APOO

protein-coding

apolipoprotein O, the group of Mitochondrial contact site and cristae organizing system subunits|Apolipoproteins

Gene summary

This gene is a member of the apolipoprotein family. Members of this protein family are involved in the transport and metabolism of lipids. The encoded protein associates with HDL, LDL and VLDL lipoproteins and is characterized by chondroitin-sulfate glycosylation. This protein may be involved in preventing lipid accumulation in the myocardium in obese and diabetic patients. Alternative splicing results in multiple transcript variants. Pseudogenes of this gene are found on chromosomes 3, 4, 5, 12 and 16.[provided by RefSeq, Sep 2009]

Previous symbols:

FAM121B

MANE transcript

NM_024122.5

Inheritance

ClinVar variants

P:1U:96B:6

Top phenotype

APOO-related disorder

gnomAD constraint

pLI —, LoF o/e 0.17

Max pathogenic AF

—

Genomic locus

chrX:23,833,353-23,907,938

External References & Databases

Ensembl (ENSG00000184831)

Transcript & Mutation Effects

hg38 • Region Span ~74.6 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

mitochondrial diseaseMODERATE

Inheritance Pattern: XL

Disease ID:MONDO:0044970

Submitter: PanelApp Australia

mitochondrial diseaseLIMITED

Inheritance Pattern: XL

Disease ID:MONDO:0044970

Submitter: Ambry Genetics

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to APOO variants in ClinVar

6 Conditions Cataloged

not specifiedTotal: 25

not providedTotal: 5

APOO-related disorderTotal: 3

Cognitive impairment and autistic featuresTotal: 1

Lactic acidosisTotal: 1

X-linked recessive mitochondrial myopathyTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_024122.5. 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			12 clinvar	2 clinvar		14
missense	1 clinvar		63 clinvar	3 clinvar	1 clinvar	68
nonsense			4 clinvar			4
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			17 clinvar			17
Total	1	0	96	5	1	103

Highest pathogenic variant AF is 0.000008279222

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 139 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_024122.5	RefSeq	NP_077027.1	8	MANE Select
ENST00000379226.9	Ensembl	ENSP00000368528.4	8	MANE Select
ENST00000439528.5	Ensembl	ENSP00000402557.1	7	Standard
ENST00000490078.2	Ensembl	ENSP00000434341.1	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

lipid transport
cristae formation

Molecular Function

protein binding

Cellular Component

Golgi membrane
extracellular region
extracellular space
mitochondrion
endoplasmic reticulum membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000379226
Coding exons: 8
Length: 74588
Individuals with no LoFs: 125439
Homozygous LoFs: 4
Heterozygous LoFs: 2
Defined: 125445
p: 0.0000239

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.0406	70	69.1	1.01	0.00000506	1259
Missense (PolyPhen)		27	20.039	1.3473		417
Synonymous	-0.233	29	27.4	1.06	0.00000229	366
Loss of Function	2.59	2	11.5	0.174	8.83e-7	195

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0.00014	0.000099	rare
East Asian	0	0.0	absent
Finnish	0.00019	0.00014	rare
European (Non-Finnish)	0.000013	0.0000088	rare
South Asian	0.000053	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Component of the MICOS complex, a large protein complex of the mitochondrial inner membrane that plays crucial roles in the maintenance of crista junctions, inner membrane architecture, and formation of contact sites to the outer membrane. Plays a crucial role in crista junction formation and mitochondrial function (PubMed:25764979). Can promote cardiac lipotoxicity by enhancing mitochondrial respiration and fatty acid metabolism in cardiac myoblasts (PubMed:24743151). Promotes cholesterol efflux from macrophage cells. Detected in HDL, LDL and VLDL. Secreted by a microsomal triglyceride transfer protein (MTTP)-dependent mechanism, probably as a VLDL-associated protein that is subsequently transferred to HDL (PubMed:16956892). {ECO:0000269|PubMed:16956892, ECO:0000269|PubMed:24743151, ECO:0000269|PubMed:25764979}.;

Recessive Scores

pRec: 0.115

Intolerance Scores

LoFtool: 0.365
RVIS EVS: 0.53
RVIS percentile EVS: 80.58

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.378

Gene Damage Prediction

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