ANKLE2

ankyrin repeat and LEM domain containing 2, the group of Ankyrin repeat domain containing|LEM domain containing

Basic information

Region (hg38): 12:132725503-132761832

Previous symbols: [ "KIAA0692" ]

Links

ENSG00000176915 ∙ NCBI:23141 ∙ OMIM:616062 ∙ HGNC:29101 ∙ Uniprot:Q86XL3 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• microcephaly 16, primary, autosomal recessive (Moderate), mode of inheritance: AR
• microcephaly 16, primary, autosomal recessive (Strong), mode of inheritance: AR
• autosomal recessive primary microcephaly (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Microcephaly, primary autosomal recessive, 16	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Cardiovascular; Craniofacial; Dermatologic; Neurologic; Ophthalmologic	25259927

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ANKLE2 gene.

• Inborn_genetic_diseases (152 variants)
• not_provided (104 variants)
• ANKLE2-related_disorder (19 variants)
• Microcephaly_16,_primary,_autosomal_recessive (17 variants)
• not_specified (6 variants)
• Microcephaly (2 variants)
• See_cases (2 variants)
• Vanishing_white_matter_disease (1 variants)
• Hypotonia (1 variants)
• Intellectual_disability (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ANKLE2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000015114.3. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				28	4	32
missense		3	138	37		178
nonsense	2	2	1			5
start loss						0
frameshift			2			2
splice donor/acceptor (+/-2bp)		1				1
Total	2	6	141	65	4

Highest pathogenic variant AF is 0.0000232824

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ANKLE2	protein_coding	protein_coding	ENST00000357997	13	36221

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.01e-10	0.978	124777	0	85	124862	0.000340

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.343	509	531	0.958	0.0000318	6073
Missense in Polyphen		139	154.97	0.89697		1874
Synonymous	-1.18	247	224	1.10	0.0000157	1898
Loss of Function	2.29	22	37.1	0.593	0.00000204	469

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000409	0.000406
Ashkenazi Jewish	0.00	0.00
East Asian	0.000399	0.000389
Finnish	0.000234	0.000232
European (Non-Finnish)	0.000347	0.000344
Middle Eastern	0.000399	0.000389
South Asian	0.000915	0.000719
Other	0.000334	0.000329

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in mitotic nuclear envelope reassembly by promoting dephosphorylation of BAF/BANF1 during mitotic exit. Coordinates the control of BAF/BANF1 dephosphorylation by inhibiting VRK1 kinase and promoting dephosphorylation of BAF/BANF1 by protein phosphatase 2A (PP2A), thereby facilitating nuclear envelope assembly. It is unclear whether it acts as a real PP2A regulatory subunit or whether it is involved in recruitment of the PP2A complex. Involved in brain development (PubMed:25259927). {ECO:0000269|PubMed:22770216, ECO:0000269|PubMed:25259927}.
• Disease: DISEASE: Microcephaly 16, primary, autosomal recessive (MCPH16) [MIM:616681]: A form of microcephaly, a disease defined as a head circumference more than 3 standard deviations below the age, sex and ethnically matched mean. Brain weight is markedly reduced and the cerebral cortex is disproportionately small. {ECO:0000269|PubMed:25259927}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Initiation of Nuclear Envelope Reformation;Nuclear Envelope Reassembly;Mitotic Anaphase;Mitotic Metaphase and Anaphase;M Phase;Cell Cycle;Cell Cycle, Mitotic (Consensus)

Intolerance Scores

• loftool: 0.805
• rvis_EVS: -0.08
• rvis_percentile_EVS: 47.22

Haploinsufficiency Scores

• pHI: 0.315
• hipred: Y
• hipred_score: 0.612
• ghis: 0.533

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.644

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ankle2

Gene ontology

• Biological process: mitotic nuclear envelope reassembly;central nervous system development;positive regulation of protein dephosphorylation;negative regulation of phosphorylation;negative regulation of apoptotic process;regulation of phosphoprotein phosphatase activity;regulation of catalytic activity;cell division
• Cellular component: endoplasmic reticulum;endoplasmic reticulum membrane;membrane;integral component of endoplasmic reticulum membrane
• Molecular function: protein binding;protein phosphatase regulator activity;protein phosphatase 2A binding