DMBX1

Chr 1

diencephalon/mesencephalon homeobox 1

Also known as: Atx, MBX, OTX3, PAXB

NCBI Gene: 127343ENSG00000197587UniProt: Q8NFW5

This gene encodes a member of the bicoid sub-family of homeodomain-containing transcription factors. The encoded protein acts as a transcription factor and may play a role in brain and sensory organ development. Two transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

70
ClinVar variants
7
Pathogenic / LP
0.93
pLI score· haploinsufficient
0
Active trials
Clinical Summary— DMBX1
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.93). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
7 Pathogenic / Likely Pathogenic· 55 VUS of 70 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.37LOEUF
pLI 0.930
Z-score 3.06
OE 0.08 (0.03–0.37)
Highly constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.83Z-score
OE missense 0.85 (0.76–0.95)
209 obs / 245.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.08 (0.03–0.37)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.85 (0.76–0.95)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.98
0≤1.21.6
LoF obs/exp: 1 / 12.9Missense obs/exp: 209 / 245.6Syn Z: 0.18

ClinVar Variant Classifications

70 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic4
Likely Pathogenic3
VUS55
Likely Benign6
Benign2
4
Pathogenic
3
Likely Pathogenic
55
VUS
6
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
4
0
4
Likely Pathogenic
0
1
2
0
3
VUS
0
50
5
0
55
Likely Benign
0
2
0
4
6
Benign
0
1
0
1
2
Total05411570

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

View in ClinVar →

Protein Context — Lollipop Plot

DMBX1 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Autozygome and high throughput confirmation of disease genes candidacy.
Maddirevula S et al.·Genet Med
2019
Accelerating novel candidate gene discovery in neurogenetic disorders via whole-exome sequencing of prescreened multiplex consanguineous families.
Alazami AM et al.·Cell Rep
2015
Roles of diencephalon/mesencephalon homeobox 1 in the development and prognosis of hepatocellular carcinoma.
Huang X et al.·Ann Hepatol
2021
A multi-omics analysis-based model to predict the prognosis of low-grade gliomas.
Du Z et al.·Sci Rep
2024Functional
MYC/Glutamine Dependency Is a Therapeutic Vulnerability in Pancreatic Cancer with Deoxycytidine Kinase Inactivation-Induced Gemcitabine Resistance.
Dash S et al.·Mol Cancer Res
2023
Serum Circulating mRNA Panel for the Early Detection of Gastric Cancer: A Potential Biomarker Test.
Peng X et al.·ChemMedChem
2024
Copy number variation analysis implicates novel pathways in patients with oculo-auriculo-vertebral-spectrum and congenital heart defects.
Guida V et al.·Clin Genet
2021Cohort
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools