ASXL1

ASXL transcriptional regulator 1

Basic information

Region (hg38): 20:32358329-32439319

Links

ENSG00000171456 ∙ NCBI:171023 ∙ OMIM:612990 ∙ HGNC:18318 ∙ Uniprot:Q8IXJ9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Bohring-Opitz syndrome (Definitive), mode of inheritance: AD
• Bohring-Opitz syndrome (Definitive), mode of inheritance: AD
• Bohring-Opitz syndrome (Strong), mode of inheritance: AD
• Bohring-Opitz syndrome (Strong), mode of inheritance: AD
• Bohring-Opitz syndrome (Strong), mode of inheritance: AD
• Bohring-Opitz syndrome (Supportive), mode of inheritance: AD
• Bohring-Opitz syndrome (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Bohring-Opitz syndrome	AD	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	Craniofacial; Dermatologic; Musculoskeletal; Neurologic	21706002; 22419483

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ASXL1 gene.

• not provided (672 variants)
• Bohring-Opitz syndrome (122 variants)
• Inborn genetic diseases (61 variants)
• not specified (39 variants)
• ASXL1-related condition (9 variants)
• Myelodysplastic syndrome (7 variants)
• Bohring-Opitz syndrome;Myelodysplastic syndrome (4 variants)
• Myelodysplastic syndrome;Bohring-Opitz syndrome (4 variants)
• Intellectual disability (4 variants)
• Abnormal brain morphology (1 variants)
• 10 conditions (1 variants)
• Myelodysplasia (1 variants)
• Moderate global developmental delay;Seizure;Hypertonia;Delayed speech and language development (1 variants)
• ASXL1-Related Disorders (1 variants)
• Autism spectrum disorder (1 variants)
• See cases (1 variants)
• dystrophia;Developmental delay (1 variants)
• Global developmental delay;Infantile muscular hypotonia (1 variants)
• Juvenile myelomonocytic leukemia;Cafe-au-lait spot (1 variants)
• Juvenile myelomonocytic leukemia (1 variants)
• Rubinstein Taybi like syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ASXL1 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			6	144	13	163
missense		1	278	85	42	406
nonsense	25	8	1			34
start loss			1			1
frameshift	38	13	3			54
inframe indel			5	2		7
splice donor/acceptor (+/-2bp)	2	2				4
splice region			3	14		17
non coding			5	29	17	51
Total	65	24	299	260	72

Highest pathogenic variant AF is 0.000113

Variants in ASXL1

This is a list of pathogenic ClinVar variants found in the ASXL1 region.

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

Position	Type	Phenotype	Significance	ClinVar
20-32358494-C-T			Likely benign (Nov 25, 2018)
20-32358685-A-ACCG		Bohring-Opitz syndrome	Conflicting classifications of pathogenicity (Jul 01, 2023)
20-32358753-TGCC-T		ASXL1-related disorder	Likely benign (Dec 21, 2023)
20-32358772-A-G			Benign (Dec 30, 2019)
20-32358776-A-C			Uncertain significance (Aug 10, 2020)
20-32358788-CAGA-C			Benign/Likely benign (Jun 23, 2023)
20-32358793-G-A			Likely benign (Aug 04, 2023)
20-32358804-A-G		Inborn genetic diseases	Uncertain significance (Jan 18, 2022)
20-32358811-G-A			Likely benign (Jul 19, 2023)
20-32358816-C-T			Uncertain significance (Oct 27, 2022)
20-32358823-C-T			Likely benign (Mar 26, 2022)
20-32358828-G-T			Uncertain significance (Dec 03, 2021)
20-32358829-C-T			Likely benign (Dec 17, 2023)
20-32358841-G-T			Likely benign (Aug 04, 2023)
20-32358843-C-T			Likely benign (Dec 14, 2023)
20-32358849-AGGGGGGCTCCGTGGGGCCCGGGGTGG-A			Likely benign (May 12, 2022)
20-32358849-A-AG			Benign (Dec 13, 2023)
20-32358851-G-A		Bohring-Opitz syndrome • Myelodysplastic syndrome;Bohring-Opitz syndrome	Benign/Likely benign (Jan 29, 2024)
20-32358884-C-T			Benign (Sep 23, 2019)
20-32359043-G-GC			Likely benign (Aug 21, 2019)
20-32359310-G-T		ASXL1-related disorder	Uncertain significance (Oct 03, 2023)
20-32366367-C-T			Likely benign (Oct 18, 2023)
20-32366372-A-G			Likely benign (Aug 12, 2022)
20-32366376-T-A			Likely benign (Sep 27, 2022)
20-32366386-A-G			Likely benign (Jul 17, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ASXL1	protein_coding	protein_coding	ENST00000375687	13	80968

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.25e-14	0.995	125652	0	96	125748	0.000382

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.636	791	843	0.938	0.0000501	10006
Missense in Polyphen		230	297.05	0.77429		3532
Synonymous	-0.416	349	339	1.03	0.0000212	3221
Loss of Function	2.77	31	52.7	0.589	0.00000322	616

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000420	0.000420
Ashkenazi Jewish	0.000595	0.000595
East Asian	0.000229	0.000217
Finnish	0.000185	0.000185
European (Non-Finnish)	0.000601	0.000589
Middle Eastern	0.000229	0.000217
South Asian	0.000196	0.000131
Other	0.000165	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Probable Polycomb group (PcG) protein involved in transcriptional regulation mediated by ligand-bound nuclear hormone receptors, such as retinoic acid receptors (RARs) and peroxisome proliferator-activated receptor gamma (PPARG). Acts as coactivator of RARA and RXRA through association with NCOA1. Acts as corepressor for PPARG and suppresses its adipocyte differentiation-inducing activity (By similarity). Non-catalytic component of the PR-DUB complex, a complex that specifically mediates deubiquitination of histone H2A monoubiquitinated at 'Lys-119' (H2AK119ub1). {ECO:0000250, ECO:0000269|PubMed:16606617, ECO:0000269|PubMed:20436459}.
• Disease: DISEASE: Bohring-Opitz syndrome (BOPS) [MIM:605039]: A syndrome characterized by severe intrauterine growth retardation, poor feeding, profound mental retardation, trigonocephaly, prominent metopic suture, exophthalmos, nevus flammeus of the face, upslanting palpebral fissures, hirsutism, and flexion of the elbows and wrists with deviation of the wrists and metacarpophalangeal joints. {ECO:0000269|PubMed:21706002}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Myelodysplastic syndrome (MDS) [MIM:614286]: A heterogeneous group of closely related clonal hematopoietic disorders. All are characterized by a hypercellular or hypocellular bone marrow with impaired morphology and maturation, dysplasia of the myeloid, megakaryocytic and/or erythroid lineages, and peripheral blood cytopenias resulting from ineffective blood cell production. Included diseases are: refractory anemia (RA), refractory anemia with ringed sideroblasts (RARS), refractory anemia with excess blasts (RAEB), refractory cytopenia with multilineage dysplasia and ringed sideroblasts (RCMD-RS); chronic myelomonocytic leukemia (CMML) is a myelodysplastic/myeloproliferative disease. MDS is considered a premalignant condition in a subgroup of patients that often progresses to acute myeloid leukemia (AML). {ECO:0000269|PubMed:19388938, ECO:0000269|PubMed:20182461}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Post-translational protein modification;Metabolism of proteins;UCH proteinases;Deubiquitination (Consensus)

Recessive Scores

• pRec: 0.0787

Intolerance Scores

• loftool: 0.955
• rvis_EVS: 0.17
• rvis_percentile_EVS: 65.77

Haploinsufficiency Scores

• pHI: 0.147
• hipred: N
• hipred_score: 0.214
• ghis: 0.523

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.756

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Asxl1
• Phenotype: cellular phenotype; homeostasis/metabolism phenotype; craniofacial phenotype; endocrine/exocrine gland phenotype; growth/size/body region phenotype; skeleton phenotype; immune system phenotype; vision/eye phenotype; digestive/alimentary phenotype; neoplasm; 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); hematopoietic system phenotype; liver/biliary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Gene ontology

• Biological process: cell morphogenesis;heart morphogenesis;transcription, DNA-templated;animal organ morphogenesis;protein deubiquitination;hemopoiesis;response to retinoic acid;negative regulation of peroxisome proliferator activated receptor signaling pathway;monoubiquitinated histone H2A deubiquitination;negative regulation of fat cell differentiation;positive regulation of transcription by RNA polymerase II;positive regulation of retinoic acid receptor signaling pathway;thymus development;bone marrow development;homeostasis of number of cells;lung saccule development
• Cellular component: nuclear chromatin;nucleus;nucleoplasm;PR-DUB complex
• Molecular function: DNA binding;chromatin binding;transcription coactivator activity;protein binding;retinoic acid receptor binding;peroxisome proliferator activated receptor binding;metal ion binding