SON

SON DNA and RNA binding protein, the group of Minor histocompatibility antigens|MicroRNA protein coding host genes|G-patch domain containing

Basic information

Region (hg38): 21:33543037-33577481

Previous symbols: [ "C21orf50" ]

Links

ENSG00000159140 ∙ NCBI:6651 ∙ OMIM:182465 ∙ HGNC:11183 ∙ Uniprot:P18583 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• ZTTK syndrome (Strong), mode of inheritance: AD
• ZTTK syndrome (Definitive), mode of inheritance: AD
• ZTTK syndrome (Supportive), mode of inheritance: AD
• ZTTK syndrome (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
ZTTK syndrome	AD	Cardiovascular	The condition can involve congenital cardiac anomalies, and awareness may allow early management	Cardiovascular; Craniofacial; Gastrointestinal; Genitourinary; Hematologic; Musculoskeletal; Neurologic; Ophthalmologic	25590979; 27256762; 27545676; 27545680

ClinVar

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

• not provided (842 variants)
• ZTTK syndrome (137 variants)
• Inborn genetic diseases (65 variants)
• SON-related condition (19 variants)
• not specified (13 variants)
• See cases (4 variants)
• Intellectual disability (4 variants)
• Global developmental delay;Failure to thrive (3 variants)
• Failure to thrive;Global developmental delay (2 variants)
• Neurodevelopmental abnormality (1 variants)
• Developmental disorder (1 variants)
• Seizure;Global developmental delay (1 variants)
• Hereditary spastic paraplegia 17 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SON gene is commonly pathogenic or not.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			9	228	24	261
missense	1		399	94	46	540
nonsense	21	5				26
start loss						0
frameshift	52	17		1	2	72
inframe indel			27	19	2	48
splice donor/acceptor (+/-2bp)	3	1				4
splice region			4	3	2	9
non coding			1	7	11	19
Total	77	23	436	349	85

Highest pathogenic variant AF is 0.00000657

Variants in SON

This is a list of pathogenic ClinVar variants found in the SON region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
21-33543101-C-T			Benign (Nov 13, 2023)
21-33543114-A-AT			Pathogenic (Jul 19, 2018)
21-33543122-G-C			Uncertain significance (Jan 13, 2023)
21-33543134-C-T			Uncertain significance (Aug 17, 2023)
21-33543140-A-G			Likely benign (Aug 16, 2022)
21-33543145-G-T			Uncertain significance (Oct 05, 2023)
21-33543150-A-AGC			Pathogenic (Jan 18, 2018)
21-33543175-C-G		SON-related disorder	Conflicting classifications of pathogenicity (Nov 03, 2023)
21-33543188-C-A			Likely benign (Nov 08, 2022)
21-33546193-C-T			Benign (Feb 01, 2024)
21-33546195-A-G			Likely benign (Apr 15, 2023)
21-33546204-C-T		not specified	Conflicting classifications of pathogenicity (Mar 17, 2023)
21-33546210-A-T			Benign (Sep 07, 2022)
21-33546212-G-A		ZTTK syndrome	Pathogenic (Sep 10, 2019)
21-33546234-G-A			Likely benign (Jun 18, 2022)
21-33546246-A-G			Benign (Dec 30, 2023)
21-33546251-CA-C		ZTTK syndrome	Pathogenic (Jul 13, 2022)
21-33546255-C-T			Likely benign (Dec 02, 2021)
21-33546256-A-G			Uncertain significance (Jan 27, 2024)
21-33546269-A-C		SON-related disorder	Uncertain significance (Feb 14, 2023)
21-33546273-G-A		SON-related disorder	Likely benign (Dec 26, 2023)
21-33546275-G-A		Inborn genetic diseases	Uncertain significance (Nov 09, 2021)
21-33546281-C-G			Uncertain significance (Nov 09, 2022)
21-33546281-C-T			Uncertain significance (Sep 15, 2022)
21-33546297-G-C		Inborn genetic diseases	Uncertain significance (Aug 08, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SON	protein_coding	protein_coding	ENST00000356577	12	34889

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	3.40e-10	125724	0	24	125748	0.0000954

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.54	1187	1.35e+3	0.882	0.0000763	15618
Missense in Polyphen		21	34.373	0.61095		310
Synonymous	-3.65	596	493	1.21	0.0000285	5118
Loss of Function	7.74	4	77.5	0.0516	0.00000441	1074

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00149	0.000800
Ashkenazi Jewish	0.00	0.00
East Asian	0.000512	0.000381
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.00000934	0.00000879
Middle Eastern	0.000512	0.000381
South Asian	0.0000378	0.0000327
Other	0.000195	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: RNA-binding protein that acts as a mRNA splicing cofactor by promoting efficient splicing of transcripts that possess weak splice sites. Specifically promotes splicing of many cell-cycle and DNA-repair transcripts that possess weak splice sites, such as TUBG1, KATNB1, TUBGCP2, AURKB, PCNT, AKT1, RAD23A, and FANCG. Probably acts by facilitating the interaction between Serine/arginine-rich proteins such as SRSF2 and the RNA polymerase II. Also binds to DNA; binds to the consensus DNA sequence: 5'- GA[GT]AN[CG][AG]CC-3'. May indirectly repress hepatitis B virus (HBV) core promoter activity and transcription of HBV genes and production of HBV virions. Essential for correct RNA splicing of multiple genes critical for brain development, neuronal migration and metabolism, including TUBG1, FLNA, PNKP, WDR62, PSMD3, PCK2, PFKL, IDH2, and ACY1 (PubMed:27545680). {ECO:0000269|PubMed:20581448, ECO:0000269|PubMed:21504830, ECO:0000269|PubMed:27545680}.
• Disease: DISEASE: ZTTK syndrome (ZTTKS) [MIM:617140]: An autosomal dominant syndrome characterized by intellectual disability, developmental delay, malformations of the cerebral cortex, epilepsy, vision problems, musculo-skeletal abnormalities, and congenital malformations. {ECO:0000269|PubMed:25590979, ECO:0000269|PubMed:27256762, ECO:0000269|PubMed:27545676, ECO:0000269|PubMed:27545680}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.101

Intolerance Scores

• loftool: 0.198
• rvis_EVS: -1.88
• rvis_percentile_EVS: 1.99

Haploinsufficiency Scores

• pHI: 0.882
• hipred: N
• hipred_score: 0.485
• ghis: 0.639

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.873

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Son

Zebrafish Information Network

• Gene name: son
• Affected structure: post-vent region
• Phenotype tag: abnormal
• Phenotype quality: shortened

Gene ontology

• Biological process: microtubule cytoskeleton organization;mitotic cytokinesis;mRNA processing;RNA splicing;negative regulation of apoptotic process;regulation of RNA splicing;regulation of mRNA splicing, via spliceosome;regulation of cell cycle
• Cellular component: nuclear speck
• Molecular function: DNA binding;RNA binding;protein binding;RS domain binding