Paroxysmal central nervous system disorders

Gene: FAAHP1

Red List (low evidence)

FAAHP1 (fatty acid amide hydrolase pseudogene 1)
EnsemblGeneIds (GRCh38): ENSG00000232022
EnsemblGeneIds (GRCh37): ENSG00000232022
FAAHP1 is in 2 panels

4 reviews

Robyn Labrum (UCLH NHS Trust)

Red List (low evidence)

pseudogene adjacent to the functional FAAH gene. One paper proposes that a microdeletion identified in a family with with pain insensitivity affects FAAH function either by removing a regulatory element for FAAH or by reducing expression of FAAHP1, which may regulate FAAH epigenetically or function as a microRNA decoy for FAAH.
Created: 23 Sep 2019, 3:56 p.m. | Last Modified: 23 Sep 2019, 3:56 p.m.
Panel Version: 0.97

Rebecca Foulger (Genomics England curator)

I don't know

Comment on list classification: Kept rating of FAAHP1 as Red following Red reviews from both London North GLH, and West Midlands, Oxford and Wessex GLH.
Created: 23 Sep 2019, 4:40 p.m. | Last Modified: 23 Sep 2019, 4:40 p.m.
Panel Version: 0.120
Review and rating from Robyn Labrum (University College London Hospitals) was collated (September 19th 2019) on behalf of London North GLH for the GMS Neurology specialist test group. Re-review of a subset of genes was conducted in September 2019 to reach a rating consensus for clinical indication R66: Paroxysmal central nervous system disorders. Suggested rating: Red.
Created: 23 Sep 2019, 3:57 p.m. | Last Modified: 23 Sep 2019, 3:57 p.m.
Panel Version: 0.98
Review and rating from Penny Clouston (Oxford Medical Genetics Laboratories, Oxford University Hospitals NHS Foundation Trust) was collated (September 19th 2019) on behalf of West Midlands, Oxford and Wessex GLH for the GMS Neurology specialist test group. Re-review of a subset of genes was conducted in September 2019 to reach a rating consensus for clinical indication R66: Paroxysmal central nervous system disorders. Suggested rating: Red.
Created: 23 Sep 2019, 12:53 p.m. | Last Modified: 23 Sep 2019, 12:53 p.m.
Panel Version: 0.96

Penny Clouston (Oxford)

Red List (low evidence)

Louise Daugherty (Genomics England Curator)

Red List (low evidence)

From HGNC the authors PMID:30929760 specify that they used hg19in their CNV analysis (GRCh37). Looking in GRCh37 annotations in the archived version of Ensembl, gene they call ‘FAAH-OUT’ was not annotated at the time, except as http://feb2014.archive.ensembl.org/Homo_sapiens/Gene/Summary?db=core;g=ENSG00000232022;r=1:46897801-46911193;tl=YL1ImqsrtgZ7MKxn-5146184-727716019. Doing a BLAST search with the FAAH cDNA on GRCh38 in Ensembl 95 detected both FAAH (ENSG00000117480) and a gene now annotated as ENSG00000232022 in the appropriate location of the genome. HGNC named this as FAAHP1 in 2014. FAAH-OUT is an alias for FAAHP1.
Created: 4 Apr 2019, 9:27 a.m.
From OMIM Habib et al. (2019) PMID: 30929760 identified a heterozygous approximately 8-kb heterozygous microdeletion on chromosome 1, about 4.7 kb downstream of the 3-prime end of the FAAH gene. Molecular cloning identified novel 5-prime exons of an expressed FAAH pseudogene, termed FAAHP1 (FAAH-OUT), that mapped within the microdeletion. The microdeletion removed the promoter and first 2 exons of the neighboring FAAHP1 gene. The authors noted that the deleted region is flanked by ALU sequences, which may predispose it to deletion by unequal crossing over. The affected woman also carried a heterozygous hypomorphic polymorphism in the FAAH gene (P129T; 602935.0001) that reduces FAAH enzyme activity. The patient's son, who exhibited some pain insensitivity, carried the microdeletion but not the hypomorphic FAAH allele. The woman's unaffected mother and daughter did not carry the microdeletion, but both carried the FAAH polymorphism in heterozygous state. The proband had approximately triple the levels of various circulating fatty acid amides normally degraded by FAAH compared with controls who were either homozygous wildtype or heterozygous for the hypomorphic FAAH allele. The authors proposed that the microdeletion affects FAAH function either by removing a regulatory element for FAAH or by reducing expression of FAAH-OUT, which may regulate FAAH epigenetically or function as a microRNA decoy for FAAH. One Colombian male sequenced in the 1000 Genomes Project carried a similar microdeletion, but his pain sensitivity was unknown, and he was homozygous wildtype for the FAAH allele. The case provided new insights into the role of the endocannabinoid system in analgesia.
Sources: Literature
Created: 4 Apr 2019, 9:27 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Pain insensitivity

Publications

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
Phenotypes
  • Pain insensitivity
Clinvar variants
Variants in FAAHP1
Penetrance
None
Publications
Panels with this gene

History Filter Activity

24 Sep 2019, Gel status: 1

Entity classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

Gene: faahp1 has been classified as Red List (Low Evidence).

23 Sep 2019, Gel status: 1

Entity classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

Gene: faahp1 has been classified as Red List (Low Evidence).

4 Apr 2019, Gel status: 1

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes

Louise Daugherty (Genomics England Curator)

gene: FAAHP1 was added gene: FAAHP1 was added to Paroxysmal neurological disorders, pain disorders and sleep disorders. Sources: Literature Mode of inheritance for gene: FAAHP1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: FAAHP1 were set to 30929760 Phenotypes for gene: FAAHP1 were set to Pain insensitivity Review for gene: FAAHP1 was set to RED