TNIP1

protein-coding

TNFAIP3 interacting protein 1

Gene summary

This gene encodes an A20-binding protein which plays a role in autoimmunity and tissue homeostasis through the regulation of nuclear factor kappa-B activation. Mutations in this gene have been associated with psoriatic arthritis, rheumatoid arthritis, and systemic lupus erythematosus. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2011]

MANE transcript

NM_006058.5

Inheritance

—

ClinVar variants

U:108B:11

Top phenotype

systemic lupus erythematosus

gnomAD constraint

pLI —, LoF o/e 0.22

Max pathogenic AF

—

Genomic locus

chr5:151,029,945-151,093,577

External References & Databases

Ensembl (ENSG00000145901)

Transcript & Mutation Effects

hg38 • Region Span ~63.6 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

systemic lupus erythematosusSUPPORTIVE

Inheritance Pattern: Unknown

Disease ID:MONDO:0007915

Submitter: Orphanet

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TNIP1 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 94

not providedTotal: 8

Amyotrophic lateral sclerosisTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_006058.5. 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			2 clinvar	3 clinvar	1 clinvar	6
missense			95 clinvar	6 clinvar	1 clinvar	102
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			10 clinvar			10
Total	0	0	108	9	2	119

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 143 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_006058.5	RefSeq	NP_006049.3	17	MANE Select
ENST00000521591.6	Ensembl	ENSP00000430760.1	17	MANE Select
NM_001252385.2	RefSeq	NP_001239314.1	16	Standard
NM_001252386.2	RefSeq	NP_001239315.1	16	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Rac1-Pak1-p38-MMP-2 pathway
Post-translational protein modification
Metabolism of proteins
EGFR1
Ovarian tumor domain proteases

Biological Process

MyD88-dependent toll-like receptor signaling pathway
translation
defense response
inflammatory response
leukocyte cell-cell adhesion

Molecular Function

protein binding
identical protein binding
mitogen-activated protein kinase binding

Cellular Component

nucleoplasm
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000389378
Coding exons: 17
Length: 63633
Individuals with no LoFs: 125735
Homozygous LoFs: 0
Heterozygous LoFs: 12
Defined: 125747
p: 0.0000477

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.757	325	366	0.889	0.0000227	4116
Missense (PolyPhen)		153	189.33	0.80813		2094
Synonymous	0.454	135	142	0.952	0.00000821	1220
Loss of Function	4.38	8	36.6	0.219	0.00000179	434

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000088	0.000088	rare
South Asian	0	0.0	absent
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Inhibits NF-kappa-B activation and TNF-induced NF-kappa- B-dependent gene expression by regulating A20/TNFAIP3-mediated deubiquitination of IKBKG; proposed to link A20/TNFAIP3 to ubiquitinated IKBKG. Involved in regulation of EGF-induced ERK1/ERK2 signaling pathway; blocks MAPK3/MAPK1 nuclear translocation and MAPK1-dependent transcription. Increases cell surface CD4(T4) antigen expression. Involved in the anti- inflammatory response of macrophages and positively regulates TLR- induced activation of CEBPB. Involved in the prevention of autoimmunity; this function implicates binding to polyubiquitin. Involved in leukocyte integrin activation during inflammation; this function is mediated by association with SELPLG and dependent on phosphorylation by SRC-family kinases. Interacts with HIV-1 matrix protein and is packaged into virions and overexpression can inhibit viral replication. May regulate matrix nuclear localization, both nuclear import of PIC (Preintegration complex) and export of GAG polyprotein and viral genomic RNA during virion production. In case of infection, promotes association of IKBKG with Shigella flexneri E3 ubiquitin-protein ligase ipah9.8 p which in turn promotes polyubiquitination of IKBKG leading to its proteasome-dependent degradation and thus is perturbing NF-kappa-B activation during bacterial infection. {ECO:0000269|PubMed:12220502, ECO:0000269|PubMed:16684768, ECO:0000269|PubMed:17016622, ECO:0000269|PubMed:17632516, ECO:0000269|PubMed:20010814}.;

Recessive Scores

pRec: 0.158

Intolerance Scores

LoFtool: 0.534
RVIS EVS: 0.67
RVIS percentile EVS: 84.68

Essentials

Essential (CRISPR): E
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.491

Gene Damage Prediction

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