LTA4H

protein-coding

leukotriene A4 hydrolase, the group of M1 metallopeptidases

Gene summary

The protein encoded by this gene is an enzyme that contains both hydrolase and aminopeptidase activities. The hydrolase activity is used in the final step of the biosynthesis of leukotriene B4, a proinflammatory mediator. The aminopeptidase activity has been shown to degrade proline-glycine-proline (PGP), a neutrophil chemoattractant and biomarker for chronic obstructive pulmonary disease (COPD). Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2015]

MANE transcript

NM_000895.3

Inheritance

—

ClinVar variants

U:75B:8

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.49

Max pathogenic AF

—

Genomic locus

chr12:96,000,753-96,043,520

External References & Databases

Ensembl (ENSG00000111144)

Transcript & Mutation Effects

hg38 • Region Span ~42.8 kb

Loading mutation effect viewer...

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 LTA4H variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 61

not providedTotal: 7

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000895.3. 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	2 clinvar	4
missense			62 clinvar	3 clinvar	1 clinvar	66
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			12 clinvar			12
Total	0	0	75	5	3	83

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 59 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_000895.3	RefSeq	NP_000886.1	19	MANE Select
ENST00000228740.7	Ensembl	ENSP00000228740.2	19	MANE Select
NM_001256643.1	RefSeq	NP_001243572.1	19	Standard
NM_001256644.1	RefSeq	NP_001243573.1	17	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
lta4h	Danio rerio	Structure: epiboly involved in gastrulation with mouth forming second Quality: delayed abnormal

Gene / Model

Organism

Observed Phenotype

lta4h

Danio rerio

Structure: epiboly involved in gastrulation with mouth forming second

Quality: delayed

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Arachidonic acid metabolism - Homo sapiens (human)
Leukotriene modifiers pathway, Pharmacodynamics
Etodolac Action Pathway
Ketoprofen Action Pathway
Ibuprofen Action Pathway

Biological Process

proteolysis
leukotriene metabolic process
leukotriene biosynthetic process
long-chain fatty acid biosynthetic process
peptide catabolic process

Molecular Function

RNA binding
aminopeptidase activity
epoxide hydrolase activity
leukotriene-A4 hydrolase activity
protein binding

Cellular Component

extracellular region
nucleus
nucleoplasm
cytosol
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000228740
Coding exons: 19
Length: 42693
Individuals with no LoFs: 125682
Homozygous LoFs: 0
Heterozygous LoFs: 66
Defined: 125748
p: 0.000262

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.48	242	316	0.766	0.0000151	3975
Missense (PolyPhen)		85	108.19	0.78565		1375
Synonymous	1.59	92	114	0.810	0.00000568	1144
Loss of Function	2.96	19	39.0	0.487	0.00000192	466

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00031	0.00031	rare
Latino/Admixed American	0.00020	0.00020	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00016	0.00016	rare
Finnish	0.00032	0.00032	rare
European (Non-Finnish)	0.00032	0.00031	rare
South Asian	0.00017	0.00016	rare
Other	0.00067	0.00065	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Epoxide hydrolase that catalyzes the final step in the biosynthesis of the proinflammatory mediator leukotriene B4. Has also aminopeptidase activity. {ECO:0000269|PubMed:11917124, ECO:0000269|PubMed:12207002, ECO:0000269|PubMed:15078870, ECO:0000269|PubMed:18804029, ECO:0000269|PubMed:1897988, ECO:0000269|PubMed:1975494, ECO:0000269|PubMed:2244921}.;

Recessive Scores

pRec: 0.208

Intolerance Scores

LoFtool: 0.814
RVIS EVS: 0.02
RVIS percentile EVS: 55.45

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.999

Gene Damage Prediction

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