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Chromosome 6
Carries the HLA (MHC) region - the most polymorphic locus in the human genome and a central player in immunity.
Schematic of chromosome 6 showing the short (p) and long (q) arms. Arm ratio per GRCh38 - banding schematic.
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Overview
Chromosome 6 is the sixth-largest human chromosome, accounting for roughly 5.5 per cent of the total genome. At 170.8 megabases, it contains approximately 1,047 protein-coding genes, making it one of the more gene-rich chromosomes. Chromosome 6 is submetacentric, meaning its centromere sits somewhat off-centre, creating a moderately shorter p (short) arm and a longer q arm. This chromosome is clinically notable for hosting the major histocompatibility complex (MHC) - known in humans as the HLA region - which is responsible for immune-cell recognition and is the most variable genetic locus in the human population.
Beyond immunity, chromosome 6 harbours genes involved in iron metabolism, neurodevelopment, chromatin remodelling, and muscle structure. Pathogenic variants in genes on chromosome 6 underlie a spectrum of conditions, from hereditary haemochromatosis and progressive neurological disorders to connective-tissue syndromes and developmental delay. Unlike some other chromosomes, whole-chromosome aneuploidy (an extra or missing copy of chromosome 6) is exceedingly rare and typically incompatible with survival to term, so clinical focus centres on single-gene disorders and small structural rearrangements.
Structure
Like all human chromosomes, chromosome 6 is divided by the centromere into two arms. The short arm (p arm) extends from the centromere to the tip at 6p25, while the long arm (q arm) stretches from the centromere to the telomere at 6q27. Because chromosome 6 is submetacentric, the q arm is noticeably longer than the p arm, giving the chromosome an asymmetric appearance during cell division when chromatin condenses into its familiar X shape. The centromere itself is a specialised region of repetitive DNA that serves as the attachment point for spindle fibres, ensuring that each daughter cell receives a complete copy during mitosis and meiosis.
At the molecular level, chromosome 6 comprises a long double helix of DNA wrapped around histone proteins to form nucleosomes, which are then coiled into chromatin fibres. During most of the cell cycle, this chromatin is loosely packed (euchromatin) to allow genes to be read and transcribed. As the cell prepares to divide, the chromatin condenses into the compact structure visible under a microscope. This dynamic packaging is regulated by chromatin-remodelling complexes, several of which are encoded by genes on chromosome 6 itself, such as ARID1B. Proper chromosome structure and packaging are essential for maintaining genomic stability and ensuring accurate gene expression.
Video: What is a karyotype?
Notable regions
The most famous region of chromosome 6 lies at 6p21.3, home to the human leukocyte antigen (HLA) complex. This dense cluster of genes encodes cell-surface proteins that present fragments of pathogens to immune cells, enabling the body to distinguish self from non-self. The HLA region is extraordinarily polymorphic - there are hundreds of different alleles (gene variants) at each HLA locus across human populations - which helps ensure that at least some individuals can mount an immune response to new infectious threats. HLA typing is essential in transplant medicine, where donor-recipient matching reduces the risk of graft rejection, and certain HLA alleles are strongly associated with autoimmune conditions such as type 1 diabetes, rheumatoid arthritis, and coeliac disease. NHS laboratories routinely perform HLA genotyping for transplant compatibility and to aid diagnosis of conditions with known HLA associations.
Further along the short arm at 6p22.2 sits HFE, the gene responsible for the majority of cases of hereditary haemochromatosis in European populations. The protein encoded by HFE regulates iron absorption in the gut by modulating the activity of hepcidin, the master iron-regulatory hormone. Two common pathogenic variants, p.C282Y and p.H63D, reduce the effectiveness of this regulation, leading to progressive iron overload in tissues such as the liver, heart, and pancreas if untreated, though not all individuals who inherit two copies of these variants will develop iron overload. Haemochromatosis is one of the most frequent single-gene disorders in people of Northern European ancestry, and diagnosis is typically confirmed by genetic testing following abnormal serum ferritin and transferrin-saturation results.
Toward the far end of the long arm at 6q27 lies PARK2, encoding the parkin protein. Biallelic pathogenic variants in PARK2 (meaning changes on both copies of the gene) cause autosomal recessive juvenile-onset Parkinson disease, a rare neurological condition characterised by early tremor, rigidity, and bradykinesia. Parkin functions as an E3 ubiquitin ligase, tagging damaged mitochondria for degradation - a quality-control process essential for nerve-cell health. Loss of parkin function allows toxic mitochondria to accumulate, eventually leading to the death of dopaminergic neurons in the substantia nigra. Genetic testing through the NHS Genomic Medicine Service can identify pathogenic PARK2 variants, informing both diagnosis and family counselling.
Notable genes
Chromosome 6 carries several genes with major clinical and research significance. HFE, HLA-A, HLA-B, and HLA-DRB1 have already been mentioned for their roles in iron metabolism and immune recognition. Within the Jeen Health gene library, ARID1B at 6q25.3 is particularly notable: it encodes a component of SWI/SNF chromatin-remodelling complexes that regulate how accessible genes are to the transcription machinery. Heterozygous pathogenic variants in ARID1B (affecting one copy of the gene) cause Coffin-Siris syndrome, a neurodevelopmental disorder characterised by intellectual disability, distinctive facial features, and hypoplasia (underdevelopment) of the fifth fingernails or toenails. The gene is large and highly intolerant of loss-of-function variants, making it a frequent finding on diagnostic exome sequencing for unexplained developmental delay.
DSP at 6p24.3 encodes desmoplakin, a structural protein that anchors intermediate filaments to cell-cell junctions called desmosomes. Pathogenic variants in DSP are a recognised cause of arrhythmogenic right ventricular cardiomyopathy, a progressive heart-muscle disease that can present with life-threatening arrhythmias in young adults. Two genes implicated in Lafora disease - a severe progressive myoclonic epilepsy - also reside on chromosome 6: EPM2A at 6q24.3 and NHLRC1 at 6p22.3. Both encode proteins that regulate glycogen metabolism in the brain, and biallelic pathogenic variants lead to the accumulation of abnormal glycogen deposits (Lafora bodies) in neurons, resulting in seizures, cognitive decline, and early mortality. Early genetic diagnosis through the NHS can guide tailored seizure management and enable families to access specialist neurological support and counselling.
Chromosomal disorders
Unlike chromosomes 13, 18, and 21, whole-chromosome aneuploidy involving an extra or missing copy of chromosome 6 (trisomy 6 or monosomy 6) is almost invariably lethal in early pregnancy and is not seen in liveborn infants. As a result, there are no characteristic chromosomal syndromes arising from complete trisomy or monosomy of chromosome 6. When mosaic trisomy 6 - where only a subset of cells carry three copies - is detected prenatally on chorionic villus sampling, it often represents confined placental mosaicism rather than true foetal involvement, although careful postnatal follow-up and chromosomal microarray on cord blood or a postnatal sample are recommended to confirm the chromosomal constitution of the baby.
Small deletions or duplications involving specific regions of chromosome 6 can occur and may be detected through chromosomal microarray analysis, particularly in children undergoing investigation for developmental delay, congenital anomalies, or autism spectrum disorder. These copy-number variants are typically de novo (new in the affected individual) rather than inherited, although parental samples should be tested to determine recurrence risk for future pregnancies. The clinical significance of a particular 6p or 6q deletion or duplication depends on its size, the genes it encompasses, and whether those genes are known to be dosage-sensitive. For example, deletions affecting the HLA region can compromise immune function, while duplications encompassing neurodevelopmental genes may contribute to intellectual disability. Interpretation of these findings is undertaken by clinical scientists within NHS genomic laboratories, drawing on national chromosomal microarray interpretation networks within NHS Genomic Laboratory Hubs.
Because chromosome 6 does not harbour any known genomic imprinting disorders - conditions where the parent of origin of a deletion or duplication affects the clinical phenotype - uniparental disomy (inheriting both copies of chromosome 6 from one parent) is not typically associated with a recognisable syndrome. Nevertheless, if uniparental disomy 6 is discovered incidentally, genetic counselling is recommended to discuss any implications, including the possibility of unmasking a recessive condition if both copies carry the same pathogenic variant.
Prenatal screening & diagnosis
Chromosome 6 abnormalities are not part of routine antenatal screening in the NHS. Non-invasive prenatal testing (NIPT), offered from around 10 weeks of pregnancy to screen for the common aneuploidies (trisomies 21, 18, and 13), does not report on chromosome 6 unless there is an incidental finding of a sex-chromosome abnormality or other rare autosomal trisomy, which would typically prompt further counselling and diagnostic testing. The NHS Fetal Anomaly Screening Programme ultrasound scan at 18 to 21 weeks may identify structural anomalies that could be associated with underlying genetic conditions, and if a significant abnormality is detected, invasive diagnostic testing - chorionic villus sampling or amniocentesis - may be offered to obtain foetal cells for karyotyping or chromosomal microarray.
If a parent is known to carry a balanced translocation involving chromosome 6, or if there is a family history of a condition caused by a gene on chromosome 6, preconception or prenatal genetic counselling through a regional genetics service can discuss options including preimplantation genetic testing or prenatal diagnosis via direct gene sequencing on a chorionic villus or amniotic-fluid sample. For single-gene conditions such as hereditary haemochromatosis or Lafora disease, carrier testing and predictive testing are available, although these are typically undertaken postnatally given the late or variable onset of many chromosome 6 disorders. Families with a history of a known pathogenic variant in a gene such as HFE or EPM2A can be referred by their GP or specialist to their local clinical genetics service for tailored risk assessment and reproductive counselling.
Inheritance & recurrence
Most clinically significant abnormalities involving chromosome 6 arise de novo, meaning they occur for the first time in the affected individual and are not inherited from either parent. This applies to the majority of pathogenic variants in neurodevelopmental genes such as ARID1B and to most copy-number variants detected on chromosomal microarray. For de novo events, the recurrence risk in future pregnancies is typically low (often quoted as approximately 1 per cent, though this varies), accounting for the small possibility of parental germline mosaicism, although this figure should be discussed in the context of individual family circumstances during a clinical genetics consultation.
For autosomal recessive conditions - where both copies of a gene must carry a pathogenic variant for the disorder to manifest - such as Lafora disease (EPM2A or NHLRC1), hereditary haemochromatosis (HFE), or autosomal recessive polycystic kidney disease (PKHD1), the pattern of inheritance is predictable. If both parents are carriers (each carrying one pathogenic variant), there is a one-in-four (25 per cent) chance with each pregnancy that the child will inherit two pathogenic variants and be affected, a one-in-two (50 per cent) chance the child will be an unaffected carrier like the parents, and a one-in-four chance the child will inherit neither variant. Carrier testing and cascade screening for at-risk relatives are important components of management for families with recessive conditions, and NHS clinical genetics services can coordinate this process.
For autosomal dominant conditions, such as arrhythmogenic cardiomyopathy due to DSP variants, an affected individual has a 50 per cent chance of passing the pathogenic variant to each child. However, penetrance (the likelihood that someone carrying the variant will develop symptoms) and expressivity (the severity of those symptoms) can be variable, meaning that not everyone who inherits a dominant pathogenic variant will necessarily develop the full clinical picture, and some may remain asymptomatic. Genetic counselling, ideally before conception or early in pregnancy, allows families to explore reproductive options including preimplantation genetic testing if they wish to avoid passing on a known familial variant. NHS regional genetics services can arrange this testing and provide ongoing support tailored to the family's needs.
Frequently asked questions
Why is chromosome 6 so important for the immune system?
Chromosome 6 carries the HLA (human leukocyte antigen) complex at 6p21.3, which encodes proteins that present fragments of pathogens on the surface of cells, allowing immune cells to recognise and respond to infections. The extreme variability of HLA genes across human populations helps ensure that at least some individuals can mount effective immune responses to new threats. HLA typing is also crucial for matching organ and bone-marrow donors to recipients.
Can you have an extra or missing copy of chromosome 6?
Complete trisomy 6 (three copies) or monosomy 6 (one copy) is almost always incompatible with survival beyond early pregnancy and is not seen in liveborn babies. Very rarely, mosaic trisomy 6 (where only some cells have an extra copy) is detected prenatally, often confined to the placenta rather than the baby itself. Small deletions or duplications of parts of chromosome 6 can occur and may be identified through chromosomal microarray testing in children with developmental concerns.
What is hereditary haemochromatosis and how is it linked to chromosome 6?
Hereditary haemochromatosis is a condition in which the body absorbs too much iron from food, leading to iron overload in organs such as the liver, heart, and pancreas. The most common genetic cause is pathogenic variants in the HFE gene at 6p22.2 on chromosome 6. Two variants, p.C282Y and p.H63D, account for the majority of cases in people of Northern European ancestry. Early diagnosis through genetic testing and regular venesection (blood removal) can prevent complications and allow individuals to lead healthy lives.
If a genetic condition runs in my family and the gene is on chromosome 6, will my children definitely inherit it?
It depends on the inheritance pattern of the specific condition. For autosomal dominant conditions (where one altered copy of the gene causes the disorder), an affected parent has a 50 per cent chance of passing the variant to each child. For autosomal recessive conditions (where both gene copies must be altered), a child is only affected if they inherit a pathogenic variant from both parents. A clinical genetics appointment can clarify the inheritance pattern for your family's specific condition and discuss options such as carrier testing or prenatal diagnosis.
How would I find out if I or my child has a chromosome 6 abnormality?
Chromosome 6 abnormalities can be detected through several tests available on the NHS. Karyotyping (examining chromosomes under a microscope) and chromosomal microarray can identify deletions, duplications, or structural rearrangements. For suspected single-gene disorders, targeted gene testing or exome sequencing can identify pathogenic variants in specific genes on chromosome 6. Your GP or specialist can refer you to your regional clinical genetics service, where a genetic counsellor or consultant can discuss which test is most appropriate based on your clinical history and family background.
Launch-set genes on chromosome 6
Genes on this chromosome that currently have dedicated pages in the library. This list grows as we publish more.