KMT5B

lysine methyltransferase 5B, the group of Lysine methyltransferases

Basic information

Region (hg38): 11:68154863-68213852

Previous symbols: [ "SUV420H1" ]

Links

ENSG00000110066 ∙ NCBI:51111 ∙ OMIM:610881 ∙ HGNC:24283 ∙ Uniprot:Q4FZB7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• intellectual disability, autosomal dominant 51 (Strong), mode of inheritance: AD
• intellectual disability, autosomal dominant 51 (Strong), mode of inheritance: AD
• complex neurodevelopmental disorder (Definitive), mode of inheritance: AD
• intellectual disability, autosomal dominant 51 (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Intellectual developmental disorder, autosomal dominant 51	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	25363768; 28191889; 29276005

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the KMT5B gene.

• not_provided (124 variants)
• Intellectual_disability,_autosomal_dominant_51 (66 variants)
• Inborn_genetic_diseases (31 variants)
• KMT5B-related_disorder (25 variants)
• See_cases (6 variants)
• not_specified (6 variants)
• Intellectual_disability (2 variants)
• Schizophrenia (1 variants)
• Autism_spectrum_disorder (1 variants)
• Global_developmental_delay (1 variants)
• Neurodevelopmental_delay (1 variants)
• Neural_tube_defect (1 variants)
• Rare_genetic_intellectual_disability (1 variants)
• Language_retardation (1 variants)
• Autistic_behavior (1 variants)
• KMT5B-related_neurodevelopmental_disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the KMT5B gene is commonly pathogenic or not. These statistics are base on transcript: NM_000017635.5. 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				17	2	19
missense	3	10	100	24	2	139
nonsense	8	8	1			17
start loss						0
frameshift	17	13	4			34
splice donor/acceptor (+/-2bp)		5	1	1		7
Total	28	36	106	42	4

Highest pathogenic variant AF is 0.0000014131

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
KMT5B	protein_coding	protein_coding	ENST00000304363	10	58966

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.00000117	125680	0	38	125718	0.000151

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.79	306	478	0.641	0.0000261	5844
Missense in Polyphen		46	136.74	0.33639		1684
Synonymous	1.46	160	185	0.863	0.0000113	1652
Loss of Function	5.72	0	38.1	0.00	0.00000228	488

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000618	0.0000615
Ashkenazi Jewish	0.00	0.00
East Asian	0.00203	0.00185
Finnish	0.00	0.00
European (Non-Finnish)	0.0000199	0.0000176
Middle Eastern	0.00203	0.00185
South Asian	0.00	0.00
Other	0.000183	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Histone methyltransferase that specifically trimethylates 'Lys-20' of histone H4. H4 'Lys-20' trimethylation represents a specific tag for epigenetic transcriptional repression. Mainly functions in pericentric heterochromatin regions, thereby playing a central role in the establishment of constitutive heterochromatin in these regions. KMT5B is targeted to histone H3 via its interaction with RB1 family proteins (RB1, RBL1 and RBL2) (By similarity). Plays a role in myogenesis by regulating the expression of target genes, such as EID3. {ECO:0000250, ECO:0000269|PubMed:23720823}.
• Disease: DISEASE: Mental retardation, autosomal dominant 51 (MRD51) [MIM:617788]: 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:28191889}. 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;Glucocorticoid receptor regulatory network;Chromatin organization (Consensus)

Recessive Scores

• pRec: 0.107

Intolerance Scores

• rvis_EVS: -0.95
• rvis_percentile_EVS: 9.21

Haploinsufficiency Scores

• pHI: 0.142
• hipred: Y
• hipred_score: 0.673
• ghis: 0.634

Essentials

• essential_gene_gene_trap: N

Mouse Genome Informatics

• Gene name: Kmt5b
• Phenotype: cellular phenotype; homeostasis/metabolism phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); 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); growth/size/body region phenotype; skeleton phenotype; immune 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); hematopoietic system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype

Gene ontology

• Biological process: muscle organ development;histone H4-K20 trimethylation
• Cellular component: condensed nuclear chromosome, centromeric region;nucleus;nucleoplasm
• Molecular function: histone-lysine N-methyltransferase activity;histone methyltransferase activity (H4-K20 specific)