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

Transcripts

Transcript IDs starting with ENST are treated as Ensembl, all others as RefSeq. Showing 4 of 32.

Transcript ID	Protein ID	Coding exons	MANE Select	MANE Plus Clinical
NM_015338.6	NP_056153.2	13	yes	-
ENST00000375687.10	ENSP00000364839.4	13	yes	-
NM_001164603.1	NP_001158075.1	5	-	-
NM_001363734.1	NP_001350663.1	12	-	-

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 (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.

• Inborn_genetic_diseases (1856 variants)
• not_provided (1084 variants)
• Bohring-Opitz_syndrome (165 variants)
• ASXL1-related_disorder (61 variants)
• not_specified (61 variants)
• Myelodysplastic_syndrome (19 variants)
• Intellectual_disability (9 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)
• Small_for_gestational_age (1 variants)
• Feeding_difficulties (1 variants)
• Cafe-au-lait_spot (1 variants)
• Hypertrichosis (1 variants)
• dystrophia (1 variants)
• Severe_intellectual_disability (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)
• 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_015338.6. 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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	739	4	745
missense	3	3	1272	294	24	1596
nonsense	38	19	5			62
start loss			1			1
frameshift	58	26	10			94
splice donor/acceptor (+/-2bp)	5	4	1			10
Total	104	52	1291	1033	28

Highest pathogenic variant AF is 0.00042764976

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
		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

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

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