ASH1L

ASH1 like histone lysine methyltransferase, the group of Bromodomain containing|Lysine methyltransferases|PHD finger proteins|SET domain containing|MicroRNA protein coding host genes

Basic information

Region (hg38): 1:155335268-155563162

Links

ENSG00000116539 ∙ NCBI:55870 ∙ OMIM:607999 ∙ HGNC:19088 ∙ Uniprot:Q9NR48 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• intellectual disability, autosomal dominant 52 (Strong), mode of inheritance: AD
• autosomal dominant non-syndromic intellectual disability (Supportive), mode of inheritance: AD
• intellectual disability, autosomal dominant 52 (Strong), mode of inheritance: AD
• syndromic complex neurodevelopmental disorder (Definitive), mode of inheritance: AD
• intellectual disability, autosomal dominant 52 (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Intellectual developmental disorder, autosomal dominant 52	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; Musculoskeletal; Neurologic	23033978; 25961944; 27824329; 28191889; 28394464

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ASH1L gene.

• not_provided (361 variants)
• Inborn_genetic_diseases (249 variants)
• Intellectual_disability,_autosomal_dominant_52 (203 variants)
• ASH1L-related_disorder (80 variants)
• not_specified (27 variants)
• Intellectual_disability (14 variants)
• See_cases (8 variants)
• Autism_spectrum_disorder (4 variants)
• ASH1L-related_neurodevelopmental_disorders (4 variants)
• Syndromic_complex_neurodevelopmental_disorder (3 variants)
• Neurodevelopmental_disorder (2 variants)
• Congenital_heart_disease (1 variants)
• Global_developmental_delay (1 variants)
• Neurodevelopmental_delay (1 variants)
• Rare_genetic_intellectual_disability (1 variants)
• Developmental_disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ASH1L gene is commonly pathogenic or not. These statistics are base on transcript: NM_000018489.3. 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			7	51	10	68
missense	4	4	557	86	8	659
nonsense	26	11	4	2		43
start loss						0
frameshift	25	17	4			46
splice donor/acceptor (+/-2bp)			2			2
Total	55	32	574	139	18

Highest pathogenic variant AF is 0.0000198264

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ASH1L	protein_coding	protein_coding	ENST00000392403	27	227540

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	1.11e-18	125739	0	7	125746	0.0000278

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.47	1179	1.57e+3	0.753	0.0000862	19455
Missense in Polyphen		514	817.3	0.6289		10032
Synonymous	1.24	518	555	0.933	0.0000278	5759
Loss of Function	10.1	3	125	0.0239	0.00000829	1557

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.0000995	0.0000992
East Asian	0.00	0.00
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000264	0.0000264
Middle Eastern	0.00	0.00
South Asian	0.0000654	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Histone methyltransferase specifically methylating 'Lys- 36' of histone H3 (H3K36me). {ECO:0000269|PubMed:21239497}.
• Disease: DISEASE: Mental retardation, autosomal dominant 52 (MRD52) [MIM:617796]: A form of mental retardation, a disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. {ECO:0000269|PubMed:23033978, ECO:0000269|PubMed:27824329, ECO:0000269|PubMed:28191889, ECO:0000269|PubMed:28394464}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Lysine degradation - Homo sapiens (human);Histone Modifications;PKMTs methylate histone lysines;Chromatin modifying enzymes;Lysine metabolism;Chromatin organization (Consensus)

Intolerance Scores

• loftool: 0.00737
• rvis_EVS: -1.8
• rvis_percentile_EVS: 2.22

Haploinsufficiency Scores

• pHI: 0.356
• hipred: Y
• hipred_score: 0.715
• ghis: 0.630

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.790

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ash1l
• Phenotype: homeostasis/metabolism phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); endocrine/exocrine gland phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); immune system phenotype; skeleton phenotype; renal/urinary system phenotype; vision/eye phenotype; hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); reproductive system phenotype; 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); embryo phenotype

Gene ontology

• Biological process: skeletal system development;negative regulation of acute inflammatory response;DNA packaging;transcription by RNA polymerase II;cell-cell signaling;single fertilization;post-embryonic development;flagellated sperm motility;interleukin-6 production;negative regulation of I-kappaB kinase/NF-kappaB signaling;negative regulation of MAPK cascade;positive regulation of transcription by RNA polymerase II;decidualization;histone H3-K4 methylation;uterus morphogenesis;histone H3-K36 dimethylation;tarsal gland development;uterine gland development
• Cellular component: nucleus;nucleoplasm;chromosome;Golgi apparatus;bicellular tight junction
• Molecular function: DNA-binding transcription factor activity, RNA polymerase II-specific;DNA binding;chromatin binding;histone-lysine N-methyltransferase activity;histone methyltransferase activity (H3-K4 specific);metal ion binding;histone methyltransferase activity (H3-K36 specific)