UTRN

protein-coding

utrophin, the group of Zinc fingers ZZ-type

Gene summary

This gene shares both structural and functional similarities with the dystrophin gene. It contains an actin-binding N-terminus, a triple coiled-coil repeat central region, and a C-terminus that consists of protein-protein interaction motifs which interact with dystroglycan protein components. The protein encoded by this gene is located at the neuromuscular synapse and myotendinous junctions, where it participates in post-synaptic membrane maintenance and acetylcholine receptor clustering. Mouse studies suggest that this gene may serve as a functional substitute for the dystrophin gene and therefore, may serve as a potential therapeutic alternative to muscular dystrophy which is caused by mutations in the dystrophin gene. Alternative splicing of the utrophin gene has been described; however, the full-length nature of these variants has not yet been determined. [provided by RefSeq, Jul 2008]

Previous symbols:

DMDL

MANE transcript

NM_007124.3

Inheritance

—

ClinVar variants

P:1U:527B:64

Top phenotype

Duchenne muscular dystrophy

gnomAD constraint

pLI —, LoF o/e 0.35

Max pathogenic AF

—

Genomic locus

chr6:144,285,335-144,853,034

External References & Databases

Ensembl (ENSG00000152818)

Transcript & Mutation Effects

hg38 • Region Span ~567.7 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

schizophreniaNO_KNOWN

Inheritance Pattern: Unknown

Disease ID:MONDO:0005090

Submitter: Labcorp Genetics (formerly Invitae)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to UTRN variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 517

not providedTotal: 56

Duchenne muscular dystrophyTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_007124.3. 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			6 clinvar	13 clinvar	12 clinvar	31
missense			502 clinvar	32 clinvar	7 clinvar	541
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)		1 clinvar	18 clinvar			19
Total	0	1	527	45	19	592

Highest pathogenic variant AF is 0.000001260554

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 24 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_007124.3	RefSeq	NP_009055.2	74	MANE Select
ENST00000367545.8	Ensembl	ENSP00000356515.3	74	MANE Select
NM_001375323.1	RefSeq	NP_001362252.1	25	Standard
ENST00000367524.8	Ensembl	ENSP00000356494.4	24	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Primary Focal Segmental Glomerulosclerosis FSGS
agrin in postsynaptic differentiation

Biological Process

positive regulation of cell-matrix adhesion
muscle contraction
muscle organ development
neuromuscular junction development
response to denervation involved in regulation of muscle adaptation

Molecular Function

actin binding
integrin binding
protein binding
zinc ion binding
vinculin binding

Cellular Component

nucleoplasm
cytoplasm
cytoskeleton
plasma membrane
dystrophin-associated glycoprotein complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000367545
Coding exons: 74
Length: 567334
Individuals with no LoFs: 125471
Homozygous LoFs: 2
Heterozygous LoFs: 275
Defined: 125748
p: 0.00110

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.371	1723	1.77e+3	0.975	0.0000951	22728
Missense (PolyPhen)		609	736.16	0.82726		9512
Synonymous	0.105	642	645	0.995	0.0000356	6203
Loss of Function	8.61	73	206	0.354	0.0000113	2381

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00057	0.00055	rare
Latino/Admixed American	0.0016	0.0015	notable
Ashkenazi Jewish	0.00030	0.00030	rare
East Asian	0.0010	0.0010	notable
Finnish	0.00088	0.00088	rare
European (Non-Finnish)	0.0014	0.0013	notable
South Asian	0.00040	0.00039	rare
Other	0.0018	0.0018	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May play a role in anchoring the cytoskeleton to the plasma membrane. {ECO:0000250}.;

Recessive Scores

pRec: 0.561

Intolerance Scores

LoFtool: 0.595
RVIS EVS: -1.55
RVIS percentile EVS: 3.26

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.871

Gene Damage Prediction

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