PGM2L1

protein-coding

phosphoglucomutase 2 like 1

Gene summary

Enables glucose-1,6-bisphosphate synthase activity and phosphoglucomutase activity. Predicted to be involved in glucose metabolic process. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_173582.6

Inheritance

ClinVar variants

P:11U:57B:10

Top phenotype

Neurodevelopmental disorder with hypotonia, dysmorphic facies, and skin abnormalities

gnomAD constraint

pLI —, LoF o/e 0.29

Max pathogenic AF

—

Genomic locus

chr11:74,330,316-74,398,433

External References & Databases

Ensembl (ENSG00000165434)

Transcript & Mutation Effects

hg38 • Region Span ~68.1 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

neurodevelopmental disorder with hypotonia, dysmorphic facies, and skin abnormalitiesSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0859347

Submitter: PanelApp Australia

neurodevelopmental disorder with hypotonia, dysmorphic facies, and skin abnormalitiesSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0859347

Submitter: Labcorp Genetics (formerly Invitae)

neurodevelopmental disorder with hypotonia, dysmorphic facies, and skin abnormalitiesSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0859347

Submitter: G2P

Clinical Genomic Database (CGD)

Neurodevelopmental disorder with hypotonia, dysmorphic facies, and skin abnormalitiesAR

Manifestation: Craniofacial; Dermatologic; Musculoskeletal; Neurologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 33979636

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PGM2L1 variants in ClinVar

6 Conditions Cataloged

Inborn genetic diseasesTotal: 51

not providedTotal: 15

Neurodevelopmental disorder with hypotonia, dysmorphic facies, and skin abnormalitiesTotal: 8

not specifiedTotal: 4

PGM2L1-related disordersTotal: 1

PGM2L1-related disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_173582.6. 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	8 clinvar		9
missense			52 clinvar	2 clinvar		54
nonsense	3 clinvar					3
start loss						0
frameshift	5 clinvar	3 clinvar				8
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	8	3	57	10	0	78

Highest pathogenic variant AF is 0.000017106673

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 20 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_173582.6	RefSeq	NP_775853.2	14	MANE Select
ENST00000298198.5	Ensembl	ENSP00000298198.4	14	MANE Select
ENST00000867622.1	Ensembl	ENSP00000537681.1	15	Standard
ENST00000867622.2	Ensembl	ENSP00000537681.1	15	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Starch and sucrose metabolism - Homo sapiens (human)
Glycogen synthetase deficiency
Glycogenosis, Type III. Cori disease, Debrancher glycogenosis
Mucopolysaccharidosis VI. Sly syndrome
Sucrase-isomaltase deficiency

Biological Process

glycogen biosynthetic process
glycogen catabolic process
galactose catabolic process
canonical glycolysis

Molecular Function

phosphoglucomutase activity
metal ion binding
glucose-1,6-bisphosphate synthase activity

Cellular Component

cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000298198
Coding exons: 14
Length: 68156
Individuals with no LoFs: 125712
Homozygous LoFs: 0
Heterozygous LoFs: 36
Defined: 125748
p: 0.000143

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.24	214	328	0.652	0.0000164	4088
Missense (PolyPhen)		84	141.61	0.59319		1701
Synonymous	1.14	98	113	0.864	0.00000537	1169
Loss of Function	3.72	9	31.5	0.285	0.00000150	411

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00019	0.00018	rare
Latino/Admixed American	0.00012	0.00012	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.000054	0.000054	rare
Finnish	0.000093	0.000092	rare
European (Non-Finnish)	0.00020	0.00019	rare
South Asian	0.00010	0.000098	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Glucose 1,6-bisphosphate synthase using 1,3- bisphosphoglycerate as a phosphate donor and a series of 1- phosphate sugars as acceptors, including glucose 1-phosphate, mannose 1-phosphate, ribose 1-phosphate and deoxyribose 1- phosphate. 5 or 6-phosphosugars are bad substrates, with the exception of glucose 6-phosphate. Also synthesizes ribose 1,5- bisphosphate. Has only low phosphopentomutase and phosphoglucomutase activities. {ECO:0000269|PubMed:17804405, ECO:0000269|PubMed:18927083}.;

Recessive Scores

pRec: 0.204

Intolerance Scores

LoFtool: 0.707
RVIS EVS: 0.51
RVIS percentile EVS: 80.2

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.152

Gene Damage Prediction

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