ANKLE1 ankyrin repeat and LEM domain containing 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: ANKLE1provided by HGNC
Official Full Name: ankyrin repeat and LEM domain containing 1provided by HGNC
Primary source: HGNC:HGNC:26812
See related: Ensembl:ENSG00000160117 MIM:619348; AllianceGenome:HGNC:26812
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: LEM3; LEMD6; ANKRD41
Summary: Enables endonuclease activity. Involved in DNA damage response and protein export from nucleus. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Nov 2024]
Expression: Biased expression in bone marrow (RPKM 8.2), lymph node (RPKM 1.3) and 2 other tissues See more
Orthologs: mouse all
NEW: Try the new Gene table
Try the new Transcript table

Genomic context

Location:: 19p13.11

Exon count:: 9

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	19	NC_000019.10 (17281901..17287646)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	19	NC_060943.1 (17416788..17422534)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	19	NC_000019.9 (17392710..17398455)

Chromosome 19 - NC_000019.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

Go to the top of the page Help

Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

Go to the top of the page Help

See details

Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

Go to the top of the page Help

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Biochemical and mechanistic analysis of the cleavage of branched DNA by human ANKLE1.
Title: Biochemical and mechanistic analysis of the cleavage of branched DNA by human ANKLE1.
Human Endonuclease ANKLE1 Localizes at the Midbody and Processes Chromatin Bridges to Prevent DNA Damage and cGAS-STING Activation.
Title: Human Endonuclease ANKLE1 Localizes at the Midbody and Processes Chromatin Bridges to Prevent DNA Damage and cGAS-STING Activation.
Dephosphocholination by Legionella effector Lem3 functions through remodelling of the switch II region of Rab1b.
Title: Dephosphocholination by Legionella effector Lem3 functions through remodelling of the switch II region of Rab1b.
Investigation of triple-negative breast cancer risk alleles in an International African-enriched cohort.
Title: Investigation of triple-negative breast cancer risk alleles in an International African-enriched cohort.
ANKLE1 N(6) -Methyladenosine-related variant is associated with colorectal cancer risk by maintaining the genomic stability.
Title: ANKLE1 N(6) -Methyladenosine-related variant is associated with colorectal cancer risk by maintaining the genomic stability.
Human ANKLE1 Is a Nuclease Specific for Branched DNA.
Title: Human ANKLE1 Is a Nuclease Specific for Branched DNA.
We used The Cancer Genome Atlas breast cancer patient data to identify ANKLE1 and ZNF404 as the target genes of candidate TF binding site SNPs in the 19p13.11 and 19q13.31 GWAS-identified loci. These SNPs are associated with the expression of ZNF404 and ANKLE1 in breast tissue.
Title: Identification of breast cancer associated variants that modulate transcription factor binding.
the domains mediating nuclear import and export of Ankle1, were identified.
Title: Nucleo-cytoplasmic shuttling of the endonuclease ankyrin repeats and LEM domain-containing protein 1 (Ankle1) is mediated by canonical nuclear export- and nuclear import signals.
Expression of RCCD1 in whole blood was also suggestively associated with disease risk (p-value: 1.2x10-05), as were expression of ACAP1 (p-value: 1.9x10-05) and LRRC25 (p-value: 5.2x10-05). While genome-wide association studies (GWAS) have implicated RCCD1 and ANKLE1 in breast cancer risk, they have not identified the remaining three genes
Title: Cis-eQTL-based trans-ethnic meta-analysis reveals novel genes associated with breast cancer risk.
Ankle1 is conserved in metazoans and contains a unique C-terminal GIY-YIG motif that confers endonuclease activity in vitro and in vivo
Title: The endonuclease Ankle1 requires its LEM and GIY-YIG motifs for DNA cleavage in vivo.

Submit: New GeneRIF Correction See all GeneRIFs (13)

Phenotypes

Go to the top of the page Help

Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
A locus on 19p13 modifies risk of breast cancer in BRCA1 mutation carriers and is associated with hormone receptor-negative breast cancer in the general population. EBI GWAS Catalog EBI GWAS CatalogPubMed
A meta-analysis of genome-wide association studies of breast cancer identifies two novel susceptibility loci at 6q14 and 20q11. EBI GWAS Catalog EBI GWAS CatalogPubMed
Common variants at 19p13 are associated with susceptibility to ovarian cancer. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study identifies 25 known breast cancer susceptibility loci as risk factors for triple-negative breast cancer. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

Go to the top of the page Help

See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

Go to the top of the page Help

Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

Go to the top of the page Help

Markers

SHGC-152141 (e-PCR)
- UniSTS:177414

AU048745 (e-PCR)
- UniSTS:145195

RH36905 (e-PCR)
- UniSTS:87932

D19S410 (e-PCR)
- UniSTS:9383

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables DNA endonuclease activity	IBA Inferred from Biological aspect of Ancestor more info
enables endonuclease activity	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in DNA damage response	IDA Inferred from Direct Assay more info	PubMed
involved_in double-strand break repair via homologous recombination	IBA Inferred from Biological aspect of Ancestor more info
involved_in negative regulation of mitotic recombination	IEA Inferred from Electronic Annotation more info
involved_in nucleic acid metabolic process	IC Inferred by Curator more info	PubMed
involved_in protein export from nucleus	IDA Inferred from Direct Assay more info	PubMed
involved_in protein export from nucleus	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of lymphoid progenitor cell differentiation	IEA Inferred from Electronic Annotation more info
involved_in regulation of myeloid progenitor cell differentiation	IEA Inferred from Electronic Annotation more info
involved_in resolution of meiotic recombination intermediates	IBA Inferred from Biological aspect of Ancestor more info

Component	Evidence Code	Pubs
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	IDA Inferred from Direct Assay more info
is_active_in nucleoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in nucleoplasm	IDA Inferred from Direct Assay more info
colocalizes_with nucleus	IDA Inferred from Direct Assay more info	PubMed
colocalizes_with nucleus	IMP Inferred from Mutant Phenotype more info	PubMed

General protein information

Go to the top of the page Help

Preferred Names: ankyrin repeat and LEM domain-containing protein 1

Names: LEM domain containing 6; LEM-domain containing 3; ankyrin repeat domain-containing protein 41

NCBI Reference Sequences (RefSeq)

Go to the top of the page Help

NEW Try the new Transcript table

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_001278443.2 → NP_001265372.2 ankyrin repeat and LEM domain-containing protein 1 isoform 2

Status: VALIDATED

Description

Transcript Variant: This variant (2) uses two alternate in-frame splice sites in the coding region, compared to variant 1. The encoded isoform (2) is shorter, compared to isoform 1.

Source sequence(s)

AC010463, AK096688, AK303628

Consensus CDS

CCDS92554.1

UniProtKB/TrEMBL

A0A494C092, A0JLW0

Related

ENSP00000498416.1, ENST00000652132.1

Conserved Domains (3) summary

cd10454
Location:413 → 528

GIY-YIG_COG3680_Meta; GIY-YIG domain of hypothetical proteins from Metazoa

cd00204
Location:12 → 117

ANK; ankyrin repeats; ankyrin repeats mediate protein-protein interactions in very diverse families of proteins. The number of ANK repeats in a protein can range from 2 to over 20 (ankyrins, for example). ANK repeats may occur in combinations with other ...

sd00045
Location:64 → 95

ANK; ANK repeat [structural motif]
NM_001278444.2 → NP_001265373.2 ankyrin repeat and LEM domain-containing protein 1 isoform 3

Status: VALIDATED

Description

Transcript Variant: This variant (3) uses an alternate in-frame splice site in the central coding region and lacks an exon in the 3' coding region, which results in a frameshift, compared to variant 1. The encoded isoform (3) is shorter and contains a distinct C-terminus, compared to isoform 1.

Source sequence(s)

AC010463, AK299977, AK303628

UniProtKB/TrEMBL

M0R002

Related

ENSP00000470895.2, ENST00000598347.2

Conserved Domains (3) summary

cd00204
Location:23 → 128

ANK; ankyrin repeats; ankyrin repeats mediate protein-protein interactions in very diverse families of proteins. The number of ANK repeats in a protein can range from 2 to over 20 (ankyrins, for example). ANK repeats may occur in combinations with other ...

sd00045
Location:75 → 106

ANK; ANK repeat [structural motif]

cl15257
Location:424 → 507

GIY-YIG_SF; GIY-YIG nuclease domain superfamily
NM_001278445.2 → NP_001265374.2 ankyrin repeat and LEM domain-containing protein 1 isoform 4

Status: VALIDATED

Description

Transcript Variant: This variant (4) uses two alternate splice sites in the coding region, and initiates translation at an alternate start codon, compared to variant 1. The encoded isoform (4) has a shorter and distinct N-terminus, compared to isoform 1.

Source sequence(s)

AC010463, AK096688, AK303628

UniProtKB/TrEMBL

M0QX15

Related

ENST00000651416.1

Conserved Domains (3) summary

cd10454
Location:410 → 525

GIY-YIG_COG3680_Meta; GIY-YIG domain of hypothetical proteins from Metazoa

cd00204
Location:2 → 114

ANK; ankyrin repeats; ankyrin repeats mediate protein-protein interactions in very diverse families of proteins. The number of ANK repeats in a protein can range from 2 to over 20 (ankyrins, for example). ANK repeats may occur in combinations with other ...

sd00045
Location:61 → 92

ANK; ANK repeat [structural motif]
NM_152363.6 → NP_689576.6 ankyrin repeat and LEM domain-containing protein 1 isoform 1

Status: VALIDATED

Description

Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).

Source sequence(s)

AC010463, AK096688, AK303628

Consensus CDS

CCDS12354.4

UniProtKB/Swiss-Prot

A8VU82, Q8N8J8, Q8NAG6

UniProtKB/TrEMBL

M0QX15

Related

ENSP00000384008.3, ENST00000404085.7

Conserved Domains (4) summary

cd10454
Location:450 → 565

GIY-YIG_COG3680_Meta; GIY-YIG domain of hypothetical proteins from Metazoa

cd12943
Location:361 → 398

LEM_ANKL1; LEM (Lap2/Emerin/Man1) domain found in ankyrin repeat and LEM domain-containing protein 1 (ANKL1)

sd00045
Location:75 → 106

ANK; ANK repeat [structural motif]

pfam12796
Location:56 → 128

Ank_2; Ankyrin repeats (3 copies)

RNA

NR_103530.2 RNA Sequence

Status: VALIDATED

Description

Transcript Variant: This variant (5) uses an alternate splice site and lacks an internal exon, compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

AC010463, AK303628