UIMC1

ubiquitin interaction motif containing 1, the group of BRCA1 A complex

Basic information

Region (hg38): 5:176905005-177022633

Links

ENSG00000087206 ∙ NCBI:51720 ∙ OMIM:609433 ∙ HGNC:30298 ∙ Uniprot:Q96RL1 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• schizophrenia (No Known Disease Relationship), mode of inheritance: Unknown

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the UIMC1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the UIMC1 gene is commonly pathogenic or not.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous					2	2
missense			32	3	2	37
nonsense						0
start loss						0
frameshift			1			1
inframe indel						0
splice donor/acceptor (+/-2bp)		1				1
splice region						0
non coding						0
Total	0	1	33	3	4

Variants in UIMC1

This is a list of pathogenic ClinVar variants found in the UIMC1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
5-176905320-G-A		not specified	Uncertain significance (Nov 17, 2022)
5-176905430-C-T		not specified	Likely benign (Nov 22, 2021)
5-176906017-G-C		not specified	Uncertain significance (Oct 03, 2022)
5-176906032-G-A		not specified	Uncertain significance (Mar 23, 2022)
5-176906041-T-A		not specified	Uncertain significance (Dec 20, 2023)
5-176907139-C-G		not specified	Uncertain significance (Jul 14, 2023)
5-176908558-C-G		not specified	Uncertain significance (Sep 29, 2023)
5-176908564-T-G		not specified	Uncertain significance (Jun 22, 2021)
5-176908615-C-A		not specified	Uncertain significance (Sep 16, 2021)
5-176908629-G-C		not specified	Uncertain significance (Nov 21, 2022)
5-176908638-TG-T		Intellectual disability	Uncertain significance (Nov 09, 2021)
5-176908657-A-C		not specified	Uncertain significance (Sep 27, 2021)
5-176908695-C-T			Likely pathogenic (Mar 01, 2018)
5-176911315-C-T		not specified	Uncertain significance (Sep 14, 2022)
5-176911380-C-T		not specified	Uncertain significance (Aug 11, 2022)
5-176943355-C-G		not specified	Uncertain significance (Apr 04, 2024)
5-176943415-G-A		not specified	Uncertain significance (Feb 10, 2022)
5-176943429-G-C		not specified	Uncertain significance (Aug 10, 2023)
5-176943430-T-C		not specified	Uncertain significance (Apr 24, 2024)
5-176943463-T-C		not specified	Uncertain significance (Aug 12, 2021)
5-176951573-G-T		not specified	Benign (Dec 15, 2014)
5-176955994-G-A			Benign (Feb 26, 2021)
5-176958153-G-A		not specified	Uncertain significance (Aug 25, 2021)
5-176968617-A-G		not specified	Likely benign (Aug 19, 2016)
5-176968665-A-G		not specified	Uncertain significance (Feb 06, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
UIMC1	protein_coding	protein_coding	ENST00000377227	14	117629

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
8.28e-7	1.00	125708	0	40	125748	0.000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.715	340	379	0.897	0.0000191	4736
Missense in Polyphen		83	112.35	0.73876		1539
Synonymous	-0.242	139	135	1.03	0.00000691	1341
Loss of Function	3.27	17	39.1	0.435	0.00000211	463

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000869	0.0000869
Ashkenazi Jewish	0.000794	0.000794
East Asian	0.000327	0.000326
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000159	0.000149
Middle Eastern	0.000327	0.000326
South Asian	0.000166	0.000163
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Ubiquitin-binding protein (PubMed:24627472). Specifically recognizes and binds 'Lys-63'-linked ubiquitin (PubMed:19328070, Ref.37). Plays a central role in the BRCA1-A complex by specifically binding 'Lys-63'-linked ubiquitinated histones H2A and H2AX at DNA lesions sites, leading to target the BRCA1-BARD1 heterodimer to sites of DNA damage at double-strand breaks (DSBs). The BRCA1-A complex also possesses deubiquitinase activity that specifically removes 'Lys-63'-linked ubiquitin on histones H2A and H2AX. Also weakly binds monoubiquitin but with much less affinity than 'Lys-63'-linked ubiquitin. May interact with monoubiquitinated histones H2A and H2B; the relevance of such results is however unclear in vivo. Does not bind Lys-48'-linked ubiquitin. May indirectly act as a transcriptional repressor by inhibiting the interaction of NR6A1 with the corepressor NCOR1. {ECO:0000269|PubMed:12080054, ECO:0000269|PubMed:17525340, ECO:0000269|PubMed:17525341, ECO:0000269|PubMed:17525342, ECO:0000269|PubMed:17621610, ECO:0000269|PubMed:17643121, ECO:0000269|PubMed:19015238, ECO:0000269|PubMed:19202061, ECO:0000269|PubMed:19261748, ECO:0000269|PubMed:19328070, ECO:0000269|PubMed:24627472, ECO:0000269|Ref.37}.
• Pathway: Homologous recombination - Homo sapiens (human);HDR through Homologous Recombination (HR) or Single Strand Annealing (SSA);DNA Repair;Nonhomologous End-Joining (NHEJ);DNA Double-Strand Break Repair;Homology Directed Repair;Post-translational protein modification;Metabolism of proteins;G2/M DNA damage checkpoint;G2/M Checkpoints;Cell Cycle Checkpoints;Metalloprotease DUBs;Deubiquitination;Cell Cycle;Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks;DNA Double Strand Break Response;Processing of DNA double-strand break ends;ATM pathway (Consensus)

Recessive Scores

• pRec: 0.178

Intolerance Scores

• loftool: 0.809
• rvis_EVS: 0.07
• rvis_percentile_EVS: 59.11

Haploinsufficiency Scores

• pHI: 0.284
• hipred: Y
• hipred_score: 0.731
• ghis: 0.490

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: H
• gene_indispensability_pred: E
• gene_indispensability_score: 0.534

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Uimc1
• Phenotype: neoplasm; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); homeostasis/metabolism phenotype; cellular phenotype

Gene ontology

• Biological process: double-strand break repair;double-strand break repair via nonhomologous end joining;response to ionizing radiation;protein deubiquitination;positive regulation of DNA repair;negative regulation of transcription, DNA-templated;histone H2A K63-linked deubiquitination;signal transduction involved in G2 DNA damage checkpoint
• Cellular component: nucleus;nucleoplasm;nuclear body;BRCA1-A complex
• Molecular function: protein binding;histone binding;K63-linked polyubiquitin modification-dependent protein binding