On this page
Chromosome 16
Home of the α-globin cluster, PKD1 (polycystic kidney disease), and the 16p11.2 autism-risk locus.
Schematic of chromosome 16 showing the short (p) and long (q) arms. Arm ratio per GRCh38 - banding schematic.
Available at Jeen Health
Clinical tests that include this
Overview
Chromosome 16 accounts for approximately 3 per cent of the human genome and contains approximately 866 protein-coding genes spread across 90.3 megabases. It is a metacentric chromosome, meaning the centromere divides it into a short arm (16p) and a long arm (16q) of similar length. Clinically, chromosome 16 is recognised for its role in haematological disorders through the α-globin gene cluster, in renal disease through PKD1, and in neurodevelopmental conditions through recurrent microdeletions and microduplications at 16p11.2.
The gene density on chromosome 16 is close to the genome-wide average, but several regions stand out for their concentration of clinically important loci. The short arm, particularly band 16p13.3, carries genes involved in oxygen transport, kidney development, and chromatin regulation. The long arm includes genes that control cell adhesion, mechanosensation, and tumour suppression. Chromosomal rearrangements involving 16p11.2 are among the most frequently observed pathogenic copy-number variants in cohorts of individuals with autism and intellectual disability, making this region a focal point for research into the genetic architecture of neurodevelopmental traits.
Structure
Like all human chromosomes, chromosome 16 exists as a linear DNA molecule packaged around histone proteins to form nucleosomes, which then coil into higher-order chromatin structures. At metaphase, when the chromosome condenses ahead of cell division, it becomes visible under the microscope as an X-shaped structure. The metacentric centromere lies near the middle, producing a short arm (p) and a long arm (q) of roughly equal length. This balanced architecture facilitates accurate segregation during mitosis and meiosis, although errors in chromosome alignment or recombination can still give rise to structural rearrangements.
The short arm spans approximately 36.3 megabases on the short arm and 54 megabases on the long arm (excluding centromeric regions). Each arm is subdivided into numbered cytogenetic bands visible by Giemsa staining. These bands reflect variations in chromatin density and gene content. The most gene-rich segments tend to be euchromatic (lightly staining), while heterochromatic regions (darkly staining) are often repeat-rich and gene-poor. Chromosome 16 does not carry the ribosomal RNA genes found on the short arms of acrocentric chromosomes, and it is not involved in sex determination, so abnormalities of chromosome 16 affect both sexes equally.
Video: What is a karyotype?
Notable regions
Band 16p13.3, at the tip of the short arm, is one of the most clinically significant regions on the chromosome. It houses PKD1, pathogenic variants in which cause autosomal dominant polycystic kidney disease, a common inherited kidney disorder characterised by the progressive growth of fluid-filled cysts that can compromise renal function over decades. The same band contains HBA1 and HBA2, the tandem genes encoding α-globin chains. Deletions or point variants affecting these genes reduce α-globin production, leading to α-thalassaemia, which ranges in severity from a clinically silent carrier state to hydrops fetalis when all four α-globin alleles are lost. Also within 16p13.3 lies TSC2, one of two genes that, when disrupted, cause tuberous sclerosis complex, a multisystem disorder marked by benign tumours in the brain, skin, kidneys, and heart.
Band 16p11.2, located further down the short arm, has emerged as a neurodevelopmental hotspot. Recurrent deletions and duplications spanning roughly 600 kilobases at this locus are among the most common copy-number variants associated with autism spectrum disorder, language delay, and intellectual disability. The mechanism involves non-allelic homologous recombination between flanking low-copy repeats, leading to loss or gain of roughly 25 genes. Affected individuals often show variable expressivity, with some meeting criteria for autism while others present primarily with speech delay, obesity, or subtle dysmorphic features. The reciprocal duplication is also associated with neurodevelopmental traits, albeit typically with milder effects, illustrating dosage sensitivity in this genomic interval.
Region 16q22.1 contains CDH1, which encodes E-cadherin, a cell-adhesion molecule essential for maintaining epithelial architecture. Germline pathogenic variants in CDH1 confer high risk of hereditary diffuse gastric cancer and lobular breast cancer, prompting consideration of prophylactic gastrectomy in some families. The same band also harbours CTCF, a master regulator of three-dimensional genome organisation. CTCF creates chromatin loops that bring distant enhancers into contact with their target genes, and disruption of CTCF binding sites or the protein itself can dysregulate entire gene networks, contributing to developmental disorders and cancer.
Notable genes
Beyond the haemoglobin and kidney-disease genes already mentioned, chromosome 16 is home to CREBBP at 16p13.3, which encodes CREB-binding protein, a histone acetyltransferase essential for chromatin remodelling and gene activation. Pathogenic variants in CREBBP cause Rubinstein-Taybi syndrome, characterised by broad thumbs and halluces, distinctive facial features, intellectual disability, and an increased risk of tumours. PALB2, situated at 16p12.2, produces a protein that acts as a molecular scaffold linking BRCA1 and BRCA2 in the repair of DNA double-strand breaks. Germline pathogenic variants in PALB2 elevate the risk of breast, ovarian, and pancreatic cancer, and affected individuals may be offered enhanced surveillance or risk-reducing surgery through NHS cancer genetics services.
PIEZO1, located at 16q24.3, encodes a mechanosensitive ion channel that allows red blood cells to sense and respond to physical forces as they squeeze through narrow capillaries. Gain-of-function variants in PIEZO1 cause dehydrated hereditary stomatocytosis (also called hereditary xerocytosis), a haemolytic anaemia in which red cells lose potassium and water, becoming rigid and prone to premature destruction. FOXC2, also on the long arm, regulates lymphatic-vessel and vein development; pathogenic variants lead to lymphoedema-distichiasis syndrome, marked by swelling of the limbs and a double row of eyelashes. These examples illustrate the functional diversity encoded on chromosome 16, from oxygen delivery and DNA repair to mechanotransduction and vascular morphogenesis.
Chromosomal disorders
Unlike chromosomes 13, 18, and 21, whole-chromosome trisomy of chromosome 16 is not compatible with survival to term. Trisomy 16 is, in fact, the most common autosomal trisomy detected in first-trimester miscarriages, accounting for a substantial fraction of early pregnancy losses. Occasionally, confined placental mosaicism for trisomy 16 is detected at chorionic villus sampling, meaning the abnormality is present in placental tissue but not in the foetus itself. Such cases may still warrant follow-up by amniocentesis and detailed ultrasound because of the risk of uniparental disomy (both copies of chromosome 16 inherited from one parent), although chromosome 16 does not carry imprinted regions that would produce a clinical syndrome analogous to Prader-Willi or Angelman syndromes.
The principal structural abnormalities of clinical significance are the recurrent 16p11.2 microdeletion and microduplication syndromes. The deletion typically removes around 600 kilobases and is associated with autism spectrum disorder, expressive-language delay, hypotonia in infancy, and a tendency toward obesity in later childhood. Brain imaging sometimes reveals subtle differences in white-matter structure or cortical thickness. The reciprocal duplication shows considerable phenotypic overlap, though affected individuals may be leaner and some present with schizophrenia or bipolar disorder in adolescence or adulthood, highlighting the complex relationship between gene dosage and brain development. Both rearrangements usually arise de novo, but familial cases do occur, with incomplete penetrance and variable expressivity complicating genetic counselling.
Other recurrent deletions on chromosome 16 have been described but are less common. Small deletions at 16p13.11 have been linked to developmental delay and epilepsy, while deletions encompassing the distal short arm may remove multiple genes including TSC2 and PKD1, producing contiguous-gene syndromes that combine features of tuberous sclerosis and polycystic kidney disease. These structural variants are typically detected by chromosomal microarray analysis, which is offered through NHS genomic laboratories when a child presents with unexplained developmental delay, multiple congenital anomalies, or autism.
Prenatal screening & diagnosis
Chromosome 16 abnormalities are not part of the standard non-invasive prenatal testing (NIPT) panel offered by the NHS, which focuses on trisomies 13, 18, and 21. However, some commercial NIPT platforms report genome-wide copy-number changes (copy-number variants) and may flag 16p11.2 deletions or duplications incidentally. Such findings require careful interpretation, as the associated neurodevelopmental traits are variable and some carriers are only mildly affected or fall within the broad normal range. If a 16p11.2 rearrangement is suspected prenatally, confirmatory testing by amniocentesis and chromosomal microarray is typically recommended, alongside detailed ultrasound to look for structural anomalies, though the majority of affected foetuses appear anatomically normal.
When trisomy 16 is detected as confined placental mosaicism at chorionic villus sampling, follow-up amniocentesis is important to establish whether the foetal cells carry the normal chromosome complement. Serial growth scans may also be arranged, as placental dysfunction secondary to aneuploidy can lead to intrauterine growth restriction. Genetic counselling explores the implications of possible uniparental disomy and the low but recognised risk of hidden mosaicism in the foetus. For families with a known history of a 16p11.2 deletion or a single-gene disorder such as tuberous sclerosis or polycystic kidney disease, preimplantation genetic testing or prenatal diagnosis may be discussed, depending on individual circumstances and values.
Inheritance & recurrence
Most pathogenic variants in genes on chromosome 16 follow autosomal dominant or autosomal recessive inheritance, depending on the gene. Autosomal dominant conditions such as polycystic kidney disease (PKD1), tuberous sclerosis (TSC2), and hereditary diffuse gastric cancer (CDH1) require only one altered copy to manifest disease, and an affected parent has a 50 per cent chance of passing the variant to each child. In practice, many cases arise from de novo variants, particularly in tuberous sclerosis, where roughly two-thirds of individuals have no family history. Recurrence risk for future siblings is low when a variant is de novo, unless there is undetected parental mosaicism, a possibility that warrants mention during genetic counselling.
Recurrent 16p11.2 deletions and duplications are also predominantly de novo events, arising from errors in meiotic recombination mediated by the repetitive sequences flanking the interval. Parents of a child with a de novo 16p11.2 rearrangement typically face a recurrence risk close to the general population baseline, though low-level germline mosaicism cannot be entirely excluded. When a 16p11.2 copy-number variant is inherited from a parent, that parent may be mildly affected, completely asymptomatic, or fall within the spectrum of traits seen in the child, underscoring the incomplete penetrance and variable expressivity of these rearrangements. Families are usually referred to NHS clinical genetics services for a detailed assessment, cascade testing of relatives when appropriate, and tailored discussion of recurrence risks and reproductive options.
Frequently asked questions
What is the 16p11.2 deletion, and how does it affect development?
The 16p11.2 deletion is a loss of roughly 600 kilobases on the short arm of chromosome 16, removing about 25 genes. It is one of the most common recurrent genetic changes linked to autism spectrum disorder, language delay, and intellectual disability, though features vary widely between individuals. Some children also show low muscle tone in infancy and a tendency toward weight gain, while brain imaging may reveal subtle structural differences.
Can chromosome 16 abnormalities be detected during pregnancy?
Whole-chromosome trisomy 16 is the leading cause of first-trimester miscarriage and is not compatible with live birth. Smaller deletions or duplications, such as 16p11.2 rearrangements, may be identified by chromosomal microarray if amniocentesis or chorionic villus sampling is performed, but they are not part of the standard NHS non-invasive prenatal test for common trisomies. Detailed ultrasound and genetic counselling are important if a 16p11.2 variant is detected prenatally, as the outcome is variable.
Is polycystic kidney disease caused by chromosome 16 inherited?
Autosomal dominant polycystic kidney disease is most often due to pathogenic variants in PKD1 on chromosome 16. It follows autosomal dominant inheritance, meaning an affected parent has a 50 per cent chance of passing the variant to each child. However, around 10 per cent of cases arise from de novo variants with no family history. Genetic testing and counselling through NHS clinical genetics can clarify risks for relatives and inform family planning.
What is α-thalassaemia, and how is it related to chromosome 16?
α-thalassaemia results from deletions or variants in the HBA1 and HBA2 genes on chromosome 16p13.3, which encode the α-globin chains of haemoglobin. Depending on how many of the four α-globin gene copies are affected, individuals may be silent carriers, have mild anaemia, or in the most severe form (loss of all four copies) experience hydrops fetalis, which is usually incompatible with survival. Carrier screening is available in some populations where α-thalassaemia is common.
If my child has a 16p11.2 deletion, will their siblings also have it?
Most 16p11.2 deletions occur as new (de novo) events, so siblings typically have a low risk of inheriting the same deletion. However, if the deletion is found in one of the parents, even if that parent is only mildly affected or asymptomatic, each sibling has a 50 per cent chance of inheriting it. Genetic testing of parents and discussion with a clinical geneticist can clarify the recurrence risk and guide decisions about further testing or family planning.
Launch-set genes on chromosome 16
Genes on this chromosome that currently have dedicated pages in the library. This list grows as we publish more.