MBD5

methyl-CpG binding domain protein 5, the group of Methyl-CpG binding domain containing|PWWP domain containing

Basic information

Region (hg38): 2:148021010-148516971

Links

ENSG00000204406 ∙ ∙ OMIM:611472 ∙ HGNC:20444 ∙ Uniprot:Q9P267 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal dominant non-syndromic intellectual disability (Supportive), mode of inheritance: AD
• intellectual disability, autosomal dominant 1 (Strong), mode of inheritance: AD
• complex neurodevelopmental disorder (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Intellectual developmental disorder, autosomal dominant 1	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; Neurologic; Ophthalmologic	17847001; 21981781

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MBD5 gene.

• Intellectual disability, autosomal dominant 1 (997 variants)
• not provided (399 variants)
• not specified (124 variants)
• Inborn genetic diseases (124 variants)
• MBD5-related condition (11 variants)
• Intellectual Disability, Dominant (7 variants)
• Intellectual disability (7 variants)
• See cases (5 variants)
• MBD5 associated neurodevelopmental disorder (4 variants)
• Seizure (3 variants)
• Autism spectrum disorder (2 variants)
• Complex neurodevelopmental disorder (1 variants)
• Intellectual disability, autosomal dominant (1 variants)
• Microcephaly (1 variants)
• Chromosome 2q23.1 deletion syndrome (1 variants)
• developmental delay with intractable seizures (1 variants)
• Hypotonia (1 variants)
• Bilateral tonic-clonic seizure (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MBD5 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			5	270	5	280
missense		3	538	125	11	677
nonsense	24	9				33
start loss		1				1
frameshift	38	9	4			51
inframe indel			11	2		13
splice donor/acceptor (+/-2bp)	3	2	1			6
splice region			6	14	4	24
non coding			4	47	24	75
Total	65	24	563	444	40

Variants in MBD5

This is a list of pathogenic ClinVar variants found in the MBD5 region.

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

Position	Type	Phenotype	Significance	ClinVar
2-148021034-A-G		not specified	Likely benign (Sep 29, 2016)
2-148021035-G-A		not specified	Likely benign (Feb 10, 2017)
2-148021062-C-T		not specified	Likely benign (Oct 16, 2015)
2-148021483-GCTGCTGCTGCTGCTA-G			Likely benign (Feb 01, 2024)
2-148021483-G-GCTGCTGCTGCTGCTA			Likely benign (Dec 01, 2023)
2-148021496-C-CTGT			Benign (Jul 01, 2022)
2-148021676-G-A			Likely benign (Feb 21, 2019)
2-148021702-G-A		not specified	Likely benign (Jun 06, 2016)
2-148178611-A-C			Benign (Jun 23, 2018)
2-148178697-T-C			Likely benign (May 02, 2018)
2-148178801-G-GT		not specified • Intellectual Disability, Dominant	Conflicting classifications of pathogenicity (Nov 01, 2022)
2-148233246-A-G			Benign (Mar 03, 2015)
2-148233249-A-G		not specified	Likely benign (Aug 02, 2017)
2-148233382-A-G		not specified	Likely benign (Oct 28, 2016)
2-148342230-C-T		not specified	Likely benign (Sep 01, 2017)
2-148342233-A-C		not specified	Likely benign (Jan 23, 2017)
2-148342233-A-T			Benign (Mar 03, 2015)
2-148342300-C-CA		Intellectual Disability, Dominant	Uncertain significance (Jun 14, 2016)
2-148342342-C-A		not specified	Likely benign (Sep 07, 2017)
2-148342440-G-A			Likely benign (Feb 08, 2022)
2-148342533-A-T			Benign (Jun 23, 2018)
2-148342583-T-C			Benign (Jun 23, 2018)
2-148458195-T-C		not specified	Benign (Feb 01, 2024)
2-148458759-A-G		Intellectual disability, autosomal dominant 1	Likely pathogenic (Oct 25, 2018)
2-148458766-G-T		Intellectual disability, autosomal dominant 1	Uncertain significance (Oct 25, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MBD5	protein_coding	protein_coding	ENST00000407073	10	497226

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.00000141	125742	0	4	125746	0.0000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.856	710	777	0.914	0.0000403	9822
Missense in Polyphen		35	42.073	0.83188		419
Synonymous	-0.611	301	288	1.05	0.0000161	3033
Loss of Function	6.04	2	46.4	0.0431	0.00000244	595

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000264	0.0000264
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Binds to heterochromatin. Does not interact with either methylated or unmethylated DNA (in vitro).
• Disease: DISEASE: Mental retardation, autosomal dominant 1 (MRD1) [MIM:156200]: 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:17847001, ECO:0000269|PubMed:22726846}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Post-translational protein modification;Metabolism of proteins;UCH proteinases;Deubiquitination (Consensus)

Recessive Scores

• pRec: 0.0958

Intolerance Scores

• loftool: 0.0116
• rvis_EVS: -2.12
• rvis_percentile_EVS: 1.52

Haploinsufficiency Scores

• pHI: 0.522
• hipred: Y
• hipred_score: 0.520
• ghis: 0.605

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.936

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Mbd5
• Phenotype: craniofacial phenotype; homeostasis/metabolism 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); growth/size/body region 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); adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); endocrine/exocrine gland phenotype; limbs/digits/tail 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); skeleton phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); liver/biliary 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)

Gene ontology

• Biological process: nervous system development;protein deubiquitination;regulation of multicellular organism growth;glucose homeostasis;regulation of behavior;positive regulation of growth hormone receptor signaling pathway
• Cellular component: nucleus;nucleoplasm;chromocenter;midbody;extracellular exosome
• Molecular function: DNA binding;chromatin binding