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Chromosome 17
The tumour-suppressor chromosome - BRCA1, TP53, and NF1 all sit here. Dense with clinical-genetics landmarks.
Schematic of chromosome 17 showing the short (p) and long (q) arms. Arm ratio per GRCh38 - banding schematic.
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Overview
Chromosome 17 represents approximately 2.5 per cent of the total DNA in human cells, making it a medium-sized chromosome. With around 1,186 protein-coding genes packed into 83.3 million base pairs, it has one of the higher gene densities in the genome. The chromosome is submetacentric, meaning its centromere sits off-centre, creating a short arm (17p) and a longer arm (17q). This asymmetry is visible under the microscope when chromosomes condense during cell division.
Chromosome 17 is perhaps best known in clinical genetics for its concentration of tumour-suppressor genes - DNA sequences that encode proteins helping to prevent uncontrolled cell growth. BRCA1, TP53, and NF1 all reside here, and pathogenic variants in these genes account for a substantial portion of hereditary cancer-predisposition syndromes seen in NHS genetics clinics. Beyond cancer genetics, chromosome 17 also harbours genes involved in skeletal development, peripheral nerve function, and metabolic pathways, making it relevant across multiple medical subspecialties.
Abnormalities of chromosome 17 range from single-gene variants, which follow Mendelian inheritance patterns, to structural rearrangements such as microdeletions that remove multiple neighbouring genes. Smith-Magenis syndrome, caused by deletion of a small segment at 17p11.2, exemplifies how loss of even a modest chromosomal region can produce a recognisable clinical pattern. Complete non-mosaic trisomy or monosomy of chromosome 17 is incompatible with survival to term, though confined placental mosaicism for trisomy 17 and rare cases of mosaic trisomy 17 have been documented. The clinical focus therefore centres on gene-level variants and segmental imbalances.
Structure
Like all human chromosomes, chromosome 17 consists of a single, enormously long DNA molecule wound around histone proteins to form nucleosomes. These nucleosomes coil further into chromatin fibres, which in turn condense dramatically during cell division to produce the familiar X-shaped structure visible under a microscope. The centromere of chromosome 17 sits closer to one end than the other, classifying it as submetacentric. The shorter arm, designated 17p (p for petit), extends from the centromere to the tip, while the longer arm, 17q, makes up the majority of the chromosome's length. The centromere itself is a specialised region of repetitive DNA that serves as the attachment point for spindle fibres, ensuring accurate segregation of chromosomes into daughter cells during mitosis and meiosis.
Each arm of the chromosome is divided into numbered cytogenetic bands based on staining patterns seen with Giemsa dye. These bands provide a coordinate system for locating genes - for example, BRCA1 maps to 17q21.31, meaning it sits on the long arm, in region 2, band 1, sub-band 3, sub-sub-band 1. While this nomenclature can appear opaque, it allows geneticists worldwide to communicate unambiguously about where a variant or rearrangement has occurred. The banding pattern also reflects underlying differences in DNA sequence composition, with darker bands generally gene-poor and richer in repetitive elements, and lighter bands more gene-dense.
Video: What is a karyotype?
Notable regions
The 17p13.1 band is home to TP53, often called the guardian of the genome. This gene encodes a transcription factor whose product detects cellular stress - whether from broken DNA strands, inadequate oxygen, or growth signals gone awry - and responds by pausing the cell cycle to permit repair, or by initiating programmed death when damage proves beyond salvage. Inherited pathogenic changes in TP53 cause Li-Fraumeni syndrome, a condition characterised by markedly increased lifetime risks of multiple cancer types, often presenting at unusually young ages. Because TP53 sits at a critical junction in growth control, somatic alterations in this gene also rank among the most frequent events in non-hereditary malignancies, making it a focal point in both germline and cancer genetics.
Moving down the short arm to 17p11.2, we encounter a genomically unstable region prone to recurrent rearrangements. This band contains PMP22, a gene whose copy number directly affects peripheral nerve function. Duplication of the segment harbouring PMP22 causes Charcot-Marie-Tooth disease type 1A (the most common form of inherited peripheral neuropathy), a hereditary neuropathy marked by progressive muscle weakness and sensory loss in the limbs. By contrast, deletion of the same region produces hereditary neuropathy with liability to pressure palsies, in which nerves become unusually susceptible to compression injury. The same 17p11.2 interval also includes RAI1, and larger deletions encompassing this gene result in Smith-Magenis syndrome, a neurodevelopmental condition with intellectual disability, sleep disturbance, and behavioural features. The recurrent nature of these rearrangements reflects the presence of low-copy repeats - blocks of near-identical DNA sequence that can misalign during meiosis, predisposing to deletion or duplication.
On the long arm, 17q11.2 houses NF1, an unusually large gene that when altered causes neurofibromatosis type 1, among the most frequently encountered single-gene conditions in clinical genetics. The condition is characterised by café-au-lait skin patches, freckling in skin folds, benign nerve-sheath tumours called neurofibromas, and an elevated risk of certain malignancies. The NF1 protein, neurofibromin, acts as a brake on cell growth pathways, so its loss tips the balance toward proliferation. Further along at 17q21.31 lies BRCA1, whose protein product coordinates the repair of double-strand DNA breaks through a process called homologous recombination. Pathogenic variants in BRCA1 significantly elevate the lifetime risk of breast and ovarian cancer, and carriers may be offered enhanced surveillance or risk-reducing surgery through NHS cancer-genetics pathways. The concentration of clinically actionable genes in these few megabases underscores why chromosome 17 features so prominently in genetic testing panels.
Notable genes
BRCA1 is perhaps the most widely recognised gene on chromosome 17, symbolising the shift toward predictive and preventive medicine in the genomic era. Since the gene's identification in the mid-1990s, BRCA1 testing, typically offered as part of multi-gene hereditary cancer panels, has become a cornerstone of hereditary cancer-risk assessment. Individuals with a pathogenic BRCA1 variant face substantially elevated risks of breast and ovarian cancer, and may also have modestly increased risks of prostate, pancreatic, and other cancers. Men with BRCA1 variants have elevated risks of prostate cancer and male breast cancer, though the overall magnitude of cancer risk in male carriers is lower than that for female carriers. NHS genomic-medicine services offer BRCA1 testing to individuals meeting specific family-history or tumour-pathology criteria, and cascade testing is offered to at-risk relatives once a pathogenic variant is identified in the family.
TP53, NF1, and RAI1 each anchor distinct clinical syndromes with characteristic management pathways. TP53 variants prompt intensive cancer surveillance starting in childhood, as Li-Fraumeni syndrome can manifest with sarcomas, brain tumours, adrenocortical carcinoma, or breast cancer at ages far younger than population norms. NF1-related neurofibromatosis type 1 requires lifelong monitoring for complications including optic-pathway gliomas in young children, plexiform neurofibromas that may undergo malignant transformation, bone abnormalities, and learning difficulties. RAI1 haploinsufficiency in Smith-Magenis syndrome leads to a complex neurodevelopmental phenotype with disrupted circadian rhythm, often necessitating multidisciplinary input from paediatrics, neurology, sleep medicine, and behavioural specialists. Beyond these high-profile genes, chromosome 17 also carries FLCN (Birt-Hogg-Dubé syndrome, with kidney tumours and lung cysts), COL1A1 (osteogenesis imperfecta and some forms of Ehlers-Danlos syndrome), and GAA (Pompe disease, a glycogen-storage disorder). This diversity illustrates how a single chromosome can touch nearly every organ system.
Chromosomal disorders
Smith-Magenis syndrome is the principal chromosomal disorder associated with chromosome 17, arising from a microdeletion at 17p11.2 that removes multiple neighbouring genes. Most cases are de novo, meaning the deletion occurs as a new event in the egg or sperm, rather than being inherited from a parent. The core gene in the deleted region is RAI1, and loss of one copy of this gene is sufficient to produce the syndrome's hallmark features: intellectual disability, typically in the mild to moderate range, distinctive craniofacial appearance, sleep disturbance with inverted melatonin rhythm, and self-injurious behaviours. Because the deletion encompasses multiple genes, affected individuals may also have heart defects, kidney anomalies, hearing loss, and short stature, though the specific constellation of features varies. Smith-Magenis syndrome is typically identified through chromosomal microarray analysis, which can detect copy-number changes far smaller than those visible on a standard karyotype.
In a small proportion of cases, Smith-Magenis syndrome results not from a deletion but from a pathogenic variant in RAI1 itself, without loss of neighbouring genes. These individuals may have a somewhat milder or different phenotype, underscoring that RAI1 is the critical gene. Reciprocal duplication of the 17p11.2 region (the mirror-image rearrangement to the Smith-Magenis deletion) produces Potocki-Lupski syndrome, characterised by developmental delay, intellectual disability, and autistic features. The existence of both deletion and duplication syndromes at the same locus illustrates the concept of dosage sensitivity: for some genes, having either too few or too many copies disrupts normal development.
Because Smith-Magenis syndrome is usually sporadic, the recurrence risk for future pregnancies is low. However, if a parent carries a balanced chromosomal rearrangement that predisposes to the deletion, recurrence risk can be much higher, so parental chromosome analysis is sometimes offered. Whole-chromosome aneuploidy of chromosome 17 (trisomy 17 or monosomy 17) is vanishingly rare in liveborn individuals and generally results in early pregnancy loss. Confined placental mosaicism for trisomy 17 - where some placental cells carry three copies - can occasionally be detected on prenatal testing and may be associated with intrauterine growth restriction, but the fetus itself typically has a normal chromosome complement.
Prenatal screening & diagnosis
Abnormalities of chromosome 17 are not among the aneuploidies screened for by non-invasive prenatal testing, as whole-chromosome gains or losses of chromosome 17 are incompatible with ongoing pregnancy. However, microdeletions such as the 17p11.2 deletion underlying Smith-Magenis syndrome can be detected by chromosomal microarray analysis performed on a sample obtained through chorionic villus sampling or amniocentesis. Microarray is not part of routine antenatal care but may be offered if an ultrasound scan identifies structural anomalies - for example, heart defects or growth restriction - that raise suspicion of an underlying genetic condition.
In families with a known hereditary cancer syndrome due to a BRCA1, TP53, or NF1 variant, preimplantation genetic testing may be considered for couples undergoing in vitro fertilisation, allowing selection of embryos that have not inherited the familial variant. This can be accessed through specialist NHS centres, though availability varies by region and funding approval is required. For Li-Fraumeni syndrome in particular, some families opt for preimplantation testing given the high penetrance and early onset of cancers. Prenatal diagnosis for these single-gene conditions is also possible via CVS or amniocentesis, though uptake varies and many families prefer postnatal testing or childhood surveillance.
When a chromosome 17 microdeletion or pathogenic variant is identified prenatally, parents are offered genetic counselling to discuss the expected phenotype, variability in outcomes, and available support. For Smith-Magenis syndrome, while intellectual disability and behavioural challenges are typical, the severity is difficult to predict from genetic findings alone, and many affected individuals lead fulfilling lives with appropriate educational and therapeutic input. NHS foetal medicine teams work closely with clinical genetics to ensure parents have balanced, up-to-date information on which to base reproductive decisions.
Inheritance & recurrence
Most Smith-Magenis syndrome cases arise de novo, meaning the 17p11.2 deletion is not present in either parent and occurred as a spontaneous error during formation of the egg or sperm. In this scenario, the recurrence risk for future siblings is generally low, accounting for the theoretical possibility of germline mosaicism (where a proportion of a parent's egg or sperm cells carry the deletion, even though it is absent from blood cells tested). If a parent is found to carry a balanced translocation involving chromosome 17, the risk of unbalanced offspring can be significantly higher, and detailed genetic counselling with discussion of prenatal diagnosis options is appropriate.
For single-gene conditions on chromosome 17, inheritance patterns follow Mendelian rules. BRCA1, TP53, and NF1 variants are typically inherited in an autosomal-dominant manner, meaning a single pathogenic variant is sufficient to confer increased disease risk, and each child of an affected parent has a fifty per cent chance of inheriting it. Penetrance - the likelihood that a variant carrier will develop symptoms - varies by gene and by specific variant. BRCA1 pathogenic variants are highly penetrant for cancer, though not every carrier will develop malignancy, and risk-reduction strategies can substantially alter outcomes. NF1 is nearly fully penetrant for the diagnostic features (café-au-lait patches, neurofibromas), but complications such as malignant peripheral nerve-sheath tumours occur in only a minority. TP53 pathogenic variants show very high penetrance, with the majority of carriers developing at least one cancer by middle age or earlier, though penetrance estimates vary by specific variant and family context.
Autosomal-recessive conditions also map to chromosome 17, such as Pompe disease (GAA variants). In these cases, both parents are typically unaffected carriers, each child has a twenty-five per cent chance of being affected, a fifty per cent chance of being a carrier, and a twenty-five per cent chance of inheriting two working copies. When a pathogenic variant is identified in a family, cascade testing of at-risk relatives is a key component of NHS genomic-medicine practice, allowing early intervention, surveillance, or reproductive counselling. Referral to a regional genetics service ensures that families receive tailored recurrence-risk estimates and discussion of options such as preimplantation genetic testing or prenatal diagnosis.
Frequently asked questions
If I carry a BRCA1 variant, does that mean I will definitely develop cancer?
No - carrying a pathogenic BRCA1 variant substantially raises lifetime cancer risk, but it is not a certainty. Many carriers never develop cancer, and risk-reduction strategies such as enhanced screening, chemoprevention, or risk-reducing surgery can significantly alter outcomes. Your NHS genetics team will discuss personalised risk estimates and management options.
How is Smith-Magenis syndrome diagnosed?
Smith-Magenis syndrome is typically diagnosed through chromosomal microarray analysis, a genetic test that detects the 17p11.2 microdeletion. The test is usually requested when a child has developmental delay, sleep disturbance, and behavioural features suggestive of the condition. In a small number of cases, targeted sequencing of the RAI1 gene identifies a pathogenic variant without a visible deletion.
Can chromosome 17 abnormalities be detected during pregnancy?
Whole-chromosome aneuploidy of chromosome 17 is extremely rare and generally leads to early pregnancy loss, so it is not included in standard prenatal screening. However, microdeletions such as the 17p11.2 deletion can be detected by chromosomal microarray if chorionic villus sampling or amniocentesis is performed, typically because an ultrasound has identified a structural anomaly.
What is the difference between the BRCA1 gene and the BRCA2 gene?
BRCA1 (on chromosome 17) and BRCA2 (on chromosome 13) are distinct genes that both play crucial roles in repairing damaged DNA. Pathogenic variants in either gene elevate breast and ovarian cancer risk, though the magnitude and age of onset can differ slightly. Both are included in NHS hereditary cancer-gene panels, and clinical management is similar for carriers of either.
If one parent has neurofibromatosis type 1, what is the chance their child will inherit it?
Neurofibromatosis type 1 follows autosomal-dominant inheritance, so each child of an affected parent has a fifty per cent chance of inheriting the pathogenic NF1 variant. However, about half of all NF1 cases arise from new variants, meaning neither parent carries it. Genetic testing and counselling through your regional genetics service can clarify the specific situation for your family.
Launch-set genes on chromosome 17
Genes on this chromosome that currently have dedicated pages in the library. This list grows as we publish more.