FA2H

Protein identityUniProt · HPA

UniProt accession

Q7L5A8

Gene

FA2H

Ensembl

ENSG00000103089

Chromosome

16

Canonical length

372 aa

Protein class

Disease related genes, Human disease related genes, Predicted intracellular proteins, Predicted membrane proteins

Subcellular location

Nuclear membrane

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

372 residues, UniProt reviewed canonical sequence.

>Q7L5A8|FA2H
     1  MAPAPPPAAS FSPSEVQRRL AAGACWVRRG ARLYDLSSFV RHHPGGEQLL RARAGQDISA
    61  DLDGPPHRHS ANARRWLEQY YVGELRGEQQ GSMENEPVAL EETQKTDPAM EPRFKVVDWD
   121  KDLVDWRKPL LWQVGHLGEK YDEWVHQPVT RPIRLFHSDL IEGLSKTVWY SVPIIWVPLV
   181  LYLSWSYYRT FAQGNVRLFT SFTTEYTVAV PKSMFPGLFM LGTFLWSLIE YLIHRFLFHM
   241  KPPSDSYYLI MLHFVMHGQH HKAPFDGSRL VFPPVPASLV IGVFYLCMQL ILPEAVGGTV
   301  FAGGLLGYVL YDMTHYYLHF GSPHKGSYLY SLKAHHVKHH FAHQKSGFGI STKLWDYCFH
   361  TLTPEKPHLK TQ

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against FA2H can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Other membrane

Secreted

No

Transmembrane segments

4

Mean surface accessibility (rSASA)

0.32

Highest tissue expression

182 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about FA2H.

Disease | AllUniProt

Conditions FA2H is implicated in, by any mechanism.

• Spastic paraplegia 35, autosomal recessive, with or without neurodegeneration (SPG35) MIM:612319

Disease | GeneticClinVar

68 pathogenic / likely-pathogenic of 430 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Hereditary spastic paraplegia 35
• Spastic paraplegia
• Hereditary spastic paraplegia
• Inborn genetic diseases
• Neurodegeneration with brain iron accumulation

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.56

gnomAD pLI

0.15

gnomAD missense Z

0.46

DepMap mean gene effect

-0.09

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• central nervous system myelin maintenance
• ceramide biosynthetic process
• establishment of skin barrier
• fatty acid biosynthetic process
• fatty acid metabolic process
• galactosylceramide biosynthetic process
• glucosylceramide biosynthetic process
• lipid modification
• peripheral nervous system myelin maintenance
• plasma membrane raft organization
• regulation of hair cycle
• sebaceous gland cell differentiation
• sphingolipid biosynthetic process
• regulation of acinar cell proliferation
• regulation of sebum secreting cell proliferation

Molecular functions

• heme binding
• iron ion binding
• 4-hydroxysphinganine ceramide fatty acyl 2-hydroxylase activity
• fatty acid 2-hydroxylase activity
• free fatty acid 2-hydroxylase activity

Cellular components

• endoplasmic reticulum
• endoplasmic reticulum membrane
• membrane

Protein domainsUniProt · Pfam · InterPro

• Cytochrome b5-like heme/steroid binding domain
• Fatty acid hydroxylase
• Cytochrome b5, heme-binding site
• Cytochrome b5-like heme/steroid binding domain superfamily
• Cytochrome b5-like Heme/Steroid binding domain
• Fatty acid hydroxylase
• Sterol desaturase Scs7

KeywordsUniProt

• Endoplasmic reticulum
• Fatty acid biosynthesis
• Fatty acid metabolism
• Heme
• Hereditary spastic paraplegia
• Iron
• Leukodystrophy
• Lipid biosynthesis
• Lipid metabolism
• Membrane
• Metal-binding
• Microsome
• Neurodegeneration
• Oxidoreductase
• Sphingolipid metabolism
• Transmembrane
• Transmembrane helix
• Zinc