TIFAB

protein-coding

TIFA inhibitor

Gene summary

Enables deubiquitinase activator activity and ubiquitin-specific protease binding activity. Involved in several processes, including cochlea morphogenesis; cranial nerve development; and hard palate morphogenesis. Acts upstream of or within negative regulation of canonical NF-kappaB signal transduction and toll-like receptor signaling pathway. Is active in cytoplasm. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_001099221.2

Inheritance

—

ClinVar variants

U:32B:5

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 1.68

Max pathogenic AF

—

Genomic locus

chr5:135,444,226-135,452,351

External References & Databases

Ensembl (ENSG00000255833)

Transcript & Mutation Effects

hg38 • Region Span ~8.1 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TIFAB variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 37

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001099221.2. 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						0
missense			32 clinvar	5 clinvar		37
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	32	5	0	37

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 3 of 3 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001099221.2	RefSeq	NP_001092691.1	1	MANE Select
ENST00000537858.2	Ensembl	ENSP00000440509.1	1	MANE Select
ENST00001134298.1	Ensembl	ENSP00000813906.1	1	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

I-kappaB kinase/NF-kappaB signaling
thorax and anterior abdomen determination
trigeminal nerve development
vestibulocochlear nerve formation
peristalsis

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000537858
Coding exons: 1
Length: 8182
Individuals with no LoFs: 124784
Homozygous LoFs: 0
Heterozygous LoFs: 16
Defined: 124800
p: 0.0000641

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.0690	99	97.1	1.02	0.00000612	1003
Missense (PolyPhen)		15	20.191	0.74292		256
Synonymous	-0.285	47	44.6	1.05	0.00000257	374
Loss of Function	-1.19	6	3.58	1.68	2.38e-7	30

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000065	0.000065	rare
Latino/Admixed American	0.00014	0.00014	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000056	0.000056	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000045	0.000044	rare
South Asian	0.00013	0.00013	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Inhibits TIFA-mediated TRAF6 activation possibly by inducing a conformational change in TIFA. {ECO:0000269|PubMed:15047173}.;

Recessive Scores

pRec: 0.0891

Intolerance Scores

LoFtool: 0.502
RVIS EVS: -0.23
RVIS percentile EVS: 37.11

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.0542

Gene Damage Prediction

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