UBE4A

ubiquitination factor E4A, the group of U-box domain containing|Armadillo like helical domain containing

Basic information

Region (hg38): 11:118359600-118399211

Links

ENSG00000110344

∙ NCBI:9354 ∙ OMIM:603753 ∙ HGNC:12499 ∙ Uniprot:Q14139 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

autosomal recessive non-syndromic intellectual disability (Supportive), mode of inheritance: AR
multiple congenital anomalies/dysmorphic syndrome (Limited), mode of inheritance: AR
neurodevelopmental disorder with hypotonia and gross motor and speech delay (Strong), mode of inheritance: AR
neurodevelopmental disorder with hypotonia and gross motor and speech delay (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neurodevelopmental disorder with hypotonia and gross motor and speech delay	AR	General	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	Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic	33420346

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the UBE4A gene.

Inborn_genetic_diseases (107 variants)
not_provided (20 variants)
Neurodevelopmental_disorder_with_hypotonia_and_gross_motor_and_speech_delay (5 variants)
UBE4A-related_disorder (5 variants)
not_specified (3 variants)
Neurodevelopmental_disorder (1 variants)
Retinitis_pigmentosa_11 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the UBE4A gene is commonly pathogenic or not. These statistics are base on transcript: NM_001204077.2. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous				7 clinvar	1 clinvar	8
missense			111 clinvar	4 clinvar		115
nonsense	2 clinvar	1 clinvar				3
start loss			1			1
frameshift	1 clinvar	3 clinvar				4
splice donor/acceptor (+/-2bp)		1 clinvar				1
Total	3	5	112	11	1

Highest pathogenic variant AF is 0.00000478839

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
UBE4A	protein_coding	protein_coding	ENST00000431736	19	39627

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.109	0.891	125727	0	17	125744	0.0000676

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.21	436	587	0.743	0.0000312	7149
Missense in Polyphen		90	183.05	0.49168		2289
Synonymous	1.35	180	205	0.880	0.00000984	1993
Loss of Function	5.11	13	53.3	0.244	0.00000300	601

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000178	0.000178
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000937	0.0000924
European (Non-Finnish)	0.0000706	0.0000703
Middle Eastern	0.00	0.00
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

Function: FUNCTION: Ubiquitin-protein ligase that probably functions as an E3 ligase in conjunction with specific E1 and E2 ligases. May also function as an E4 ligase mediating the assembly of polyubiquitin chains on substrates ubiquitinated by another E3 ubiquitin ligase. Mediates 'Lys-48'-linked polyubiquitination of substrates. {ECO:0000250|UniProtKB:E9Q735, ECO:0000250|UniProtKB:P54860}.;
Pathway: Ubiquitin mediated proteolysis - Homo sapiens (human);miR-targeted genes in epithelium - TarBase;miR-targeted genes in lymphocytes - TarBase;miR-targeted genes in muscle cell - TarBase;Immune System;Adaptive Immune System;Antigen processing: Ubiquitination & Proteasome degradation;Class I MHC mediated antigen processing & presentation (Consensus)

Recessive Scores

pRec: 0.0990

Intolerance Scores

loftool: 0.600
rvis_EVS: -1.09
rvis_percentile_EVS: 7.15

Haploinsufficiency Scores

pHI: 0.206
hipred: Y
hipred_score: 0.639
ghis: 0.531

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.869

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Ube4a
Phenotype

Gene ontology

Biological process: protein polyubiquitination;ubiquitin-dependent protein catabolic process;ubiquitin-dependent ERAD pathway
Cellular component: ubiquitin ligase complex;nucleus;cytoplasm
Molecular function: protein binding;ubiquitin-ubiquitin ligase activity