DONSON

Chr 21AR

DNA replication fork stabilization factor DONSON

Also known as: B17, C21orf60, MGORS10, MIMIS, MISSLA

NCBI Gene: 29980ENSG00000159147UniProt: Q9NYP3OMIM: 611428

DONSON encodes a replisome component that maintains genome stability by protecting stalled or damaged replication forks and is required for efficient cell-cycle checkpoint activation. Biallelic mutations cause autosomal recessive Meier-Gorlin syndrome and microcephaly-micromelia syndrome, characterized by prenatal-onset growth restriction affecting head circumference, stature, and limb development. The gene shows minimal constraint against loss-of-function variants in the general population.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
ARLOEUF 0.913 OMIM phenotypes
Clinical Summary— DONSON
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
112 unique Pathogenic / Likely Pathogenic· 135 VUS of 383 total submissions
Explore recent and relevant literature in Research Assistant →
📖
GeneReview available — DONSON
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.91LOEUF
pLI 0.000
Z-score 1.92
OE 0.59 (0.39–0.91)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.24Z-score
OE missense 0.96 (0.86–1.06)
239 obs / 249.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.59 (0.39–0.91)
0≤0.351.4
Missense OE0.96 (0.86–1.06)
0≤0.61.4
Synonymous OE1.01
0≤1.21.6
LoF obs/exp: 15 / 25.5Missense obs/exp: 239 / 249.8Syn Z: -0.08

ClinVar Variant Classifications

383 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic94
Likely Pathogenic18
VUS135
Likely Benign96
Benign17
Conflicting11
94
Pathogenic
18
Likely Pathogenic
135
VUS
96
Likely Benign
17
Benign
11
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
23
6
65
0
94
Likely Pathogenic
14
3
1
0
18
VUS
1
119
13
2
135
Likely Benign
0
8
37
51
96
Benign
0
4
9
4
17
Conflicting
—11
Total3814012557371

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

View in ClinVar →

Protein Context — Lollipop Plot

DONSON · 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
The expanding genetic and clinical landscape associated with Meier-Gorlin syndrome.
Nielsen-Dandoroff E et al.·Eur J Hum Genet
2023Review
Mutations in DONSON disrupt replication fork stability and cause microcephalic dwarfism.
Reynolds JJ et al.·Nat Genet
2017
Linked-read genome sequencing identifies biallelic pathogenic variants in DONSON as a novel cause of Meier-Gorlin syndrome.
Knapp KM et al.·J Med Genet
2020
Microcephalic primordial dwarfism with predominant Meier-Gorlin phenotype, ichthyosis, and multiple joint deformities-Further expansion of DONSON Cell Cycle-opathy phenotypic spectrum.
Nerakh G et al.·Am J Med Genet A
2022Case report
Integrated genome and transcriptome sequencing identifies a noncoding mutation in the genome replication factor DONSON as the cause of microcephaly-micromelia syndrome.
Evrony GD et al.·Genome Res
2017
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