Apoa4 Gene Detail

Summary

• Symbol
  Apoa4
• Name
  apolipoprotein A-IV
• Synonyms
  Apoa-4

• Feature Type
  protein coding gene
• IDs
  MGI:88051
  NCBI Gene: 11808
• Alliance
  genome feature page
• Transcription Start Sites
  41 TSS
• Candidate for QTL
  2 QTL

Location &
Maps

• Sequence Map
  Chr9:46152142-46154756 bp, + strand

  From NCBI annotation of GRCm39
  

• View this region in JBrowse
  

• Genome Browsers
  Ensembl | UCSC | NCBI

• Genetic Map
  Chromosome 9, 25.36 cM
• Mapping Data
  9 experiments

Strain
Comparison

• SNPs within 2kb
  165 from dbSNP Build 142
• Strain Annotations
  19
• RFLP
  1

Strain	Gene Model ID	Feature Type	Coordinates
C57BL/6J	MGI_C57BL6J_88051	protein coding gene	Chr9:46151994-46154757 (+)
129S1/SvImJ	ENSMUSG00200018395	protein coding gene	Chr9:43238299-43241050 (+)
A/J	ENSMUSG00195022568	protein coding gene	Chr9:42998328-43001091 (+)
AKR/J	ENSMUSG00220033282	protein coding gene	Chr9:43078003-43080766 (+)
BALB/cJ	ENSMUSG00180022810	protein coding gene	Chr9:43110006-43112769 (+)
C3H/HeJ	ENSMUSG00175012182	protein coding gene	Chr9:43121836-43124599 (+)
C57BL/6NJ	ENSMUSG00215029217	protein coding gene	Chr9:43071857-43074620 (+)
CAROLI/EiJ	MGP_CAROLIEiJ_G0032157	protein coding gene	Chr9:43116920-43119685 (+)
CAST/EiJ	ENSTCUG00005013655	protein coding gene	Chr9:43065400-43068179 (+)
CBA/J	ENSMUSG00210016212	protein coding gene	Chr9:43161606-43164381 (+)
DBA/2J	ENSMUSG00185011705	protein coding gene	Chr9:43236565-43239328 (+)
FVB/NJ	ENSMUSG00205029323	protein coding gene	Chr9:43476347-43479110 (+)
JF1/MsJ	ENSUMUG00000015207	protein coding gene	Chr9:43278668-43281419 (+)
LP/J	ENSMUSG00230035428	protein coding gene	Chr9:43528572-43531323 (+)
NOD/ShiLtJ	ENSMUSG00190019167	protein coding gene	Chr9:43315189-43317952 (+)
NZO/HlLtJ	ENSMUSG00225042763	protein coding gene	Chr9:43488292-43491055 (+)
PWK/PhJ	ENSLUMG00010018029	protein coding gene	Chr9:43242081-43244844 (+)
SPRET/EiJ	ENSMSPG00010010577	protein coding gene	Chr9:43995279-43998030 (+)
WSB/EiJ	ENSIUOG00005018605	protein coding gene	Chr9:42726550-42729313 (+)

Homology

• Human Ortholog
  APOA4, apolipoprotein A4

• Vertebrate Orthologs
  6

Vertebrate Orthology Source

Alliance of Genome Resources

• Human Ortholog
  APOA4, apolipoprotein A4
  
• Synonyms
  ADTKD6
• Links
  HGNC:602

  NCBI Gene ID: 337

  UniProt: P06727

  
  
• Chr Location
  11q23.3; chr11:116820700-116823304 (-)  GRCh38

---

• MGI Vertebrate Homology
  Apoa4 stringent orthology
  1 human;1 mouse;1 rat;4 zebrafish
  
• HCOP
  vertebrate homology predictions: APOA4
• Gene Tree
  Apoa4
  

Human Diseases

• Diseases
  5 with human APOA4 associations

Human Disease

Mouse Models

Alzheimer's disease

IDs

Alzheimer's disease      

DOID:10652
ICD10CM:G30
ICD9CM:331.0
KEGG:05010
MESH:D000544
NCI:C2866
UMLS_CUI:C0002395

View 1 model

Mouse Models

Human Disease Modeled: Alzheimer's disease

Allelic Composition	Genetic Background	Reference	Phenotypes
Apoa4tm1Bres/Apoa4tm1Bres Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas/?	involves: 129S4/SvJae * C57BL/6 * SJL	J:169682	View

autosomal dominant tubulointerstitial kidney disease 6

IDs

autosomal dominant tubulointerstitial kidney disease 6      

DOID:0061121
OMIM:621106

colitis

IDs

colitis      

DOID:0060180
EFO:0003872
ICD10CM:K52.9
MESH:D003092
NCI:C26723
UMLS_CUI:C0009319

myocardial infarction

IDs

myocardial infarction      

DOID:5844
EFO:0000612
ICD10CM:I21
MESH:D009203
NCI:C27996
OMIM:608557
UMLS_CUI:C0027051

ulcerative colitis

IDs

ulcerative colitis      

DOID:8577
DOID:8576
DOID:9016
EFO:0000729
ICD10CM:K51
ICD9CM:556
ICD9CM:556.5
ICD9CM:556.9
MESH:D003093
NCI:C2952
UMLS_CUI:C0009324
UMLS_CUI:C0375359

Click on a disease name to see all genes associated with that disease.

• Mutations/Alleles
  1 with disease annotations

• References
  1 with disease annotations

Mutations,
Alleles, and
Phenotypes

• Phenotype Summary
  8 phenotypes from 1 allele in 2 genetic backgrounds
  5 phenotypes from multigenic genotypes
  30 phenotype references
  

• All Mutations and Alleles
  9
• Endonuclease-mediated
  7
• Targeted
  2
• Genomic Mutations
  1 involving Apoa4
• Incidental Mutations
  Mutagenetix , APF , CvDC
• Find Mice (IMSR)
  24 strains or lines available
• Comparison Matrix
  Gene Expression + Phenotype

Mice homozygous for disruption of this gene have lower HDL cholesterol levels but normal lipid absorption, growth, and feeding behavior.

Gene Ontology
(GO)
Classifications

• All GO Annotations
  100
• GO References
  14

Expression

• Assay Results
  618
• Tissues
  16
• cDNA Data
  17
• Literature Summary
  15

Images

Tissue x Stage Matrix

Comparison Matrix

Gene Expression + Phenotype

• Other Mouse Links
  Allen Institute
  GEO
  Expression Atlas
• Other Vertebrate Links
  GEISHA APOA4
  Xenbase apoa4
  ZFIN apoa4a, apoa4b.1, apoa4b.2, apoa4b.3

Sequences &
Gene Models

• All Sequences
  41
• RefSeq
  2
• UniProt
  4
• CCDS
  CCDS23142.1

• Ensembl
  ENSMUSG00000032080 (Evidence)
• NCBI Gene
  11808

Representative Sequences			Length	Strain/Species
genomic	11808	NCBI Gene Model | MGI Sequence Detail	2615	C57BL/6J
transcript	NM_007468	RefSeq | MGI Sequence Detail	1666	C57BL/6
polypeptide	P06728	UniProt | EBI | MGI Sequence Detail	395	Not Applicable

Protein
Information

• UniProt
  4 Sequences
• Protein Ontology
  PR:000004143 apolipoprotein A-IV
  (term hierarchy)
• InterPro Domains
  IPR050163 Apolipoprotein A1/A4/E
  IPR000074 Apolipoprotein A/E
• GlyGen
  P06728 1 site, 1 O-linked glycan (1 site)

Molecular
Reagents

• All nucleic 25

  Genomic 3

  cDNA 18

  Primer pair 3

  Other 1

  
  

  Microarray probesets 4

Other
Accession IDs

MGD-MRK-1366, MGD-MRK-1369

References

• Summaries
  All 110

  Developmental Gene Expression 15

  Diseases 1

  Gene Ontology 14

  Phenotypes 30
• Earliest
  J:24996 Mahley RW, et al., Plasma lipoproteins: apolipoprotein structure and function. J Lipid Res. 1984 Dec 1;25(12):1277-94
• Latest
  J:345621 Adams DJ, et al., Genetic determinants of micronucleus formation in vivo. Nature. 2024 Mar;627(8002):130-136

TSS for Apoa4:

(View these features in JBrowse)

Transcription Start Site	Location	Distance from Gene 5'-end
Tssr84863	Chr9:46152038-46152043 (+)	-101 bp
Tssr84864	Chr9:46152080-46152091 (+)	-56 bp
Tssr2855	Chr9:46152117-46152127 (+)	-20 bp
Tssr2856	Chr9:46152133-46152148 (+)	-1 bp
Tssr84865	Chr9:46152208-46152218 (+)	71 bp
Tssr2857	Chr9:46152268-46152277 (+)	131 bp
Tssr2858	Chr9:46152323-46152340 (+)	190 bp
Tssr84866	Chr9:46152350-46152366 (+)	216 bp
Tssr2859	Chr9:46152388-46152398 (+)	251 bp
Tssr2860	Chr9:46152754-46152761 (+)	616 bp
Tssr84867	Chr9:46152768-46152787 (+)	636 bp
Tssr84868	Chr9:46152802-46152828 (+)	673 bp
Tssr84869	Chr9:46152846-46152858 (+)	710 bp
Tssr84870	Chr9:46153401-46153418 (+)	1,268 bp
Tssr84871	Chr9:46153485-46153494 (+)	1,348 bp
Tssr84872	Chr9:46153565-46153579 (+)	1,430 bp
Tssr84873	Chr9:46153583-46153676 (+)	1,488 bp
Tssr84874	Chr9:46153687-46153740 (+)	1,572 bp
Tssr84875	Chr9:46153742-46153747 (+)	1,603 bp
Tssr84876	Chr9:46153748-46153758 (+)	1,611 bp
Tssr84877	Chr9:46153769-46153790 (+)	1,638 bp
Tssr84878	Chr9:46153792-46153820 (+)	1,664 bp
Tssr84879	Chr9:46153821-46153841 (+)	1,689 bp
Tssr84880	Chr9:46153848-46153885 (+)	1,725 bp
Tssr84881	Chr9:46153903-46153928 (+)	1,774 bp
Tssr84882	Chr9:46153930-46153940 (+)	1,793 bp
Tssr84883	Chr9:46153954-46153963 (+)	1,817 bp
Tssr84884	Chr9:46153966-46154009 (+)	1,846 bp
Tssr84885	Chr9:46154020-46154031 (+)	1,884 bp
Tssr84886	Chr9:46154073-46154084 (+)	1,937 bp
Tssr84887	Chr9:46154092-46154099 (+)	1,954 bp
Tssr84888	Chr9:46154198-46154205 (+)	2,060 bp
Tssr84889	Chr9:46154211-46154216 (+)	2,072 bp
Tssr84890	Chr9:46154299-46154310 (+)	2,163 bp
Tssr84891	Chr9:46154329-46154338 (+)	2,192 bp
Tssr84892	Chr9:46154340-46154345 (+)	2,201 bp
Tssr84893	Chr9:46154403-46154413 (+)	2,266 bp
Tssr84894	Chr9:46154440-46154451 (+)	2,304 bp
Tssr84895	Chr9:46154459-46154470 (+)	2,323 bp
Tssr84896	Chr9:46154673-46154683 (+)	2,536 bp
Tssr84897	Chr9:46154702-46154720 (+)	2,569 bp

Apoa4 is Candidate Gene for:

QTL	Genetic Location*	Genome Location (GRCm39)	Reference	QTL Note
Cq4	Chr9, 17.80 cM	Chr9:32411751-32411890	J:99474	Linkage analysis was performed on 3 separate F2 crosses in 3 previous studies: J: 54322, J:87328 and J:94251 to map QTLs associated with plasma cholesterol levels. Cq1, Cq2, and Cq6 mapped to mouse Chromosome 1, Cq3 mapped to mouse Chromosome 3, and Cq4 and Cq5 mapped to mouse Chromosome 9. Cq2 and Cq6 map to the same location on distal mouse Chromosome 1 at approximately 100 cM. Cq2 was identified in a (C57BL/6J x KK-A)F2 intercross and Cq6 was identified in a (C57BL/6J x RR)F2 intercross. Apoa2 wasinvestigated as a possible candidate gene. The Apoa2 allele is found in KK and RR strains and is associated with increased cholesterol levels while inbred strain C57BL/6J carries the Apoa2 allele. It is thought that the Apoa2 allele may be responsible for the QTL effects of Cq2 and Cq6. Inbred strains A/J and SM/J carry the Apoa2 allele. It was previously unknown whether the Apoa2 and Apoa2 alleles had the same or different influences on plasma cholesterol level. An F2 intercross between congenic strains C57BL/6J-Apoa2 and C57BL/6J-Apoa2 revealed no physiological differences between the Apoa2 and Apoa2 alleles. Therefore, the Apoa2 allele confers increased plasma cholesterol compared to the Apoa2 and Apoa2 alleles. Cq4 and Cq5 map to the same location on mouse Chromosome 9 at approximately 27 cM and Apoa1 and Apoa4 were investigated as possible candidate genes. Cq4 was identified in a (C57BL/6J x KK-A)F2 intercross and Cq5 was identified in a (KK x RR)F2 intercross. Sequence analysis of Apoa1 revealed that polymorphic differences between the involved strains did not correlate to cholesterol phenotype. Analysis of Apoa4 revealed a silent polymorphism (C771T) that exhibits complete correlation to cholesterol phenotype. Inbred strain KK carries the T allele whereas inbred strain C57BL/6J and RR carry the C allele. Another polymorphism in Apoa4 was detected involving a 12 nucleotide insertion encoding Glu-Gln-Ala/Val-Gln. Inbred strain KK carries 3 repeats, inbred strain C57BL/6J carries 4 repeats, and inbred strain RR carries 5 repeats. However, it could not be determined if this particular polymorphism explains the QTL effect of Cq4 and Cq5 on cholesterol levels.
Cq5	Chr9, 26.83 cM	Chr9:49452421-49452546	J:99474	Linkage analysis was performed on 3 separate F2 crosses in 3 previous studies: J: 54322, J:87328 and J:94251 to map QTLs associated with plasma cholesterol levels. Cq1, Cq2, and Cq6 mapped to mouse Chromosome 1, Cq3 mapped to mouse Chromosome 3, and Cq4 and Cq5 mapped to mouse Chromosome 9. Cq2 and Cq6 map to the same location on distal mouse Chromosome 1 at approximately 100 cM. Cq2 was identified in a (C57BL/6J x KK-A)F2 intercross and Cq6 was identified in a (C57BL/6J x RR)F2 intercross. Apoa2 wasinvestigated as a possible candidate gene. The Apoa2 allele is found in KK and RR strains and is associated with increased cholesterol levels while inbred strain C57BL/6J carries the Apoa2 allele. It is thought that the Apoa2 allele may be responsible for the QTL effects of Cq2 and Cq6. Inbred strains A/J and SM/J carry the Apoa2 allele. It was previously unknown whether the Apoa2 and Apoa2 alleles had the same or different influences on plasma cholesterol level. An F2 intercross between congenic strains C57BL/6J-Apoa2 and C57BL/6J-Apoa2 revealed no physiological differences between the Apoa2 and Apoa2 alleles. Therefore, the Apoa2 allele confers increased plasma cholesterol compared to the Apoa2 and Apoa2 alleles. Cq4 and Cq5 map to the same location on mouse Chromosome 9 at approximately 27 cM and Apoa1 and Apoa4 were investigated as possible candidate genes. Cq4 was identified in a (C57BL/6J x KK-A)F2 intercross and Cq5 was identified in a (KK x RR)F2 intercross. Sequence analysis of Apoa1 revealed that polymorphic differences between the involved strains did not correlate to cholesterol phenotype. Analysis of Apoa4 revealed a silent polymorphism (C771T) that exhibits complete correlation to cholesterol phenotype. Inbred strain KK carries the T allele whereas inbred strain C57BL/6J and RR carry the C allele. Another polymorphism in Apoa4 was detected involving a 12 nucleotide insertion encoding Glu-Gln-Ala/Val-Gln. Inbred strain KK carries 3 repeats, inbred strain C57BL/6J carries 4 repeats, and inbred strain RR carries 5 repeats. However, it could not be determined if this particular polymorphism explains the QTL effect of Cq4 and Cq5 on cholesterol levels.

*cM position of peak correlated region/marker