TAFA1

Chr 3

TAFA chemokine like family member 1

Also known as: FAM19A1, TAFA-1

NCBI Gene: 407738 ENSG00000183662 UniProt: Q7Z5A9 OMIM: 617495

This gene encodes a small secreted protein that functions as a brain-specific chemokine and serves as a ligand for CMKLR2, regulating neural stem cell proliferation and differentiation. Mutations in TAFA1 cause autosomal recessive developmental and epileptic encephalopathy characterized by severe intellectual disability, refractory seizures, and brain malformations. The pathogenic mechanism appears to involve loss of function of this secreted regulatory factor critical for normal brain development.

OMIM ResearchSummary from RefSeq, UniProt

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. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

LOEUF 0.74

Clinical Summary— TAFA1

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.23) despite low pLI — interpret in context.

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ClinVar Variants

15 VUS of 15 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.74LOEUF

pLI 0.331

Z-score 2.07

OE 0.23 (0.10–0.74)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.92Z-score

OE missense 0.71 (0.57–0.89)

57 obs / 80.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.23 (0.10–0.74)

0≤0.351.4

Missense OE?0.71 (0.57–0.89)

0≤0.61.4

Synonymous OE?1.05

0≤1.21.6

LoF obs/exp: 2 / 8.5Missense obs/exp: 57 / 80.2Syn Z: -0.19

ClinVar Variant Classifications

15 submitted variants in ClinVar

ClinVar

Classification Summary

VUS15

VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	15	15
Likely Benign	0	0
Benign	0	0
Total	15	15

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

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11 pathogenic / likely-pathogenic (of 23) ClinVar copy-number / structural variants overlap TAFA1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →