SON

Chr 21AD

SON DNA and RNA binding protein

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

NCBI Gene: 6651 ENSG00000159140 UniProt: P18583 OMIM: 182465

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.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

This gene encodes a protein that contains multiple simple repeats. The encoded protein binds RNA and promotes pre-mRNA splicing, particularly of transcripts with poor splice sites. The protein also recognizes a specific DNA sequence found in the human hepatitis B virus (HBV) and represses HBV core promoter activity. There is a pseudogene for this gene on chromosome 1. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

ZTTK syndromeMIM #617140

Clinical highlights

Gene-disease validity (ClinGen)

ZTTK syndrome · ADDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

821

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.12

LOEUF· LoF intol.

LOF

Mechanism· G2P

📖

GeneReview available — SON

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.12LOEUF

pLI 1.000

Z-score 7.74

OE 0.05 (0.02–0.12)

Highly constrained

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

Missense Constraint?

1.54Z-score

OE missense 0.88 (0.84–0.93)

1187 obs / 1346.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.05 (0.02–0.12)

0≤0.351.4

Missense OE?0.88 (0.84–0.93)

0≤0.61.4

Synonymous OE?1.21

0≤1.21.6

LoF obs/exp: 4 / 77.5Missense obs/exp: 1187 / 1346.1Syn Z: -3.65

ClinVar Variant Classifications

0 submitted variants in ClinVar

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.

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

📖

GeneReview available — SON

Authoritative clinical overview · NCBI Bookshelf · Recommended first read

Open GeneReview ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

Metastatic Solid TumorAdvanced Cancer

High Definition Medicine for Solid Tumors Oncology

RECRUITING

NCT06590506Centro Nacional de Investigaciones Oncologicas CARLOS IIIStarted 2023-03-02

Wearable

Huntington Disease

A Study to Investigate the Efficacy, Safety and Tolerability of Votoplam in Participants With Huntington's Disease

RECRUITING

NCT07326709Phase PHASE3Novartis PharmaceuticalsStarted 2026-03-24

Votoplam (blinded)Placebo

Non Small Cell Lung Cancer

Activity of Lorlatinib Based on ALK Resistance Mutations Detected on Blood in ALK Positive NSCLC Patients

ACTIVE NOT RECRUITING

NCT04127110Phase PHASE2European Organisation for Research and Treatment of Cancer - EORTCStarted 2020-11-17

Lorlatinib

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

Obstructive Hypertrophic Cardiomyopathy

A Prospective Registry Study to Assess Real-world Patient Characteristics, Treatment Patterns, and Longitudinal Outcomes in Patients Receiving Mavacamten and Other Treatments for Symptomatic Obstructive Hypertrophic Cardiomyopathy (Obstructive-HCM)

RECRUITING

NCT05489705Bristol-Myers SquibbStarted 2022-08-16

MavacamtenNon-mavacamten symptomatic oHCM therapy

Carcinoma, Non-Small-Cell Lung

A Study of Clinical Outcomes in Participants With EGFR Mutated Advanced Non-Small Cell Lung Cancer (NSCLC) in a Real-World Setting

RECRUITING

NCT07230691Janssen Research & Development, LLCStarted 2025-12-03

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