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 (Strong), mode of inheritance: AD
Koolen-de Vries syndrome due to a point mutation (Supportive), mode of inheritance: AD
Koolen-de Vries syndrome (Definitive), 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 (1038 variants)
not_provided (261 variants)
not_specified (192 variants)
Inborn_genetic_diseases (149 variants)
KANSL1-related_disorder (20 variants)
Intellectual_disability (7 variants)
See_cases (3 variants)
Syndromic_intellectual_disability (2 variants)
Dystonia,_early-onset,_and/or_spastic_paraplegia (1 variants)
Craniosynostosis_syndrome (1 variants)
Global_developmental_delay (1 variants)
Neurodevelopmental_delay (1 variants)
Chromatinopathy (1 variants)
Dysplastic_corpus_callosum (1 variants)
Congenital_myopathy (1 variants)
Neurodevelopmental_abnormality (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 KANSL1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000015443.4. 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	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			5 clinvar	262 clinvar	3 clinvar	270
missense	2 clinvar	9 clinvar	433 clinvar	243 clinvar	26 clinvar	713
nonsense	13 clinvar	14 clinvar	8 clinvar	1 clinvar		36
start loss			1			1
frameshift	50 clinvar	22 clinvar	15 clinvar			87
splice donor/acceptor (+/-2bp)	9 clinvar	6 clinvar	3 clinvar	1 clinvar		19
Total	74	51	465	507	29

Highest pathogenic variant AF is 0.00002912045

Loading clinvar variants...

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

loftool
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)