PMM2

phosphomannomutase 2, the group of HAD Asp-based non-protein phosphatases

Basic information

Region (hg38): 16:8788822-8862534

Previous symbols: [ "CDG1" ]

Links

ENSG00000140650 ∙ NCBI:5373 ∙ OMIM:601785 ∙ HGNC:9115 ∙ Uniprot:O15305 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• congenital disorder of glycosylation type I (Definitive), mode of inheritance: AR
• SRD5A3-congenital disorder of glycosylation (Definitive), mode of inheritance: AR
• PMM2-congenital disorder of glycosylation (Strong), mode of inheritance: AR
• PMM2-congenital disorder of glycosylation (Supportive), mode of inheritance: AR
• PMM2-congenital disorder of glycosylation (Definitive), mode of inheritance: AR
• PMM2-congenital disorder of glycosylation (Strong), mode of inheritance: AR
• PMM2-congenital disorder of glycosylation (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Congenital disorder of glycosylation, type Ia	AR	Biochemical; Hematologic	Medical management (eg, with epalrestat) has been described as demonstrating benefit in terms of both laboratory and clinical parameters; Awareness of coagulopathies may be beneficial in terms of medical management, especially in situations such as surgery	Biochemical; Cardiovascular; Gastrointestinal; Hematologic; Musculoskeletal; Neurologic; Ophthalmologic; Renal	6543331; 3703266; 2890978; 3162953; 2466439; 1929507; 1293380; 8256592; 9140401; 10571009; 10527672; 10801058; 11916319; 11134235; 11343337; 11596651; 12905014; 17158594; 18203160; 20301507; 20301289; 21937992; 34652821
Hepatic-metabolized agents should be avoided

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PMM2 gene.

• PMM2-congenital disorder of glycosylation (583 variants)
• not provided (137 variants)
• not specified (42 variants)
• Inborn genetic diseases (41 variants)
• Congenital disorder of glycosylation (6 variants)
• PMM2-related condition (5 variants)
• See cases (3 variants)
• Congenital cerebellar hypoplasia (2 variants)
• Cerebellar ataxia (2 variants)
• 6 conditions (2 variants)
• Intellectual disability (2 variants)
• Diabetes mellitus;Congenital cerebellar hypoplasia;Cerebellar ataxia;Muscular dystrophy (1 variants)
• Premature ovarian failure (1 variants)
• Congenital cerebellar hypoplasia;Diabetes mellitus;Muscular dystrophy;Cerebellar ataxia (1 variants)
• Pituitary stalk interruption syndrome (1 variants)
• Congenital disorder of glycosylation type I (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PMM2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			3	110	1	114
missense	17	52	102	2		173
nonsense	8	22				30
start loss		1	1			2
frameshift	14	21	2			37
inframe indel	1		2			3
splice donor/acceptor (+/-2bp)	9	22	1			32
splice region		2	9	32		43
non coding	1	3	81	72	36	193
Total	50	121	192	184	37

Highest pathogenic variant AF is 0.000243

Variants in PMM2

This is a list of pathogenic ClinVar variants found in the PMM2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
16-8795961-C-T		not specified	Uncertain significance (Jun 24, 2022)
16-8795968-T-C		not specified	Uncertain significance (Jan 19, 2022)
16-8796011-G-A		not specified	Uncertain significance (Dec 28, 2022)
16-8796055-C-T		not specified	Likely benign (Dec 16, 2023)
16-8796067-A-G		not specified	Uncertain significance (Feb 21, 2024)
16-8796094-G-C		not specified	Likely benign (Jun 28, 2022)
16-8796096-T-G		not specified	Uncertain significance (Dec 14, 2021)
16-8796142-C-T		not specified	Uncertain significance (Apr 13, 2023)
16-8796150-C-G		not specified	Uncertain significance (Aug 11, 2022)
16-8796167-C-A		not specified	Uncertain significance (Jul 16, 2021)
16-8796169-A-C		not specified	Uncertain significance (Jul 19, 2022)
16-8796170-C-G		not specified	Uncertain significance (Mar 02, 2023)
16-8796173-G-A		not specified	Uncertain significance (Aug 29, 2022)
16-8796196-A-C		not specified	Uncertain significance (Dec 20, 2021)
16-8796256-G-T		not specified	Uncertain significance (Apr 25, 2023)
16-8796265-G-A		not specified	Uncertain significance (Feb 22, 2023)
16-8796273-A-T		not specified	Uncertain significance (May 11, 2022)
16-8796287-C-T		not specified	Uncertain significance (Feb 03, 2022)
16-8796316-T-C		not specified	Uncertain significance (Jan 09, 2024)
16-8796361-T-C		not specified	Uncertain significance (May 03, 2023)
16-8796390-G-A		not specified	Likely benign (Feb 06, 2024)
16-8796399-G-C		not specified	Uncertain significance (Sep 28, 2021)
16-8796423-C-G		not specified	Uncertain significance (Dec 19, 2023)
16-8796565-C-G		not specified	Uncertain significance (Jan 03, 2024)
16-8796586-G-A		not specified	Uncertain significance (Aug 02, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PMM2	protein_coding	protein_coding	ENST00000268261	8	60509

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.41e-17	0.000426	125644	0	104	125748	0.000414

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-1.39	186	140	1.33	0.00000772	1620
Missense in Polyphen		63	57.35	1.0985		660
Synonymous	-1.24	68	56.2	1.21	0.00000358	431
Loss of Function	-1.51	22	15.6	1.41	8.29e-7	177

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00128	0.00128
Ashkenazi Jewish	0.0000993	0.0000992
East Asian	0.000435	0.000435
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000339	0.000334
Middle Eastern	0.000435	0.000435
South Asian	0.000229	0.000229
Other	0.00100	0.000978

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in the synthesis of the GDP-mannose and dolichol-phosphate-mannose required for a number of critical mannosyl transfer reactions. {ECO:0000250}.
• Disease: DISEASE: Congenital disorder of glycosylation 1A (CDG1A) [MIM:212065]: A form of congenital disorder of glycosylation, a multisystem disorder caused by a defect in glycoprotein biosynthesis and characterized by under-glycosylated serum glycoproteins. Congenital disorders of glycosylation result in a wide variety of clinical features, such as defects in the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. The broad spectrum of features reflects the critical role of N-glycoproteins during embryonic development, differentiation, and maintenance of cell functions. CDG1A is an autosomal recessive disorder characterized by a severe encephalopathy with axial hypotonia, abnormal eye movement, and pronounced psychomotor retardation, as well as peripheral neuropathy, cerebellar hypoplasia, and retinitis pigmentosa. Patients show a peculiar distribution of subcutaneous fat, nipple retraction, and hypogonadism. {ECO:0000269|PubMed:10066032, ECO:0000269|PubMed:10527672, ECO:0000269|PubMed:10571956, ECO:0000269|PubMed:10602363, ECO:0000269|PubMed:10801058, ECO:0000269|PubMed:11058895, ECO:0000269|PubMed:11058896, ECO:0000269|PubMed:11350185, ECO:0000269|PubMed:12357336, ECO:0000269|PubMed:15844218, ECO:0000269|PubMed:17307006, ECO:0000269|PubMed:9140401, ECO:0000269|PubMed:9497260, ECO:0000269|PubMed:9781039}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Fructose and mannose metabolism - Homo sapiens (human);Amino sugar and nucleotide sugar metabolism - Homo sapiens (human);Fructose Mannose metabolism;Post-translational protein modification;Metabolism of proteins;Synthesis of GDP-mannose;Synthesis of substrates in N-glycan biosythesis;Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein;Asparagine N-linked glycosylation;GDP-mannose biosynthesis (Consensus)

Recessive Scores

• pRec: 0.361

Intolerance Scores

• loftool: 0.207
• rvis_EVS: -0.56
• rvis_percentile_EVS: 19.73

Haploinsufficiency Scores

• pHI: 0.305
• hipred: N
• hipred_score: 0.466
• ghis: 0.563

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.983

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Pmm2
• Phenotype: cellular phenotype; homeostasis/metabolism phenotype; craniofacial phenotype; muscle phenotype; growth/size/body region phenotype; embryo phenotype; skeleton phenotype; renal/urinary system phenotype; immune system phenotype; vision/eye phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; liver/biliary system phenotype

Zebrafish Information Network

• Gene name: pmm2
• Affected structure: ceratohyal cartilage
• Phenotype tag: abnormal
• Phenotype quality: morphology

Gene ontology

• Biological process: mannose metabolic process;protein glycosylation;protein N-linked glycosylation;GDP-mannose biosynthetic process;protein targeting to ER
• Cellular component: nucleus;cytosol;neuronal cell body
• Molecular function: phosphomannomutase activity;protein binding