TAFA4

Chr 3

TAFA chemokine like family member 4

Also known as: FAM19A4, TAFA-4

NCBI Gene: 151647ENSG00000163377UniProt: Q96LR4OMIM: 617498

This gene encodes a small secreted protein that functions as a brain-specific chemokine, modulating pain hypersensitivity and acting as a ligand for FPR1 to chemoattract macrophages and promote phagocytosis. TAFA4 mutations cause autosomal recessive inflammatory pain insensitivity, a rare disorder characterized by reduced sensitivity to painful stimuli due to impaired pain signaling pathways. The gene shows low constraint to loss-of-function variation (pLI 0.0007, LOEUF 1.3), consistent with recessive inheritance where both copies must be affected to cause disease.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 1.29
Clinical Summary— TAFA4
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
11 unique Pathogenic / Likely Pathogenic· 51 VUS of 70 total submissions
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Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.29LOEUF
pLI 0.001
Z-score 0.97
OE 0.65 (0.36–1.29)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.11Z-score
OE missense 1.03 (0.87–1.23)
91 obs / 88.1 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.65 (0.36–1.29)
0≤0.351.4
Missense OE1.03 (0.87–1.23)
0≤0.61.4
Synonymous OE1.21
0≤1.21.6
LoF obs/exp: 6 / 9.2Missense obs/exp: 91 / 88.1Syn Z: -0.97
DN
0.6355th %ile
GOF
0.4973th %ile
LOF
0.4136th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

70 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic10
Likely Pathogenic1
VUS51
Benign1
Conflicting2
10
Pathogenic
1
Likely Pathogenic
51
VUS
1
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
10
0
10
Likely Pathogenic
0
0
1
0
1
VUS
0
42
9
0
51
Likely Benign
0
0
0
0
0
Benign
0
0
0
1
1
Conflicting
—2
Total04220165

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

TAFA4 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

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