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Chromosome 19
The most gene-dense chromosome in the human genome - carries APOE (Alzheimer/cardiovascular risk) and LDLR (familial hypercholesterolaemia).
Schematic of chromosome 19 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 19 spans approximately 58.6 million base pairs (58.6 Mb), making it one of the smallest autosomes in the human karyotype. Despite its compact size, it carries around 1,474 protein-coding genes, giving it the highest gene density of any chromosome-more than one gene per 40,000 base pairs on average. This concentration of genetic information means that chromosome 19 plays a disproportionately large role in human health and disease.
Clinically, chromosome 19 is perhaps best known for hosting APOE at 19q13.32, which influences both late-onset Alzheimer disease risk and cardiovascular health, and LDLR at 19p13.2, the major gene underlying familial hypercholesterolaemia. The chromosome also carries genes linked to inherited cancer syndromes, cardiac muscle disorders, and a range of metabolic and developmental conditions recognised within the NHS Genomic Medicine Service.
Chromosome 19 is metacentric, meaning its centromere sits roughly in the middle, dividing it into a short arm (p) and a long arm (q) of fairly similar length. During cell division, the spindle fibres attach to the centromere, allowing the chromosome to be pulled apart evenly so that each daughter cell receives one copy.
Structure
Chromosome 19 is organised into a short arm (the p arm) and a long arm (the q arm), separated by the centromere near the chromosome's midpoint. Because the centromere is centrally positioned, chromosome 19 appears roughly X-shaped when condensed at metaphase, the stage of cell division when chromosomes are most visible under a microscope. This metacentric architecture is typical of many medium-sized autosomes and facilitates accurate segregation during mitosis and meiosis.
Like all chromosomes, chromosome 19 begins as a single long DNA molecule wound around histone proteins to form nucleosomes-bead-like structures that help package the genetic material. These nucleosomes are further coiled and folded into chromatin fibres, which condense progressively until, just before a cell divides, they form the compact, rod-like chromosome visible in a karyotype. Between cell divisions, chromosome 19 unfolds into a less condensed state so that its genes can be accessed for transcription and protein synthesis. The extreme gene density on this chromosome means that much of its length is composed of active, coding DNA rather than long stretches of non-coding sequence.
Video: What is a karyotype?
Notable regions
The q13.32 region on the long arm of chromosome 19 is home to APOE, the apolipoprotein E gene. The protein encoded by APOE helps transport cholesterol and other fats through the bloodstream, and genetic variation at this locus has profound effects on health. The APOE gene exists in three common forms (ε2, ε3, and ε4), and inheriting one or two copies of the ε4 variant substantially increases the risk of developing late-onset Alzheimer disease-the strongest and most reproducible common genetic risk factor for this condition. APOE variants also influence cardiovascular disease risk and the body's response to dietary fat, making this one of the most clinically significant genetic loci in the genome.
The p13.2 band, near the tip of the short arm, contains LDLR, which encodes the low-density lipoprotein receptor. This receptor sits on cell surfaces and removes cholesterol-carrying LDL particles from the blood. Pathogenic variants in LDLR cause familial hypercholesterolaemia, an autosomal dominant condition characterised by markedly elevated blood cholesterol from birth and a substantially increased risk of early coronary heart disease. Familial hypercholesterolaemia is one of the most common inherited metabolic disorders, affecting approximately one in 250 people in the UK, and is a priority condition within NHS cascade testing programmes, where relatives of an affected proband are offered genetic testing to identify those who would benefit from early lipid-lowering treatment.
Further along the short arm, at 19p13.3, sits STK11, a tumour suppressor gene that encodes serine/threonine kinase 11. Inherited pathogenic variants in STK11 cause Peutz-Jeghers syndrome, an autosomal dominant condition associated with benign polyps (hamartomas) in the gastrointestinal tract and distinctive pigmented spots on the lips and oral mucosa. People with Peutz-Jeghers syndrome face a substantially increased lifetime risk of several cancers, including bowel, breast, pancreatic, and gynaecological malignancies, and are offered structured surveillance under NHS protocols to enable earlier detection.
Notable genes
In addition to APOE, LDLR, and STK11, chromosome 19 carries numerous genes with important roles in human biology and disease. TNNI3 at 19q13.42 encodes cardiac troponin I, a protein found exclusively in heart muscle that regulates the contraction-relaxation cycle. Pathogenic variants in TNNI3 can cause familial restrictive cardiomyopathy, a rare and serious form of inherited heart muscle disease recognised by NHS specialist cardiac genetics services. Another gene, KMT2B at 19q13.12, encodes an enzyme that modifies histone proteins and thereby influences which genes are switched on or off in the developing brain; variants in KMT2B underlie DYT28, a childhood-onset dystonia syndrome.
CALM3 at 19q13.32 produces calmodulin, a calcium-binding protein essential for many cellular processes, and variants can cause inherited cardiac arrhythmias. MAP2K2 at 19p13.3 and PPP2R1A at 19q13.41 are both implicated in cell-signalling pathways and, when altered, can contribute to developmental disorders and cancer predisposition. The sheer number of genes packed into chromosome 19 means that panels for NHS genomic testing frequently include multiple genes from this chromosome, spanning cardiology, neurology, oncology, and metabolic medicine.
Chromosomal disorders
Unlike the larger autosomes (such as chromosomes 13, 18, and 21), complete trisomy or monosomy of chromosome 19 is not observed in live births, as such imbalances are incompatible with development and typically result in early pregnancy loss. Similarly, chromosome 19 is not known to host recurrent microdeletion or microduplication syndromes of the type seen on chromosomes 15, 22, or 7, nor does it carry an imprinted region that could lead to parent-of-origin-dependent disorders such as Prader-Willi or Angelman syndrome.
However, structural rearrangements involving chromosome 19-such as balanced translocations or inversions-are occasionally identified during diagnostic karyotyping or chromosomal microarray analysis, especially in individuals undergoing investigation for recurrent miscarriage, infertility, or unexplained developmental delay. When a parent carries a balanced rearrangement involving chromosome 19, there is a risk that offspring may inherit an unbalanced form, leading to partial trisomy or monosomy for a segment of the chromosome. The clinical consequences depend on the size and gene content of the duplicated or deleted region.
Because chromosome 19 is so gene-dense, even relatively small imbalances can have significant phenotypic effects, and such cases are typically discussed at regional NHS genomic medicine multidisciplinary team meetings to guide counselling and recurrence-risk estimation. In practice, most chromosome 19-related genetic conditions seen in NHS clinics arise from single-gene pathogenic variants (such as those in LDLR or STK11) rather than from large-scale chromosomal abnormalities.
Prenatal screening & diagnosis
Whole-chromosome aneuploidy of chromosome 19 is not compatible with life, so non-invasive prenatal testing (NIPT) and routine antenatal screening programmes do not screen for trisomy or monosomy 19. However, chromosome 19 is included in the full karyotype analysis or chromosomal microarray performed when amniocentesis or chorionic villus sampling is carried out for other indications, such as an abnormal ultrasound finding, increased nuchal translucency, or a family history of a genetic condition.
If a parent is known to carry a balanced translocation or inversion involving chromosome 19, prenatal diagnosis may be offered in subsequent pregnancies to determine whether the fetus has inherited a balanced or unbalanced chromosome complement. This is typically done by karyotyping foetal cells obtained via amniocentesis at around 15 weeks' gestation, or via chorionic villus sampling at 11-14 weeks. Chromosomal microarray can provide higher resolution and may detect small deletions or duplications not visible on standard karyotype.
In families with a known pathogenic variant in a chromosome 19 gene-such as LDLR (familial hypercholesterolaemia) or STK11 (Peutz-Jeghers syndrome)-targeted prenatal testing or preimplantation genetic testing can be arranged through NHS specialist genetics services, though such testing is usually reserved for conditions with severe early-onset manifestations rather than adult-onset disorders.
Inheritance & recurrence
Most pathogenic variants in chromosome 19 genes follow typical Mendelian inheritance patterns. Familial hypercholesterolaemia (LDLR) and Peutz-Jeghers syndrome (STK11), for example, are both autosomal dominant conditions: a person with a pathogenic variant has a 50% chance of passing it to each child, regardless of the child's sex. Other conditions, such as some forms of restrictive cardiomyopathy (TNNI3) or childhood-onset dystonia (KMT2B), can also show autosomal dominant inheritance, though penetrance and expressivity vary, meaning not everyone who inherits a variant will develop symptoms, and the severity can differ widely even within the same family.
Some chromosome 19 genes are associated with autosomal recessive conditions, where both copies of the gene must carry pathogenic variants for the disease to manifest. In such cases, parents are typically unaffected carriers, and each of their children has a 25% chance of being affected, a 50% chance of being a carrier, and a 25% chance of inheriting two working copies.
De novo variants-new changes that arise in a child but were not present in either parent-can also occur in chromosome 19 genes, particularly in genes involved in neurodevelopment or cancer predisposition. When a pathogenic variant is identified in a child with no family history, parental testing is usually recommended to clarify recurrence risk. If the variant is confirmed as de novo, the recurrence risk for future siblings is typically low (though not zero, because of the possibility of germline mosaicism). NHS clinical genetics services provide tailored counselling to families, taking into account the specific gene, the inheritance pattern, and the family history.
Frequently asked questions
Why is chromosome 19 called the most gene-dense chromosome?
Chromosome 19 carries approximately 1,474 protein-coding genes across just 58.6 million base pairs, meaning it has the highest concentration of genes per unit of DNA of any chromosome. This density reflects the fact that chromosome 19 contains relatively few long stretches of non-coding DNA, and much of its length is devoted to functional genes.
Can you inherit a whole extra copy of chromosome 19?
No. Complete trisomy 19 (three copies instead of two) or monosomy 19 (one copy instead of two) is not compatible with life and results in very early pregnancy loss, typically before a pregnancy is clinically recognised. For this reason, trisomy or monosomy 19 is not seen in live births and is not part of routine antenatal screening.
What does the APOE ε4 variant mean for Alzheimer disease risk?
The ε4 form of APOE is the strongest common genetic risk factor for late-onset Alzheimer disease. Inheriting one copy increases risk, and inheriting two copies increases it further. However, APOE ε4 is neither necessary nor sufficient to cause Alzheimer disease-many people with the variant never develop dementia, and many people who develop Alzheimer disease do not carry ε4.
If I have familial hypercholesterolaemia due to an LDLR variant, will my children definitely inherit it?
Each of your children has a 50% chance of inheriting the LDLR pathogenic variant, because familial hypercholesterolaemia is autosomal dominant. If a child inherits the variant, early diagnosis and treatment can substantially reduce the risk of heart disease, which is why NHS cascade testing is offered to relatives of people with confirmed familial hypercholesterolaemia.
How is a chromosome 19 gene variant diagnosed?
Diagnosis typically begins with clinical assessment and family history, followed by targeted genetic testing of the suspected gene (such as LDLR or STK11) or a broader gene panel if the clinical picture is less clear. Testing is usually arranged through NHS clinical genetics services or specialist clinics. Results are interpreted by a clinical scientist and discussed with you by a genetic counsellor or consultant, who will explain what the finding means for you and your family.
Launch-set genes on chromosome 19
Genes on this chromosome that currently have dedicated pages in the library. This list grows as we publish more.