UBR7

protein-coding

ubiquitin protein ligase E3 component n-recognin 7, the group of Ubiquitin protein ligase E3 component n-recognins

Gene summary

This gene encodes a UBR box-containing protein that belongs to the E3 ubiquitin ligase family. The protein also contains a plant homeodomain (PHD) in the C-terminus. In mammals, the encoded protein recognizes N-degrons, the destabilizing N-terminal residues of short-lived proteins, which results in ubiquitinylation, and proteolysis via the proteasome. [provided by RefSeq, Jul 2016]

Previous symbols:

C14orf130

MANE transcript

NM_175748.4

Inheritance

ClinVar variants

P:9U:41B:9

Top phenotype

Li-Campeau syndrome

gnomAD constraint

pLI —, LoF o/e 0.21

Max pathogenic AF

—

Genomic locus

chr14:93,207,241-93,229,215

External References & Databases

Ensembl (ENSG00000012963)

Transcript & Mutation Effects

hg38 • Region Span ~22.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Li-Campeau syndromeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0030963

Submitter: PanelApp Australia

Li-Campeau syndromeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0030963

Submitter: G2P

Li-Campeau syndromeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0030963

Submitter: Labcorp Genetics (formerly Invitae)

intellectual disabilityLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0001071

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Li-Campeau syndromeAR

Manifestation: Cardiovascular; Craniofacial; Endocrine; Genitourinary; Neurologic; Musculoskeletal

Intervention: Cardiovascular; Endocrine

Rationale: The condition can involve congenital cardiac anomalies, and awareness may allow early management; Among other features, the condition can include hypothyroidism, and awareness may allow medical management

Refs: 33340455

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to UBR7 variants in ClinVar

6 Conditions Cataloged

not specifiedTotal: 34

Li-Campeau syndromeTotal: 9

not providedTotal: 7

Mild intellectual disabilityTotal: 1

Global developmental delayTotal: 1

Long QT syndromeTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_175748.4. 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				4 clinvar		4
missense			37 clinvar	5 clinvar		42
nonsense	1 clinvar	3 clinvar	1 clinvar			5
start loss						0
frameshift	2 clinvar	1 clinvar				3
splice donor/acceptor (+/-2bp)	2 clinvar		3 clinvar			5
Total	5	4	41	9	0	59

Highest pathogenic variant AF is 0.00000974777

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 30 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_175748.4	RefSeq	NP_786924.2	11	MANE Select
ENST00000013070.11	Ensembl	ENSP00000013070.6	11	MANE Select
ENST00000553674.1	Ensembl	ENSP00000450470.1	2	Standard
ENST00000553857.5	Ensembl	ENSP00000451785.1	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

biological_process
protein ubiquitination

Molecular Function

molecular_function
zinc ion binding
ubiquitin protein ligase activity

Cellular Component

cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000013070
Coding exons: 11
Length: 22161
Individuals with no LoFs: 125732
Homozygous LoFs: 0
Heterozygous LoFs: 16
Defined: 125748
p: 0.0000636

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.85	145	223	0.651	0.0000108	2821
Missense (PolyPhen)		38	89.644	0.4239		1195
Synonymous	1.04	68	79.9	0.851	0.00000403	712
Loss of Function	3.54	5	23.5	0.212	9.92e-7	311

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00035	0.00031	rare
Latino/Admixed American	0.000035	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000081	0.000079	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: E3 ubiquitin-protein ligase which is a component of the N-end rule pathway. Recognizes and binds to proteins bearing specific N-terminal residues that are destabilizing according to the N-end rule, leading to their ubiquitination and subsequent degradation. {ECO:0000250}.;

Recessive Scores

pRec: 0.118

Intolerance Scores

LoFtool: 0.470
RVIS EVS: 0.02
RVIS percentile EVS: 55.22

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.801

Gene Damage Prediction

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