KANSL1

KAT8 regulatory NSL complex subunit 1, the group of NSL histone acetyltransferase complex

Basic information

Region (hg38): 17:46029916-46225389

Previous symbols: [ "KIAA1267" ]

Links

ENSG00000120071 ∙ NCBI:284058 ∙ OMIM:612452 ∙ HGNC:24565 ∙ Uniprot:Q7Z3B3 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Koolen-de Vries syndrome (Definitive), mode of inheritance: AD
• Koolen-de Vries syndrome due to a point mutation (Supportive), mode of inheritance: AD
• Koolen-de Vries syndrome (Strong), mode of inheritance: AD
• Koolen-de Vries syndrome (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Koolen-de Vries syndrome	AD	Cardiovascular	The condition can involve congenital cardiac anomalies, and awareness may allow early management	Cardiovascular; Craniofacial; Dermatologic; Genitourinary; Musculoskeletal; Neurologic	22482802; 22544363; 26306646; 28440867

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the KANSL1 gene.

• Koolen-de Vries syndrome (30 variants)
• not provided (24 variants)
• Inborn genetic diseases (6 variants)
• Intellectual disability (3 variants)
• KANSL1-related disorder (1 variants)
• Global developmental delay (1 variants)
• Neurodevelopmental delay (1 variants)
• See cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the KANSL1 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			1	242	12	255
missense		6	335	140	42	523
nonsense	12	6	6			24
start loss						0
frameshift	35	15	8			58
inframe indel			4	3		7
splice donor/acceptor (+/-2bp)	8	4	1	1		14
splice region			20	27	4	51
non coding			7	94	83	184
Total	55	31	362	480	137

Variants in KANSL1

This is a list of pathogenic ClinVar variants found in the KANSL1 region.

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

Position	Type	Phenotype	Significance	ClinVar
17-46029924-CT-C		Syndromic intellectual disability	Uncertain significance (Jun 14, 2016)
17-46029951-CCTT-C			Benign (Jul 01, 2022)
17-46029955-CT-C		Syndromic intellectual disability • MAPT-Related Spectrum Disorders	Benign (Jun 14, 2016)
17-46029955-C-CT		Syndromic intellectual disability	Uncertain significance (Jun 14, 2016)
17-46030121-GT-G		MAPT-Related Spectrum Disorders • Syndromic intellectual disability	Benign (Jun 14, 2016)
17-46030121-G-GT		Syndromic intellectual disability	Uncertain significance (Jun 14, 2016)
17-46030147-GT-G		MAPT-Related Spectrum Disorders • Syndromic intellectual disability	Benign (Jun 14, 2016)
17-46030240-A-AT		MAPT-Related Spectrum Disorders	Benign (Jun 14, 2016)
17-46030240-A-ATT		Syndromic intellectual disability	Uncertain significance (Jun 14, 2016)
17-46030280-A-C		MAPT-Related Spectrum Disorders • Syndromic intellectual disability	Likely benign (Jun 14, 2016)
17-46030372-C-CA		Syndromic intellectual disability	Uncertain significance (Jun 14, 2016)
17-46030448-A-G		Syndromic intellectual disability • MAPT-Related Spectrum Disorders	Likely benign (Jun 14, 2016)
17-46030449-G-C		Syndromic intellectual disability • MAPT-Related Spectrum Disorders	Likely benign (Jun 14, 2016)
17-46030522-G-C		Syndromic intellectual disability	Conflicting classifications of pathogenicity (Feb 01, 2023)
17-46030590-GA-G		MAPT-Related Spectrum Disorders • Syndromic intellectual disability	Benign (Jun 14, 2016)
17-46030734-C-T		Syndromic intellectual disability • MAPT-Related Spectrum Disorders	Benign (Jun 14, 2016)
17-46030836-A-G		MAPT-Related Spectrum Disorders	Benign (Jun 14, 2016)
17-46030850-A-G		MAPT-Related Spectrum Disorders • Syndromic intellectual disability	Likely benign (Jun 14, 2016)
17-46030989-G-A		MAPT-Related Spectrum Disorders	Benign (Jun 14, 2016)
17-46031088-C-A		MAPT-Related Spectrum Disorders • Syndromic intellectual disability	Likely benign (Jun 14, 2016)
17-46031116-A-AGCCCTCT		MAPT-Related Spectrum Disorders • Syndromic intellectual disability	Benign (Jun 14, 2016)
17-46031259-G-A		Syndromic intellectual disability • MAPT-Related Spectrum Disorders	Likely benign (Jun 14, 2016)
17-46031438-CAATA-C		MAPT-Related Spectrum Disorders • Syndromic intellectual disability	Likely benign (Jul 17, 2018)
17-46031440-ATAGT-A		Syndromic intellectual disability	Uncertain significance (Jun 14, 2016)
17-46031459-A-T			Benign (Mar 03, 2015)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
KANSL1	protein_coding	protein_coding	ENST00000262419	14	195452

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.000285	125711	0	37	125748	0.000147

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.23	551	638	0.863	0.0000372	7091
Missense in Polyphen		144	227.12	0.63403		2429
Synonymous	-0.806	258	242	1.07	0.0000134	2286
Loss of Function	5.75	6	49.8	0.120	0.00000327	531

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000289	0.0000289
Ashkenazi Jewish	0.000497	0.000496
East Asian	0.00	0.00
Finnish	0.000601	0.000601
European (Non-Finnish)	0.000116	0.000114
Middle Eastern	0.00	0.00
South Asian	0.000163	0.000163
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: As part of the NSL complex it is involved in acetylation of nucleosomal histone H4 on several lysine residues and therefore may be involved in the regulation of transcription. {ECO:0000269|PubMed:20018852, ECO:0000269|PubMed:22547026}.
• Pathway: Pathways Affected in Adenoid Cystic Carcinoma;Chromatin modifying enzymes;HATs acetylate histones;Chromatin organization (Consensus)

Recessive Scores

• pRec: 0.137

Intolerance Scores

• rvis_EVS: -0.32
• rvis_percentile_EVS: 30.95

Haploinsufficiency Scores

• pHI: 0.602
• hipred: Y
• hipred_score: 0.741
• ghis: 0.543

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: N
• gene_indispensability_score: 0.114

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High

Mouse Genome Informatics

• Gene name: Kansl1
• Phenotype: nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Gene ontology

• Biological process: histone H4-K5 acetylation;histone H4-K8 acetylation;histone H4-K16 acetylation
• Cellular component: histone acetyltransferase complex;condensed chromosome kinetochore;nucleus;nucleoplasm;NSL complex;MLL1 complex
• Molecular function: protein binding;histone acetyltransferase binding;histone acetyltransferase activity (H4-K5 specific);histone acetyltransferase activity (H4-K8 specific);histone acetyltransferase activity (H4-K16 specific)