FA2H fatty acid 2-hydroxylase [Homo sapiens (human)] - Gene

Summary

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Official Symbol: FA2Hprovided by HGNC
Official Full Name: fatty acid 2-hydroxylaseprovided by HGNC
Primary source: HGNC:21197
See related: Ensembl:ENSG00000103089; HPRD:16873; MIM:611026; Vega:OTTHUMG00000137603
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: FAAH; FAH1; SCS7; SPG35; FAXDC1
Summary: This gene encodes a protein that catalyzes the synthesis of 2-hydroxysphingolipids, a subset of sphingolipids that contain 2-hydroxy fatty acids. Sphingolipids play roles in many cellular processes and their structural diversity arises from modification of the hydrophobic ceramide moiety, such as by 2-hydroxylation of the N-acyl chain, and the existence of many different head groups. Mutations in this gene have been associated with leukodystrophy dysmyelinating with spastic paraparesis with or without dystonia.[provided by RefSeq, Mar 2010]

Genomic context

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Location :: 16q23

Sequence :: Chromosome: 16; NC_000016.9 (74746853..74808729, complement)

See FA2H in Epigenomics, MapViewer

Chromosome 16 - NC_000016.9 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

Bibliography

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GeneRIFs: Gene References Into Functions What's a GeneRIF?

we report a novel mutation in FA2H gene in two sibs presenting with adult onset complicated spastic paraparesis and thin corpus callosum
Title: Atypical adult onset complicated spastic paraparesis with thin corpus callosum in two patients carrying a novel FA2H mutation.
This study did not find any mutations in the FA2H gene in patients with neurodegeneration with brain iron accumulation.
Title: C19orf12 and FA2H mutations are rare in Italian patients with neurodegeneration with brain iron accumulation.
a novel homozygous c.270+3A>T mutation altered FA2H function led to a severe phenotype, with clinical features overlapping those in three FA2H-associated disorders
Title: FA2H-related disorders: a novel c.270+3A>T splice-site mutation leads to a complex neurodegenerative phenotype.
The 2-hydroxylated sphingomyelin (SM) profiles were characterized in blood and fibroblasts from patients harboring a deleterious FA2H mutation.
Title: 2-Hydroxylated sphingomyelin profiles in cells from patients with mutated fatty acid 2-hydroxylase.
Mutations in FA2H are associated with hereditary spastic paraplegia.
Title: Mutation of FA2H underlies a complicated form of hereditary spastic paraplegia (SPG35).
Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
Title: Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.
Observational study of gene-disease association. (HuGE Navigator)
Title: Fine mapping and association studies of a high-density lipoprotein cholesterol linkage region on chromosome 16 in French-Canadian subjects.
Mutations in FA2H are associated with leukodystrophy with spastic paraparesis and dystonia.
Title: Mutations in the fatty acid 2-hydroxylase gene are associated with leukodystrophy with spastic paraparesis and dystonia.
the human FA2H gene encodes a fatty acid 2-hydroxylase involved in the formation of myelin 2-hydroxy galactosylceramides and -sulfatides
Title: The human FA2H gene encodes a fatty acid 2-hydroxylase.
late differentiation-linked increases in FA2H expression are essential for epidermal permeability barrier homeostasis.
Title: Fatty acid 2-hydroxylase, encoded by FA2H, accounts for differentiation-associated increase in 2-OH ceramides during keratinocyte differentiation.

Submit: New GeneRIF Correction

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Fatty acid hydroxylase-associated neurodegeneration (FAHN) is characterized by central nervous system involvement including corticospinal tract involvement (spasticity), mixed movement disorder (ataxia/dystonia), eye findings (optic atrophy, oculomotor abnormalities) early in the disease course, and progressive intellectual impairment and seizures later in the disease course. FAHN is considered to be a subtype of neurodegeneration with brain iron accumulation (NBIA). To date, a total of 25 individuals from seven families of diverse ethnicity with FAHN have been described; much is yet to be learned about the clinical manifestations and natural history.

Diagnosis Testing

The diagnosis of FAHN may be suspected when characteristic neurologic findings are accompanied by supportive findings on brain MRI. FA2H is the only gene in which mutations are known to FAHN.

Genetic Counseling

FAHN is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. If the disease-causing mutations have been identified in an affected family member, prenatal testing for at-risk pregnancies is possible through laboratories offering either prenatal testing for the gene of interest or custom testing.

References

PMID: 21735565

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description
Fatty acid 2 hydroxylase	Q9NRR5	UBQLN4		HPRD	PubMed
BioGRID:122570	BioGRID:121223	UBQLN4		BioGRID	PubMed	Two-hybrid

General gene information

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Markers

D16S2953 (e-PCR)
- UniSTS:83281

D16S430E (e-PCR)
- UniSTS:147345

SHGC-8141 (e-PCR)
- UniSTS:24537

RH65017 (e-PCR)
- UniSTS:89080

Genotypes

See FA2H SNP Geneview Report
See FA2H SNP Genotype Report
See FA2H SNP Variation Viewer Report

Homology

Homologs of the FA2H gene: The FA2H gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, fruit fly, C.elegans, S.cerevisiae, K.lactis, E.gossypii, S.pombe, M.oryzae, N.crassa, A.thaliana, and rice.
Map Viewer (Mouse, Rat)
OrthoDB: The Hierarchical Catalog of Eukaryotic Orthologs

Clone Names

FLJ25287

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
fatty acid alpha-hydroxylase activity	IEA Inferred from Electronic Annotation more info
heme binding	IEA Inferred from Electronic Annotation more info
iron ion binding	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
cell death	IEA Inferred from Electronic Annotation more info
central nervous system myelin maintenance	IEA Inferred from Electronic Annotation more info
electron transport chain	IEA Inferred from Electronic Annotation more info
fatty acid biosynthetic process	IEA Inferred from Electronic Annotation more info
lipid modification	IEA Inferred from Electronic Annotation more info
peripheral nervous system myelin maintenance	IEA Inferred from Electronic Annotation more info
regulation of cell proliferation	IEA Inferred from Electronic Annotation more info
regulation of hair cycle	IEA Inferred from Electronic Annotation more info
sebaceous gland cell differentiation	IEA Inferred from Electronic Annotation more info
sphingolipid metabolic process	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
endoplasmic reticulum membrane	IEA Inferred from Electronic Annotation more info
integral to membrane	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: fatty acid 2-hydroxylase

Names: fatty acid 2-hydroxylase; fatty acid alpha-hydroxylase; fatty acid hydroxylase domain containing 1; spastic paraplegia 35 (autosomal recessive)

NP_077282.3

EC 1.-.-.-

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_017070.1 RefSeqGene

Range

5001..66877

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_024306.4 → NP_077282.3 fatty acid 2-hydroxylase

Status: REVIEWED

Source sequence(s)

AA857184, BC017049, DA890369

Consensus CDS

CCDS10911.1

UniProtKB/Swiss-Prot

Q7L5A8

Related

ENSP00000219368, OTTHUMP00000174940, ENST00000219368, OTTHUMT00000269015

Conserved Domains (3) summary

COG3000
Location:210 – 367
Blast Score: 133

ERG3; Sterol desaturase [Lipid metabolism]

pfam00173
Location:15 – 85
Blast Score: 143

Cyt-b5; Cytochrome b5-like Heme/Steroid binding domain

cl01132
Location:128 – 366
Blast Score: 654

FA_hydroxylase; Fatty acid hydroxylase superfamily

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 104

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh37.p10 Primary Assembly

Genomic

NC_000016.9 Reference GRCh37.p10 Primary Assembly

Range

74746853..74808729, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000148.1 Alternate HuRef

Range

60496759..60558638, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CHM1_1.0

Genomic

NC_018927.1 Alternate CHM1_1.0

Range

75759775..75821636, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	ABBA01058108.1 (26765..88644)	None
genomic	AC004685.1	AAC23496.1
genomic	AC009132.9 (178565..215754)	None
genomic	AMYH01007812.1 (172807..234668)	None
genomic	CH471114.2	EAW95677.1
		EAW95678.1
mRNA	AA857184.1	None
mRNA	AJ278219.1	CAC20436.1
mRNA	AK058016.1	BAB71632.1
mRNA	AK303878.1	BAH14072.1
mRNA	AK315512.1	BAG37893.1
mRNA	BC002679.2	AAH02679.2
mRNA	BC004263.1	AAH04263.2
mRNA	BC010453.1	None
mRNA	BC017049.1	AAH17049.2
mRNA	DA890369.1	None