TNFRSF1A

Chr 12

TNF receptor superfamily member 1A

Also known as: CD120a, FPF, TBP1, TNF-R, TNF-R-I, TNF-R55, TNFAR, TNFR1

NCBI Gene: 7132ENSG00000067182UniProt: P19438

This gene encodes a member of the TNF receptor superfamily of proteins. The encoded receptor is found in membrane-bound and soluble forms that interact with membrane-bound and soluble forms, respectively, of its ligand, tumor necrosis factor alpha. Binding of membrane-bound tumor necrosis factor alpha to the membrane-bound receptor induces receptor trimerization and activation, which plays a role in cell survival, apoptosis, and inflammation. Proteolytic processing of the encoded receptor results in release of the soluble form of the receptor, which can interact with free tumor necrosis factor alpha to inhibit inflammation. Mutations in this gene underlie tumor necrosis factor receptor-associated periodic syndrome (TRAPS), characterized by fever, abdominal pain and other features. Mutations in this gene may also be associated with multiple sclerosis in human patients. [provided by RefSeq, Sep 2016]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtPeriodic fever, familial, autosomal dominant
UniProtMultiple sclerosis 5

Clinical highlights

Gene-disease validity (ClinGen)
TNF receptor 1-associated periodic fever syndrome · ADDefinitivesufficient evidence for diagnostic panels
Interpreting a novel variant
This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Curated gene-level mechanism — a prior for triage, not a per-variant call.
3
Active trials
99
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.24
LOEUF· LoF intol.
Multiple*
Mechanism· predicted
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?
0.24LOEUF
pLI 0.995
Z-score 3.94
OE 0.05 (0.02–0.24)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?
2.10Z-score
OE missense 0.64 (0.56–0.72)
170 obs / 266.5 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?
LoF OE?0.05 (0.02–0.24)
0≤0.351.4
Missense OE?0.64 (0.56–0.72)
0≤0.61.4
Synonymous OE?0.97
0≤1.21.6
LoF obs/exp: 1 / 20.1Missense obs/exp: 170 / 266.5Syn Z: 0.25

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

TNFRSF1A · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients