FASN

protein-coding

fatty acid synthase, the group of 7BS orphan methyltransferases|Short chain dehydrogenase/reductase superfamily

Gene summary

The enzyme encoded by this gene is a multifunctional protein. Its main function is to catalyze the synthesis of palmitate from acetyl-CoA and malonyl-CoA, in the presence of NADPH, into long-chain saturated fatty acids. In some cancer cell lines, this protein has been found to be fused with estrogen receptor-alpha (ER-alpha), in which the N-terminus of FAS is fused in-frame with the C-terminus of ER-alpha. [provided by RefSeq, Jul 2008]

MANE transcript

NM_004104.5

Inheritance

ClinVar variants

P:1U:1171B:882

Top phenotype

Epileptic encephalopathy

gnomAD constraint

pLI —, LoF o/e 0.09

Max pathogenic AF

—

Genomic locus

chr17:82,078,338-82,098,294

External References & Databases

Ensembl (ENSG00000169710)

Transcript & Mutation Effects

hg38 • Region Span ~20.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

neurodevelopmental disorderLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0700092

Submitter: G2P

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to FASN variants in ClinVar

15 Conditions Cataloged

Epileptic encephalopathyTotal: 2307

not specifiedTotal: 477

not providedTotal: 112

FASN-related disorderTotal: 86

ThrombocytopeniaTotal: 1

EsotropiaTotal: 1

Neurodevelopmental disorderTotal: 1

TremorTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004104.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			16 clinvar	763 clinvar	33 clinvar	812
missense			1118 clinvar	72 clinvar	14 clinvar	1204
nonsense			6 clinvar			6
start loss						0
frameshift			13 clinvar			13
splice donor/acceptor (+/-2bp)	1 clinvar		18 clinvar			19
Total	1	0	1171	835	47	2054

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 23 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_004104.5	RefSeq	NP_004095.4	42	MANE Select
ENST00000306749.4	Ensembl	ENSP00000304592.2	42	MANE Select
ENST00000580382.1	Ensembl	ENSP00000462949.1	3	Standard
ENST00000634990.1	Ensembl	ENSP00000488964.1	42	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

AMPK signaling pathway - Homo sapiens (human)
Fatty acid biosynthesis - Homo sapiens (human)
Insulin signaling pathway - Homo sapiens (human)
Fatty Acid Biosynthesis
AMP-activated Protein Kinase (AMPK) Signaling

Biological Process

osteoblast differentiation
acetyl-CoA metabolic process
fatty acid metabolic process
fatty acid biosynthetic process
ether lipid biosynthetic process

Molecular Function

RNA binding
fatty acid synthase activity
[acyl-carrier-protein] S-acetyltransferase activity
[acyl-carrier-protein] S-malonyltransferase activity
3-oxoacyl-[acyl-carrier-protein] synthase activity

Cellular Component

Golgi apparatus
cytosol
plasma membrane
membrane
melanosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000306749
Coding exons: 42
Length: 19995
Individuals with no LoFs: 125176
Homozygous LoFs: 0
Heterozygous LoFs: 20
Defined: 125196
p: 0.0000799

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.36	1302	1.57e+3	0.832	0.000116	15928
Missense (PolyPhen)		283	557.4	0.50772		5804
Synonymous	-6.79	989	752	1.32	0.0000621	5338
Loss of Function	8.82	10	110	0.0911	0.00000577	1158

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00027	0.00025	rare
Latino/Admixed American	0.00012	0.00012	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.000054	0.000046	rare
European (Non-Finnish)	0.000066	0.000062	rare
South Asian	0.00014	0.00013	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Fatty acid synthetase catalyzes the formation of long- chain fatty acids from acetyl-CoA, malonyl-CoA and NADPH. This multifunctional protein has 7 catalytic activities as an acyl carrier protein.;

Recessive Scores

pRec: 0.170

Intolerance Scores

LoFtool: 0.0279
RVIS EVS: -3.39
RVIS percentile EVS: 0.38

Essentials

Essential (CRISPR): E
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.982

Gene Damage Prediction

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