ASXL3

ASXL transcriptional regulator 3

Basic information

Region (hg38): 18:33578219-33751195

Previous symbols: [ "KIAA1713" ]

Links

ENSG00000141431 ∙ NCBI:80816 ∙ OMIM:615115 ∙ HGNC:29357 ∙ Uniprot:Q9C0F0 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• severe feeding difficulties-failure to thrive-microcephaly due to ASXL3 deficiency syndrome (Definitive), mode of inheritance: AD
• severe feeding difficulties-failure to thrive-microcephaly due to ASXL3 deficiency syndrome (Strong), mode of inheritance: AD
• severe feeding difficulties-failure to thrive-microcephaly due to ASXL3 deficiency syndrome (Strong), mode of inheritance: AD
• severe feeding difficulties-failure to thrive-microcephaly due to ASXL3 deficiency syndrome (Supportive), 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
Bainbridge-Ropers 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	23383720

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ASXL3 gene.

• not_provided (459 variants)
• Inborn_genetic_diseases (265 variants)
• Severe_feeding_difficulties-failure_to_thrive-microcephaly_due_to_ASXL3_deficiency_syndrome (259 variants)
• ASXL3-related_disorder (71 variants)
• not_specified (57 variants)
• Intellectual_disability (16 variants)
• See_cases (7 variants)
• Autism_spectrum_disorder (4 variants)
• Global_developmental_delay (3 variants)
• Syndromic_intellectual_disability (2 variants)
• Neurodevelopmental_disorder (2 variants)
• Decreased_activity_of_mitochondrial_complex_I (1 variants)
• intellectual_deficiency (1 variants)
• Ventricular_septal_defect (1 variants)
• Gastrostomy_tube_feeding_in_infancy (1 variants)
• Hereditary_ataxia (1 variants)
• Marfanoid_habitus_and_intellectual_disability (1 variants)
• Sleep_abnormality (1 variants)
• Rare_syndromic_intellectual_disability (1 variants)
• Neurodevelopmental_abnormality (1 variants)
• Atypical_behavior (1 variants)
• Strabismus (1 variants)
• Generalized_hypotonia (1 variants)
• Abnormal_brain_morphology (1 variants)
• Vascular_disorder (1 variants)
• Cleft_palate (1 variants)
• Decreased_head_circumference (1 variants)
• Absent_speech (1 variants)
• Language_retardation (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ASXL3 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000030632.3. 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	1		8	70	17	96
missense	5	3	333	174	15	530
nonsense	40	39	4			83
start loss						0
frameshift	84	62	6	1	1	154
splice donor/acceptor (+/-2bp)	4	6				10
Total	134	110	351	245	33

Highest pathogenic variant AF is 0.00176437

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ASXL3	protein_coding	protein_coding	ENST00000269197	12	172578

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.00000156	124624	0	14	124638	0.0000562

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.607	1097	1.16e+3	0.950	0.0000588	14607
Missense in Polyphen		296	369.71	0.80062		4842
Synonymous	-0.125	448	445	1.01	0.0000251	4534
Loss of Function	7.02	8	72.6	0.110	0.00000386	993

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000937	0.0000936
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000556	0.0000556
Finnish	0.0000929	0.0000928
European (Non-Finnish)	0.0000635	0.0000619
Middle Eastern	0.0000556	0.0000556
South Asian	0.0000659	0.0000654
Other	0.00	0.00

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). {ECO:0000250}.

Intolerance Scores

• loftool: 0.222
• rvis_EVS: -0.67
• rvis_percentile_EVS: 15.87

Haploinsufficiency Scores

• pHI: 0.108
• hipred: Y
• hipred_score: 0.553
• ghis: 0.528

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.254

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Asxl3

Gene ontology

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