ASXL3

ASXL transcriptional regulator 3

Basic information

Region (hg38): 18:33578218-33751195

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 (385 variants)
• Severe feeding difficulties-failure to thrive-microcephaly due to ASXL3 deficiency syndrome (185 variants)
• Inborn genetic diseases (99 variants)
• not specified (47 variants)
• Intellectual disability (7 variants)
• See cases (7 variants)
• ASXL3-related condition (6 variants)
• Autism spectrum disorder (4 variants)
• Neurodevelopmental disorder (2 variants)
• Gastrostomy tube feeding in infancy;Decreased activity of mitochondrial complex I;Global developmental delay;Absent speech;Generalized hypotonia (1 variants)
• Abnormal brain morphology (1 variants)
• Marfanoid habitus and intellectual disability (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.

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	42	18	66
missense		1	178	87	24	290
nonsense	29	24	2			55
start loss						0
frameshift	59	29	2	1	1	92
inframe indel			8			8
splice donor/acceptor (+/-2bp)	3	2				5
splice region			3			3
non coding			1	22	46	69
Total	91	56	197	152	89

Variants in ASXL3

This is a list of pathogenic ClinVar variants found in the ASXL3 region.

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

Position	Type	Phenotype	Significance	ClinVar
18-33578269-C-A			Benign (Jan 13, 2019)
18-33578458-CCCG-C			Benign (Aug 06, 2019)
18-33578458-CCCGCCGCCG-C			Likely benign (Sep 23, 2019)
18-33578458-C-CCCG			Benign (Sep 15, 2019)
18-33578458-C-CCCGCCG			Likely benign (Oct 02, 2019)
18-33578460-CGCCGCCGCCGCCG-C			Likely benign (Aug 26, 2019)
18-33578640-CAA-C			Likely pathogenic (Jul 19, 2018)
18-33578660-G-A		Inborn genetic diseases	Uncertain significance (Dec 06, 2021)
18-33578667-G-A		Severe feeding difficulties-failure to thrive-microcephaly due to ASXL3 deficiency syndrome	Likely pathogenic (Dec 14, 2021)
18-33578904-G-GCGTCCGGGAC			Likely benign (Nov 02, 2020)
18-33578991-C-T			Benign (Aug 10, 2018)
18-33607554-T-C			Benign (Mar 29, 2020)
18-33607600-G-A			Uncertain significance (Oct 22, 2021)
18-33607606-C-T		not specified	Uncertain significance (Mar 06, 2024)
18-33607611-C-T			Uncertain significance (Apr 01, 2021)
18-33607742-G-A		Severe feeding difficulties-failure to thrive-microcephaly due to ASXL3 deficiency syndrome	Benign (Dec 05, 2021)
18-33607946-C-A			Benign (Jul 27, 2018)
18-33607970-T-G			Likely benign (Aug 17, 2018)
18-33616691-GAA-G		ASXL3-related disorder	Uncertain significance (Aug 09, 2023)
18-33626925-A-G			Benign (Sep 01, 2022)
18-33644557-TG-T			Likely benign (Jul 26, 2018)
18-33644560-A-AC			Likely benign (Nov 14, 2019)
18-33644949-G-A			Uncertain significance (Jan 01, 2024)
18-33644951-G-A		not specified • Severe feeding difficulties-failure to thrive-microcephaly due to ASXL3 deficiency syndrome • ASXL3-related disorder	Benign/Likely benign (Dec 05, 2021)
18-33644983-C-T		Inborn genetic diseases	Likely benign (Jun 02, 2023)

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