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PMM2

phosphomannomutase 2

The PMM2 gene provides instructions for producing the phosphomannomutase 2 enzyme, which plays a critical role in glycosylation, a vital biological process for modifying proteins. PMM2 is integral to the initial steps of glycosylation, a process that attaches sugar molecules to proteins, enabling them to perform diverse functions within the body.

Chromosome 16p13.2 Autosomal recessive HGNC:9115 Tier C
PMM2 16p13.2 p arm q arm 16

PMM2 is located on the short (p) arm of chromosome 16, at band 16p13.2. Arm ratio per GRCh38 - banding schematic.

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Clinical tests that include this

Carrier Screening panel
PMM2 is 1 of 1,008 genes on this panel
Expanded carrier screening for recessive and X-linked conditions

Overview

The PMM2 gene, also known as phosphomannomutase 2, is crucial for human health, primarily due to its involvement in glycosylation. This fundamental biological process involves the attachment of sugar molecules, known as oligosaccharides, to proteins. Proper glycosylation is essential for many proteins to function correctly and for overall cellular health. Dysregulation of this process, often due to variants in genes like PMM2, can lead to a range of inherited disorders.

What the gene does

The PMM2 gene encodes the enzyme phosphomannomutase 2, which acts as a catalyst in a specific step of the glycosylation pathway. This enzyme facilitates the conversion of mannose-6-phosphate to mannose-1-phosphate. Subsequently, mannose-1-phosphate is transformed into GDP-mannose. This GDP-mannose then serves as a donor molecule, transferring a mannose sugar unit to a growing oligosaccharide chain. Once the oligosaccharide reaches its correct size and structure, it can be attached to a protein, enabling the protein to perform its specialised biological roles. This modification is critical for a wide variety of protein functions across different physiological systems.

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Chromosome location

The PMM2 gene is located on chromosome 16, specifically at position 16p13.2. This location refers to the short (p) arm of chromosome 16, within region 13 and band 2. The precise genomic coordinates help in identifying the gene's exact position within the human genome.

Protein structure

Domain architecture has not been experimentally characterised in detail for this protein.

Key variants

Genetic variations within the PMM2 gene can alter the function of the phosphomannomutase 2 enzyme. These changes can range from single nucleotide substitutions to larger deletions or insertions, impacting the enzyme's ability to participate in glycosylation. Over 115 distinct pathogenic variants have been identified that are associated with clinical conditions.

The table below shows the top 10 pathogenic or likely-pathogenic variants currently classified in ClinVar for PMM2.
View all on ClinVar →

Sample of pathogenic variants

10 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.

Variant (HGVS) Protein change Classification Evidence Associated condition
c.179-1G>C
single nucleotide variant
 - Pathogenic/Likely pathogenic ★★☆☆ PMM2-congenital disorder of glycosylation
c.193G>A
single nucleotide variant
 p.Asp65Asn Pathogenic/Likely pathogenic ★★☆☆ PMM2-congenital disorder of glycosylation
c.253C>T
single nucleotide variant
 p.Gln85Ter Pathogenic/Likely pathogenic ★★☆☆ PMM2-congenital disorder of glycosylation
c.34_36delinsTAA
Indel
 p.Asp12Ter Pathogenic/Likely pathogenic ★★☆☆ PMM2-congenital disorder of glycosylation
c.385G>C
single nucleotide variant
 p.Val129Leu Pathogenic/Likely pathogenic ★★☆☆ PMM2-congenital disorder of glycosylation
c.64C>T
single nucleotide variant
 p.Gln22Ter Pathogenic ★★☆☆ PMM2-congenital disorder of glycosylation
c.667G>A
single nucleotide variant
 p.Asp223Asn Pathogenic/Likely pathogenic ★★☆☆ PMM2-congenital disorder of glycosylation
c.669C>A
single nucleotide variant
 p.Asp223Glu Pathogenic/Likely pathogenic ★★☆☆ PMM2-congenital disorder of glycosylation
c.715A>T
single nucleotide variant
 p.Arg239Trp Pathogenic ★★☆☆ PMM2-congenital disorder of glycosylation
c.79G>T
single nucleotide variant
 p.Glu27Ter Pathogenic/Likely pathogenic ★★☆☆ PMM2-congenital disorder of glycosylation

Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.

Associated conditions

Variants in the PMM2 gene are primarily associated with Congenital disorder of glycosylation Ia, also known as PMM2-CDG. This is an autosomal recessive condition, meaning an individual must inherit two copies of a pathogenic variant (one from each parent) to develop the disorder. It is characterised by a range of symptoms including developmental delay, reduced muscle tone, and an unusual fat distribution.

Inheritance pattern

Conditions caused by pathogenic PMM2 variants typically follow autosomal recessive inheritance.

♀ Carrier parent 1 altered copy ♂ Carrier parent 1 altered copy Affected Carrier Carrier Unaffected Affected Carrier Unaffected Circles = females · Squares = males

When both parents are carriers, each child has a 25% chance of being affected, 50% of being a carrier, and 25% of being unaffected.

Carrier frequency by population How common is heterozygous PMM2 carrier status across ancestry groups?

UK clinical status

The PMM2 gene is included in several NHS England Genomic Medicine Service clinical panels, indicating its recognised clinical significance within the UK healthcare system. These panels include 'Congenital disorders of glycosylation', 'Congenital hyperinsulinism', 'Intellectual disability', and 'Undiagnosed metabolic disorders', among others, all listed with a 'green' status, signifying that variants in PMM2 are considered causally associated with these conditions.

Green-listed
High evidence · clinically actionable in NHS testing
Included in NHS GMS signed-off panels
Congenital hyperinsulinism · R144 NHS GMS → Fetal anomalies · R21 NHS GMS → Hereditary neuropathy or pain disorder · R78 NHS GMS → Likely inborn error of metabolism · R98 NHS GMS → Primary lymphoedema · R136 NHS GMS → Congenital disorders of glycosylation NHS GMS → DDG2P NHS GMS → Early onset or syndromic epilepsy NHS GMS →
NHS Genomic Medicine Service Jeen carrier screening

Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory

Frequently asked questions

What is the role of the PMM2 gene?

The PMM2 gene provides instructions for the phosphomannomutase 2 enzyme, which is vital for glycosylation. This enzyme helps attach sugar molecules to proteins, a process essential for proteins to function correctly throughout the body.

What condition is associated with PMM2 gene variants?

Pathogenic variants in the PMM2 gene are primarily associated with Congenital disorder of glycosylation Ia (PMM2-CDG). This is an inherited condition affecting development and various bodily functions.

How is Congenital disorder of glycosylation Ia inherited?

Congenital disorder of glycosylation Ia follows an autosomal recessive inheritance pattern. This means an individual must inherit two copies of a pathogenic PMM2 variant, one from each parent, to develop the condition.

References

  1. de la Morena-Barrio ME, Hernández-Caselles T, Corral J. GPI-anchor and GPI-anchored protein expression in PMM2-CDG patients. Orphanet journal of rare diseases. 2013. PMID: 24139637
  2. Grünewald S. The clinical spectrum of phosphomannomutase 2 deficiency (CDG-Ia). Biochimica et biophysica acta. 2009. PMID: 19272306
  3. Freeze HH. Towards a therapy for phosphomannomutase 2 deficiency, the defect in CDG-Ia patients. Biochimica et biophysica acta. 2009. PMID: 19339218
  4. Haeuptle MA, Hennet T. Congenital disorders of glycosylation: an update on defects affecting the biosynthesis of dolichol-linked oligosaccharides. Human mutation. 2009. PMID: 19862844
  5. Gao N, Shang J, Lehrman MA. Analysis of glycosylation in CDG-Ia fibroblasts by fluorophore-assisted carbohydrate electrophoresis: implications for extracellular glucose and intracellular mannose 6-phosphate. The Journal of biological chemistry. 2005. PMID: 15708848
  6. Adam MP, Bick S, Mirzaa GM. PMM2-CDG. 1993. PMID: 20301289
Educational content. This page is not medical or genetic advice, is not individually reviewed by a clinician for each reader, and should not replace a consultation with a qualified healthcare professional or genetic counsellor. If you are considering genetic testing or acting on a test result, book a consultation.
Data sources Last updated 11 October 2026. Content compiled from HGNC · MedlinePlus Genetics · ClinGen · Genomics England PanelApp · NHS National Genomic Test Directory · ClinVar · UniProt · AlphaFold .