KDM2B

protein-coding

lysine demethylase 2B, the group of F-box and leucine rich repeat proteins|PHD finger proteins|Zinc fingers CXXC-type|Lysine demethylases|MicroRNA protein coding host genes

Gene summary

This gene encodes a member of the F-box protein family which is characterized by an approximately 40 amino acid motif, the F-box. The F-box proteins constitute one of the four subunits of ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box), which function in phosphorylation-dependent ubiquitination. The F-box proteins are divided into 3 classes: Fbws containing WD-40 domains, Fbls containing leucine-rich repeats, and Fbxs containing either different protein-protein interaction modules or no recognizable motifs. The protein encoded by this gene belongs to the Fbls class. Multiple alternatively spliced transcript variants have been found for this gene, but the full-length nature of some variants has not been determined. [provided by RefSeq, Jul 2008]

Previous symbols:

FBXL10

MANE transcript

NM_032590.5

Inheritance

ClinVar variants

P:22U:259B:43

Top phenotype

neurodevelopmental disorder

gnomAD constraint

pLI —, LoF o/e 0.09

Max pathogenic AF

—

Genomic locus

chr12:121,429,096-121,582,279

External References & Databases

Ensembl (ENSG00000089094)

Transcript & Mutation Effects

hg38 • Region Span ~153.2 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

neurodevelopmental disorderMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0700092

Submitter: G2P

neurodevelopmental disorderSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0700092

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to KDM2B variants in ClinVar

15 Conditions Cataloged

Inborn genetic diseasesTotal: 153

not providedTotal: 139

KDM2B-related disorderTotal: 43

Neurodevelopmental disorder with congenital cardiac defects and variable renal and ocular abnormalitiesTotal: 10

not specifiedTotal: 3

Neurodevelopmental disorderTotal: 2

KDM2B-related syndromeTotal: 1

Fetal anomalies with a likely genetic causeTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_032590.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			4 clinvar	22 clinvar	6 clinvar	32
missense	7 clinvar	9 clinvar	230 clinvar	14 clinvar		260
nonsense			8 clinvar			8
start loss						0
frameshift	2 clinvar	3 clinvar	10 clinvar	1 clinvar		16
splice donor/acceptor (+/-2bp)		1 clinvar	7 clinvar			8
Total	9	13	259	37	6	324

Highest pathogenic variant AF is 6.8426226e-7

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 73 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_032590.5	RefSeq	NP_115979.3	23	MANE Select
ENST00000377071.9	Ensembl	ENSP00000366271.3	23	MANE Select
NM_001005366.2	RefSeq	NP_001005366.1	23	Standard
NM_001439014.1	RefSeq	NP_001425943.1	23	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

HDMs demethylate histones
Chromatin modifying enzymes
Chromatin organization

Biological Process

negative regulation of transcription by RNA polymerase II
spermatogenesis
midbrain-hindbrain boundary morphogenesis
fourth ventricle development
lateral ventricle development

Molecular Function

RNA polymerase II proximal promoter sequence-specific DNA binding
DNA binding
protein binding
zinc ion binding
rRNA binding

Cellular Component

nucleus
nucleoplasm
nucleolus
PcG protein complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000377071
Coding exons: 23
Length: 152021
Individuals with no LoFs: 124787
Homozygous LoFs: 0
Heterozygous LoFs: 7
Defined: 124794
p: 0.0000280

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	3.44	573	856	0.669	0.0000575	8701
Missense (PolyPhen)		125	303.21	0.41225		2996
Synonymous	0.173	353	357	0.988	0.0000252	2589
Loss of Function	6.87	6	66.4	0.0904	0.00000337	735

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.000056	0.000056	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000036	0.000026	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Histone demethylase that demethylates 'Lys-4' and 'Lys- 36' of histone H3, thereby playing a central role in histone code. Preferentially demethylates trimethylated H3 'Lys-4' and dimethylated H3 'Lys-36' residue while it has weak or no activity for mono- and tri-methylated H3 'Lys-36'. Preferentially binds the transcribed region of ribosomal RNA and represses the transcription of ribosomal RNA genes which inhibits cell growth and proliferation. May also serve as a substrate-recognition component of the SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex. {ECO:0000269|PubMed:16362057, ECO:0000269|PubMed:17994099}.;

Recessive Scores

pRec: 0.109

Intolerance Scores

LoFtool: 0.628
RVIS EVS: -2.17
RVIS percentile EVS: 1.42

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.624

Gene Damage Prediction

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