SON

Chr 21AD

SON DNA and RNA binding protein

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

NCBI Gene: 6651ENSG00000159140UniProt: P18583

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]

Primary Disease Associations & Inheritance

ZTTK syndromeMIM #617140
AD
482
ClinVar variants
42
Pathogenic / LP
1.00
pLI score· haploinsufficient
12
Active trials
Clinical Summary— SON
🧬
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.
📋
ClinVar Variants
42 Pathogenic / Likely Pathogenic· 285 VUS of 482 total submissions
💊
Clinical Trials
12 active or recruiting trials — potential therapeutic options may be available
Some data sources returned errors (1)

clinvar: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
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?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.54Z-score
OE missense 0.88 (0.84–0.93)
1187 obs / 1346.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.05 (0.02–0.12)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.88 (0.84–0.93)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.21
0≤1.21.6
LoF obs/exp: 4 / 77.5Missense obs/exp: 1187 / 1346.1Syn Z: -3.65

ClinVar Variant Classifications

482 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic33
Likely Pathogenic9
VUS285
Likely Benign140
Benign10
Conflicting5
33
Pathogenic
9
Likely Pathogenic
285
VUS
140
Likely Benign
10
Benign
5
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
13
0
20
0
33
Likely Pathogenic
7
2
0
0
9
VUS
1
250
33
1
285
Likely Benign
0
34
11
95
140
Benign
0
7
1
2
10
Conflicting
—5
Total212936598482

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

View 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.

Gene2Phenotype Curations

SON-related intellectual disability, congenital malformations, and failure to thrive

definitive
ADLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

ZTTK syndrome

MIM #617140

Molecular basis of disorder known

Autosomal dominant
📖
GeneReview available — SON
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Establishing the phenotypic spectrum of ZTTK syndrome by analysis of 52 individuals with variants in SON.
Dingemans AJM et al.·Eur J Hum Genet
2022
L'orthodontie du sourire.
Frindel F·Orthod Fr
2008
Estimated Prevalence, Tumor Spectrum, and Neurofibromatosis Type 1-Like Phenotype of CDKN2A-Related Melanoma-Astrocytoma Syndrome.
Sargen MR et al.·JAMA Dermatol
2023
Dominant ARL3-related retinitis pigmentosa.
Holtan JP et al.·Ophthalmic Genet
2019
Optical genome mapping unveils hidden structural variants in neurodevelopmental disorders.
Schrauwen I et al.·Sci Rep
2024
A novel dominant-negative variant of IRF8 in a mother and son: Clinical, phenotypic and biological characteristics.
Ham H et al.·J Allergy Clin Immunol
2025
Clinical practice: Obsessive-compulsive disorder.
Grant JE·N Engl J Med
2014Review
SMAD5 as a novel gene for familial pulmonary arterial hypertension.
Cao D et al.·Clin Sci (Lond)
2025
Detection of genomic variants by genome sequencing in foetuses with central nervous system abnormalities.
Wang Y et al.·Ann Med
2024
Origin of pathogenic variant and mosaicism in families with a sporadic case of haemophilia B.
Mårtensson A et al.·Haemophilia
2024
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Familial Occurrence of Anti-NF155 Autoimmune Nodopathy in Father and Son: Expanding the Spectrum of IgG4-Related Nodopathies.
Sharma R et al.·Case Rep Neurol Med
2026🔓 Open Access
A new species of Hemiphyllodactylus Bleeker, 1860 (Squamata, Gekkonidae) from Son La Province, Vietnam.
Ha HB et al.·Zookeys
2026🔓 Open Access
Hemiphyllodactylus ziegleri sp. nov. (Squamata, Gekkonidae), a new karst-dwelling gecko species from Son La Province, Vietnam.
Pham AV et al.·Zookeys
2026🔓 Open Access
Gender disparities in childhood vaccination in India: exploring the role of son preference using NFHS-5 data.
Barik S et al.·Front Public Health
2025🔓 Open Access
Yunnan field mouse Apodemus ilex O. Thomas, 1922 (Rodentia, Muridae); a new species and genus for the Vietnamese fauna, first recorded from Son La Province.
Balakirev AE et al.·Biodivers Data J
2026🔓 Open AccessFunctional
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
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
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.

ACTIVE NOT RECRUITING
NCT06382948Phase PHASE3MedSIRStarted 2024-12-05
EverolimusElacestrantPlacebo
Genetic DiseaseImmune DysfunctionNeurological Diseases or Conditions

Natural History of Type 1 Interferonopathies: Insights From a European Cohort

RECRUITING
NCT07040774Imagine InstituteStarted 2025-10-01
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
Sleep Apnea, Obstructive

Intermitent Hypoxia and Its Pathophysiology Consequences in the Sleep Apnea-Hypopnea Syndrome.

ENROLLING BY INVITATION
NCT04444778Phase NAAlberto Alonso FernandezStarted 2020-07-20
CPAP
HealthyGestational Diabetes MellitusType 2 Diabetes Mellitus

Elucidation of Breast Milk Composition and Structure Over the First Year of Lactation: UC Davis Lactation Study

ACTIVE NOT RECRUITING
NCT01817127University of California, DavisStarted 2009-04-01
Metastatic Solid TumorAdvanced Cancer

High Definition Medicine for Solid Tumors Oncology

RECRUITING
NCT06590506Centro Nacional de Investigaciones Oncologicas CARLOS IIIStarted 2023-03-02
Wearable
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 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
Chronic Migraine HeadacheRadiofrequency AblationGreater Occipital Nerve Block

The Effect of Interventional Procedures on Serum CGRP and PACAP-38 Levels in Chronic Migraine

ACTIVE NOT RECRUITING
NCT07395908Phase NAAydin Adnan Menderes UniversityStarted 2025-05-29
Greater occipital nerve Pulse radiofrequencyGreater occipital nerve block
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
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

External Resources

Links to major genomics databases and tools