End
ENSE00001131212	13694759	13694954
ENSE00003613114	13700317	13700492
ENSE00003988752	13728612	13732346
ENSE00004022987	13714509	13714680
ENSE00004022991	13707900	13708079
ENSE00004022997	13711764	13711808
ENSE00004022998	13721730	13721859
ENSE00004023005	13668668	13668806
ENSE00004023013	13712966	13713033
ENSE00004023014	13711928	13712046
ENSE00004023015	13710693	13710870
ENSE00004023023	13727556	13727683

Expression profiles

Bgee: expression breadth ubiquitous, 252 present calls, max score 98.10.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 34.3979 / max 473.6693, expressed in 1804 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
113175	18.7738	1785
113176	14.7294	1746
113178	0.4477	226
113177	0.4469	213

Top tissues by expression

256 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
corpus callosum	UBERON:0002336	98.10	gold quality
esophagus squamous epithelium	UBERON:0006920	96.34	gold quality
jejunal mucosa	UBERON:0000399	96.33	gold quality
oral cavity	UBERON:0000167	95.68	gold quality
monocyte	CL:0000576	95.59	gold quality
spinal cord	UBERON:0002240	95.48	gold quality
rectum	UBERON:0001052	95.44	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	95.44	gold quality
bone marrow cell	CL:0002092	95.43	gold quality
subthalamic nucleus	UBERON:0001906	95.39	gold quality
esophagus mucosa	UBERON:0002469	95.28	gold quality
leukocyte	CL:0000738	95.27	gold quality
inferior vagus X ganglion	UBERON:0005363	95.13	gold quality
colonic epithelium	UBERON:0000397	95.11	gold quality
bone marrow	UBERON:0002371	94.94	gold quality
pylorus	UBERON:0001166	94.90	gold quality
mucosa of sigmoid colon	UBERON:0004993	94.73	gold quality
calcaneal tendon	UBERON:0003701	94.48	gold quality
tibia	UBERON:0000979	94.13	gold quality
duodenum	UBERON:0002114	94.11	gold quality
colonic mucosa	UBERON:0000317	94.08	gold quality
smooth muscle tissue	UBERON:0001135	94.00	gold quality
medulla oblongata	UBERON:0001896	93.89	gold quality
lower esophagus mucosa	UBERON:0035834	93.52	gold quality
palpebral conjunctiva	UBERON:0001812	93.45	gold quality
Brodmann (1909) area 46	UBERON:0006483	93.37	gold quality
dorsal plus ventral thalamus	UBERON:0001897	93.35	gold quality
islet of Langerhans	UBERON:0000006	93.04	gold quality
stomach	UBERON:0000945	93.01	gold quality
tibial nerve	UBERON:0001323	92.93	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.22

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

191 targeting FAR1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-25-3P	99.98	74.60	1817

Literature-anchored findings (GeneRIF, showing 6)

• fatty alcohol synthesis in mammals is accomplished by two fatty acyl-CoA reductase isozymes that are expressed at high levels in tissues known to synthesize wax monoesters and ether lipids (PMID:15220348)
• wax monoester synthesis in mammals involves a two step biosynthetic pathway catalyzed by fatty acyl-CoA reductase and wax synthase enzymes (PMID:15220349)
• ether lipid biosynthesis in mammalian cells is regulated by a negative feedback mechanism that senses cellular plasmalogen levels and appropriately increases or decreases Far1 (PMID:20071337)
• Expression of Far1 increased plasmalogen synthesis in wild-type Chinese hamster ovary cells, strongly suggesting that Far1 is a rate-limiting enzyme for plasmalogen synthesis. (PMID:24108123)
• A peroxisomal disorder of severe intellectual disability, epilepsy, and cataracts due to fatty acyl-CoA reductase 1 deficiency. (PMID:25439727)
• An autosomal dominant neurological disorder caused by de novo variants in FAR1 resulting in uncontrolled synthesis of ether lipids. (PMID:33239752)

Cross-species orthologs

21 orthologs

Organism	Symbol	Gene ID
danio_rerio	far1	ENSDARG00000006899
mus_musculus	Far1	ENSMUSG00000030759
rattus_norvegicus	Far1	ENSRNOG00000013176
drosophila_melanogaster	FarO	FBGN0023550
drosophila_melanogaster	CG4020	FBGN0029821
drosophila_melanogaster	Sgp	FBGN0032055
drosophila_melanogaster	CG1441	FBGN0033464
drosophila_melanogaster	CG8306	FBGN0034142
drosophila_melanogaster	CG8303	FBGN0034143
drosophila_melanogaster	CG5065	FBGN0034145
drosophila_melanogaster	CG10096	FBGN0038032
drosophila_melanogaster	CG10097	FBGN0038033
drosophila_melanogaster	CG17562	FBGN0038449
drosophila_melanogaster	CG17560	FBGN0038450
drosophila_melanogaster	CG14893	FBGN0038451
drosophila_melanogaster	CG4770	FBGN0038751
drosophila_melanogaster	CG12268	FBGN0039131
drosophila_melanogaster	wat	FBGN0039620
drosophila_melanogaster	CG30427	FBGN0043792
drosophila_melanogaster	CG34342	FBGN0085371
caenorhabditis_elegans		WBGENE00022200

Paralogs (1): FAR2 (ENSG00000064763)

Protein

Protein identifiers

Fatty acyl-CoA reductase 1 — Q8WVX9 (reviewed: Q8WVX9)

Alternative names: Male sterility domain-containing protein 2

All UniProt accessions (10): A0A8V8TQT9, A0AAQ5BHJ7, A0AAQ5BHK0, A0AAQ5BHL0, A0AAQ5BHL3, A0AAQ5BHL4, A0AAQ5BHM1, A0AAQ5BHN8, E9PNW8, Q8WVX9

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the reduction of saturated and unsaturated C16 or C18 fatty acyl-CoA to fatty alcohols. It plays an essential role in the production of ether lipids/plasmalogens which synthesis requires fatty alcohols. In parallel, it is also required for wax monoesters production since fatty alcohols also constitute a substrate for their synthesis.

Subunit / interactions. Interacts with PEX19; PEX19 mediates the targeting of FAR1 to peroxisomes.

Subcellular location. Peroxisome membrane.

Disease relevance. 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. The disease is caused by variants affecting the gene represented in this entry. Cataracts, spastic paraparesis, and speech delay (CSPSD) [MIM:619338] An autosomal dominant disease characterized by bilateral cataracts apparent at birth or in infancy, spastic paraparesis, truncal hypotonia, delayed psychomotor development, and speech delay. The disease is caused by variants affecting the gene represented in this entry.

Induction. Down-regulated by ether lipids/plasmalogen that induce its degradation (at protein level).

Similarity. Belongs to the fatty acyl-CoA reductase family.

RefSeq proteins (1): NP_115604* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013120	FAR_NAD-bd	Domain
IPR026055	FAR	Family
IPR033640	FAR_C	Domain
IPR036291	NAD(P)-bd_dom_sf	Homologous_superfamily

Pfam: PF03015, PF07993

Enzyme classification (BRENDA):

• EC 1.2.1.84 — alcohol-forming fatty acyl-CoA reductase (NADPH) (BRENDA: 19 organisms, 75 substrates, 2 inhibitors, 1 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

1 substrates with measured Km, best-characterized 1. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
NADPH	0.06	1

Catalyzed reactions (Rhea), 8 shown:

• hexadecanoyl-CoA + 2 NADPH + 2 H(+) = hexadecan-1-ol + 2 NADP(+) + CoA (RHEA:36315)
• octadecanoyl-CoA + 2 NADPH + 2 H(+) = octadecan-1-ol + 2 NADP(+) + CoA (RHEA:36319)
• (9Z)-octadecenoyl-CoA + 2 NADPH + 2 H(+) = (9Z)-octadecen-1-ol + 2 NADP(+) + CoA (RHEA:36323)
• (9Z,12Z)-octadecadienoyl-CoA + 2 NADPH + 2 H(+) = (9Z,12Z)-octadecadien-1-ol + 2 NADP(+) + CoA (RHEA:36363)
• a long-chain fatty acyl-CoA + 2 NADPH + 2 H(+) = a long-chain primary fatty alcohol + 2 NADP(+) + CoA (RHEA:52716)
• eicosanoyl-CoA + 2 NADPH + 2 H(+) = eicosan-1-ol + 2 NADP(+) + CoA (RHEA:81727)
• 16-methylheptadecanoyl-CoA + 2 NADPH + 2 H(+) = 16-methylheptadecan-1-ol + 2 NADP(+) + CoA (RHEA:81763)
• 18-methylnonadecanoyl-CoA + 2 NADPH + 2 H(+) = 18-methylnonadecan-1-ol + 2 NADP(+) + CoA (RHEA:81767)

UniProt features (13 total): sequence variant 7, topological domain 2, chain 1, sequence conflict 1, transmembrane region 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8WVX9-F1	94.13	0.88

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9640463	Wax biosynthesis

MSigDB gene sets: 271 (showing top): RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, CEBPB_01, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, GOBP_PHOSPHOLIPID_BIOSYNTHETIC_PROCESS, GOBP_GLYCEROLIPID_METABOLIC_PROCESS, GTGCCTT_MIR506, GOBP_FATTY_ACYL_COA_METABOLIC_PROCESS, MILI_PSEUDOPODIA_HAPTOTAXIS_UP, GOBP_AMIDE_METABOLIC_PROCESS, ATTCTTT_MIR186

GO Biological Process (7): ether lipid biosynthetic process (GO:0008611), wax biosynthetic process (GO:0010025), long-chain fatty-acyl-CoA metabolic process (GO:0035336), glycerophospholipid biosynthetic process (GO:0046474), lipid metabolic process (GO:0006629), lipid biosynthetic process (GO:0008610), fatty acid derivative metabolic process (GO:1901568)

GO Molecular Function (5): oxidoreductase activity (GO:0016491), alcohol-forming very long-chain fatty acyl-CoA reductase activity (GO:0080019), alcohol-forming long-chain fatty acyl-CoA reductase activity (GO:0102965), protein binding (GO:0005515), oxidoreductase activity, acting on the aldehyde or oxo group of donors, NAD or NADP as acceptor (GO:0016620)

GO Cellular Component (3): peroxisome (GO:0005777), peroxisomal membrane (GO:0005778), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Wax and plasmalogen biosynthesis	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
lipid metabolic process	2
oxidoreductase activity, acting on the aldehyde or oxo group of donors, NAD or NADP as acceptor	2
lipid biosynthetic process	1
ether lipid metabolic process	1
glycerol ether biosynthetic process	1
wax metabolic process	1
fatty acid derivative biosynthetic process	1
fatty-acyl-CoA metabolic process	1
glycerophospholipid metabolic process	1
phospholipid biosynthetic process	1
glycerolipid biosynthetic process	1
primary metabolic process	1
biosynthetic process	1
catalytic activity	1
binding	1
oxidoreductase activity, acting on the aldehyde or oxo group of donors	1
microbody	1
peroxisome	1
microbody membrane	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1416 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FAR1	AGPS	O00116	841
FAR1	GNPAT	O15228	832
FAR1	PEX7	O00628	679
FAR1	PEX10	O60683	672
FAR1	TPP1	O14773	656
FAR1	ECI2	O75521	609
FAR1	ALDH3A2	P51648	572
FAR1	CGA	P01215	542
FAR1	PEX19	P40855	537
FAR1	PEX13	Q92968	516
FAR1	PEDS1	A5PLL7	510
FAR1	ACSL4	O60488	493
FAR1	PEX5	P50542	490
FAR1	PEX12	O00623	480
FAR1	CROT	Q9UKG9	476

IntAct

115 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
BAG6	FAR1	psi-mi:“MI:0915”(physical association)	0.560
KLF11	FAR1	psi-mi:“MI:0915”(physical association)	0.560
COL26A1	FAR1	psi-mi:“MI:0915”(physical association)	0.560
ILK	ILVBL	psi-mi:“MI:0914”(association)	0.530
EGFR	NDUFA4	psi-mi:“MI:0914”(association)	0.530
TUBA1A	TUBAL3	psi-mi:“MI:0914”(association)	0.420
FLT4	ILVBL	psi-mi:“MI:0914”(association)	0.420
MET	NDUFA4	psi-mi:“MI:2364”(proximity)	0.420
SDC1	ILVBL	psi-mi:“MI:0915”(physical association)	0.400
FAR1	ATXN1	psi-mi:“MI:0915”(physical association)	0.370
Rpl35	RPS6	psi-mi:“MI:0914”(association)	0.350
	ESYT2	psi-mi:“MI:0914”(association)	0.350
	HAX1	psi-mi:“MI:0914”(association)	0.350
MAPK6		psi-mi:“MI:0914”(association)	0.350
RIPK4	VWA8	psi-mi:“MI:0914”(association)	0.350
HA	ESYT2	psi-mi:“MI:0914”(association)	0.350

BioGRID (135): FAR1 (Affinity Capture-MS), FAR1 (Affinity Capture-MS), FAR1 (Affinity Capture-MS), FAR1 (Affinity Capture-MS), FAR1 (Affinity Capture-MS), FAR1 (Affinity Capture-MS), FAR1 (Proximity Label-MS), FAR1 (Affinity Capture-MS), FAR1 (Affinity Capture-MS), FAR1 (Affinity Capture-MS), FAR1 (Affinity Capture-MS), FAR1 (Affinity Capture-MS), FAR1 (Affinity Capture-MS), FAR1 (Affinity Capture-MS), FAR1 (Affinity Capture-MS)

ESM2 similar proteins: A0A0K0JFP3, A1ZAI3, A1ZAI5, B3MZN7, B3NY19, B4M891, B4NDG5, F1QLP1, O02298, O16881, O44952, O60825, P26285, P37059, P56523, P70265, Q02337, Q02338, Q0KHU5, Q0P5J1, Q0WRB0, Q1PEI6, Q39152, Q43793, Q5R834, Q5XGF7, Q5ZM72, Q66H50, Q6DCT3, Q6NRV4, Q7T2D1, Q7TNT2, Q7ZXF5, Q80XN0, Q80ZF7, Q8HZT6, Q8IZV5, Q8LG50, Q8MS59, Q8WVX9

Diamond homologs: A0A1U8QWA2, A0A2I1CSH4, A1ZAI3, A1ZAI5, B0G0Z9, B8NTZ9, D4AU31, E9F8M3, P07702, P37693, Q0P5J1, Q54TW0, Q5R834, Q5ZM72, Q66H50, Q7TNT2, Q7ZXF5, Q86AE3, Q8MS59, Q8WVX9, Q922J9, Q960W6, Q96K12, A0A481WNP4, A0A7T8F1L4, Q54T36, Q558Y6, A0A1B2CTC5, A0A317VEE1, A8M6W3, B0CN26, B8N0E8, B8NWW5, C0LTL9, D9XF47, D9XF49, O30408, O30409, O31827, O68006

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 102 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Peroxisomal protein import	5	13.3×	1e-03
Constitutive Signaling by Aberrant PI3K in Cancer	5	9.8×	3e-03
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	6	8.9×	2e-03
MAPK family signaling cascades	5	7.9×	6e-03
RAF/MAP kinase cascade	7	6.6×	2e-03
PIP3 activates AKT signaling	6	6.2×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

429 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	8
Likely pathogenic	5
Uncertain significance	192
Likely benign	184
Benign	22

Top pathogenic / likely-pathogenic (13)

Variant ID	HGVS	Classification
1373657	NC_000011.10:g.13710693del	Pathogenic
1510175	NM_032228.6(FAR1):c.945G>A (p.Trp315Ter)	Pathogenic
162213	NM_032228.6(FAR1):c.787C>T (p.Arg263Ter)	Pathogenic
162214	NM_032228.6(FAR1):c.1094A>G (p.Asp365Gly)	Pathogenic
2751366	NM_032228.6(FAR1):c.397C>T (p.Arg133Ter)	Pathogenic
426339	NM_032228.6(FAR1):c.1439G>T (p.Arg480Leu)	Pathogenic
4718132	NM_032228.6(FAR1):c.234_235del (p.Lys78fs)	Pathogenic
860111	NM_032228.6(FAR1):c.163C>T (p.Arg55Ter)	Pathogenic
162212	NM_032228.6(FAR1):c.495_507delinsT (p.Glu165_Pro169delinsAsp)	Likely pathogenic
2445439	NM_032228.6(FAR1):c.1438C>A (p.Arg480Ser)	Likely pathogenic
3573853	NM_032228.6(FAR1):c.955+1G>A	Likely pathogenic
3891774	NM_032228.6(FAR1):c.1522C>T (p.Arg508Ter)	Likely pathogenic
800893	NM_032228.6(FAR1):c.772G>A (p.Gly258Arg)	Likely pathogenic

SpliceAI

2788 predictions. Top by Δscore:

Variant	Effect	Δscore
11:13668807:G:A	donor_loss	1.0000
11:13668808:T:G	donor_loss	1.0000
11:13694755:TTAGG:T	acceptor_loss	1.0000
11:13694756:TAGG:T	acceptor_loss	1.0000
11:13694757:A:AG	acceptor_gain	1.0000
11:13694757:AG:A	acceptor_gain	1.0000
11:13694758:G:A	acceptor_loss	1.0000
11:13694758:G:GG	acceptor_gain	1.0000
11:13694758:GG:G	acceptor_gain	1.0000
11:13694950:GCAAG:G	donor_gain	1.0000
11:13694953:AG:A	donor_gain	1.0000
11:13694954:GG:G	donor_gain	1.0000
11:13694955:G:GG	donor_gain	1.0000
11:13700315:A:AG	acceptor_gain	1.0000
11:13700315:A:G	acceptor_loss	1.0000
11:13700316:G:GG	acceptor_gain	1.0000
11:13700316:GC:G	acceptor_gain	1.0000
11:13700316:GCT:G	acceptor_gain	1.0000
11:13700492:GGT:G	donor_loss	1.0000
11:13700493:G:GA	donor_loss	1.0000
11:13700493:G:GG	donor_gain	1.0000
11:13707899:GAGAT:G	acceptor_gain	1.0000
11:13707970:G:GT	donor_gain	1.0000
11:13708027:G:GT	donor_gain	1.0000
11:13708059:G:GT	donor_gain	1.0000
11:13708063:C:G	donor_gain	1.0000
11:13708078:GA:G	donor_gain	1.0000
11:13708080:G:GG	donor_gain	1.0000
11:13710689:CCAGG:C	acceptor_loss	1.0000
11:13710690:CAGGT:C	acceptor_loss	1.0000

AlphaMissense

3410 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:13710770:A:T	K208I	0.999
11:13710830:G:C	R228T	0.999
11:13710830:G:T	R228M	0.999
11:13711767:T:A	W243R	0.999
11:13711767:T:C	W243R	0.999
11:13710850:A:C	S235R	0.998
11:13710852:T:A	S235R	0.998
11:13710852:T:G	S235R	0.998
11:13711791:A:C	S251R	0.998
11:13711793:T:A	S251R	0.998
11:13711793:T:G	S251R	0.998
11:13711937:G:A	G260R	0.998
11:13711937:G:C	G260R	0.998
11:13711938:G:A	G260E	0.998
11:13727624:G:C	K442N	0.998
11:13727624:G:T	K442N	0.998
11:13728661:T:A	W479R	0.998
11:13728661:T:C	W479R	0.998
11:13710771:A:C	K208N	0.997
11:13710771:A:T	K208N	0.997
11:13710831:G:C	R228S	0.997
11:13710831:G:T	R228S	0.997
11:13710836:C:G	S230W	0.997
11:13711765:G:A	G242E	0.997
11:13711994:G:C	D279H	0.997
11:13711995:A:T	D279V	0.997
11:13727586:T:A	W430R	0.997
11:13727586:T:C	W430R	0.997
11:13728617:G:C	R464P	0.997
11:13710778:G:C	A211P	0.996

dbSNP variants (sampled 300 via entrez): RS1000039912 (11:13716090 A>G), RS1000080898 (11:13702965 T>G), RS1000091819 (11:13716482 C>A,G,T), RS1000177495 (11:13695212 T>C), RS1000180189 (11:13728992 C>T), RS1000191201 (11:13682541 C>G), RS1000300996 (11:13677935 A>T), RS1000458506 (11:13702826 T>A), RS1000607791 (11:13689870 G>A), RS1000614752 (11:13704066 T>A,G), RS1000632850 (11:13695702 T>G), RS1000637544 (11:13690153 A>G), RS1000740599 (11:13722239 T>C), RS1000825394 (11:13667519 C>T), RS1000844274 (11:13671547 A>G)

Disease associations

OMIM: gene MIM:616107 | disease phenotypes: MIM:616154

GenCC curated gene-disease

Disease	Classification	Inheritance
fatty acyl-CoA reductase 1 deficiency	Definitive	Autosomal recessive
spastic paraparesis-cataracts-speech delay syndrome	Strong	Autosomal dominant
fatty acyl-CoA reductase 1 upregulation	Strong	Autosomal dominant
hereditary spastic paraplegia 9A	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (2)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
fatty acyl-CoA reductase 1 upregulation	Moderate	AD
fatty acyl-CoA reductase 1 deficiency	Moderate	AR

Mondo (4): fatty acyl-CoA reductase 1 deficiency (MONDO:0014510), spastic paraparesis-cataracts-speech delay syndrome (MONDO:0036212), hereditary spastic paraplegia 9A (MONDO:0011006), fatty acyl-CoA reductase 1 upregulation (MONDO:0100230)

Orphanet (1): Fatty acyl-CoA reductase 1 deficiency (Orphanet:438178)

HPO phenotypes

47 total (30 of 47 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000219	Thin upper lip vermilion
HP:0000252	Microcephaly
HP:0000253	Progressive microcephaly
HP:0000256	Macrocephaly
HP:0000280	Coarse facial features
HP:0000316	Hypertelorism
HP:0000319	Smooth philtrum
HP:0000343	Long philtrum
HP:0000400	Macrotia
HP:0000508	Ptosis
HP:0000518	Cataract
HP:0000750	Delayed speech and language development
HP:0001118	Juvenile cataract
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001257	Spasticity
HP:0001260	Dysarthria
HP:0001263	Global developmental delay
HP:0001272	Cerebellar atrophy
HP:0001285	Spastic tetraparesis
HP:0001305	Dandy-Walker malformation
HP:0001510	Growth delay
HP:0001999	Abnormal facial shape
HP:0002059	Cerebral atrophy
HP:0002069	Bilateral tonic-clonic seizure
HP:0002121	Generalized non-motor (absence) seizure
HP:0002187	Profound intellectual disability

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST003172_1	Visceral adipose tissue adjusted for BMI	2.000000e-07
GCST003542_143	Night sleep phenotypes	2.000000e-06
GCST003991_21	Childhood ear infection	6.000000e-07
GCST005182_13	Common carotid intima-media thickness in HIV negative individuals	5.000000e-06
GCST006606_6	Response to TNF inhibitor in rheumatoid arthritis (change in swollen 28-joint count)	2.000000e-08
GCST006609_7	Response to TNF inhibitor in rheumatoid arthritis (change in tender 28-joint count)	7.000000e-06
GCST012310_16	Schizophrenia x sex interaction	6.000000e-06
GCST012311_32	Schizophrenia x sex interaction	6.000000e-06

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0007904	susceptibility to childhood ear infection measurement
EFO:0004653	response to TNF antagonist
EFO:0005413	joint damage measurement
EFO:0008343	sex interaction measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C536868	Spastic paraplegia 9, autosomal dominant (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066465 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

ChEMBL bioactivities

2 potent at pChembl≥5 of 3 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.33	Kd	4692	nM	CHEMBL3752910
5.33	ED50	4692	nM	CHEMBL3752910

PubChem BioAssay actives

1 with measured affinity, of 4 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148370: Binding affinity to human FAR1 incubated for 45 mins by Kinobead based pull down assay	kd	4.6918	uM

CTD chemical–gene interactions

36 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, decreases methylation	3
Valproic Acid	decreases expression, increases expression	3
aristolochic acid I	decreases expression	1
methylmercuric chloride	decreases expression	1
methyleugenol	decreases expression	1
bisphenol A	decreases methylation	1
arsenite	affects binding, decreases reaction	1
methylparaben	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
ICG 001	decreases expression	1
abrine	decreases expression	1
jinfukang	decreases expression	1
LDN 193189	affects cotreatment, decreases expression	1
NSC 689534	affects binding, decreases expression	1
Resveratrol	increases expression, affects cotreatment	1
Leflunomide	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Cannabidiol	increases expression	1
Copper	affects binding, decreases expression	1
Doxorubicin	decreases expression	1
Endosulfan	decreases expression	1
Formaldehyde	decreases expression	1
Ivermectin	increases expression	1
Methotrexate	decreases expression	1
Methyl Methanesulfonate	decreases expression	1
NADP	affects binding, increases activity	1
Plant Extracts	affects cotreatment, increases expression	1
Plant Oils	increases expression	1
Potassium Dichromate	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651412	Binding	Binding affinity to human FAR1 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.