ZMYM3

protein-coding

zinc finger MYM-type containing 3, the group of Zinc fingers MYM-type

Gene summary

This gene is located on the X chromosome and is subject to X inactivation. It is highly conserved in vertebrates and most abundantly expressed in the brain. The encoded protein is a component of histone deacetylase-containing multiprotein complexes that function through modifying chromatin structure to keep genes silent. A chromosomal translocation (X;13) involving this gene is associated with X-linked cognitive disability. Several alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jan 2010]

Previous symbols:

ZNF261

MANE transcript

NM_201599.3

Inheritance

ClinVar variants

P:16U:180B:39

Top phenotype

Intellectual developmental disorder, X-linked 112

gnomAD constraint

pLI —, LoF o/e 0.02

Max pathogenic AF

—

Genomic locus

chrX:71,239,624-71,255,146

External References & Databases

Ensembl (ENSG00000147130)

Transcript & Mutation Effects

hg38 • Region Span ~15.5 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

syndromic intellectual disabilityNO_KNOWN

Inheritance Pattern: XL

Disease ID:MONDO:0000508

Submitter: Illumina

intellectual developmental disorder, X-linked 112MODERATE

Inheritance Pattern: XL

Disease ID:MONDO:0957496

Submitter: G2P

intellectual developmental disorder, X-linked 112STRONG

Inheritance Pattern: XL

Disease ID:MONDO:0957496

Submitter: PanelApp Australia

intellectual disabilityLIMITED

Inheritance Pattern: XL

Disease ID:MONDO:0001071

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Intellectual developmental disorder, X-linked 112XL

Manifestation: Craniofacial; Musculoskeletal; Neurologic

Intervention: General

Rationale: 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

Refs: 24721225; 36586412

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ZMYM3 variants in ClinVar

11 Conditions Cataloged

not providedTotal: 137

Inborn genetic diseasesTotal: 78

ZMYM3-related disorderTotal: 22

Intellectual developmental disorder, X-linked 112Total: 16

not specifiedTotal: 9

Neurodevelopmental disorderTotal: 1

HyporeflexiaTotal: 1

Abnormal facial shapeTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_201599.3. 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	1 clinvar		5 clinvar	26 clinvar	3 clinvar	35
missense		12 clinvar	169 clinvar	9 clinvar	1 clinvar	191
nonsense						0
start loss						0
frameshift			3 clinvar			3
splice donor/acceptor (+/-2bp)	2 clinvar	1 clinvar	3 clinvar			6
Total	3	13	180	35	4	235

Highest pathogenic variant AF is 0.000008940625

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 58 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_201599.3	RefSeq	NP_963893.1	24	MANE Select
ENST00000314425.9	Ensembl	ENSP00000322845.5	24	MANE Select
NM_001171162.1	RefSeq	NP_001164633.1	24	Standard
NM_001171163.1	RefSeq	NP_001164634.1	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

regulation of transcription by RNA polymerase II
cytoskeleton organization
multicellular organism development
regulation of cell morphogenesis

Molecular Function

DNA-binding transcription factor activity, RNA polymerase II-specific
DNA binding
zinc ion binding

Cellular Component

nucleus
nucleoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000353904
Coding exons: 24
Length: 15523
Individuals with no LoFs: 122830
Homozygous LoFs: 1
Heterozygous LoFs: 0
Defined: 122831
p: 0.00000407

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	4.31	261	543	0.480	0.0000453	8908
Missense (PolyPhen)		87	248.42	0.35021		3916
Synonymous	-0.297	210	205	1.03	0.0000160	2722
Loss of Function	6.05	1	44.6	0.0224	0.00000343	775

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000012	0.0000090	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Plays a role in the regulation of cell morphology and cytoskeletal organization. {ECO:0000269|PubMed:21834987}.;

Recessive Scores

pRec: 0.142

Intolerance Scores

LoFtool: 0.0320
RVIS EVS: -1.18
RVIS percentile EVS: 5.97

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.892

Gene Damage Prediction

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