SON

Chr 21AD

SON DNA and RNA binding protein

Also known as: BASS1, C21orf50, DBP-5, NREBP, SON3, TOKIMS

The protein binds RNA and promotes pre-mRNA splicing, particularly for transcripts with poor splice sites. Loss-of-function mutations cause ZTTK syndrome, an autosomal dominant neurodevelopmental disorder. The gene is highly intolerant to loss-of-function variants, consistent with haploinsufficiency as the mechanism of disease.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismADLOEUF 0.121 OMIM phenotype
Clinical SummarySON
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Gene-Disease Validity (ClinGen)
ZTTK syndrome · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
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Clinical Trials
12 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.12LOEUF
pLI 1.000
Z-score 7.74
OE 0.05 (0.020.12)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint
1.54Z-score
OE missense 0.88 (0.840.93)
1187 obs / 1346.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.05 (0.020.12)
00.351.4
Missense OE0.88 (0.840.93)
00.61.4
Synonymous OE1.21
01.21.6
LoF obs/exp: 4 / 77.5Missense obs/exp: 1187 / 1346.1Syn Z: -3.65
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveSON-related intellectual disability, congenital malformations, and failure to thriveLOFAD
DN
0.18100th %ile
GOF
0.13100th %ile
LOF
0.84top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · 1 literature citation · LOEUF 0.12

Literature Evidence

LOFDetailed phenotyping of 14 patients with SON haploinsufficiency identified kidney anomalies in 8 patients, including horseshoe kidney, unilateral renal hypoplasia, and renal cysts.PMID:31005274

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

SON · 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

AmyloidosisAmyloid CardiomyopathyTransthyretin Amyloidosis

Acoramidis Transthyretin Amyloidosis Prevention Trial in the Young (ACT-EARLY) Study in Asymptomatic Carriers of a Pathogenic TTR Variant

RECRUITING
NCT06563895Phase PHASE3Eidos Therapeutics, a BridgeBio companyStarted 2025-05-12
AcoramidisPlacebo oral tablet
Advanced Breast CancerER-positive Breast CancerHER2-negative Breast Cancer

Elacestrant + Everolimus in Patients ER+/HER2-, ESR1mut, Advanced Breast Cancer Progressing to ET and CDK4/6i.

RECRUITING
NCT06382948Phase PHASE3MedSIRStarted 2024-12-05
EverolimusElacestrantPlacebo
Non Small Cell Lung Cancer Stage IIINeoadjuvant Treatment

Study of ctDNA as Prognostic Factor on Resectable Stage IIIA NSCLC Patients Treated With Neoadjuvant Treatment

ACTIVE NOT RECRUITING
NCT05382052Fundación GECPStarted 2022-06-17
Lung Cancer - Non Small CellEGFR Exon 19 Deletion Mutation

Utilizing Long-read Sequencing to Investigate the EGFR Landscape of EGFR Positive Lung Cancer Patients

RECRUITING
NCT06659458Our Lady of the Lake HospitalStarted 2025-01-01
blood drawGene sequencing
16P11.2 Deletion Syndrome16p11.2 Duplications1Q21.1 Deletion

Online Study of People Who Have Genetic Changes and Features of Autism: Simons Searchlight

RECRUITING
NCT01238250Simons SearchlightStarted 2010-10
Lung DiseasesLung Cancer Screening

Validation of the SPOT-MAS Lung Test Using Circulating Tumor DNA for the Detection of Lung Cancer

NOT YET RECRUITING
NCT07126626Gene SolutionsStarted 2025-08-18
Multiple Myeloma in Relapse

Study of Elranatamab for Relapsed or Refractory Myeloma in Patients Previously Exposed to Three-drug Classes

RECRUITING
NCT06282978Phase PHASE2PETHEMA FoundationStarted 2023-11-23
Elranatamab (PF-06863135)
Lung DiseasesCarcinoma, Non-Small-Cell LungResectable Lung Non-Small Cell Carcinoma

Study of Treatment With Sacituzumab and Zimberelimab for Patients With Lung Cancer Confined to the Chest and Previously Operated on Who Were Not Disease-free.

RECRUITING
NCT06431633Phase PHASE3Fundación GECPStarted 2025-02-04
ZimberelimabSacituzumab govitecanCisplatin
Advanced Solid TumorDiffuse Large B Cell LymphomaLymphoma, T-Cell

A Study of Tulmimetostat DZR123 (CPI-0209) in Patients With Advanced Solid Tumors and Lymphomas

RECRUITING
NCT04104776Phase PHASE1, PHASE2Novartis PharmaceuticalsStarted 2019-09-18
TulmimetostatEnzalutamide
Metastatic Solid TumorAdvanced Cancer

High Definition Medicine for Solid Tumors Oncology

RECRUITING
NCT06590506Centro Nacional de Investigaciones Oncologicas CARLOS IIIStarted 2023-03-02
Wearable
Non-Small Cell Lung Cancer

Double Blind Placebo Controlled Controlled Study of Adjuvant MEDI4736 In Completely Resected NSCLC

ACTIVE NOT RECRUITING
NCT02273375Phase PHASE3Canadian Cancer Trials GroupStarted 2015-02-24
MEDI4736Placebo
Breast Cancer

NeoadjuVAnt muLti-agENT Chemotherapy or Patritumab Deruxtecan With or Without endocrINE Therapy for High-risk HR+/HER2- Breast Cancer - VALENTINE Trial

ACTIVE NOT RECRUITING
NCT05569811Phase PHASE2SOLTI Breast Cancer Research GroupStarted 2022-11-25
Patritumab deruxtecanChemotherapyLetrozole
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Like son, like son.
Maurer BT·JAAPA
2023
When There Are no Daughters.
Callister C·J Am Geriatr Soc
2025
A Letter to My Daughter.
Datta S·J Emerg Med
2022
The Son: What if love is not enough?
Morgan J·Lancet Child Adolesc Health
2023
Top 5 full-text resultsSearch PubTator3 ↗