PMM1

protein-coding

phosphomannomutase 1, the group of HAD Asp-based non-protein phosphatases

Gene summary

Phosphomannomutase catalyzes the conversion between D-mannose 6-phosphate and D-mannose 1-phosphate which is a substrate for GDP-mannose synthesis. GDP-mannose is used for synthesis of dolichol-phosphate-mannose, which is essential for N-linked glycosylation and thus the secretion of several glycoproteins as well as for the synthesis of glycosyl-phosphatidyl-inositol (GPI) anchored proteins. [provided by RefSeq, Jul 2008]

MANE transcript

NM_002676.3

Inheritance

—

ClinVar variants

P:1U:52B:1

Top phenotype

Global developmental delay, absent or hypoplastic corpus callosum, and dysmorphic facies

gnomAD constraint

pLI —, LoF o/e 0.71

Max pathogenic AF

—

Genomic locus

chr22:41,576,900-41,589,871

External References & Databases

Ensembl (ENSG00000100417)

Transcript & Mutation Effects

hg38 • Region Span ~13.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PMM1 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 46

not providedTotal: 1

Global developmental delay, absent or hypoplastic corpus callosum, and dysmorphic faciesTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002676.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	1 clinvar		2
missense		1 clinvar	48 clinvar			49
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	1	52	1	0	54

Highest pathogenic variant AF is 6.8439897e-7

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 54 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_002676.3	RefSeq	NP_002667.2	8	MANE Select
ENST00000216259.8	Ensembl	ENSP00000216259.7	8	MANE Select
ENST00000414636.1	Ensembl	ENSP00000400889.1	3	Standard
ENST00000896615.1	Ensembl	ENSP00000566674.1	8	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Fructose and mannose metabolism - Homo sapiens (human)
Amino sugar and nucleotide sugar metabolism - Homo sapiens (human)
Fructose intolerance, hereditary
Fructose and Mannose Degradation
Fructosuria

Biological Process

mannose metabolic process
protein N-linked glycosylation
GDP-mannose biosynthetic process
protein targeting to ER
cellular response to leukemia inhibitory factor

Molecular Function

phosphomannomutase activity
protein binding
metal ion binding

Cellular Component

cytosol
neuronal cell body

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000216259
Coding exons: 8
Length: 12997
Individuals with no LoFs: 125676
Homozygous LoFs: 0
Heterozygous LoFs: 72
Defined: 125748
p: 0.000286

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.840	137	168	0.817	0.0000106	1721
Missense (PolyPhen)		40	68.615	0.58297		643
Synonymous	0.123	74	75.4	0.982	0.00000533	506
Loss of Function	1.07	11	15.5	0.708	9.28e-7	157

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.00061	0.00061	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00099	0.00098	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00018	0.00018	rare
South Asian	0.00023	0.00023	rare
Other	0.00066	0.00065	rare

dbNSFP Gene Annotations

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. In addition, may be responsible for the degradation of glucose-1,6-bisphosphate in ischemic brain. {ECO:0000269|PubMed:16540464}.;

Recessive Scores

pRec: 0.233

Intolerance Scores

LoFtool: 0.321
RVIS EVS: -0.4
RVIS percentile EVS: 26.53

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.987

Gene Damage Prediction

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