TAFA3

Summary

TAFA3 (TAFA chemokine like family member 3, HGNC:21590) is a protein-coding gene on chromosome 1p13.2, encoding Chemokine-like protein TAFA-3 (Q7Z5A8). Plays a role in the regulation of microglia polarization.

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 encoding multiple isoforms have been observed for this gene.

Source: NCBI Gene 284467 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 44 total
• MANE Select transcript: NM_182759

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21590
Approved symbol	TAFA3
Name	TAFA chemokine like family member 3
Location	1p13.2
Locus type	gene with protein product
Status	Approved
Aliases	TAFA-3
Ensembl gene	ENSG00000184599
Ensembl biotype	protein_coding
OMIM	617497
Entrez	284467

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000361886, ENST00000369630

RefSeq mRNA: 2 — MANE Select: NM_182759 NM_001004440, NM_182759

CCDS: CCDS30806, CCDS856

Canonical transcript exons

ENST00000361886 — 6 exons

Exon	Start	End
ENSE00001315682	112723016	112723165
ENSE00001331903	112722233	112722348
ENSE00001435893	112724013	112724137
ENSE00001865267	112720577	112720634
ENSE00003475063	112726629	112727235
ENSE00003920834	112718905	112719299

Expression profiles

Bgee: expression breadth broad, 83 present calls, max score 72.39.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1870 / max 42.6393, expressed in 56 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
4704	0.0894	25
201621	0.0818	20
4703	0.0158	5

Top tissues by expression

115 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	72.39	gold quality
right testis	UBERON:0004534	72.14	gold quality
testis	UBERON:0000473	72.05	gold quality
thymus	UBERON:0002370	71.67	silver quality
cerebellar vermis	UBERON:0004720	70.30	gold quality
cerebellum	UBERON:0002037	68.65	gold quality
cerebellar cortex	UBERON:0002129	68.60	gold quality
cerebellar hemisphere	UBERON:0002245	68.50	gold quality
right hemisphere of cerebellum	UBERON:0014890	68.38	gold quality
quadriceps femoris	UBERON:0001377	64.14	gold quality
substantia nigra	UBERON:0002038	62.24	gold quality
spinal cord	UBERON:0002240	58.39	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	58.34	gold quality
primary visual cortex	UBERON:0002436	54.77	gold quality
prefrontal cortex	UBERON:0000451	54.32	gold quality
right adrenal gland	UBERON:0001233	53.97	gold quality
frontal cortex	UBERON:0001870	52.56	gold quality
right ovary	UBERON:0002118	51.25	gold quality
hypothalamus	UBERON:0001898	51.17	gold quality
adrenal gland	UBERON:0002369	50.52	gold quality
right frontal lobe	UBERON:0002810	50.27	gold quality
lower esophagus mucosa	UBERON:0035834	50.24	gold quality
cerebral cortex	UBERON:0000956	50.12	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	50.12	gold quality
brain	UBERON:0000955	49.74	gold quality
amygdala	UBERON:0001876	49.53	gold quality
temporal lobe	UBERON:0001871	49.24	gold quality
ovary	UBERON:0000992	49.18	gold quality
Brodmann (1909) area 9	UBERON:0013540	49.00	gold quality
anterior cingulate cortex	UBERON:0009835	48.70	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-7316	yes	31.61
E-ANND-3	no	0.98

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

34 targeting TAFA3, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-6753-3P	99.93	66.57	637
HSA-MIR-7107-3P	99.93	66.73	627
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-4527	99.66	67.43	714
HSA-MIR-7152-5P	99.60	69.33	2094
HSA-MIR-3128	99.50	67.85	1258
HSA-MIR-6868-5P	99.06	65.69	1284
HSA-MIR-3124-3P	98.87	68.95	2123
HSA-MIR-3074-5P	98.82	66.56	1414
HSA-MIR-4686	98.77	66.87	964
HSA-MIR-6769B-5P	98.73	64.91	1092
HSA-MIR-4450	98.26	68.35	725
HSA-MIR-93-3P	98.15	66.65	1309
HSA-MIR-4632-5P	97.82	65.38	1470
HSA-MIR-4799-3P	97.78	65.97	893
HSA-MIR-4667-5P	97.61	66.67	1683
HSA-MIR-4720-5P	97.46	65.67	893
HSA-MIR-5588-5P	97.46	65.70	913
HSA-MIR-663B	97.40	62.91	664
HSA-MIR-331-5P	96.59	67.94	705
HSA-MIR-7108-5P	96.42	66.17	598

Literature-anchored findings (GeneRIF, showing 1)

• FAM19A3 modulates the microglia/macrophage polarization dynamics and ameliorates cerebral ischemia. (PMID:25595455)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	tafa3b	ENSDARG00000020292
danio_rerio	tafa4b	ENSDARG00000062471
danio_rerio	tafa3a	ENSDARG00000079446
mus_musculus	Tafa3	ENSMUSG00000055865
rattus_norvegicus	Tafa3	ENSRNOG00000030253

Paralogs (3): TAFA4 (ENSG00000163377), TAFA1 (ENSG00000183662), TAFA2 (ENSG00000198673)

Protein

Protein identifiers

Chemokine-like protein TAFA-3 — Q7Z5A8 (reviewed: Q7Z5A8)

All UniProt accessions (1): Q7Z5A8

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in the regulation of microglia polarization.

Subcellular location. Secreted.

Tissue specificity. Brain-specific.

Similarity. Belongs to the TAFA family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q7Z5A8-1	1, TAFA3	yes
Q7Z5A8-2	2, TAFA3.2

RefSeq proteins (2): NP_001004440, NP_877436* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR020350	Chemokine-like_TAFA	Family
IPR051743	TAFA_chemokine-like	Family

Pfam: PF12020

UniProt features (3 total): signal peptide 1, chain 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7Z5A8-F1	87.45	0.66

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 102 (showing top): GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_POSITIVE_REGULATION_OF_MACROPHAGE_ACTIVATION, GOBP_INFLAMMATORY_RESPONSE, GOBP_REGULATION_OF_MACROPHAGE_ACTIVATION, GOBP_POSITIVE_REGULATION_OF_RESPONSE_TO_EXTERNAL_STIMULUS, GOBP_NEGATIVE_REGULATION_OF_MULTICELLULAR_ORGANISMAL_PROCESS, GOBP_MYELOID_LEUKOCYTE_ACTIVATION, GOBP_REGULATION_OF_RESPONSE_TO_STRESS, GOBP_POSITIVE_REGULATION_OF_CELL_ACTIVATION, GOBP_MACROPHAGE_ACTIVATION, GOBP_NEGATIVE_REGULATION_OF_DEFENSE_RESPONSE, GOBP_NEGATIVE_REGULATION_OF_INFLAMMATORY_RESPONSE, GOBP_REGULATION_OF_RESPONSE_TO_EXTERNAL_STIMULUS, GOBP_NEGATIVE_REGULATION_OF_CELL_ACTIVATION, GOBP_REGULATION_OF_INFLAMMATORY_RESPONSE

GO Biological Process (3): negative regulation of microglial cell activation (GO:1903979), positive regulation of microglial cell activation (GO:1903980), signal transduction (GO:0007165)

GO Molecular Function (1): receptor ligand activity (GO:0048018)

GO Cellular Component (2): obsolete extracellular space (GO:0005615), extracellular region (GO:0005576)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
microglial cell activation	2
regulation of microglial cell activation	2
negative regulation of macrophage activation	1
negative regulation of neuroinflammatory response	1
positive regulation of macrophage activation	1
positive regulation of neuroinflammatory response	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
signaling receptor binding	1
signal transduction	1
signaling receptor activator activity	1
cellular anatomical structure	1

Protein interactions and networks

STRING

398 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TAFA3	KRTAP19-5	Q3LI72	578
TAFA3	TSNAX	Q99598	460
TAFA3	NT5DC3	Q86UY8	434
TAFA3	GUCY1A1	Q02108	422
TAFA3	PRR30	Q53SZ7	417
TAFA3	NCLN	Q969V3	400
TAFA3	FAXDC2	Q96IV6	373
TAFA3	KBTBD12	Q3ZCT8	337
TAFA3	LZTS3	O60299	333
TAFA3	CCDC171	Q6TFL3	324
TAFA3	TMEM215	Q68D42	314
TAFA3	ARPP21	Q9UBL0	310
TAFA3	GLRA1	P23415	307
TAFA3	ARL15	Q9NXU5	307
TAFA3	LRRTM2	O43300	295

IntAct

3 interactions, top by confidence:

A	B	Type	Score
CFTR	TAFA3	psi-mi:“MI:0915”(physical association)	0.370
TAFA3	FUOM	psi-mi:“MI:0914”(association)	0.350

BioGRID (141): FLAD1 (Affinity Capture-MS), DHPS (Affinity Capture-MS), FUOM (Affinity Capture-MS), MAPK9 (Affinity Capture-MS), PPP2R2D (Affinity Capture-MS), THNSL1 (Affinity Capture-MS), JMJD4 (Affinity Capture-MS), PRMT7 (Affinity Capture-MS), C17orf70 (Affinity Capture-MS), PPP2CA (Affinity Capture-MS), LRP1B (Affinity Capture-MS), PBK (Affinity Capture-MS), KDM1B (Affinity Capture-MS), CRYZL1 (Affinity Capture-MS), NHLRC2 (Affinity Capture-MS)

ESM2 similar proteins: A0A291NVT7, A0A4Y5X186, A0A4Y5X1A7, B0VXV3, B0VXV4, O42493, O43278, P01060, P05486, P08163, P0DN42, P0DN43, P0DTJ2, P0DTJ3, P16229, P17668, P48250, P56688, P58990, P67862, Q00945, Q07662, Q07663, Q08E66, Q23247, Q2XXR7, Q2XXR8, Q330K6, Q4R128, Q56R10, Q56R11, Q58T08, Q7M428, Q7TPG5, Q7TPG6, Q7TPG7, Q7TPG8, Q7TQN3, Q7Z5A8, Q7Z5A9

Diamond homologs: M0R7X9, Q3ZBS2, Q5R6N2, Q7TPG5, Q7TPG6, Q7TPG7, Q7TPG8, Q7Z5A7, Q7Z5A8, Q7Z5A9, Q8N3H0, Q91WE9, Q96LR4, Q9N0D3

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

44 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	34
Likely benign	10
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

939 predictions. Top by Δscore:

Variant	Effect	Δscore
1:112722357:G:GT	donor_gain	1.0000
1:112720630:AAAAG:A	donor_gain	0.9900
1:112720631:AAAG:A	donor_gain	0.9900
1:112720631:AAAGG:A	donor_loss	0.9900
1:112720632:AAG:A	donor_gain	0.9900
1:112720632:AAGG:A	donor_loss	0.9900
1:112720633:AG:A	donor_gain	0.9900
1:112720634:GG:G	donor_gain	0.9900
1:112720635:G:GG	donor_gain	0.9900
1:112720635:GTAA:G	donor_loss	0.9900
1:112721941:GA:G	donor_gain	0.9900
1:112721943:G:GG	donor_gain	0.9900
1:112721949:G:GG	donor_gain	0.9900
1:112722362:G:GA	donor_gain	0.9900
1:112723014:A:AG	acceptor_gain	0.9900
1:112723014:AGT:A	acceptor_gain	0.9900
1:112723015:G:GA	acceptor_gain	0.9900
1:112723015:GT:G	acceptor_gain	0.9900
1:112723015:GTG:G	acceptor_gain	0.9900
1:112723015:GTGC:G	acceptor_gain	0.9900
1:112723162:GACG:G	donor_gain	0.9900
1:112723166:G:GC	donor_loss	0.9900
1:112723166:G:GG	donor_gain	0.9900
1:112723167:TGAG:T	donor_loss	0.9900
1:112723168:GAGT:G	donor_loss	0.9900
1:112726627:A:C	acceptor_loss	0.9900
1:112721946:GGA:G	donor_gain	0.9800
1:112721947:GAG:G	donor_gain	0.9800
1:112722231:AG:A	acceptor_gain	0.9800
1:112722232:GG:G	acceptor_gain	0.9800

AlphaMissense

849 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:112724038:G:C	W97C	0.999
1:112724038:G:T	W97C	0.999
1:112724101:G:C	W118C	0.999
1:112724101:G:T	W118C	0.999
1:112724099:T:A	W118R	0.995
1:112724099:T:C	W118R	0.995
1:112723105:T:A	C69S	0.993
1:112723106:G:C	C69S	0.993
1:112724072:T:A	C109S	0.993
1:112724073:G:C	C109S	0.993
1:112723156:T:A	C86S	0.992
1:112723157:G:C	C86S	0.992
1:112724039:T:A	C98S	0.992
1:112724040:G:C	C98S	0.992
1:112723113:T:G	C71W	0.989
1:112724036:T:A	W97R	0.989
1:112724036:T:C	W97R	0.989
1:112723105:T:C	C69R	0.988
1:112724097:G:A	G117E	0.987
1:112724105:T:A	C120S	0.987
1:112724106:G:C	C120S	0.987
1:112723133:G:A	G78D	0.986
1:112724054:T:A	C103S	0.986
1:112724055:G:C	C103S	0.986
1:112724107:C:G	C120W	0.986
1:112723111:T:A	C71S	0.985
1:112723112:G:C	C71S	0.985
1:112723157:G:A	C86Y	0.985
1:112724047:G:A	M100I	0.985
1:112724047:G:C	M100I	0.985

dbSNP variants (sampled 300 via entrez): RS1000495836 (1:112727205 A>G), RS1000807781 (1:112717122 A>C), RS1001014954 (1:112721569 C>G), RS1001155217 (1:112717298 G>A,C), RS1001804335 (1:112717782 C>T), RS1002020586 (1:112722832 G>A), RS1002109330 (1:112717497 T>C,G), RS1002134502 (1:112722637 G>A,T), RS1002708795 (1:112719069 G>A,T), RS1002810484 (1:112719817 GCC>G), RS1002819315 (1:112725415 A>C), RS1003213851 (1:112719305 T>A), RS1003265990 (1:112724178 C>A,T), RS1004909243 (1:112717365 T>C), RS1005148377 (1:112717240 G>A)

Disease associations

OMIM: gene MIM:617497 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST002930_16	Cobalt levels	7.000000e-06
GCST010002_392	Refractive error	8.000000e-20

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

9 total (human), top 9 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, increases methylation	2
abrine	increases expression	1
(+)-JQ1 compound	decreases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Endosulfan	increases expression	1
Triclosan	increases expression	1
Aflatoxin B1	decreases methylation	1
Okadaic Acid	increases expression	1
Permethrin	decreases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.