ASXL2

ASXL transcriptional regulator 2

Basic information

Region (hg38): 2:25733753-25878487

Links

ENSG00000143970 ∙ NCBI:55252 ∙ OMIM:612991 ∙ HGNC:23805 ∙ Uniprot:Q76L83 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Shashi-Pena syndrome (Moderate), mode of inheritance: AD
• Shashi-Pena syndrome (Strong), mode of inheritance: AD
• syndromic intellectual disability (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Shashi-Pena syndrome	AD	Cardiovascular	Individuals have been described with congenital heart anomalies, and awareness may enable early diagnosis and management	Cardiovascular; Craniofacial; Endocrine; Dermatologic; Neurologic	27693232

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ASXL2 gene.

• Shashi-Pena syndrome (4 variants)
• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ASXL2 gene is commonly pathogenic or not.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	84	10	96
missense		2	208	30	20	260
nonsense	2	3	2			7
start loss						0
frameshift	3	1	4			8
inframe indel			6	1	1	8
splice donor/acceptor (+/-2bp)		1		1		2
splice region			4	6	3	13
non coding			5	20	10	35
Total	5	7	227	136	41

Variants in ASXL2

This is a list of pathogenic ClinVar variants found in the ASXL2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
2-25742019-T-C		not specified	Uncertain significance (Jan 10, 2024)
2-25742038-G-C		ASXL2-related disorder	Likely benign (Nov 08, 2022)
2-25742052-C-T			Uncertain significance (Aug 06, 2022)
2-25742053-G-A		ASXL2-related disorder	Likely benign (Apr 14, 2023)
2-25742056-C-G			Likely benign (Jul 01, 2023)
2-25742071-G-A			Likely benign (Jun 26, 2023)
2-25742075-C-G		Shashi-Pena syndrome	Uncertain significance (Jan 05, 2024)
2-25742078-T-C			Uncertain significance (Sep 26, 2022)
2-25742080-A-G			Likely benign (Feb 05, 2018)
2-25742092-A-G			Likely benign (Nov 22, 2022)
2-25742095-G-A			Likely benign (Oct 03, 2023)
2-25742103-C-G		Shashi-Pena syndrome	Uncertain significance (Apr 08, 2022)
2-25742105-T-A			Uncertain significance (Apr 06, 2023)
2-25742105-T-C			Uncertain significance (Dec 12, 2023)
2-25742109-A-C			Likely pathogenic (Sep 22, 2020)
2-25742113-G-C			Uncertain significance (May 28, 2023)
2-25742143-C-T			Likely benign (May 03, 2022)
2-25742149-C-T		ASXL2-related disorder	Benign/Likely benign (Jan 19, 2024)
2-25742150-G-A			Uncertain significance (Oct 23, 2022)
2-25742154-C-T		Inborn genetic diseases	Uncertain significance (Dec 21, 2022)
2-25742167-C-G		not specified	Uncertain significance (Jan 03, 2024)
2-25742170-T-C			Likely benign (Oct 01, 2022)
2-25742172-C-T		Inborn genetic diseases	Likely benign (May 30, 2023)
2-25742173-G-A		ASXL2-related disorder	Likely benign (Dec 14, 2023)
2-25742179-C-T			Likely benign (Dec 14, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ASXL2	protein_coding	protein_coding	ENST00000435504	13	144764

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	5.85e-7	124630	0	11	124641	0.0000441

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.71	609	740	0.823	0.0000375	9309
Missense in Polyphen		154	255.77	0.6021		3263
Synonymous	-1.40	315	285	1.11	0.0000157	2947
Loss of Function	6.37	3	53.2	0.0564	0.00000268	693

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000167	0.000158
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000458	0.0000442
Middle Eastern	0.00	0.00
South Asian	0.0000654	0.0000654
Other	0.000166	0.000165

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Putative Polycomb group (PcG) protein. PcG proteins act by forming multiprotein complexes, which are required to maintain the transcriptionally repressive state of homeotic genes throughout development. PcG proteins are not required to initiate repression, but to maintain it during later stages of development. They probably act via methylation of histones, rendering chromatin heritably changed in its expressibility (By similarity). Involved in transcriptional regulation mediated by ligand-bound nuclear hormone receptors, such as peroxisome proliferator-activated receptor gamma (PPARG). Acts as coactivator for PPARG and enhances its adipocyte differentiation-inducing activity; the function seems to involve differential recruitment of acetylated and methylated histone H3. {ECO:0000250, ECO:0000269|PubMed:21047783}.
• Disease: DISEASE: Shashi-Pena syndrome (SHAPNS) [MIM:617190]: An autosomal dominant syndrome characterized by delayed psychomotor development, intellectual disability of variable severity, macrocephaly, prominent eyes, arched eyebrows, hypertelorism, a glabellar nevus flammeus, neonatal feeding difficulties, and hypotonia. Some patients may also have atrial septal defect, episodic hypoglycemia, changes in bone mineral density, and/or seizures. {ECO:0000269|PubMed:27693232}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Note=A chromosomal aberration involving ASXL2 is a cause of therapy-related myelodysplastic syndrome. Translocation t(2;8)(p23;p11.2) with KAT6A generates a KAT6A-ASXL2 fusion protein.
• Pathway: Post-translational protein modification;Metabolism of proteins;UCH proteinases;Deubiquitination (Consensus)

Recessive Scores

• pRec: 0.0771

Haploinsufficiency Scores

• pHI: 0.338
• hipred: N
• hipred_score: 0.371
• ghis: 0.568

Essentials

• essential_gene_CRISPR2: S
• gene_indispensability_pred: E
• gene_indispensability_score: 0.626

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Asxl2
• Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); skeleton phenotype; growth/size/body region phenotype

Gene ontology

• Biological process: transcription, DNA-templated;animal organ morphogenesis;protein deubiquitination;positive regulation of peroxisome proliferator activated receptor signaling pathway;positive regulation of fat cell differentiation;positive regulation of transcription by RNA polymerase II
• Cellular component: nuclear chromatin;nucleus;nucleoplasm;PR-DUB complex
• Molecular function: DNA binding;chromatin binding;peroxisome proliferator activated receptor binding;metal ion binding