NPLOC4

NPL4 homolog, ubiquitin recognition factor, the group of Zinc fingers

Basic information

Region (hg38): 17:81556887-81648465

Links

ENSG00000182446 ∙ NCBI:55666 ∙ OMIM:606590 ∙ HGNC:18261 ∙ Uniprot:Q8TAT6 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NPLOC4 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NPLOC4 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					1	1
missense			21	2	2	25
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	21	2	3

Variants in NPLOC4

This is a list of pathogenic ClinVar variants found in the NPLOC4 region.

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

Position	Type	Phenotype	Significance	ClinVar
17-81559289-G-C		not specified	Uncertain significance (Mar 23, 2022)
17-81559353-G-A			Benign (Jun 26, 2018)
17-81559359-G-A		not specified	Uncertain significance (Mar 16, 2024)
17-81559375-C-T		not specified	Uncertain significance (Sep 17, 2021)
17-81559378-C-T		not specified	Uncertain significance (Jun 13, 2022)
17-81559396-G-C			Likely benign (Nov 19, 2018)
17-81559406-G-A			Benign (Feb 23, 2018)
17-81565517-C-T		not specified	Uncertain significance (Sep 20, 2023)
17-81567475-G-A		not specified	Uncertain significance (Feb 16, 2023)
17-81569036-C-T		not specified	Uncertain significance (Nov 07, 2022)
17-81569071-G-T		not specified	Uncertain significance (Feb 23, 2023)
17-81569088-A-C		not specified	Uncertain significance (Nov 09, 2021)
17-81572047-C-A			Benign (Dec 31, 2019)
17-81572085-C-T		not specified	Likely benign (Apr 08, 2024)
17-81596166-A-G		not specified	Uncertain significance (Jul 26, 2022)
17-81604685-C-T		not specified	Uncertain significance (Mar 06, 2023)
17-81606704-G-A		not specified	Uncertain significance (Dec 19, 2022)
17-81606711-C-T		not specified	Uncertain significance (Sep 21, 2023)
17-81608811-C-G		not specified	Uncertain significance (Aug 17, 2022)
17-81610230-C-T		not specified	Uncertain significance (Dec 19, 2022)
17-81613349-C-T		not specified	Uncertain significance (Oct 25, 2022)
17-81613400-C-T		not specified	Uncertain significance (Jul 09, 2021)
17-81613411-T-C		not specified	Uncertain significance (Jun 29, 2022)
17-81613420-G-A		not specified	Likely benign (Oct 13, 2023)
17-81622177-C-G		not specified	Uncertain significance (Sep 22, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NPLOC4	protein_coding	protein_coding	ENST00000331134	17	91583

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.0000166	124634	0	4	124638	0.0000160

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.20	185	355	0.522	0.0000209	3975
Missense in Polyphen		42	141.4	0.29704		1562
Synonymous	-0.479	153	146	1.05	0.0000100	1133
Loss of Function	5.36	1	35.4	0.0283	0.00000183	407

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000290	0.0000290
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000265	0.0000265
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: The ternary complex containing UFD1, VCP and NPLOC4 binds ubiquitinated proteins and is necessary for the export of misfolded proteins from the ER to the cytoplasm, where they are degraded by the proteasome. The NPLOC4-UFD1-VCP complex regulates spindle disassembly at the end of mitosis and is necessary for the formation of a closed nuclear envelope (By similarity). Acts as a negative regulator of type I interferon production via the complex formed with VCP and UFD1, which binds to DDX58/RIG-I and recruits RNF125 to promote ubiquitination and degradation of DDX58/RIG-I (PubMed:26471729). {ECO:0000250|UniProtKB:Q9ES54, ECO:0000269|PubMed:26471729}.
• Pathway: Protein processing in endoplasmic reticulum - Homo sapiens (human);DNA Repair;Translesion Synthesis by POLH;Translesion synthesis by Y family DNA polymerases bypasses lesions on DNA template;DNA Damage Bypass (Consensus)

Intolerance Scores

• rvis_EVS: -0.71
• rvis_percentile_EVS: 14.57

Haploinsufficiency Scores

• pHI: 0.259
• hipred: Y
• hipred_score: 0.814
• ghis: 0.517

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.727

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Nploc4

Gene ontology

• Biological process: ubiquitin-dependent protein catabolic process;Golgi organization;ubiquitin-dependent ERAD pathway;retrograde protein transport, ER to cytosol;negative regulation of type I interferon production;negative regulation of RIG-I signaling pathway;error-free translesion synthesis
• Cellular component: nucleus;nucleoplasm;endoplasmic reticulum;cytosol;VCP-NPL4-UFD1 AAA ATPase complex;UFD1-NPL4 complex;nuclear outer membrane-endoplasmic reticulum membrane network
• Molecular function: protein binding;ubiquitin protein ligase binding;ubiquitin binding;metal ion binding