AOAH

protein-coding

acyloxyacyl hydrolase

Gene summary

This locus encodes both the light and heavy subunits of acyloxyacyl hydrolase. The encoded enzyme catalyzes the hydrolysis of acyloxylacyl-linked fatty acyl chains from bacterial lipopolysaccharides, effectively detoxifying these molecules. The encoded protein may play a role in modulating host inflammatory response to gram-negative bacteria. Alternatively spliced transcript variants have been described.[provided by RefSeq, Apr 2010]

MANE transcript

NM_001637.4

Inheritance

—

ClinVar variants

U:82B:12

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.69

Max pathogenic AF

—

Genomic locus

chr7:36,509,308-36,724,549

External References & Databases

Ensembl (ENSG00000136250)

Transcript & Mutation Effects

hg38 • Region Span ~215.2 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 AOAH variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 90

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001637.4. 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				3 clinvar		3
missense			81 clinvar	8 clinvar		89
nonsense				1 clinvar		1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	82	12	0	94

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 35 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001637.4	RefSeq	NP_001628.1	21	MANE Select
ENST00000617537.5	Ensembl	ENSP00000483783.1	21	MANE Select
NM_001177506.2	RefSeq	NP_001170977.1	22	Standard
NM_001177507.2	RefSeq	NP_001170978.1	20	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

fatty acid metabolic process
lipopolysaccharide catabolic process

Molecular Function

calcium ion binding
acyloxyacyl hydrolase activity

Cellular Component

extracellular region
cytoplasmic vesicle

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000258749
Coding exons: 21
Length: 211699
Individuals with no LoFs: 125174
Homozygous LoFs: 2
Heterozygous LoFs: 572
Defined: 125748
p: 0.00229

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.321	297	313	0.949	0.0000164	3788
Missense (PolyPhen)		119	126.4	0.94147		1503
Synonymous	1.13	106	122	0.870	0.00000747	1021
Loss of Function	1.80	27	39.2	0.690	0.00000175	470

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0011	0.0010	notable
Latino/Admixed American	0.0013	0.0013	notable
Ashkenazi Jewish	0.0031	0.0031	notable
East Asian	0.00092	0.00092	rare
Finnish	0.0025	0.0025	notable
European (Non-Finnish)	0.0032	0.0032	notable
South Asian	0.0012	0.0012	notable
Other	0.0024	0.0024	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Removes the secondary (acyloxyacyl-linked) fatty acyl chains from the lipid A region of bacterial lipopolysaccharides (PubMed:1883828, PubMed:8089145, PubMed:29343645). By breaking down LPS, terminates the host response to bacterial infection and prevents prolonged and damaging inflammatory responses (By similarity). In peritoneal macrophages, seems to be important for recovery from a state of immune tolerance following infection by Gram-negative bacteria (By similarity). {ECO:0000250|UniProtKB:O35298, ECO:0000269|PubMed:1883828, ECO:0000269|PubMed:29343645, ECO:0000269|PubMed:8089145}.;

Recessive Scores

pRec: 0.115

Intolerance Scores

RVIS EVS: 0.96
RVIS percentile EVS: 90.15

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.0956

Gene Damage Prediction

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