ZMYM3

Chr XXLR

zinc finger MYM-type containing 3

Also known as: DXS6673E, MYM, XFIM, XLID112, ZNF198L2, ZNF261

NCBI Gene: 9203 ENSG00000147130 UniProt: Q14202 OMIM: 300061

The encoded protein is a component of histone deacetylase-containing complexes that modify chromatin structure to maintain gene silencing and also regulates cell morphology and cytoskeletal organization. Mutations cause X-linked intellectual disability, with the gene being highly constrained against loss-of-function variants (pLI 1.0, LOEUF 0.11). Males are affected through X-linked inheritance, while females may have variable expression due to X-inactivation.

OMIM ResearchSummary from RefSeq, UniProt

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]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Intellectual developmental disorder, X-linked 112MIM #301111

XLR

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Intellectual developmental disorder, X-linked 112; no ClinGen or GenCC tier

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.11

LOEUF· LoF intol.

LOF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

0.11LOEUF

pLI 1.000

Z-score 6.05

OE 0.02 (0.01–0.11)

Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint?

4.31Z-score

OE missense 0.48 (0.43–0.53)

261 obs / 543.5 exp

Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?

LoF OE?0.02 (0.01–0.11)

0≤0.351.4

Missense OE?0.48 (0.43–0.53)

0≤0.61.4

Synonymous OE?1.03

0≤1.21.6

LoF obs/exp: 1 / 44.6Missense obs/exp: 261 / 543.5Syn Z: -0.30

Background carrier burden — how many people carry a rare variant somewhere in ZMYM3?

gnomAD v4 · ~732k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 120

752 rare PASS variants

Rare truncating (LoF)

1 in 280

71 rare PASS variants

Rare synonymous (reference)

1 in 210

423 rare PASS variants

Rare missense and truncating variants are carried at similar rates in ZMYM3; this gene does not show strong loss-of-function constraint by this measure. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~561k	1 in 190	1 in 270
South Asian	~36k	1 in 100	1 in 560
Remaining (unassigned)	~31k	1 in 100	1 in 350
European (Finnish)	~27k	1 in 660	1 in 1,600
Admixed American	~23k	1 in 140	1 in 170
African / African American	~21k	1 in 99	1 in 220
East Asian	~20k	1 in 110	1 in 2,200
Ashkenazi Jewish	~13k	1 in 220	1 in 280
Middle Eastern	~2,758	1 in 100	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 24 of 24 coding exons well covered in gnomAD exomes. Genomes: 23 of 24 (exon 15 below).? see exons ↓