DONSON

DNA replication fork stabilization factor DONSON

Basic information

Region (hg38): 21:33559542-33588706

Previous symbols: [ "C21orf60" ]

Links

ENSG00000159147 ∙ NCBI:29980 ∙ OMIM:611428 ∙ HGNC:2993 ∙ Uniprot:Q9NYP3 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• microcephaly, short stature, and limb abnormalities (Strong), mode of inheritance: AR
• microcephaly, short stature, and limb abnormalities (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Microcephaly, short stature, and limb abnormalities (MISSLA); Microcephaly-Micromelia syndrome	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Musculoskeletal; Neurologic	28191891; 28630177

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DONSON gene.

• not_provided (198 variants)
• Inborn_genetic_diseases (71 variants)
• Microcephaly,_short_stature,_and_limb_abnormalities (21 variants)
• DONSON-related_disorder (15 variants)
• Microcephaly-micromelia_syndrome (7 variants)
• Meier-Gorlin_syndrome (6 variants)
• not_specified (5 variants)
• Microcephaly (3 variants)
• DONSON-related_Meier-Gorlin_syndrome (2 variants)
• Meier-Gorlin_syndrome_1 (2 variants)
• See_cases (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DONSON gene is commonly pathogenic or not. These statistics are base on transcript: NM_000017613.4. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	46	4	52
missense	4	4	107	13	3	131
nonsense	5	4				9
start loss						0
frameshift	15	5	2			22
splice donor/acceptor (+/-2bp)	2	4				6
Total	26	17	111	59	7

Highest pathogenic variant AF is 0.0000470931

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DONSON	protein_coding	protein_coding	ENST00000303071	10	29167

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.32e-7	0.950	125697	0	51	125748	0.000203

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.243	239	250	0.957	0.0000123	3613
Missense in Polyphen		73	91.029	0.80194		1192
Synonymous	-0.0753	91	90.1	1.01	0.00000449	1173
Loss of Function	1.92	15	25.5	0.589	0.00000140	311

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000207	0.000206
Ashkenazi Jewish	0.000713	0.000695
East Asian	0.000218	0.000217
Finnish	0.00	0.00
European (Non-Finnish)	0.000224	0.000220
Middle Eastern	0.000218	0.000217
South Asian	0.000294	0.000294
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Replisome component that maintains genome stability by protecting stalled or damaged replication forks. After the induction of replication stress, required for the stabilization of stalled replication forks, the efficient activation of the intra- S-phase and G/2M cell-cycle checkpoints and the maintenance of genome stability. {ECO:0000269|PubMed:28191891}.
• Disease: DISEASE: Microcephaly-micromelia syndrome (MIMIS) [MIM:251230]: A severe autosomal recessive disorder characterized by intrauterine growth restriction, marked microcephaly, craniofacial anomalies, skeletal dysplasia, and variable malformations of the limbs, particularly the upper limbs. It usually results in death in utero or in the perinatal period. {ECO:0000269|PubMed:28630177}. Note=The disease is caused by mutations affecting the gene represented in this entry. This extremely rare syndrome is caused by an intronic mutation that leads to the retention of intron 6, probably resulting in non-sense mediated mRNA decay. This isoform has also been detected in healthy tissues, but at much lower levels than in MIMIS samples. {ECO:0000269|PubMed:28630177}.; DISEASE: Microcephaly, short stature, and limb abnormalities (MISSLA) [MIM:617604]: An autosomal recessive disorder characterized by intrauterine growth retardation, microcephaly, variable short stature, and limb abnormalities mainly affecting the upper limb and radial ray. Mild intellectual disability and developmental delay is observed in some patients. {ECO:0000269|PubMed:28191891}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Intolerance Scores

• loftool: 0.261
• rvis_EVS: 0.31
• rvis_percentile_EVS: 72.38

Haploinsufficiency Scores

• pHI: 0.0820
• hipred: N
• hipred_score: 0.229
• ghis: 0.562

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: N
• gene_indispensability_score: 0.339

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Donson
• Phenotype: mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span)

Gene ontology

• Biological process: DNA damage checkpoint;DNA replication;mitotic G2 DNA damage checkpoint;multicellular organism development;nuclear DNA replication;replication fork protection
• Cellular component: nucleus;replication fork;replisome
• Molecular function: protein binding