ANKLE2 (ankyrin repeat and LEM domain containing 2)

Gene

• Entrez ID: 23141
• Gene name: Ankyrin repeat and LEM domain containing 2
• Gene symbol: ANKLE2
• Synonyms (NCBI Gene): KIAA0692, LEMD7, Lem4, MCPH16
• Chromosome: 12
• Chromosome location: 12q24.33
• Summary: This gene encodes a member of the LEM family of inner nuclear membrane proteins. The encoded protein functions as a mitotic regulator through postmitotic formation of the nuclear envelope. Mutations in this gene cause morphology defects in the nuclear env

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs201785518	G>A	Pathogenic	Genic downstream transcript variant, non coding transcript variant, coding sequence variant, intron variant, stop gained, downstream transcript variant
rs863225465	G>C	Pathogenic, likely-pathogenic	Intron variant, missense variant, coding sequence variant
rs1185537869	C>A	Pathogenic	Non coding transcript variant, missense variant, coding sequence variant, 5 prime UTR variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT031684	hsa-miR-16-5p	Proteomics	18668040
MIRT049020	hsa-miR-92a-3p	CLASH	23622248
MIRT782320	hsa-miR-1231	CLIP-seq
MIRT782321	hsa-miR-1303	CLIP-seq
MIRT782322	hsa-miR-146a	CLIP-seq
MIRT782323	hsa-miR-146b-5p	CLIP-seq
MIRT782324	hsa-miR-1539	CLIP-seq
MIRT782325	hsa-miR-188-5p	CLIP-seq
MIRT782326	hsa-miR-18a	CLIP-seq
MIRT782327	hsa-miR-18b	CLIP-seq
MIRT782328	hsa-miR-191	CLIP-seq
MIRT782329	hsa-miR-3120-5p	CLIP-seq
MIRT782330	hsa-miR-3123	CLIP-seq
MIRT782331	hsa-miR-3185	CLIP-seq
MIRT782332	hsa-miR-3192	CLIP-seq
MIRT782333	hsa-miR-3193	CLIP-seq
MIRT782334	hsa-miR-339-5p	CLIP-seq
MIRT782335	hsa-miR-34c-3p	CLIP-seq
MIRT782336	hsa-miR-3646	CLIP-seq
MIRT782337	hsa-miR-3662	CLIP-seq
MIRT782338	hsa-miR-3670	CLIP-seq
MIRT782339	hsa-miR-3908	CLIP-seq
MIRT782340	hsa-miR-3920	CLIP-seq
MIRT782341	hsa-miR-3925-5p	CLIP-seq
MIRT782342	hsa-miR-3942-5p	CLIP-seq
MIRT782343	hsa-miR-4261	CLIP-seq
MIRT782344	hsa-miR-4268	CLIP-seq
MIRT782345	hsa-miR-4314	CLIP-seq
MIRT782346	hsa-miR-4422	CLIP-seq
MIRT782347	hsa-miR-4448	CLIP-seq
MIRT782348	hsa-miR-450b-3p	CLIP-seq
MIRT782349	hsa-miR-4523	CLIP-seq
MIRT782350	hsa-miR-4645-3p	CLIP-seq
MIRT782351	hsa-miR-4646-5p	CLIP-seq
MIRT782352	hsa-miR-4652-3p	CLIP-seq
MIRT782353	hsa-miR-4663	CLIP-seq
MIRT782354	hsa-miR-4670-3p	CLIP-seq
MIRT782355	hsa-miR-4703-5p	CLIP-seq
MIRT782356	hsa-miR-4713-3p	CLIP-seq
MIRT782357	hsa-miR-4735-3p	CLIP-seq
MIRT782358	hsa-miR-4761-5p	CLIP-seq
MIRT782359	hsa-miR-4762-3p	CLIP-seq
MIRT782360	hsa-miR-4766-3p	CLIP-seq
MIRT782361	hsa-miR-4774-5p	CLIP-seq
MIRT782362	hsa-miR-4777-5p	CLIP-seq
MIRT782363	hsa-miR-4778-5p	CLIP-seq
MIRT782364	hsa-miR-483-3p	CLIP-seq
MIRT782365	hsa-miR-487b	CLIP-seq
MIRT782366	hsa-miR-495	CLIP-seq
MIRT782367	hsa-miR-514	CLIP-seq
MIRT782368	hsa-miR-514b-3p	CLIP-seq
MIRT782369	hsa-miR-532-3p	CLIP-seq
MIRT782370	hsa-miR-541	CLIP-seq
MIRT782371	hsa-miR-548c-3p	CLIP-seq
MIRT782372	hsa-miR-548p	CLIP-seq
MIRT782373	hsa-miR-566	CLIP-seq
MIRT782374	hsa-miR-570	CLIP-seq
MIRT782375	hsa-miR-579	CLIP-seq
MIRT782376	hsa-miR-580	CLIP-seq
MIRT782377	hsa-miR-589	CLIP-seq
MIRT782378	hsa-miR-629	CLIP-seq
MIRT782379	hsa-miR-638	CLIP-seq
MIRT782380	hsa-miR-654-5p	CLIP-seq
MIRT782381	hsa-miR-662	CLIP-seq
MIRT782382	hsa-miR-769-3p	CLIP-seq
MIRT782383	hsa-miR-889	CLIP-seq
MIRT782384	hsa-miR-934	CLIP-seq
MIRT1930936	hsa-miR-1228	CLIP-seq
MIRT1930937	hsa-miR-1229	CLIP-seq
MIRT1930938	hsa-miR-149	CLIP-seq
MIRT1930939	hsa-miR-3140-5p	CLIP-seq
MIRT1930940	hsa-miR-338-5p	CLIP-seq
MIRT1930941	hsa-miR-342-3p	CLIP-seq
MIRT782337	hsa-miR-3662	CLIP-seq
MIRT1930942	hsa-miR-3942-3p	CLIP-seq
MIRT1930943	hsa-miR-4282	CLIP-seq
MIRT1930944	hsa-miR-4715-3p	CLIP-seq
MIRT782360	hsa-miR-4766-3p	CLIP-seq
MIRT1930945	hsa-miR-4786-5p	CLIP-seq
MIRT1930946	hsa-miR-4799-5p	CLIP-seq
MIRT782365	hsa-miR-487b	CLIP-seq
MIRT782374	hsa-miR-570	CLIP-seq
MIRT1930947	hsa-miR-769-5p	CLIP-seq
MIRT1930948	hsa-miR-885-5p	CLIP-seq
MIRT2171466	hsa-miR-124	CLIP-seq
MIRT2171467	hsa-miR-140-3p	CLIP-seq
MIRT782325	hsa-miR-188-5p	CLIP-seq
MIRT782328	hsa-miR-191	CLIP-seq
MIRT2171468	hsa-miR-203	CLIP-seq
MIRT2171469	hsa-miR-3065-3p	CLIP-seq
MIRT782329	hsa-miR-3120-5p	CLIP-seq
MIRT2171470	hsa-miR-3145-3p	CLIP-seq
MIRT2171471	hsa-miR-3163	CLIP-seq
MIRT2171472	hsa-miR-3180-5p	CLIP-seq
MIRT782334	hsa-miR-339-5p	CLIP-seq
MIRT2171473	hsa-miR-340	CLIP-seq
MIRT782335	hsa-miR-34c-3p	CLIP-seq
MIRT2171474	hsa-miR-377	CLIP-seq
MIRT2171475	hsa-miR-4469	CLIP-seq
MIRT2171476	hsa-miR-4539	CLIP-seq
MIRT782354	hsa-miR-4670-3p	CLIP-seq
MIRT2171477	hsa-miR-4683	CLIP-seq
MIRT2171478	hsa-miR-4700-3p	CLIP-seq
MIRT2171479	hsa-miR-4717-3p	CLIP-seq
MIRT2171480	hsa-miR-4727-5p	CLIP-seq
MIRT2171481	hsa-miR-4733-5p	CLIP-seq
MIRT782360	hsa-miR-4766-3p	CLIP-seq
MIRT2171482	hsa-miR-4768-3p	CLIP-seq
MIRT2171483	hsa-miR-4769-3p	CLIP-seq
MIRT2171484	hsa-miR-4802-3p	CLIP-seq
MIRT782365	hsa-miR-487b	CLIP-seq
MIRT2171485	hsa-miR-506	CLIP-seq
MIRT2171486	hsa-miR-520a-5p	CLIP-seq
MIRT2171487	hsa-miR-525-5p	CLIP-seq
MIRT2171488	hsa-miR-548an	CLIP-seq
MIRT782374	hsa-miR-570	CLIP-seq
MIRT2171489	hsa-miR-642a	CLIP-seq
MIRT2443657	hsa-miR-3655	CLIP-seq
MIRT2474436	hsa-miR-1245b-3p	CLIP-seq
MIRT2474437	hsa-miR-1297	CLIP-seq
MIRT2474438	hsa-miR-1298	CLIP-seq
MIRT2171467	hsa-miR-140-3p	CLIP-seq
MIRT2474439	hsa-miR-154	CLIP-seq
MIRT2474440	hsa-miR-205	CLIP-seq
MIRT2474441	hsa-miR-26a	CLIP-seq
MIRT2474442	hsa-miR-26b	CLIP-seq
MIRT2474443	hsa-miR-3141	CLIP-seq
MIRT2474444	hsa-miR-3665	CLIP-seq
MIRT2171474	hsa-miR-377	CLIP-seq
MIRT2474445	hsa-miR-4465	CLIP-seq
MIRT2474446	hsa-miR-4710	CLIP-seq
MIRT1930944	hsa-miR-4715-3p	CLIP-seq
MIRT782358	hsa-miR-4761-5p	CLIP-seq
MIRT2474447	hsa-miR-4792	CLIP-seq
MIRT2474448	hsa-miR-657	CLIP-seq
MIRT782321	hsa-miR-1303	CLIP-seq
MIRT782330	hsa-miR-3123	CLIP-seq
MIRT2474443	hsa-miR-3141	CLIP-seq
MIRT1930940	hsa-miR-338-5p	CLIP-seq
MIRT782335	hsa-miR-34c-3p	CLIP-seq
MIRT782341	hsa-miR-3925-5p	CLIP-seq
MIRT1930944	hsa-miR-4715-3p	CLIP-seq
MIRT782358	hsa-miR-4761-5p	CLIP-seq
MIRT782374	hsa-miR-570	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0004860	Function	Protein kinase inhibitor activity	IDA	22770216
GO:0005515	Function	Protein binding	IPI	22770216, 33961781, 34819669
GO:0005783	Component	Endoplasmic reticulum	IBA
GO:0005783	Component	Endoplasmic reticulum	IEA
GO:0005789	Component	Endoplasmic reticulum membrane	IDA	22770216
GO:0005789	Component	Endoplasmic reticulum membrane	IEA
GO:0005789	Component	Endoplasmic reticulum membrane	TAS
GO:0007084	Process	Mitotic nuclear membrane reassembly	IBA
GO:0007084	Process	Mitotic nuclear membrane reassembly	IMP	22770216
GO:0007399	Process	Nervous system development	IEA
GO:0007417	Process	Central nervous system development	IDA	25259927
GO:0016020	Component	Membrane	HDA	19946888
GO:0016020	Component	Membrane	IEA
GO:0019888	Function	Protein phosphatase regulator activity	TAS	22770216
GO:0031468	Process	Nuclear membrane reassembly	IEA
GO:0042326	Process	Negative regulation of phosphorylation	IDA	22770216
GO:0043066	Process	Negative regulation of apoptotic process	IDA	25259927
GO:0050790	Process	Regulation of catalytic activity	TAS	22770216
GO:0051301	Process	Cell division	IEA
GO:0051721	Function	Protein phosphatase 2A binding	IBA
GO:0051721	Function	Protein phosphatase 2A binding	IDA	22770216

Other IDs

• MIM: 616062
• HGNC: 29101
• e!Ensembl: ENSG00000176915

Protein

• UniProt ID: Q86XL3
• Protein name: Ankyrin repeat and LEM domain-containing protein 2 (LEM domain-containing protein 4)
• Protein function: Involved in mitotic nuclear envelope reassembly by promoting dephosphorylation of BAF/BANF1 during mitotic exit (PubMed:22770216). Coordinates the control of BAF/BANF1 dephosphorylation by inhibiting VRK1 kinase and promoting dephosphorylation o
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF03020	LEM	72 → 110	LEM domain	Domain
  PF01693	Cauli_VI	211 → 249	Caulimovirus viroplasmin	Family

• Sequence:

  MLWPRLAAAEWAALAWELLGASVLLIAVRWLVRRLGPRPGGLGRSGTPVPPPSAAAAPAS
  GEMTMDALLARLKLLNPDDLREEIVKAGLKCGPITSTTRFIFEKKLAQALLEQGGRLSSF
  YHHEAGVTALSQDPQRILKPAEGNPTDQAGFSEDRDFGYSVGLNPPEEEAVTSKTCSVPP
  SDTDTYRAGATASKEPPLYYGVCPVYEDVPARNERIYVYENKKEALQAVKMIKGSRFKAF
  STREDAEKFARGICDYFPSPSKTSLPLSPVKTAPLFSNDRLKDGLCLSESETVNKERANS
  YKNPRTQDLTAKLRKAVEKGEEDTFSDLIWSNPRYLIGSGDNPTIVQEGCRYNVMHVAAK
  ENQASICQLTLDVLENPDFMRLMYPDDDEAMLQKRIRYVVDLYLNTPDKMGYDTPLHFAC
  KFGNADVVNVLSSHHLIVKNSRNKYDKTPEDVICERSKNKSVELKERIREYLKGHYYVPL
  LRAEETSSPVIGELWSPDQTAEASHVSRYGGSPRDPVLTLRAFAGPLSPAKAEDFRKLWK
  TPPREKAGFLHHVKKSDPERGFERVGRELAHELGYPWVEYWEFLGCFVDLSSQEGLQRLE
  EYLTQQEIGKKAQQETGEREASCRDKATTSGSNSISVRAFLDEDDMSLEEIKNRQNAARN
  NSPPTVGAFGHTRCSAFPLEQEADLIEAAEPGGPHSSRNGLCHPLNHSRTLAGKRPKAPR
  GEEAHLPPVSDLTVEFDKLNLQNIGRSVSKTPDESTKTKDQILTSRINAVERDLLEPSPA
  DQLGNGHRRTESEMSARIAKMSLSPSSPRHEDQLEVTREPARRLFLFGEEPSKLDQDVLA
  ALECADVDPHQFPAVHRWKSAVLCYSPSDRQSWPSPAVKGRFKSQLPDLSGPHSYSPGRN
  SVAGSNPAKPGLGSPGRYSPVHGSQLRRMARLAELAAL

• Sequence length: 938

Pathways

Reactome:

Initiation of Nuclear Envelope (NE) Reformation

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Hypotonia	Pathogenic	rs1380982250	RCV001268940	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Intellectual disability	Pathogenic	rs1380982250	RCV001268940	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Microcephaly	Likely pathogenic	rs863225465	RCV000203271	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Microcephaly 16, primary, autosomal recessive	Likely pathogenic; Pathogenic	rs863225465, rs753596204, rs753680111, rs1185537869, rs1380982250	RCV000202421 RCV003152518 RCV004594876 RCV000786054 RCV003992460	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Vanishing white matter disease	Pathogenic	rs1380982250	RCV001268940	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Acute myeloid leukemia	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ANKLE2-related disorder	Likely benign; Uncertain significance; Benign; Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
AUTOSOMAL RECESSIVE PRIMARY MICROCEPHALY	—	Disgenet, Orphanet Disgenet, Orphanet Disgenet, Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cervical cancer	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CHILDHOOD ATAXIA WITH CENTRAL NERVOUS SYSTEM HYPOMYELINIZATION	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Lung cancer	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant tumor of esophagus	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Sarcoma	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SCHIZOPHRENIA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thymoma	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine carcinosarcoma	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Agenesis of corpus callosum	Agenesis Of Corpus Callosum	HPO_DG			★☆☆☆☆ Found in Text Mining only
Autosomal Recessive Primary Microcephaly	Microcephaly	ORPHANET_DG	25259927		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Autosomal recessive primary microcephaly	Microcephaly	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Autosomal Recessive Primary Microcephaly	Microcephaly	BEFREE	27519304		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Blepharoptosis	Ptosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Breast Carcinoma	Breast Carcinoma	BEFREE	30301939		★☆☆☆☆ Found in Text Mining only
Cryptorchidism	Cryptorchidism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Dwarfism	Dwarfism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Glaucoma	Glaucoma	HPO_DG			★☆☆☆☆ Found in Text Mining only
Global developmental delay	Developmental Delay	HPO_DG			★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of breast	Breast Cancer	BEFREE	30301939		★☆☆☆☆ Found in Text Mining only
Microcephaly	Microcephaly	Pubtator	30214071	Associate	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Microcephaly	Microcephaly	BEFREE	30550790, 31735666		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Microcephaly	Microcephaly	HPO_DG			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
MICROCEPHALY 16, PRIMARY, AUTOSOMAL RECESSIVE	Microcephaly	UNIPROT_DG	25259927		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
MICROCEPHALY 16, PRIMARY, AUTOSOMAL RECESSIVE	Microcephaly	GENOMICS_ENGLAND_DG	25259927		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
MICROCEPHALY 16, PRIMARY, AUTOSOMAL RECESSIVE	Microcephaly	CTD_human_DG			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
MICROCEPHALY 16, PRIMARY, AUTOSOMAL RECESSIVE	Microcephaly	CLINVAR_DG			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Micrognathism	Micrognathism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	30301939		★☆☆☆☆ Found in Text Mining only
Neuronal heterotopia	Neuronal Heterotopia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Oestrogen receptor positive breast cancer	Oestrogen Receptor Positive Breast Cancer	BEFREE	30301939		★☆☆☆☆ Found in Text Mining only
Ovarian Neoplasms	Ovarian neoplasm	Pubtator	35619151	Associate	★☆☆☆☆ Found in Text Mining only
Pachygyria	Pachygyria	HPO_DG			★☆☆☆☆ Found in Text Mining only
Ptosis	Ptosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Severe intellectual disability	Mental retardation	HPO_DG			★☆☆☆☆ Found in Text Mining only
Spastic Quadriplegia	Spastic Quadriplegia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Unilateral agenesis of kidney	Renal aplasia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Vesico-Ureteral Reflux	Vesicoureteral Reflux	HPO_DG			★☆☆☆☆ Found in Text Mining only