TAFA1

Summary

TAFA1 (TAFA chemokine like family member 1, HGNC:21587) is a protein-coding gene on chromosome 3p14.1, encoding Chemokine-like protein TAFA-1 (Q7Z5A9). Regulatory factor which is ligand for CMKLR2 and is involved in the modulation of neural stem-cell proliferation and differentiation.

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.

Source: NCBI Gene 407738 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 16 total
• MANE Select transcript: NM_213609

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21587
Approved symbol	TAFA1
Name	TAFA chemokine like family member 1
Location	3p14.1
Locus type	gene with protein product
Status	Approved
Aliases	TAFA-1
Ensembl gene	ENSG00000183662
Ensembl biotype	protein_coding
OMIM	617495
Entrez	407738

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000478136, ENST00000491017, ENST00000496687

RefSeq mRNA: 2 — MANE Select: NM_213609 NM_001252216, NM_213609

CCDS: CCDS54606

Canonical transcript exons

ENST00000478136 — 5 exons

Exon	Start	End
ENSE00001294156	68538756	68538880
ENSE00001312175	68417280	68417420
ENSE00001816274	68544486	68545621
ENSE00001853594	68006624	68006744
ENSE00001941850	68004247	68004702

Expression profiles

Bgee: expression breadth ubiquitous, 157 present calls, max score 96.29.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 2.5273 / max 388.9571, expressed in 113 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
37213	1.2204	94
37214	0.9771	86
37217	0.1622	45
37212	0.1175	25
37216	0.0329	21
37215	0.0172	10

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
middle temporal gyrus	UBERON:0002771	96.29	gold quality
endothelial cell	CL:0000115	95.21	gold quality
Brodmann (1909) area 23	UBERON:0013554	95.16	gold quality
pons	UBERON:0000988	94.25	gold quality
Brodmann (1909) area 46	UBERON:0006483	91.52	gold quality
superior frontal gyrus	UBERON:0002661	90.41	gold quality
entorhinal cortex	UBERON:0002728	89.11	gold quality
postcentral gyrus	UBERON:0002581	88.19	gold quality
parietal lobe	UBERON:0001872	87.73	gold quality
primary visual cortex	UBERON:0002436	87.68	gold quality
occipital lobe	UBERON:0002021	86.13	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	85.82	gold quality
cortical plate	UBERON:0005343	85.54	gold quality
frontal cortex	UBERON:0001870	85.19	gold quality
prefrontal cortex	UBERON:0000451	85.09	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.68	gold quality
cerebral cortex	UBERON:0000956	84.63	gold quality
neocortex	UBERON:0001950	84.38	gold quality
Brodmann (1909) area 9	UBERON:0013540	84.04	gold quality
Ammon’s horn	UBERON:0001954	84.01	gold quality
temporal lobe	UBERON:0001871	82.09	gold quality
right frontal lobe	UBERON:0002810	81.87	gold quality
anterior cingulate cortex	UBERON:0009835	81.17	gold quality
dorsal root ganglion	UBERON:0000044	80.03	gold quality
amygdala	UBERON:0001876	77.16	gold quality
forebrain	UBERON:0001890	72.98	gold quality
trigeminal ganglion	UBERON:0001675	72.79	gold quality
ventricular zone	UBERON:0003053	71.29	gold quality
seminal vesicle	UBERON:0000998	70.92	gold quality
ganglionic eminence	UBERON:0004023	70.69	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-HCAD-30	yes	1597.13
E-HCAD-35	yes	1413.89
E-HCAD-25	yes	81.92
E-ANND-3	no	3.72

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

132 targeting TAFA1, 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-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	tafa1a	ENSDARG00000062357
mus_musculus	Tafa1	ENSMUSG00000059187
rattus_norvegicus	Tafa1	ENSRNOG00000070575

Paralogs (3): TAFA4 (ENSG00000163377), TAFA3 (ENSG00000184599), TAFA2 (ENSG00000198673)

Protein

Protein identifiers

Chemokine-like protein TAFA-1 — Q7Z5A9 (reviewed: Q7Z5A9)

All UniProt accessions (1): Q7Z5A9

UniProt curated annotations — full annotation on UniProt →

Function. Regulatory factor which is ligand for CMKLR2 and is involved in the modulation of neural stem-cell proliferation and differentiation.

Subcellular location. Secreted.

Tissue specificity. Brain-specific.

Similarity. Belongs to the TAFA family.

RefSeq proteins (2): NP_001239145, NP_998774* (*=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, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7Z5A9-F1	85.90	0.64

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 165 (showing top): RNGTGGGC_UNKNOWN, FREAC2_01, HNF3ALPHA_Q6, NKX25_02, AREB6_01, GOBP_NEUROGENESIS, CREBP1_Q2, TGACCTY_ERR1_Q2, TAL1ALPHAE47_01, LHX3_01, GGGTGGRR_PAX4_03, CEBPB_01, CREB_Q4, GOBP_NEURAL_PRECURSOR_CELL_PROLIFERATION, TCF4_Q5

GO Biological Process (4): regulation of signaling receptor activity (GO:0010469), neuroblast differentiation (GO:0014016), regulation of neuroblast proliferation (GO:1902692), signal transduction (GO:0007165)

GO Molecular Function (2): receptor ligand activity (GO:0048018), protein binding (GO:0005515)

GO Cellular Component (3): obsolete extracellular space (GO:0005615), endoplasmic reticulum (GO:0005783), extracellular region (GO:0005576)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of signal transduction	1
signaling receptor activity	1
regulation of molecular function	1
cell differentiation	1
generation of neurons	1
neuroblast proliferation	1
regulation of neural precursor cell proliferation	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
binding	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

964 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TAFA1	CMKLR2	P46091	658
TAFA1	NECAB2	Q7Z6G3	506
TAFA1	NRXN2	Q9P2S2	485
TAFA1	NRXN1	Q9ULB1	471
TAFA1	FAM110A	Q9BQ89	437
TAFA1	TMEM182	Q6ZP80	420
TAFA1	FAM163A	Q96GL9	413
TAFA1	EFCAB10	A6NFE3	404
TAFA1	TAFA5	Q7Z5A7	399
TAFA1	SNX29	Q8TEQ0	396
TAFA1	KCNK2	O95069	391
TAFA1	STPG2	Q8N412	379
TAFA1	RPAP3	Q9H6T3	370
TAFA1	GLRA3	O75311	363
TAFA1	SMIM13	P0DJ93	362

IntAct

7 interactions, top by confidence:

A	B	Type	Score
TAFA1	RABGGTB	psi-mi:“MI:0915”(physical association)	0.560
RABGGTB	TAFA1	psi-mi:“MI:0915”(physical association)	0.560
TAFA1	ZER1	psi-mi:“MI:0914”(association)	0.530
TAFA1	M6PR	psi-mi:“MI:0914”(association)	0.350
TAFA1	SEZ6L2	psi-mi:“MI:0914”(association)	0.350

BioGRID (10): FAM19A1 (Two-hybrid), NRXN3 (Affinity Capture-MS), ZER1 (Affinity Capture-MS), M6PR (Affinity Capture-MS), ZER1 (Affinity Capture-MS), NRXN3 (Affinity Capture-MS), NCSTN (Affinity Capture-MS), POMGNT2 (Affinity Capture-MS), PLXNA1 (Affinity Capture-MS), SEZ6L2 (Affinity Capture-MS)

ESM2 similar proteins: A0A291NVT7, A0A4Y5X186, A0A4Y5X1A7, A0A7S8RFI7, A0S864, A7X3V0, B2ZG38, B3EWX6, C0HLS6, C0HLS9, C0HLT1, C0HLT2, C0HM40, C5H8E7, C9E1S2, D3GGZ8, O12961, P01060, P01066, P05486, P0C6A4, P0DN42, P0DN43, P0DQE9, P0DTJ2, P0DTJ3, P0DUA3, P10776, P19860, P22737, P36985, P58990, P81743, Q00945, Q10037, Q2XXR7, Q2XXR8, Q3BK15, Q4R128, Q56R11

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	16
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

4844 predictions. Top by Δscore:

Variant	Effect	Δscore
3:68082949:G:GT	donor_gain	1.0000
3:68378564:GAA:G	donor_gain	1.0000
3:68378565:A:T	donor_gain	1.0000
3:68378571:T:G	donor_gain	1.0000
3:68417274:T:A	acceptor_gain	1.0000
3:68417274:TGCCA:T	acceptor_loss	1.0000
3:68417275:GCCA:G	acceptor_loss	1.0000
3:68417276:CCA:C	acceptor_loss	1.0000
3:68417277:CA:C	acceptor_loss	1.0000
3:68417278:A:AC	acceptor_loss	1.0000
3:68417278:A:AG	acceptor_gain	1.0000
3:68417278:AGAAG:A	acceptor_gain	1.0000
3:68417279:G:C	acceptor_loss	1.0000
3:68417279:G:GA	acceptor_gain	1.0000
3:68417279:GA:G	acceptor_gain	1.0000
3:68417279:GAA:G	acceptor_gain	1.0000
3:68417279:GAAGG:G	acceptor_gain	1.0000
3:68417417:GATG:G	donor_gain	1.0000
3:68417421:G:GG	donor_gain	1.0000
3:68417421:GTA:G	donor_loss	1.0000
3:68417422:T:A	donor_loss	1.0000
3:68006622:A:AG	acceptor_gain	0.9900
3:68006623:G:GG	acceptor_gain	0.9900
3:68006623:GA:G	acceptor_gain	0.9900
3:68006623:GAGA:G	acceptor_gain	0.9900
3:68059160:GAC:G	donor_gain	0.9900
3:68082870:T:TA	donor_gain	0.9900
3:68082949:G:T	donor_gain	0.9900
3:68218678:G:GG	donor_gain	0.9900
3:68317277:T:TA	donor_gain	0.9900

AlphaMissense

866 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:68417291:T:A	C44S	1.000
3:68417291:T:C	C44R	1.000
3:68417292:G:A	C44Y	1.000
3:68417292:G:C	C44S	1.000
3:68417292:G:T	C44F	1.000
3:68417293:T:G	C44W	1.000
3:68417315:T:A	C52S	1.000
3:68417316:G:C	C52S	1.000
3:68417317:T:G	C52W	1.000
3:68417319:G:A	C53Y	1.000
3:68417345:T:C	S62P	1.000
3:68417360:T:A	C67S	1.000
3:68417360:T:C	C67R	1.000
3:68417361:G:A	C67Y	1.000
3:68417361:G:C	C67S	1.000
3:68417361:G:T	C67F	1.000
3:68417362:T:G	C67W	1.000
3:68417366:T:A	C69S	1.000
3:68417366:T:C	C69R	1.000
3:68417367:G:A	C69Y	1.000
3:68417367:G:C	C69S	1.000
3:68417367:G:T	C69F	1.000
3:68417368:T:G	C69W	1.000
3:68417385:C:A	A75D	1.000
3:68417387:G:A	G76R	1.000
3:68417387:G:C	G76R	1.000
3:68417388:G:A	G76E	1.000
3:68417388:G:T	G76V	1.000
3:68417405:C:T	P82S	1.000
3:68417406:C:A	P82H	1.000

dbSNP variants (sampled 300 via entrez): RS1000000515 (3:68211475 T>A), RS1000003330 (3:68008663 T>G), RS1000005102 (3:68512161 G>A), RS1000023083 (3:68518709 G>A), RS1000023653 (3:68068370 A>G), RS1000026239 (3:68083963 C>T), RS1000031604 (3:68400172 C>T), RS1000032253 (3:68014777 A>G), RS1000048106 (3:68388816 G>A,C,T), RS1000050437 (3:68337160 T>C), RS1000051093 (3:68024980 G>A), RS1000051405 (3:68211294 T>C), RS1000052155 (3:68324608 G>A), RS1000052385 (3:68251373 T>G), RS1000058304 (3:68181056 G>A,T)

Disease associations

OMIM: gene MIM:617495 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST002337_118	Amyotrophic lateral sclerosis (sporadic)	4.000000e-07
GCST006658_13	Longevity	3.000000e-06
GCST009256_3	Superior temporal sulcus banks volume	5.000000e-06
GCST009307_14	Spatial memory	7.000000e-06
GCST012489_41	Heel bone mineral density x serum urate levels interaction	1.000000e-12
GCST012490_223	Femur bone mineral density x serum urate levels interaction	2.000000e-10
GCST012490_630	Femur bone mineral density x serum urate levels interaction	3.000000e-09

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004874	memory performance
EFO:0004531	urate measurement
EFO:0009270	heel bone mineral density

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

6 total (human), top 6 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, decreases methylation	2
bisphenol A	decreases expression, increases methylation	1
aflatoxin B2	increases methylation	1
CGP 52608	affects binding, increases reaction	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Hydralazine	affects cotreatment, increases expression	1

Clinical trials (associated diseases)

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