ASH1L
Basic information
Region (hg38): 1:155335267-155563162
Links
Phenotypes
GenCC
Source:
- intellectual disability, autosomal dominant 40 (Strong), mode of inheritance: AD
- 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
Clinical Genomic Database
Source:
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
- not provided (212 variants)
- Intellectual disability, autosomal dominant 52 (127 variants)
- Inborn genetic diseases (73 variants)
- ASH1L-related condition (15 variants)
- not specified (8 variants)
- See cases (8 variants)
- ASH1L-related neurodevelopmental disorders (4 variants)
- Autism spectrum disorder (4 variants)
- Intellectual disability (4 variants)
- Neurodevelopmental disorder (2 variants)
- Global developmental delay (1 variants)
- Developmental disorder (1 variants)
- ASH1L-Related Disorder (1 variants)
- Neurodevelopmental delay (1 variants)
- Global developmental delay;Seizure (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.
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 | 19 | 31 | ||||
missense | 271 | 32 | 314 | |||
nonsense | 12 | 21 | ||||
start loss | 0 | |||||
frameshift | 15 | 27 | ||||
inframe indel | 9 | |||||
splice donor/acceptor (+/-2bp) | 0 | |||||
splice region ? | 3 | 3 | ||||
non coding ? | 4 | |||||
Total | 27 | 19 | 288 | 54 | 18 |
Highest pathogenic variant AF is 0.00000657
Variants in ASH1L
This is a list of pathogenic ClinVar variants found in the ASH1L region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
Position | Type | Phenotype | Significance | ClinVar |
---|---|---|---|---|
1-155337668-G-A | Inborn genetic diseases • ASH1L-related disorder | Likely benign (Feb 05, 2024) | ||
1-155337684-G-C | Intellectual disability, autosomal dominant 52 | Uncertain significance (Feb 14, 2022) | ||
1-155337700-C-CT | Intellectual disability, autosomal dominant 52 | Pathogenic (Dec 05, 2017) | ||
1-155337743-C-T | Intellectual disability, autosomal dominant 52 | Uncertain significance (Apr 04, 2024) | ||
1-155337746-C-T | Uncertain significance (Feb 10, 2020) | |||
1-155338121-A-G | Autism spectrum disorder | Likely benign (Aug 08, 2022) | ||
1-155338146-G-A | Inborn genetic diseases | Uncertain significance (Nov 27, 2023) | ||
1-155338199-C-T | Intellectual disability, autosomal dominant 52 | Uncertain significance (Apr 26, 2023) | ||
1-155338207-T-G | ASH1L-related disorder | Likely benign (Oct 01, 2023) | ||
1-155338208-GT-G | Uncertain significance (Oct 28, 2022) | |||
1-155338213-T-A | Uncertain significance (Aug 06, 2019) | |||
1-155338230-C-T | Inborn genetic diseases | Likely benign (Apr 17, 2023) | ||
1-155338235-G-A | Inborn genetic diseases | Uncertain significance (Sep 06, 2022) | ||
1-155338250-C-A | Intellectual disability, autosomal dominant 52 | Uncertain significance (Nov 03, 2018) | ||
1-155338251-G-A | Intellectual disability, autosomal dominant 52 | Uncertain significance (Dec 13, 2019) | ||
1-155338317-T-G | Inborn genetic diseases | Uncertain significance (Dec 17, 2021) | ||
1-155338328-G-A | Uncertain significance (Oct 26, 2022) | |||
1-155338370-C-T | See cases | Uncertain significance (May 04, 2023) | ||
1-155339342-C-A | Intellectual disability, mild;Delayed speech and language development;Seizure | Uncertain significance (Dec 03, 2019) | ||
1-155339344-TGTA-T | Inborn genetic diseases | Uncertain significance (Dec 04, 2023) | ||
1-155341925-A-G | not specified | Uncertain significance (Dec 08, 2022) | ||
1-155341949-T-C | Intellectual disability, autosomal dominant 52 | Uncertain significance (Aug 23, 2018) | ||
1-155341950-T-G | Inborn genetic diseases | Uncertain significance (Feb 01, 2024) | ||
1-155341982-G-A | Uncertain significance (Jun 01, 2023) | |||
1-155342004-G-C | not specified | Uncertain significance (Sep 01, 2023) |
GnomAD
Source:
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:
- 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)