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Chromosome 5
Home of the APC gene (familial adenomatous polyposis) and SMN1 (spinal muscular atrophy).
Schematic of chromosome 5 showing the short (p) and long (q) arms. Arm ratio per GRCh38 - banding schematic.
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Overview
Chromosome 5 is one of the 23 pairs of human chromosomes and accounts for roughly 181.5 million base pairs of DNA, making it the fifth-largest chromosome in the genome. It carries approximately 876 genes that encode proteins with roles spanning cellular growth regulation, mitochondrial energy production, nerve function, and blood vessel formation. Clinically, this chromosome is best known for two landmark genes: APC, pathogenic variants of which cause familial adenomatous polyposis and significantly raise colorectal cancer risk, and SMN1, loss of which results in spinal muscular atrophy, a severe motor neurone disorder that, prior to recent therapeutic advances, was a leading genetic cause of infant mortality. Beyond single-gene disorders, deletion of the short arm of chromosome 5 gives rise to cri-du-chat syndrome, a recognisable constellation of developmental and physical features.
Chromosome 5 is classified as submetacentric, meaning its centromere sits off-centre, creating a short arm (5p) and a longer arm (5q). This asymmetry influences how the chromosome pairs and segregates during cell division. Because chromosome 5 is an autosome rather than a sex chromosome, everyone inherits two copies, one from each parent, and conditions linked to genes on chromosome 5 follow autosomal inheritance patterns. The diversity of genes on this chromosome underscores the range of biological processes that can be disrupted when structural or sequence-level changes occur.
Structure
Like all human chromosomes, chromosome 5 consists of a single, enormously long DNA molecule wound around histone proteins to form nucleosomes. These nucleosomes are further coiled and compacted into chromatin fibres, which condense dramatically during cell division to produce the recognisable X-shaped structure visible under a microscope at metaphase. The centromere, located closer to one end than the other, acts as the attachment point for spindle fibres that pull sister chromatids apart during mitosis and meiosis. In chromosome 5, this off-centre placement defines a short arm (5p) that is noticeably smaller than the long arm (5q).
The p arm and q arm each contain distinct sets of genes and regulatory regions. Cytogeneticists use a banding pattern created by chemical stains to divide each arm into numbered regions and sub-bands, providing a standardised map for locating genes and describing deletions or duplications. This numbering system runs outward from the centromere, so 5p15 is near the tip of the short arm, whilst 5q22 sits well along the long arm. Understanding this anatomy is essential when interpreting karyotype reports or chromosomal microarray results that identify structural abnormalities by their cytogenetic address.
Video: What is a karyotype?
Notable regions
The 5q22.2 band is home to APC, one of the most intensively studied tumour-suppressor genes. APC encodes a protein that restrains the Wnt signalling pathway, a critical regulator of cell division and differentiation in the lining of the colon. Pathogenic variants in APC cause familial adenomatous polyposis, a condition characterised by the development of hundreds to thousands of polyps in the colon and rectum during adolescence and early adulthood. Without preventive surgery, these polyps almost invariably progress to colorectal cancer. The APC protein also contributes to chromosome segregation and cytoskeletal organisation, and somatic mutations in this gene are found in the majority of sporadic colorectal cancers, highlighting its central role in maintaining normal intestinal tissue.
Further along the long arm, at 5q13.2, lies SMN1, the survival motor neurone 1 gene. This gene produces a protein essential for the assembly of small nuclear ribonucleoproteins, molecular machines involved in splicing messenger RNA. Motor neurones, which relay signals from the spinal cord to muscles, are particularly vulnerable to reduced levels of the SMN protein. Homozygous loss or inactivation of SMN1, often through deletion, results in spinal muscular atrophy, a disorder that causes progressive muscle weakness and wasting. The severity of spinal muscular atrophy correlates inversely with the number of copies of a nearly identical neighbouring gene, SMN2, which can partially compensate for the loss of SMN1. Newborn screening for spinal muscular atrophy is now offered across the NHS in England, enabling early identification and access to disease-modifying therapies.
At the opposite end of the chromosome, the 5p15.2 region represents the critical interval for cri-du-chat syndrome. Deletions encompassing this portion of the short arm remove multiple genes, and the constellation of features in affected individuals reflects the combined impact of losing these genes. The name of the syndrome, French for "cry of the cat," refers to the distinctive high-pitched cry observed in infancy, caused by structural differences in the larynx. Children with cri-du-chat syndrome typically show intellectual disability, delayed motor development, distinctive facial features, and low birth weight. The size of the deletion varies between individuals, and larger deletions that extend beyond the critical region tend to correlate with more pronounced developmental challenges.
Notable genes
Beyond APC and SMN1, chromosome 5 harbours several other clinically and biologically important genes. SDHA, located at 5p15.33, encodes a subunit of succinate dehydrogenase, an enzyme complex embedded in the inner mitochondrial membrane that participates in both the citric acid cycle and the electron transport chain. Pathogenic variants in SDHA impair cellular energy production and are associated with Leigh syndrome, a severe neurological disorder of early childhood, as well as an increased risk of certain tumours such as paragangliomas and phaeochromocytomas (rare tumours of neuroendocrine tissue). RASA1, at 5q14.3, produces a protein that regulates signalling by the RAS family of proteins, which control cell growth and blood vessel formation. Pathogenic changes in RASA1 lead to capillary malformation-arteriovenous malformation syndrome, including the more severe presentation known as Parkes Weber syndrome, characterised by vascular anomalies and limb overgrowth. HINT1, positioned at 5q23.3, encodes a protein involved in nerve function, and recessive variants cause an axonal neuropathy with neuromyotonia, a rare disorder featuring progressive muscle weakness and involuntary muscle activity.
Chromosomal disorders
Cri-du-chat syndrome arises from a deletion of material from the short arm of chromosome 5, most commonly involving a deletion that includes the critical 5p15.2 region. The deletion is usually de novo, meaning it occurs as a new event during the formation of the egg or sperm, rather than being inherited from a parent. The size of the deleted segment varies, but even relatively small terminal deletions that remove the critical region can produce the characteristic features. Affected individuals present with a high-pitched, cat-like cry in infancy, moderate to severe intellectual disability, delayed speech and motor skills, microcephaly, and a distinctive facial appearance that may include widely spaced eyes, a small jaw, and low-set ears. Growth is typically slow, and some individuals have heart defects or other structural anomalies. Most people with cri-du-chat syndrome require lifelong support, though the degree of developmental challenge varies. Diagnosis is confirmed by chromosomal microarray or karyotype, both of which can detect deletions of this size.
Ring chromosome 5 is a rare structural abnormality in which the ends of both the short and long arms are deleted and the remaining chromosome forms a circular structure. Because genetic material from both arms is lost, ring chromosome 5 can produce a clinical picture that overlaps with cri-du-chat syndrome if the 5p critical region is involved, alongside additional features reflecting loss of sequences from the long arm. The severity depends on how much material is missing and whether the ring is stable across cell divisions. Mosaicism, in which only some cells carry the ring chromosome, can modify the phenotype.
Isochromosome 5p, in which the short arm is duplicated and the long arm is absent, has been reported in rare cases, typically in association with complex chromosomal rearrangements or as a feature of certain tumours rather than as a constitutional abnormality. At the single-gene level, the recurrent microdeletions or duplications that encompass only one or two genes are not considered whole-chromosomal disorders but are better understood as contiguous gene syndromes, such as the deletions that remove SMN1 in spinal muscular atrophy.
Prenatal screening & diagnosis
Non-invasive prenatal testing (NIPT), which analyses cell-free foetal DNA in maternal blood, is primarily designed to screen for the common whole-chromosome aneuploidies involving chromosomes 13, 18, and 21. It is not routinely used to detect deletions of chromosome 5, though some extended NIPT panels can identify large deletions or duplications as incidental findings. When ultrasound examination during pregnancy identifies structural anomalies such as heart defects, growth restriction, or abnormal amniotic fluid volume, further investigation with chromosomal microarray or karyotype may be offered. Chromosomal microarray can detect deletions of the size typically seen in cri-du-chat syndrome, whilst karyotyping remains the gold standard for visualising balanced rearrangements and ring chromosomes.
Newborn bloodspot screening in England now includes testing for spinal muscular atrophy, a condition caused by biallelic loss of SMN1 on chromosome 5. This screening, rolled out in England from 2021, allows early identification of affected infants before the onset of symptoms, enabling prompt initiation of disease-modifying therapies that can significantly alter the disease trajectory. For families with a known history of familial adenomatous polyposis linked to APC, predictive genetic testing can be offered to at-risk relatives, often during adolescence, to guide decisions about surveillance colonoscopy and preventive surgery.
Inheritance & recurrence
Most cases of cri-du-chat syndrome result from de novo deletions of 5p, meaning the deletion arises as a new event in the affected individual and neither parent carries a chromosomal abnormality. In these families, the recurrence risk for future pregnancies is low, typically quoted at around one percent, reflecting the background population risk for chromosome abnormalities. However, in a minority of cases (approximately 10 to 15 percent reported in clinical series), one parent carries a balanced translocation involving chromosome 5, in which genetic material has been exchanged with another chromosome but no net loss or gain has occurred. Parents with balanced translocations are typically healthy but face a significantly elevated risk of having children with unbalanced chromosome complements, including deletions of 5p. Karyotyping both parents is therefore recommended whenever a child is diagnosed with cri-du-chat syndrome, to clarify recurrence risk and inform discussions about prenatal testing options for subsequent pregnancies.
Conditions caused by single-gene variants on chromosome 5 follow conventional Mendelian inheritance. Familial adenomatous polyposis, linked to pathogenic variants in APC, is inherited in an autosomal dominant pattern, so an affected individual has a 50 percent chance of passing the variant to each child. Many cases, however, arise from de novo variants. Spinal muscular atrophy follows autosomal recessive inheritance: both parents of an affected child are typically carriers of a single SMN1 deletion or pathogenic variant, and each subsequent pregnancy carries a 25 percent recurrence risk. Referral to an NHS clinical genetics service is recommended for tailored genetic counselling, carrier testing for at-risk relatives, and discussion of reproductive options including preimplantation genetic testing.
Frequently asked questions
What is cri-du-chat syndrome and how is it diagnosed?
Cri-du-chat syndrome is caused by a deletion of part of the short arm of chromosome 5, most often involving the critical 5p15.2 region. Affected individuals typically have a high-pitched cry in infancy, intellectual disability, delayed development, and distinctive facial features. Diagnosis is confirmed by chromosomal microarray or karyotype, both available through the NHS.
Can chromosome 5 abnormalities be detected during pregnancy?
Large deletions such as those causing cri-du-chat syndrome can be detected by chromosomal microarray or karyotype if these tests are performed on a sample obtained through chorionic villus sampling or amniocentesis, typically offered when ultrasound findings raise concern. Standard NIPT does not routinely screen for deletions of chromosome 5.
What is familial adenomatous polyposis and how does it relate to chromosome 5?
Familial adenomatous polyposis is an inherited condition caused by pathogenic variants in the APC gene on chromosome 5. Affected individuals develop hundreds to thousands of polyps in the colon, which can progress to colorectal cancer if not managed with surveillance and preventive surgery. Genetic testing and counselling are available through NHS clinical genetics services.
Is spinal muscular atrophy screened for in newborns?
Yes, newborn bloodspot screening for spinal muscular atrophy was introduced across England in 2021. The test looks for homozygous loss of the SMN1 gene on chromosome 5. Early detection allows treatment to begin before symptoms appear, which can improve outcomes significantly.
If my child has a chromosome 5 deletion, will my next child be affected?
Most deletions of chromosome 5 occur de novo, meaning they are not inherited and the recurrence risk is low. However, around 10 to 15 percent of cases involve a balanced translocation in one parent, which carries a higher recurrence risk. Parental karyotyping and genetic counselling through an NHS clinical genetics service can clarify your family's specific situation.
Launch-set genes on chromosome 5
Genes on this chromosome that currently have dedicated pages in the library. This list grows as we publish more.