TAFA4

Chr 3

TAFA chemokine like family member 4

Also known as: FAM19A4, TAFA-4

NCBI Gene: 151647ENSG00000163377UniProt: Q96LR4

This gene is a member of the TAFA family which is composed of five highly homologous genes that encode small secreted proteins. These proteins contain conserved cysteine residues at fixed positions, and are distantly related to MIP-1alpha, a member of the CC-chemokine family. The TAFA proteins are predominantly expressed in specific regions of the brain, and are postulated to function as brain-specific chemokines or neurokines, that act as regulators of immune and nervous cells. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, Nov 2011]

65
ClinVar variants
11
Pathogenic / LP
0.00
pLI score
2
Active trials
Clinical Summary— TAFA4
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
11 Pathogenic / Likely Pathogenic· 51 VUS of 65 total submissions
💊
Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
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?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.11Z-score
OE missense 1.03 (0.87–1.23)
91 obs / 88.1 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.65 (0.36–1.29)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.03 (0.87–1.23)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.21
0≤1.21.6
LoF obs/exp: 6 / 9.2Missense obs/exp: 91 / 88.1Syn Z: -0.97

ClinVar Variant Classifications

65 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.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
TAFA4 relieves injury-induced mechanical hypersensitivity through LDL receptors and modulation of spinal A-type K(+) current.
Yoo S et al.·Cell Rep
2021
Cross-species transcriptomic atlas of dorsal root ganglia reveals species-specific programs for sensory function.
Jung M et al.·Nat Commun
2023
Role of specialized sensory neuron subtypes in modulating peripheral immune responses.
Crosson T et al.·Immunity
2025Review
Signals from the TAFA4-PTEN-PU.1 axis alleviate nasal allergy by modulating the expression of FcεRI in mast cells.
Zhou C et al.·Clin Exp Immunol
2023
Low methylation marker levels among human papillomavirus-vaccinated women with cervical high-grade squamous intraepithelial lesions.
Louvanto K et al.·Int J Cancer
2024
Method for quantitative detection of FAM19A4 by flow cytometry using latex beads as solid carrier.
Li T et al.·J Biosci Bioeng
2018
DNA methylation at individual CpG-sites of EPB41L3, HTERT and FAM19A4 are useful for detection of cervical high-grade squamous intraepithelial lesions (HSIL) or worse: Analysis of individual CpG-sites outperforms averaging.
Molano M et al.·Tumour Virus Res
2024
The Role of Methylation as an Epigenetic Marker in HPV-Related Oral Lesions.
Buttà M et al.·J Med Virol
2025
Colposcopy referrals and CIN3 detection after triage by host cell DNA methylation and/or HPV genotyping in HPV positive women with low-grade cytology from a population-based Dutch primary HPV screening trial.
Verhoef L et al.·Int J Cancer
2025
Neuron-macrophage interaction in the healing process of the skin.
Soler Palacios B et al.·Allergy
2022
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Cervical Intraepithelial Neoplasia Grade 2

Evaluation of the PreCursor-M+® in CIN2

RECRUITING
NCT06403618European Institute of OncologyStarted 2024-06-17
Cervix CancerHPV InfectionCervical High Grade Squamous Intraepithelial Lesion

Optimization of Cervical Cancer Screening Among Women Living With HIV in Latin American Countries

ACTIVE NOT RECRUITING
NCT06002126Phase NAWeill Medical College of Cornell UniversityStarted 2023-08-02
Xpert HPVQIAsure Methylation Test

External Resources

Links to major genomics databases and tools