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Chromosome 14
Acrocentric - carries the α1-antitrypsin locus (SERPINA1) and the immunoglobulin heavy-chain cluster.
Schematic of chromosome 14 showing the short (p) and long (q) arms. Arm ratio per GRCh38 - banding schematic.
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Overview
Chromosome 14 accounts for roughly 3.5 per cent of the total genome, making it one of the mid-sized human chromosomes. It carries approximately 820 protein-coding genes distributed along 107.0 million base pairs. Clinically, chromosome 14 is recognised for SERPINA1, variants in which cause alpha-1 antitrypsin deficiency and can lead to early-onset emphysema and liver disease, and for the immunoglobulin heavy-chain cluster at 14q32.33, which is frequently involved in translocations seen in B-cell lymphomas and multiple myeloma.
Chromosome 14 is classified as acrocentric, meaning its centromere sits very close to one end, creating a long arm (designated 14q) that contains the vast majority of genes and a short arm (14p) composed largely of repetitive ribosomal RNA sequences. The short arm contributes to the nucleolar organiser region in the cell nucleus, where ribosomal subunits are assembled. During cell division, the centromere anchors spindle fibres that pull sister chromatids apart, ensuring each daughter cell inherits one copy of chromosome 14.
Beyond immune and respiratory function, chromosome 14 harbours genes important for cardiac muscle contraction, microRNA processing, and calcium signalling. Pathogenic variants in these genes are linked to conditions ranging from familial cardiomyopathy to inherited tumour syndromes, underscoring the chromosome's broad clinical significance.
Structure
Chromosome 14's structure reflects its acrocentric classification. The centromere divides the chromosome into a very short p arm and a long q arm that extends from the centromere to the telomere at the far end. The short arm is dominated by tandem arrays of ribosomal DNA that transcribe the RNA components of ribosomes, the cellular machines that translate messenger RNA into protein. These ribosomal clusters from chromosomes 13, 14, 15, 21, and 22 coalesce in the nucleolus during interphase, forming the nucleolar organiser regions. The long arm contains the protein-coding genes, regulatory elements, and intergenic sequences that define the chromosome's functional landscape.
At the molecular level, the DNA double helix of chromosome 14 wraps around histone proteins to form repeating units called nucleosomes, which resemble beads on a string. These nucleosomes coil into progressively tighter structures, ultimately condensing into the compact X-shaped chromosome visible under the microscope during metaphase. Chemical modifications to histones and DNA itself, collectively termed the epigenome, determine which stretches of chromosome 14 are accessible for gene transcription and which remain silent. This packaging ensures that 107 million base pairs can fit inside a nucleus only a few micrometres across while remaining organised enough for the cell to access specific genes on demand.
Video: What is a karyotype?
Notable regions
The 14q32.13 band is home to SERPINA1, the gene encoding alpha-1 antitrypsin, a protease inhibitor synthesised primarily in the liver and secreted into the bloodstream. Alpha-1 antitrypsin protects lung tissue from neutrophil elastase, an enzyme released during inflammation. Pathogenic variants in SERPINA1, most commonly the Z allele (p.Glu342Lys), cause the protein to misfold and accumulate in liver cells rather than being secreted. Individuals homozygous for the Z allele face increased risk of early-onset emphysema, particularly if they smoke, and a subset develop chronic liver disease or cirrhosis. The Z allele has a carrier rate of approximately 1 in 25 in Northern European populations, though rates vary by specific ancestry group within Europe. The condition is managed through smoking cessation, intravenous alpha-1 antitrypsin augmentation therapy in selected cases, and liver transplantation when cirrhosis is advanced.
Further along the long arm, the 14q32.33 band contains the immunoglobulin heavy-chain locus (IGH), a large cluster of gene segments that undergo programmed DNA rearrangement in developing B cells to generate the vast diversity of antibodies the immune system requires. Each B cell randomly selects one variable (V), one diversity (D), and one joining (J) segment, splicing them together to create a unique heavy-chain sequence. This process, combined with similar rearrangements at the light-chain loci on other chromosomes, produces billions of distinct antibody molecules. The IGH locus is also a frequent breakpoint in chromosomal translocations involving B-cell malignancies. Translocations such as t(8;14) in Burkitt lymphoma and t(11;14) in mantle cell lymphoma juxtapose oncogenes next to the powerful IGH regulatory elements, driving uncontrolled cell proliferation. Detection of these translocations through fluorescence in situ hybridisation or next-generation sequencing informs prognosis and treatment decisions in haematological oncology.
The short arm of chromosome 14 (14p) is largely composed of ribosomal RNA genes arranged in tandem repeats. These sequences do not encode proteins but are transcribed into the 18S, 5.8S, and 28S ribosomal RNAs that form the structural and catalytic core of ribosomes. Because protein synthesis depends on a steady supply of ribosomes, cells maintain hundreds of copies of these genes across the five acrocentric chromosomes. Variation in copy number or sequence at these loci typically has little functional consequence owing to this redundancy, though rare structural rearrangements involving the short arms of acrocentrics can lead to Robertsonian translocations, discussed further below.
Notable genes
SERPINA1 and IGH have already been highlighted, but chromosome 14 also carries several other clinically important genes. DICER1, located at 14q32.13, encodes an enzyme that cleaves precursor RNA molecules into microRNAs, small regulatory molecules that fine-tune gene expression across nearly every cellular pathway. Germline pathogenic variants in DICER1 cause DICER1 syndrome, an autosomal dominant condition characterised by predisposition to a range of benign and malignant tumours, including pleuropulmonary blastoma in young children, cystic nephroma, ovarian Sertoli-Leydig cell tumours, and multinodular goitre. Tumours in DICER1 syndrome often follow a two-hit model, requiring both the inherited germline variant and a somatic mutation in the RNase IIIb domain of the second allele.
MYH7 at 14q11.2 encodes the beta-myosin heavy chain, the major contractile protein in cardiac muscle and slow-twitch skeletal muscle fibres. Pathogenic variants in MYH7 are a leading cause of hypertrophic cardiomyopathy, a condition in which the heart muscle thickens abnormally, and dilated cardiomyopathy, where the left ventricle enlarges and weakens. MYH7 variants are also associated with left ventricular non-compaction and certain skeletal myopathies. Inheritance is typically autosomal dominant with variable expressivity, meaning family members carrying the same variant may have markedly different clinical presentations. Cascade screening of relatives and regular cardiac surveillance are central to management. Other genes on chromosome 14 include CALM1, which encodes a calcium-sensing protein involved in cardiac electrical activity and linked to long QT syndrome and catecholaminergic polymorphic ventricular tachycardia, and MAX, a transcription factor whose variants that impair MAX function predispose to phaeochromocytoma and paraganglioma.
Chromosomal disorders
Whole-chromosome trisomy or monosomy of chromosome 14 is typically incompatible with survival to term, and thus mosaic forms are exceedingly rare. Instead, the most common structural abnormalities involving chromosome 14 are Robertsonian translocations, in which the long arms of two acrocentric chromosomes fuse at or near the centromere and the short arms are lost. Because the short arms carry only ribosomal RNA genes present in multiple copies on other acrocentrics, carriers of a balanced Robertsonian translocation involving chromosome 14 and another acrocentric (most often chromosome 13, 15, 21, or 22) are typically healthy but face an increased risk of unbalanced chromosome complements in their offspring. For example, a rob(14;21) carrier may produce gametes that lead to trisomy 21 (Down syndrome) in the next generation. Preconception or prenatal genetic counselling and testing options, including non-invasive prenatal testing and diagnostic chromosomal microarray or karyotype, are available through NHS Genomic Medicine services.
Another recognised disorder is UPD(14), uniparental disomy of chromosome 14, in which both copies of the chromosome are inherited from one parent. Chromosome 14 contains imprinted regions, meaning certain genes are expressed only from the maternal or paternal copy. Maternal uniparental disomy of chromosome 14 (UPD(14)mat) typically presents with growth restriction, early puberty, and truncal obesity, whereas paternal uniparental disomy (UPD(14)pat) is associated with a more severe phenotype including polyhydramnios, thoracic dystrophy, developmental delay, and characteristic facial features. These conditions arise not from loss or gain of genetic material but from aberrant expression of imprinted genes in the 14q32 region. Diagnosis is made through methylation analysis or microsatellite marker studies that reveal the parental origin of the chromosomes.
Prenatal screening & diagnosis
Because whole-chromosome aneuploidy of chromosome 14 is lethal, it is not part of routine antenatal screening panels. Non-invasive prenatal testing offered by the NHS primarily screens for trisomies 21, 18, and 13, alongside sex-chromosome aneuploidies. However, structural rearrangements involving chromosome 14, such as Robertsonian translocations, may be identified during karyotyping performed for other indications, such as recurrent miscarriage, a family history of chromosomal rearrangement, or abnormal ultrasound findings.
If a parent is known to carry a balanced Robertsonian translocation involving chromosome 14, the couple may be offered preimplantation genetic testing if pursuing in vitro fertilisation, chorionic villus sampling, or amniocentesis to determine whether the fetus has inherited a balanced or unbalanced form. Chromosomal microarray analysis can detect submicroscopic deletions or duplications along chromosome 14 that would be missed on standard karyotype. The NHS Fetal Anomaly Screening Programme includes detailed anomaly scans at around 20 weeks' gestation; findings such as growth restriction or structural anomalies may prompt referral to a foetal medicine specialist and consideration of diagnostic genetic testing. Parents are supported by regional genomic laboratory hubs and clinical genetics services to interpret results and understand recurrence risks.
Inheritance & recurrence
Most pathogenic variants in single genes on chromosome 14 follow Mendelian inheritance patterns. Conditions such as hypertrophic cardiomyopathy due to MYH7 variants and DICER1 syndrome are typically autosomal dominant, meaning a single altered copy is sufficient to confer disease risk. Each child of an affected parent has a 50 per cent chance of inheriting the variant, though penetrance and expressivity vary. Alpha-1 antitrypsin deficiency caused by SERPINA1 variants follows an autosomal recessive pattern for the severe ZZ genotype; carrier parents (each with one Z allele) have a one in four risk of an affected child with each pregnancy.
Structural rearrangements such as Robertsonian translocations can be de novo or inherited. If a parent carries a balanced translocation, the recurrence risk for an unbalanced karyotype in future pregnancies depends on which chromosomes are involved and which parent is the carrier. Empirical recurrence risks are used because segregation is complex. Uniparental disomy of chromosome 14 is almost always a sporadic event arising through errors in meiosis or post-zygotic rescue of a trisomic conception, so recurrence risk for future siblings is low. Families with a personal or family history of a condition linked to chromosome 14 should be referred to NHS clinical genetics services for tailored risk assessment, testing options, and reproductive counselling.
Frequently asked questions
What is alpha-1 antitrypsin deficiency and how common is it?
Alpha-1 antitrypsin deficiency is an inherited condition caused by pathogenic variants in the SERPINA1 gene on chromosome 14. It leads to low levels of alpha-1 antitrypsin protein in the blood, increasing the risk of lung disease (particularly emphysema in smokers) and, in some cases, liver disease. It is one of the most common inherited disorders in people of Northern European ancestry, with the Z allele having a carrier rate of approximately 1 in 25 in Northern European populations, though rates vary by specific ancestry group within Europe.
Can chromosome 14 abnormalities be detected during pregnancy?
Structural rearrangements such as Robertsonian translocations involving chromosome 14 can be detected through diagnostic tests like chorionic villus sampling or amniocentesis, particularly if there is a known family history or recurrent pregnancy loss. Whole-chromosome trisomy 14 is not compatible with survival and is not part of routine antenatal screening. If a translocation is suspected, couples can discuss testing options with a foetal medicine specialist through the NHS.
What is a Robertsonian translocation and why does it matter?
A Robertsonian translocation occurs when the long arms of two acrocentric chromosomes (such as 14 and 21) fuse together, with loss of the short arms. Carriers are usually healthy because the short arms contain only redundant ribosomal genes, but they have an increased risk of producing eggs or sperm with unbalanced chromosome numbers. This can lead to miscarriage or, in some cases, a child with a chromosome disorder such as Down syndrome.
Are heart conditions linked to chromosome 14 inherited?
Yes, pathogenic variants in the MYH7 gene on chromosome 14 cause inherited forms of hypertrophic cardiomyopathy and related heart muscle disorders. These conditions follow an autosomal dominant pattern, so a child of an affected parent has a 50 per cent chance of inheriting the variant. Not everyone who inherits a pathogenic MYH7 variant will develop symptoms to the same degree, so regular cardiac monitoring and family screening are recommended.
What is DICER1 syndrome and how is it managed?
DICER1 syndrome is an inherited cancer predisposition condition caused by pathogenic variants in the DICER1 gene on chromosome 14. It increases the risk of certain tumours, including pleuropulmonary blastoma, ovarian tumours, thyroid nodules, and cystic kidney lesions. Management involves regular surveillance with imaging and clinical examinations tailored to age and sex, coordinated through specialist cancer genetics services within the NHS, to enable early detection and treatment of any tumours that arise.
Launch-set genes on chromosome 14
Genes on this chromosome that currently have dedicated pages in the library. This list grows as we publish more.