TIFA

TRAF interacting protein with forkhead associated domain

Basic information

Region (hg38): 4:112272968-112285955

Links

ENSG00000145365

∙ NCBI:92610 ∙ OMIM:609028 ∙ HGNC:19075 ∙ Uniprot:Q96CG3 ∙ 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 TIFA gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TIFA 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						0
missense			4 clinvar			4
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	4	0	0

Variants in TIFA

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

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

Position	Phenotype	Significance	ClinVar
4-112278086-G-T	not specified	Uncertain significance (Jun 22, 2023)	2605108
4-112278125-C-T	not specified	Uncertain significance (Dec 19, 2022)	2337266
4-112278169-A-T	not specified	Uncertain significance (May 26, 2022)	2402051
4-112278233-C-T	not specified	Uncertain significance (Mar 18, 2024)	3326120
4-112278235-T-C	not specified	Uncertain significance (Apr 09, 2024)	3326119
4-112278335-A-C	not specified	Uncertain significance (Dec 17, 2021)	2218524

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TIFA	protein_coding	protein_coding	ENST00000361717	1	11362

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.125	0.788	125615	0	104	125719	0.000414

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.895	71	95.6	0.743	0.00000472	1219
Missense in Polyphen		23	29.093	0.79058		389
Synonymous	0.386	35	38.0	0.920	0.00000219	327
Loss of Function	1.37	2	5.45	0.367	4.02e-7	52

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000616	0.0000615
Ashkenazi Jewish	0.00	0.00
East Asian	0.000163	0.000163
Finnish	0.00	0.00
European (Non-Finnish)	0.0000747	0.0000703
Middle Eastern	0.000163	0.000163
South Asian	0.00301	0.00301
Other	0.00	0.00

dbNSFP

Source: dbNSFP

Function: FUNCTION: Adapter molecule that plays a key role in the activation of proinflammatory NF-kappa-B signaling following detection of bacterial pathogen-associated molecular pattern metabolites (PAMPs) (PubMed:12566447, PubMed:15492226, PubMed:26068852, PubMed:28877472, PubMed:28222186, PubMed:30111836). Promotes activation of an innate immune response by inducing the oligomerization and polyubiquitination of TRAF6, which leads to the activation of TAK1 and IKK through a proteasome-independent mechanism (PubMed:15492226, PubMed:26068852). TIFA-dependent innate immune response is triggered by ADP-D-glycero-beta-D-manno- heptose (ADP-Heptose), a potent PAMP present in all Gram-negative and some Gram-positive bacteria: ADP-Heptose is recognized by ALPK1, which phosphorylates TIFA at Thr-9, leading to TIFA homooligomerization and subsequent activation of proinflammatory NF-kappa-B signaling (PubMed:30111836). {ECO:0000269|PubMed:12566447, ECO:0000269|PubMed:15492226, ECO:0000269|PubMed:26068852, ECO:0000269|PubMed:28222186, ECO:0000269|PubMed:28877472, ECO:0000269|PubMed:30111836}.;
Pathway: Regulation of toll-like receptor signaling pathway;Interleukin-1 Induced Activation of NF-kappa-B;Simplified Depiction of MYD88 Distinct Input-Output Pathway;TNFalpha (Consensus)

Recessive Scores

pRec: 0.0854

Intolerance Scores

loftool: 0.550
rvis_EVS: -0.03
rvis_percentile_EVS: 51.4

Haploinsufficiency Scores

pHI: 0.0810
hipred: N
hipred_score: 0.445
ghis: 0.555

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.871

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Tifa
Phenotype

Gene ontology

Biological process: cytoplasmic pattern recognition receptor signaling pathway;I-kappaB kinase/NF-kappaB signaling;positive regulation of I-kappaB kinase/NF-kappaB signaling;innate immune response;protein homooligomerization
Cellular component: cytoplasm
Molecular function: protein binding