MXD3

Chr 5

MAX dimerization protein 3

Also known as: BHLHC13, MAD3, MYX

The protein functions as a transcriptional repressor that forms heterodimers with MAX to bind E-box DNA sequences and regulate gene expression, antagonizing MYC transcriptional activity. Mutations cause autosomal dominant intellectual disability with variable features that may include developmental delay and behavioral abnormalities. The gene shows tolerance to loss-of-function variants (low constraint), suggesting the clinical phenotype may result from altered protein function rather than simple protein loss.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
7
Pubs (1 yr)
61
P/LP submissions
0%
P/LP missense
1.21
LOEUF
DN
Mechanism· predicted
Clinical SummaryMXD3
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
59 unique Pathogenic / Likely Pathogenic· 53 VUS of 130 total submissions
Some data sources returned errors (1)

pubtator: TimeoutError: The operation was aborted due to timeout

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.21LOEUF
pLI 0.003
Z-score 1.15
OE 0.58 (0.301.21)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.19Z-score
OE missense 0.95 (0.821.11)
120 obs / 126.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.58 (0.301.21)
00.351.4
Missense OE0.95 (0.821.11)
00.61.4
Synonymous OE1.28
01.21.6
LoF obs/exp: 5 / 8.6Missense obs/exp: 120 / 126.1Syn Z: -1.66
DN
0.74top 25%
GOF
0.5268th %ile
LOF
0.3939th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

130 submitted variants in ClinVar

Classification Summary

Pathogenic53
Likely Pathogenic6
VUS53
Likely Benign7
53
Pathogenic
6
Likely Pathogenic
53
VUS
7
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
53
0
53
Likely Pathogenic
0
0
6
0
6
VUS
0
45
8
0
53
Likely Benign
0
5
1
1
7
Benign
0
0
0
0
0
Total050681119

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

View in ClinVar →

Protein Context — Lollipop Plot

MXD3 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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