MBD5

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

Basic information

Region (hg38): 2:148021011-148516971

Links

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

Transcripts

Transcript IDs starting with ENST are treated as Ensembl, all others as RefSeq. Showing 4 of 40.

Transcript ID	Protein ID	Coding exons	MANE Select	MANE Plus Clinical
NM_001378120.1	NP_001365049.1	10	yes	-
ENST00000642680.2	ENSP00000493871.2	10	yes	-
NM_018328.5	NP_060798.2	10	-	-
NM_001438854.1	NP_001425783.1	10	-	-

Phenotypes

GenCC

Source: genCC

• complex neurodevelopmental disorder (Definitive), mode of inheritance: AD
• intellectual disability, autosomal dominant 1 (Strong), mode of inheritance: AD
• autosomal dominant non-syndromic intellectual disability (Supportive), mode of inheritance: AD
• intellectual disability, autosomal dominant 1 (Strong), 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 (1415 variants)
• not_provided (505 variants)
• Inborn_genetic_diseases (241 variants)
• not_specified (137 variants)
• MBD5-related_disorder (45 variants)
• Intellectual_disability (12 variants)
• See_cases (5 variants)
• MBD5_associated_neurodevelopmental_disorder (4 variants)
• Autism_spectrum_disorder (2 variants)
• Seizure (2 variants)
• Bilateral_tonic-clonic_seizure (1 variants)
• Microcephaly (1 variants)
• Developmental_and_epileptic_encephalopathy,_31A (1 variants)
• Complex_neurodevelopmental_disorder (1 variants)
• Chromosome_2q23.1_deletion_syndrome (1 variants)
• Hypotonia (1 variants)
• developmental_delay_with_intractable_seizures (1 variants)
• Cleft_palate (1 variants)
• Intellectual_disability,_autosomal_dominant (1 variants)
• Autistic_behavior (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. These statistics are base on transcript: NM_001378120.1. 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			10	369	4	383
missense	1	6	870	249	12	1138
nonsense	26	13	3			42
start loss		1				1
frameshift	52	15	4			71
splice donor/acceptor (+/-2bp)	4	4	5			13
Total	83	39	892	618	16

Highest pathogenic variant AF is 0.000010261266

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
		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

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

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