UGDH

protein-coding

UDP-glucose 6-dehydrogenase

Gene summary

The protein encoded by this gene converts UDP-glucose to UDP-glucuronate and thereby participates in the biosynthesis of glycosaminoglycans such as hyaluronan, chondroitin sulfate, and heparan sulfate. These glycosylated compounds are common components of the extracellular matrix and likely play roles in signal transduction, cell migration, and cancer growth and metastasis. The expression of this gene is up-regulated by transforming growth factor beta and down-regulated by hypoxia. Alternative splicing results in multiple transcript variants.[provided by RefSeq, May 2010]

MANE transcript

NM_003359.4

Inheritance

AR, AD

ClinVar variants

P:27U:63B:12

Top phenotype

Developmental and epileptic encephalopathy 84 (Jamuar syndrome)

gnomAD constraint

pLI —, LoF o/e 0.41

Max pathogenic AF

—

Genomic locus

chr4:39,498,755-39,528,311

External References & Databases

Ensembl (ENSG00000109814)

Transcript & Mutation Effects

hg38 • Region Span ~29.6 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

developmental and epileptic encephalopathy, 84STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0032918

Submitter: Labcorp Genetics (formerly Invitae)

developmental and epileptic encephalopathy, 84STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0032918

Submitter: PanelApp Australia

congenital heart diseaseNO_KNOWN

Inheritance Pattern: AD

Disease ID:MONDO:0005453

Submitter: ClinGen

*UGDH* was first reported in relation to autosomal dominant congenital heart disease in 2009 (Smith et al., PMID: 19506109). At least two unique missense variants were reported in three probands with atrioventricular septal defects (PMID: 19506109). This gene-disease relationship is also supported by expression data in mouse embryos and two zebrafish models (PMID: 11533493, 22815472, 22815472). In summary, the evidence supporting the relationship between *UGDH* and autosomal dominant congenital heart disease has been disputed and no valid evidence remains to support the claim. More evidence is needed to either support or entirely refute the role *UGDH* plays in this disease. This classification was approved by the ClinGen Congenital Heart Disease GCEP on the meeting date June 10th, 2024 (SOP Version 10).

developmental and epileptic encephalopathy, 84STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0032918

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Developmental and epileptic encephalopathy 84 (Jamuar syndrome)AR

Manifestation: Craniofacial; 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: 32001716

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to UGDH variants in ClinVar

7 Conditions Cataloged

Inborn genetic diseasesTotal: 35

not providedTotal: 25

Developmental and epileptic encephalopathy, 84Total: 25

Epileptic encephalopathyTotal: 23

UGDH-related disorderTotal: 5

not specifiedTotal: 1

West syndromeTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_003359.4. 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	9 clinvar		10
missense		22 clinvar	56 clinvar	3 clinvar		81
nonsense	1 clinvar	2 clinvar	1 clinvar			4
start loss						0
frameshift	1 clinvar	1 clinvar	1 clinvar			3
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	2	25	63	12	0	102

Highest pathogenic variant AF is 0.00020398729

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 58 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_003359.4	RefSeq	NP_003350.1	11	MANE Select
ENST00000316423.11	Ensembl	ENSP00000319501.6	11	MANE Select
NM_001184700.2	RefSeq	NP_001171629.1	10	Standard
NM_001184701.2	RefSeq	NP_001171630.1	9	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
ugdh	Danio rerio	Structure: atrioventricular valve Quality: aplastic abnormal

Gene / Model

Organism

Observed Phenotype

ugdh

Danio rerio

Structure: atrioventricular valve

Quality: aplastic

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Ascorbate and aldarate metabolism - Homo sapiens (human)
Amino sugar and nucleotide sugar metabolism - Homo sapiens (human)
Pentose and glucuronate interconversions - Homo sapiens (human)
Galactosemia III
Galactosemia II (GALK)

Biological Process

gastrulation with mouth forming second
UDP-glucose metabolic process
glycosaminoglycan biosynthetic process
UDP-glucuronate biosynthetic process
electron transport chain

Molecular Function

UDP-glucose 6-dehydrogenase activity
electron transfer activity
NAD binding

Cellular Component

nucleus
nucleoplasm
cytosol
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000316423
Coding exons: 11
Length: 29557
Individuals with no LoFs: 125708
Homozygous LoFs: 0
Heterozygous LoFs: 39
Defined: 125747
p: 0.000155

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.30	164	271	0.606	0.0000141	3247
Missense (PolyPhen)		45	120.06	0.3748		1479
Synonymous	1.00	78	90.1	0.866	0.00000442	945
Loss of Function	2.53	9	21.8	0.414	9.84e-7	290

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000067	0.000062	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000064	0.000054	rare
Finnish	0.000047	0.000046	rare
European (Non-Finnish)	0.00026	0.00025	rare
South Asian	0.00026	0.00026	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Involved in the biosynthesis of glycosaminoglycans; hyaluronan, chondroitin sulfate, and heparan sulfate.;

Recessive Scores

pRec: 0.110

Intolerance Scores

LoFtool: 0.461
RVIS EVS: -0.14
RVIS percentile EVS: 43.57

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.976

Gene Damage Prediction

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