DMXL2

Chr 15ADAR

Dmx like 2

Also known as: DEE81, DFNA71, EIEE81, PEPNS, RC3

NCBI Gene: 23312ENSG00000104093UniProt: Q8TDJ6OMIM: 612186

This protein contains 12 WD domains and serves as a scaffold protein for synaptic vesicle components, functioning as a key controller of neuronal and endocrine homeostatic processes. Mutations cause developmental and epileptic encephalopathy 81, polyendocrine-polyneuropathy syndrome, and autosomal dominant deafness, with both autosomal dominant and recessive inheritance patterns reported. The gene is highly constrained against loss-of-function variants (pLI ~1.0, LOEUF 0.158), indicating that even single functional copies are critical for normal development.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismAD/ARLOEUF 0.163 OMIM phenotypes
Clinical Summary— DMXL2
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Gene-Disease Validity (ClinGen)
nonsyndromic genetic hearing loss · ADLimited

Limited evidence — not for standalone diagnostic reporting

⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
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ClinVar Variants
42 unique Pathogenic / Likely Pathogenic· 157 VUS of 499 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.16LOEUF
pLI 1.000
Z-score 10.06
OE 0.10 (0.07–0.16)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
2.37Z-score
OE missense 0.83 (0.79–0.87)
1297 obs / 1560.0 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.10 (0.07–0.16)
0≤0.351.4
Missense OE0.83 (0.79–0.87)
0≤0.61.4
Synonymous OE1.03
0≤1.21.6
LoF obs/exp: 15 / 146.4Missense obs/exp: 1297 / 1560.0Syn Z: -0.61
DN
0.3495th %ile
GOF
0.2597th %ile
LOF
0.80top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · 60% of P/LP variants are LoF · LOEUF 0.16

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

499 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic40
Likely Pathogenic2
VUS157
Likely Benign242
Benign23
Conflicting6
40
Pathogenic
2
Likely Pathogenic
157
VUS
242
Likely Benign
23
Benign
6
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
23
1
16
0
40
Likely Pathogenic
2
0
0
0
2
VUS
1
144
12
0
157
Likely Benign
1
9
102
130
242
Benign
0
10
5
8
23
Conflicting
—6
Total27164135138470

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

DMXL2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients