TIFAB

Summary

TIFAB (TIFA inhibitor, HGNC:34024) is a protein-coding gene on chromosome 5q31.1, encoding TRAF-interacting protein with FHA domain-containing protein B (Q6ZNK6). Inhibits TIFA-mediated TRAF6 activation possibly by inducing a conformational change in TIFA.

Predicted to enable deubiquitinase activator activity. Involved in several processes, including cochlea morphogenesis; cranial nerve development; and hard palate morphogenesis.

Source: NCBI Gene 497189 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 41 total
• MANE Select transcript: NM_001099221

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:34024
Approved symbol	TIFAB
Name	TIFA inhibitor
Location	5q31.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000255833
Ensembl biotype	protein_coding
OMIM	612663
Entrez	497189

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000537858

RefSeq mRNA: 1 — MANE Select: NM_001099221 NM_001099221

CCDS: CCDS43365

Canonical transcript exons

ENST00000537858 — 2 exons

Exon	Start	End
ENSE00002222452	135444226	135449949
ENSE00002264372	135452209	135452351

Expression profiles

Bgee: expression breadth broad, 51 present calls, max score 80.29.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.7306 / max 121.5735, expressed in 146 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
63536	0.4289	134
63538	0.1599	63
63539	0.1037	30
63537	0.0381	17

Top tissues by expression

228 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
pancreatic ductal cell	CL:0002079	80.29	silver quality
vermiform appendix	UBERON:0001154	71.89	gold quality
lymph node	UBERON:0000029	68.92	gold quality
granulocyte	CL:0000094	66.70	gold quality
caecum	UBERON:0001153	66.65	gold quality
leukocyte	CL:0000738	65.54	gold quality
monocyte	CL:0000576	65.28	gold quality
palpebral conjunctiva	UBERON:0001812	64.87	silver quality
ileal mucosa	UBERON:0000331	63.39	gold quality
decidua	UBERON:0002450	61.44	gold quality
rectum	UBERON:0001052	60.99	gold quality
deltoid	UBERON:0001476	59.37	silver quality
tibialis anterior	UBERON:0001385	59.10	silver quality
gall bladder	UBERON:0002110	57.64	gold quality
buccal mucosa cell	CL:0002336	57.27	gold quality
epithelial cell of pancreas	CL:0000083	57.11	gold quality
secondary oocyte	CL:0000655	57.00	gold quality
esophagus squamous epithelium	UBERON:0006920	56.65	gold quality
bone marrow cell	CL:0002092	56.62	gold quality
postcentral gyrus	UBERON:0002581	56.42	gold quality
cardiac muscle of right atrium	UBERON:0003379	55.42	gold quality
mucosa of transverse colon	UBERON:0004991	55.42	gold quality
mucosa of sigmoid colon	UBERON:0004993	54.93	gold quality
left ventricle myocardium	UBERON:0006566	54.23	gold quality
kidney epithelium	UBERON:0004819	53.93	gold quality
colonic mucosa	UBERON:0000317	53.85	silver quality
colonic epithelium	UBERON:0000397	53.81	gold quality
parietal lobe	UBERON:0001872	53.60	gold quality
upper arm skin	UBERON:0004263	53.52	gold quality
cerebellar vermis	UBERON:0004720	53.37	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-CURD-112	yes	12.21
E-ANND-3	no	1.22

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

67 targeting TIFAB, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-6759-5P	99.99	66.54	785
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-6793-5P	99.97	65.95	758
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488
HSA-MIR-548D-5P	99.94	71.23	3502
HSA-MIR-548H-5P	99.94	71.24	3488
HSA-MIR-548I	99.94	71.25	3481
HSA-MIR-548J-5P	99.94	71.14	3489
HSA-MIR-548O-5P	99.94	71.24	3488
HSA-MIR-548W	99.94	71.24	3488
HSA-MIR-548Y	99.94	71.28	3514
HSA-MIR-659-3P	99.85	70.69	1620
HSA-MIR-320A-3P	99.77	69.73	2107

Literature-anchored findings (GeneRIF, showing 3)

• TIFAB loss increases TRAF6 protein and the dynamic range of TLR4 signaling (PMID:26458771)
• TIFAB Regulates USP15-Mediated p53 Signaling during Stressed and Malignant Hematopoiesis. (PMID:32101751)
• TIFA and TIFAB: FHA-domain proteins involved in inflammation, hematopoiesis, and disease. (PMID:32910997)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Tifab	ENSMUSG00000049625
rattus_norvegicus	Tifab	ENSRNOG00000011947

Paralogs (1): TIFA (ENSG00000145365)

Protein

Protein identifiers

TRAF-interacting protein with FHA domain-containing protein B — Q6ZNK6 (reviewed: Q6ZNK6)

Alternative names: TIFA-like protein

All UniProt accessions (1): Q6ZNK6

UniProt curated annotations — full annotation on UniProt →

Function. Inhibits TIFA-mediated TRAF6 activation possibly by inducing a conformational change in TIFA.

Subunit / interactions. Interacts with TIFA.

RefSeq proteins (1): NP_001092691* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000253	FHA_dom	Domain
IPR008984	SMAD_FHA_dom_sf	Homologous_superfamily
IPR033621	TIFA	Family

Pfam: PF00498

UniProt features (2 total): chain 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6ZNK6-F1	89.68	0.80

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 260 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GOBP_DIGESTION, GOBP_HEMATOPOIETIC_PROGENITOR_CELL_DIFFERENTIATION, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_COGNITION, GOBP_AXIS_SPECIFICATION, GOBP_BEHAVIOR, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_EMBRYONIC_AXIS_SPECIFICATION, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_CELLULAR_RESPONSE_TO_BIOTIC_STIMULUS, GOBP_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, GOBP_CRANIAL_NERVE_MORPHOGENESIS, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_CRANIAL_NERVE_DEVELOPMENT

GO Biological Process (30): toll-like receptor signaling pathway (GO:0002224), hematopoietic progenitor cell differentiation (GO:0002244), thorax and anterior abdomen determination (GO:0007356), trigeminal nerve development (GO:0021559), vestibulocochlear nerve formation (GO:0021650), myeloid cell differentiation (GO:0030099), peristalsis (GO:0030432), auditory behavior (GO:0031223), lipopolysaccharide-mediated signaling pathway (GO:0031663), genitalia morphogenesis (GO:0035112), inner ear morphogenesis (GO:0042472), positive regulation of canonical NF-kappaB signal transduction (GO:0043123), negative regulation of canonical NF-kappaB signal transduction (GO:0043124), positive regulation of translation (GO:0045727), regulation of muscle organ development (GO:0048634), genitalia development (GO:0048806), inner ear development (GO:0048839), neuromuscular process controlling balance (GO:0050885), cellular response to cAMP (GO:0071320), mastication (GO:0071626), cochlea development (GO:0090102), cochlea morphogenesis (GO:0090103), craniofacial suture morphogenesis (GO:0097094), learned vocalization behavior (GO:0098583), negative regulation of relaxation of muscle (GO:1901078), regulation of intrinsic apoptotic signaling pathway in response to osmotic stress by p53 class mediator (GO:1902238), cellular response to Thyroid stimulating hormone (GO:1904401), negative regulation of saliva secretion (GO:1905747), hard palate morphogenesis (GO:1905748), regulation of gene expression (GO:0010468)

GO Molecular Function (4): deubiquitinase activator activity (GO:0035800), ribonucleoprotein complex binding (GO:0043021), ubiquitin-specific protease binding (GO:1990381), protein binding (GO:0005515)

GO Cellular Component (2): cytoplasm (GO:0005737), cytosolic large ribosomal subunit (GO:0022625)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
hemopoiesis	2
cell differentiation	2
canonical NF-kappaB signal transduction	2
regulation of canonical NF-kappaB signal transduction	2
pattern recognition receptor signaling pathway	1
zygotic determination of anterior/posterior axis, embryo	1
anterior/posterior pattern specification	1
cranial nerve development	1
cranial nerve formation	1
vestibulocochlear nerve morphogenesis	1
phasic smooth muscle contraction	1
mechanosensory behavior	1
response to auditory stimulus	1
cell surface receptor signaling pathway	1
cellular response to lipopolysaccharide	1
developmental process involved in reproduction	1
animal organ morphogenesis	1
genitalia development	1
ear morphogenesis	1
embryonic morphogenesis	1
inner ear development	1
positive regulation of intracellular signal transduction	1
negative regulation of intracellular signal transduction	1
translation	1
regulation of translation	1
positive regulation of gene expression	1
positive regulation of protein metabolic process	1
muscle organ development	1
regulation of developmental process	1
sex differentiation	1
animal organ development	1
reproductive structure development	1
ear development	1
anatomical structure development	1
musculoskeletal movement	1
neuromuscular process	1
response to cAMP	1
cellular response to nitrogen compound	1
cellular response to oxygen-containing compound	1
digestive system process	1

Protein interactions and networks

STRING

768 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TIFAB	RNF223	E7ERA6	698
TIFAB	TRAF6	Q9Y4K3	646
TIFAB	TLX2	O43763	512
TIFAB	GLOD5	A6NK44	510
TIFAB	TMEM231	Q9H6L2	427
TIFAB	OGFOD1	Q8N543	427
TIFAB	PIM3	Q86V86	419
TIFAB	PPFIBP2	Q8ND30	418
TIFAB	MRRF	Q96E11	412
TIFAB	AADACL4	Q5VUY2	400
TIFAB	CCR8	P51685	398
TIFAB	USP15	Q9Y4E8	367
TIFAB	NFKB1	P19838	366
TIFAB	RPS14	P06366	358
TIFAB	PCSK1N	Q9UHG2	325

IntAct

9 interactions, top by confidence:

A	B	Type	Score
TIFA	TIFAB	psi-mi:“MI:0915”(physical association)	0.620
TIFAB	USP15	psi-mi:“MI:0915”(physical association)	0.590
TIFA	Traf6	psi-mi:“MI:0914”(association)	0.500
TIFAB		psi-mi:“MI:0204”(deubiquitination reaction)	0.440
TIFAB	DDX3X	psi-mi:“MI:0914”(association)	0.350
Traf6	TIFAB	psi-mi:“MI:0914”(association)	0.350

BioGRID (1): TIFAB (Affinity Capture-MS)

ESM2 similar proteins: A2RRH5, A2VDM0, A6QP75, A7E3N7, B2RUP2, D3ZI76, O75161, Q0VG06, Q14DK4, Q1LZ97, Q3SZD4, Q3TAA7, Q499N3, Q4FZD7, Q4VBE8, Q53B87, Q53B88, Q5BK67, Q5D0E6, Q5RDC3, Q60I26, Q60I27, Q69Z89, Q6NUI2, Q6P5Z2, Q6ZNK6, Q86UR1, Q8BTM9, Q8C0R7, Q8CJ00, Q8IV45, Q8JZM6, Q8K045, Q8N1F8, Q8NAC3, Q8R4L0, Q8R5I4, Q8TDF6, Q8TE82, Q8VCM2

Diamond homologs: Q5BK67, Q6ZNK6, Q8JZM6, A2VDM0, Q5XIB9, Q793I8, Q96CG3

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

41 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	36
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

522 predictions. Top by Δscore:

Variant	Effect	Δscore
5:135452204:CTTA:C	donor_loss	1.0000
5:135452205:TTAC:T	donor_loss	1.0000
5:135452206:TA:T	donor_loss	1.0000
5:135452207:A:AC	donor_gain	1.0000
5:135452207:AC:A	donor_gain	1.0000
5:135452208:C:CG	donor_gain	1.0000
5:135452208:CC:C	donor_gain	1.0000
5:135452208:CCT:C	donor_gain	1.0000
5:135452208:CCTT:C	donor_gain	1.0000
5:135452208:CCTTA:C	donor_gain	1.0000
5:135449707:AGGG:A	donor_gain	0.9700
5:135445862:T:C	acceptor_gain	0.9600
5:135449958:T:TC	acceptor_gain	0.9600
5:135449739:G:GA	donor_gain	0.9500
5:135449950:C:CC	acceptor_gain	0.9500
5:135449958:T:C	acceptor_gain	0.9500
5:135444512:C:CC	acceptor_gain	0.9200
5:135449494:T:TA	donor_gain	0.9100
5:135444510:TG:T	acceptor_gain	0.9000
5:135449495:C:A	donor_gain	0.8900
5:135446754:T:TA	donor_gain	0.8800
5:135444812:T:C	acceptor_gain	0.8500
5:135446623:AACTG:A	donor_gain	0.8500
5:135449514:AG:A	donor_gain	0.8500
5:135444695:T:TC	acceptor_gain	0.8400
5:135449948:TCCT:T	acceptor_loss	0.8400
5:135449949:CCTGG:C	acceptor_loss	0.8400
5:135449951:T:C	acceptor_loss	0.8400
5:135446444:ACCCG:A	donor_gain	0.8300
5:135446445:CCCGC:C	donor_gain	0.8300

AlphaMissense

1011 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:135449721:G:C	F73L	0.985
5:135449721:G:T	F73L	0.985
5:135449723:A:G	F73L	0.985
5:135449680:T:A	N87I	0.969
5:135449722:A:G	F73S	0.958
5:135449619:G:C	F107L	0.955
5:135449619:G:T	F107L	0.955
5:135449621:A:G	F107L	0.955
5:135449703:G:C	S79R	0.953
5:135449703:G:T	S79R	0.953
5:135449705:T:G	S79R	0.953
5:135449712:C:A	K76N	0.949
5:135449712:C:G	K76N	0.949
5:135449565:A:C	F125L	0.948
5:135449565:A:T	F125L	0.948
5:135449567:A:G	F125L	0.948
5:135449561:A:G	C127R	0.942
5:135449620:A:G	F107S	0.937
5:135449605:A:C	M112R	0.934
5:135449626:A:T	V105D	0.934
5:135449755:G:T	P62H	0.927
5:135449605:A:T	M112K	0.923
5:135449599:A:T	V114D	0.920
5:135449874:A:C	F22L	0.920
5:135449874:A:T	F22L	0.920
5:135449876:A:G	F22L	0.920
5:135449559:G:C	C127W	0.914
5:135449566:A:G	F125S	0.914
5:135449767:A:T	L58Q	0.914
5:135449605:A:G	M112T	0.910

dbSNP variants (sampled 300 via entrez): RS1000088351 (5:135452813 A>C), RS1000476115 (5:135447971 C>G), RS1000516626 (5:135446157 AC>A), RS1000846504 (5:135451284 C>T), RS1001330660 (5:135450704 T>C), RS1001431619 (5:135450536 G>A), RS1001559869 (5:135445565 C>A,G,T), RS1001893830 (5:135444594 C>G,T), RS1002032453 (5:135449350 T>G), RS1002367668 (5:135449199 C>A,T), RS1002412686 (5:135449003 C>T), RS1002580919 (5:135446638 T>A,C,G), RS1003076742 (5:135451280 A>G), RS1003257223 (5:135453536 T>C), RS1003818246 (5:135450041 C>T)

Disease associations

OMIM: gene MIM:612663 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST007192_1	Coronary artery aneurysm in Kawasaki disease	2.000000e-07

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

8 total (human), top 8 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
CGP 52608	increases reaction, affects binding	1
gardiquimod	increases expression, decreases reaction	1
Air Pollutants	affects expression, increases abundance	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Malathion	decreases expression	1
Nickel	increases expression	1
Ozone	affects expression, increases abundance	1
Protein Kinase Inhibitors	decreases reaction, increases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.