FAAH

protein-coding

fatty acid amide hydrolase

Gene summary

This gene encodes a protein that is responsible for the hydrolysis of a number of primary and secondary fatty acid amides, including the neuromodulatory compounds anandamide and oleamide. [provided by RefSeq, Jul 2008]

MANE transcript

NM_001441.3

Inheritance

—

ClinVar variants

P:1U:69B:20

Top phenotype

FAAH-related disorder

gnomAD constraint

pLI —, LoF o/e 0.73

Max pathogenic AF

—

Genomic locus

chr1:46,394,317-46,413,848

External References & Databases

Ensembl (ENSG00000117480)

Transcript & Mutation Effects

hg38 • Region Span ~19.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to FAAH variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 61

not providedTotal: 16

FAAH-related disorderTotal: 2

Polysubstance abuse, susceptibility toTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001441.3. 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			2 clinvar	5 clinvar	6 clinvar	13
missense			57 clinvar	6 clinvar	3 clinvar	66
nonsense			2 clinvar			2
start loss						0
frameshift		1 clinvar	1 clinvar			2
splice donor/acceptor (+/-2bp)			7 clinvar			7
Total	0	1	69	11	9	90

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 98 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001441.3	RefSeq	NP_001432.2	15	MANE Select
ENST00000243167.9	Ensembl	ENSP00000243167.8	15	MANE Select
ENST00000484697.5	Ensembl	ENSP00000481641.1	2	Standard
ENST00000877141.1	Ensembl	ENSP00000547200.1	15	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Retrograde endocannabinoid signaling - Homo sapiens (human)
Cannabinoid receptor signaling
Gastric ulcer formation
metabolism of anandamide an endogenous cannabinoid
Metabolism of lipids

Biological Process

fatty acid catabolic process
arachidonic acid metabolic process

Molecular Function

amidase activity
protein binding
fatty acid amide hydrolase activity
acylglycerol lipase activity
oleamide hydrolase activity

Cellular Component

endoplasmic reticulum membrane
cytoskeleton
integral component of membrane
organelle membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000243167
Coding exons: 15
Length: 19584
Individuals with no LoFs: 125656
Homozygous LoFs: 0
Heterozygous LoFs: 92
Defined: 125748
p: 0.000366

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.638	276	307	0.898	0.0000182	3670
Missense (PolyPhen)		110	128.47	0.85623		1532
Synonymous	-0.362	139	134	1.04	0.00000834	1216
Loss of Function	1.34	20	27.6	0.725	0.00000130	331

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00025	0.00025	rare
Latino/Admixed American	0.000089	0.000087	rare
Ashkenazi Jewish	0.00030	0.00030	rare
East Asian	0.00049	0.00049	rare
Finnish	0.0017	0.0017	notable
European (Non-Finnish)	0.00023	0.00023	rare
South Asian	0.00033	0.00033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Degrades bioactive fatty acid amides like oleamide, the endogenous cannabinoid, anandamide and myristic amide to their corresponding acids, thereby serving to terminate the signaling functions of these molecules. Hydrolyzes polyunsaturated substrate anandamide preferentially as compared to monounsaturated substrates. {ECO:0000269|PubMed:17015445}.;

Recessive Scores

pRec: 0.162

Intolerance Scores

LoFtool: 0.812
RVIS EVS: -0.47
RVIS percentile EVS: 23.43

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.754

Gene Damage Prediction

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