GeneBe

ASXL1

ASXL transcriptional regulator 1

Basic information

Region (hg38): 20:32358330-32439319

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

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Bohring-Opitz syndromeADGeneralGenetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testingCraniofacial; Dermatologic; Musculoskeletal; Neurologic21706002; 22419483

ClinVar

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

  • Inborn_genetic_diseases (1434 variants)
  • not_provided (993 variants)
  • Bohring-Opitz_syndrome (162 variants)
  • ASXL1-related_disorder (61 variants)
  • not_specified (53 variants)
  • Myelodysplastic_syndrome (18 variants)
  • Intellectual_disability (8 variants)
  • Autism_spectrum_disorder (2 variants)
  • Microcephaly (2 variants)
  • Delayed_speech_and_language_development (2 variants)
  • Juvenile_myelomonocytic_leukemia (2 variants)
  • Rubinstein_Taybi_like_syndrome (2 variants)
  • Global_developmental_delay (2 variants)
  • Myelodysplasia (1 variants)
  • Glabellar_hemangioma (1 variants)
  • Feeding_difficulties (1 variants)
  • Small_for_gestational_age (1 variants)
  • Cafe-au-lait_spot (1 variants)
  • Hypertrichosis (1 variants)
  • dystrophia (1 variants)
  • Seizure (1 variants)
  • Atypical_chronic_myeloid_leukemia,_BCR-ABL1_negative (1 variants)
  • Neurodevelopmental_abnormality (1 variants)
  • Moderate_global_developmental_delay (1 variants)
  • Delayed_gross_motor_development (1 variants)
  • Hypertonia (1 variants)
  • Abnormal_corpus_callosum_morphology (1 variants)
  • Prominent_metopic_ridge (1 variants)
  • Developmental_delay (1 variants)
  • Hereditary_cancer (1 variants)
  • Abnormal_brain_morphology (1 variants)
  • See_cases (1 variants)
  • Intellectual_disability,_severe (1 variants)
  • Congenital_cerebellar_hypoplasia (1 variants)
  • Floppy_infant (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. These statistics are base on transcript: NM_000015338.6. 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.

EffectPLPVUSLBBSum
synonymous
2
clinvar
605
clinvar
4
clinvar
 611
missense
3
clinvar
2
clinvar
1005
clinvar
269
clinvar
27
clinvar
 1306
nonsense
36
clinvar
17
clinvar
5
clinvar
 58
start loss
1
 1
frameshift
58
clinvar
21
clinvar
6
clinvar
 85
splice donor/acceptor (+/-2bp)
5
clinvar
2
clinvar
1
clinvar
 8
Total 102 42 1020 874 31

Highest pathogenic variant AF is 0.00042764976

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
ASXL1protein_codingprotein_codingENST00000375687 1380968
pLI Probability
LOF Intolerant 		pRec Probability
LOF Recessive 		Individuals with
no LOFs 		Individuals with
Homozygous LOFs 		Individuals with
Heterozygous LOFs 		Defined p
1.25e-140.9951256520961257480.000382
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense0.6367918430.9380.000050110006
Missense in Polyphen230297.050.774293532
Synonymous-0.4163493391.030.00002123221
Loss of Function2.773152.70.5890.00000322616

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0004200.000420
Ashkenazi Jewish0.0005950.000595
East Asian0.0002290.000217
Finnish0.0001850.000185
European (Non-Finnish)0.0006010.000589
Middle Eastern0.0002290.000217
South Asian0.0001960.000131
Other0.0001650.000163

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

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

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