TCAF2

Summary

TCAF2 (TRPM8 channel associated factor 2, HGNC:26878) is a protein-coding gene on chromosome 7q35, encoding TRPM8 channel-associated factor 2 (A6NFQ2). Negatively regulates the plasma membrane cation channel TRPM8 activity.

Enables transmembrane transporter binding activity. Involved in negative regulation of anion channel activity; positive regulation of cell migration; and positive regulation of protein targeting to membrane. Located in cell junction and plasma membrane.

Source: NCBI Gene 285966 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 91 total
• MANE Select transcript: NM_001363538

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26878
Approved symbol	TCAF2
Name	TRPM8 channel associated factor 2
Location	7q35
Locus type	gene with protein product
Status	Approved
Aliases	FLJ40722, GATD9B
Ensembl gene	ENSG00000170379
Ensembl biotype	protein_coding
OMIM	616252
Entrez	285966

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 8 protein_coding

ENST00000357344, ENST00000411935, ENST00000425618, ENST00000441159, ENST00000444908, ENST00000518791, ENST00000643242, ENST00000684770

RefSeq mRNA: 5 — MANE Select: NM_001363538 NM_001130026, NM_001363538, NM_001365428, NM_001365429, NM_173678

CCDS: CCDS34769, CCDS47735, CCDS87559, CCDS94223

Canonical transcript exons

ENST00000684770 — 8 exons

Exon	Start	End
ENSE00002443125	143723211	143723450
ENSE00002460631	143724360	143724697
ENSE00002528833	143721281	143721378
ENSE00002533605	143722658	143722871
ENSE00003734225	143719683	143720674
ENSE00003916233	143702984	143703617
ENSE00003918454	143727413	143730410
ENSE00003921191	143620974	143621020

Expression profiles

Bgee: expression breadth ubiquitous, 132 present calls, max score 81.49.

FANTOM5 (CAGE): breadth broad, TPM avg 1.5379 / max 45.7408, expressed in 638 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
81801	0.7872	422
81802	0.6015	277
204988	0.1492	53

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
islet of Langerhans	UBERON:0000006	81.49	gold quality
esophagus mucosa	UBERON:0002469	78.35	gold quality
lower esophagus mucosa	UBERON:0035834	77.55	gold quality
placenta	UBERON:0001987	76.63	gold quality
blood	UBERON:0000178	76.45	gold quality
vagina	UBERON:0000996	74.11	gold quality
granulocyte	CL:0000094	73.93	gold quality
lymph node	UBERON:0000029	73.29	gold quality
ectocervix	UBERON:0012249	72.59	gold quality
vermiform appendix	UBERON:0001154	72.16	gold quality
skin of leg	UBERON:0001511	71.80	gold quality
zone of skin	UBERON:0000014	71.46	gold quality
skin of abdomen	UBERON:0001416	70.95	gold quality
uterine cervix	UBERON:0000002	70.65	gold quality
esophagus	UBERON:0001043	70.63	gold quality
bone marrow	UBERON:0002371	70.46	gold quality
minor salivary gland	UBERON:0001830	70.27	gold quality
tonsil	UBERON:0002372	70.05	gold quality
bone marrow cell	CL:0002092	69.98	silver quality
saliva-secreting gland	UBERON:0001044	69.77	gold quality
thoracic mammary gland	UBERON:0005200	69.13	gold quality
upper lobe of left lung	UBERON:0008952	68.89	gold quality
pancreas	UBERON:0001264	68.53	gold quality
urinary bladder	UBERON:0001255	68.51	gold quality
myometrium	UBERON:0001296	68.49	gold quality
lung	UBERON:0002048	68.42	gold quality
colonic epithelium	UBERON:0000397	68.39	silver quality
gall bladder	UBERON:0002110	67.38	gold quality
right lung	UBERON:0002167	67.03	gold quality
left adrenal gland	UBERON:0001234	67.01	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.56

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

30 targeting TCAF2, 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-6851-5P	100.00	65.63	1294
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-6817-3P	99.79	68.35	2126
HSA-MIR-3059-5P	99.70	69.93	2491
HSA-MIR-6892-3P	99.68	66.40	1178
HSA-MIR-10394-5P	99.65	66.83	1852
HSA-MIR-1205	99.65	66.76	1826
HSA-MIR-18A-3P	99.56	65.68	1092
HSA-MIR-330-3P	99.41	69.95	2521
HSA-MIR-4721	99.26	66.05	818
HSA-MIR-6738-3P	99.03	67.14	1326
HSA-MIR-5001-3P	98.91	67.28	1394
HSA-MIR-3908	98.75	67.31	1160
HSA-MIR-4780	98.57	64.75	611
HSA-MIR-6880-5P	98.08	65.59	1282
HSA-MIR-6881-3P	98.04	68.24	1777
HSA-MIR-4456	97.50	64.88	1678
HSA-MIR-4786-5P	97.45	67.89	924
HSA-MIR-938	97.41	68.28	656
HSA-MIR-3616-3P	96.96	65.45	983
HSA-MIR-6886-3P	96.96	66.36	844
HSA-MIR-5194	96.77	63.91	1021
HSA-MIR-1236-5P	96.62	66.38	856
HSA-MIR-1226-5P	96.50	65.28	643
HSA-MIR-6738-5P	96.33	63.61	815
HSA-MIR-1914-3P	95.07	63.37	762
HSA-MIR-4765	93.11	66.17	737

Literature-anchored findings (GeneRIF, showing 5)

• Report novel TRP channel-associated factors that modulate TRPM8 activity. (PMID:25559186)
• Evidence for opposing selective forces operating on human-specific duplicated TCAF genes in Neanderthals and humans. (PMID:34433829)
• TCAF2 is associated with the immune microenvironment, promotes pathogenesis, and impairs prognosis in glioma. (PMID:37506986)
• TCAF2 in Pericytes Promotes Colorectal Cancer Liver Metastasis via Inhibiting Cold-Sensing TRPM8 Channel. (PMID:37635201)
• TCAF2 drives glioma cellular migratory/invasion properties through STAT3 signaling. (PMID:38019450)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	si:ch211-210b2.2	ENSDARG00000009402
danio_rerio	si:ch211-210b2.4	ENSDARG00000095212
danio_rerio	si:ch211-210b2.3	ENSDARG00000096927
danio_rerio	zgc:162193	ENSDARG00000098171
mus_musculus	Tcaf2	ENSMUSG00000029851
rattus_norvegicus	Tcaf2c	ENSRNOG00000066894
rattus_norvegicus		ENSRNOG00000073993

Paralogs (2): TCAF1 (ENSG00000198420), TCAF2C (ENSG00000283528)

Protein

Protein identifiers

TRPM8 channel-associated factor 2 — A6NFQ2 (reviewed: A6NFQ2)

Alternative names: TRP channel-associated factor 2

All UniProt accessions (2): A6NFQ2, Q8N1I1

UniProt curated annotations — full annotation on UniProt →

Function. Negatively regulates the plasma membrane cation channel TRPM8 activity. Involved in the recruitment of TRPM8 to the cell surface. Promotes prostate cancer cell migration stimulation in a TRPM8-dependent manner.

Subunit / interactions. Isoform 2 interacts with TRPM8 (via N-terminus and C-terminus domains); the interaction inhibits TRPM8 channel activity. Interacts with TRPV6.

Subcellular location. Cell membrane.

Tissue specificity. Isoform 2 is expressed in the prostate and in cancerous prostate samples.

Similarity. Belongs to the TCAF family.

Isoforms (3)

UniProt ID	Names	Canonical?
A6NFQ2-1	1	yes
A6NFQ2-2	2
A6NFQ2-3	3

RefSeq proteins (5): NP_001123498, NP_001350467, NP_001352357, NP_001352358, NP_775949 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR029062	Class_I_gatase-like	Homologous_superfamily
IPR031161	Peptidase_M60_dom	Domain
IPR035423	M60-like_N	Domain
IPR042279	Pep_M60_3	Homologous_superfamily
IPR051244	TCAF	Family

Pfam: PF13402, PF17291

UniProt features (7 total): splice variant 3, sequence conflict 2, chain 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A6NFQ2-F1	92.74	0.82

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 93 (showing top): GOBP_NEGATIVE_REGULATION_OF_TRANSMEMBRANE_TRANSPORT, BENPORATH_ES_WITH_H3K27ME3, GOBP_NEGATIVE_REGULATION_OF_TRANSPORTER_ACTIVITY, GOBP_PROTEIN_TARGETING, GOBP_REGULATION_OF_PROTEIN_TARGETING_TO_MEMBRANE, GOBP_PROTEIN_TARGETING_TO_MEMBRANE, GOBP_NEGATIVE_REGULATION_OF_TRANSPORT, GOBP_REGULATION_OF_CELLULAR_LOCALIZATION, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_MEMBRANE, GOBP_NEGATIVE_REGULATION_OF_MOLECULAR_FUNCTION, GOBP_LOCALIZATION_WITHIN_MEMBRANE, GOBP_REGULATION_OF_TRANSPORT, GOBP_NEGATIVE_REGULATION_OF_MONOATOMIC_ION_TRANSPORT, GOBP_REGULATION_OF_MONOATOMIC_ION_TRANSPORT, chr7q35

GO Biological Process (3): negative regulation of anion channel activity (GO:0010360), positive regulation of cell migration (GO:0030335), positive regulation of protein targeting to membrane (GO:0090314)

GO Molecular Function (2): transmembrane transporter binding (GO:0044325), protein binding (GO:0005515)

GO Cellular Component (3): plasma membrane (GO:0005886), cell junction (GO:0030054), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
monoatomic anion channel activity	1
negative regulation of ion transmembrane transporter activity	1
negative regulation of anion transmembrane transport	1
cell migration	1
regulation of cell migration	1
positive regulation of cell motility	1
protein targeting to membrane	1
positive regulation of cellular process	1
regulation of protein targeting to membrane	1
positive regulation of establishment of protein localization	1
protein binding	1
binding	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

430 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TCAF2	TRPM8	Q7Z2W7	538
TCAF2	PTPN20	Q4JDL3	458
TCAF2	CTAGE6	Q86UF2	447
TCAF2	DUSP22	Q9NRW4	392
TCAF2	ARLN	Q8WVX3	370
TCAF2	A0A0A6YYL1	A0A0A6YYL1	352
TCAF2	ZNF565	Q8N9K5	348
TCAF2	ZNF394	Q53GI3	322
TCAF2	PFKFB4	Q16877	317
TCAF2	ARHGEF5	Q12774	303
TCAF2	GPRIN2	O60269	302
TCAF2	GTF2IRD2B	Q6EKJ0	296
TCAF2	ZNF682	O95780	292
TCAF2	JHY	Q6NUN7	291
TCAF2	SERF1A	O75920	289

IntAct

77 interactions, top by confidence:

A	B	Type	Score
EFNB3	DENND11	psi-mi:“MI:0914”(association)	0.640
GYPA	TCAF2	psi-mi:“MI:0914”(association)	0.640
CD27	TCAF2	psi-mi:“MI:0914”(association)	0.640
LRRC15	TCAF2	psi-mi:“MI:0914”(association)	0.560
TCAF2	LRRC15	psi-mi:“MI:0915”(physical association)	0.560
C3AR1	TMEM120B	psi-mi:“MI:0914”(association)	0.530
MANSC1	KLRG2	psi-mi:“MI:0914”(association)	0.530
IGFBP6	TCAF2	psi-mi:“MI:0914”(association)	0.530
DLK1	TCAF2	psi-mi:“MI:0914”(association)	0.530
MADCAM1	TCAF2	psi-mi:“MI:0914”(association)	0.530
TMEM108	TCAF2	psi-mi:“MI:0914”(association)	0.530
RELL1	TCAF2	psi-mi:“MI:0914”(association)	0.530
HAVCR2	TCAF2	psi-mi:“MI:0914”(association)	0.530
NPDC1	TCAF2	psi-mi:“MI:0914”(association)	0.530
FLRT1	TCAF2	psi-mi:“MI:0914”(association)	0.530
VSIG4	TCAF2	psi-mi:“MI:0914”(association)	0.530
ODAPH	TCAF2	psi-mi:“MI:0914”(association)	0.530
GYPB	TCAF2	psi-mi:“MI:0914”(association)	0.530

BioGRID (68): FAM115C (Affinity Capture-MS), FAM115C (Affinity Capture-MS), FAM115C (Affinity Capture-MS), FAM115C (Affinity Capture-MS), FAM115C (Synthetic Lethality), FAM115C (Affinity Capture-MS), FAM115C (Affinity Capture-MS), FAM115C (Affinity Capture-MS), FAM115C (Affinity Capture-MS), FAM115C (Affinity Capture-MS), FAM115C (Affinity Capture-MS), FAM115C (Affinity Capture-MS), FAM115C (Affinity Capture-MS), FAM115C (Affinity Capture-MS), FAM115C (Affinity Capture-MS)

ESM2 similar proteins: A1L1C2, A3KNW0, A6H603, A6NFQ2, A6QLU7, A9ULG4, B1H1N7, E1BE10, E2RD63, O35405, O55230, O60294, O60906, O75771, O95479, P21709, P51839, P56201, Q0V8L6, Q149M9, Q1JPJ9, Q28DT3, Q2KJJ8, Q2TBP8, Q4R583, Q5FVH2, Q5R4Y7, Q5XIA3, Q60750, Q643R3, Q6NVG1, Q6QHF9, Q80XS7, Q865R1, Q8BG07, Q8BYR1, Q8C0L6, Q8CFX1, Q8IV08, Q8N0W3

Diamond homologs: A4IG42, A5PJN5, A6NFQ2, A6QLU7, Q5R8R3, Q5XHI4, Q6P6V7, Q6QR59, Q8BNE1, Q921K8, Q9Y4C2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	82
Likely benign	5
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

2473 predictions. Top by Δscore:

Variant	Effect	Δscore
7:143727410:CAGC:C	acceptor_loss	1.0000
7:143727411:A:AG	acceptor_gain	1.0000
7:143727411:A:C	acceptor_loss	1.0000
7:143727412:G:GA	acceptor_gain	1.0000
7:143727412:GC:G	acceptor_gain	1.0000
7:143623760:A:AG	acceptor_gain	0.9900
7:143623761:G:GG	acceptor_gain	0.9900
7:143623761:GCA:G	acceptor_gain	0.9900
7:143624019:G:GG	donor_gain	0.9900
7:143702979:A:AG	acceptor_gain	0.9900
7:143702980:G:GG	acceptor_gain	0.9900
7:143702980:GCA:G	acceptor_gain	0.9900
7:143719677:TTCCA:T	acceptor_loss	0.9900
7:143719678:TCCA:T	acceptor_loss	0.9900
7:143719681:A:AT	acceptor_loss	0.9900
7:143719682:G:GT	acceptor_loss	0.9900
7:143719682:GGTAT:G	acceptor_gain	0.9900
7:143723447:GCTG:G	donor_gain	0.9900
7:143724496:G:GT	donor_gain	0.9900
7:143727412:GCT:G	acceptor_gain	0.9900
7:143727412:GCTC:G	acceptor_gain	0.9900
7:143727412:GCTCC:G	acceptor_gain	0.9900
7:143625338:G:A	acceptor_gain	0.9800
7:143700932:GC:G	donor_gain	0.9800
7:143701659:G:GT	donor_gain	0.9800
7:143702976:TGCA:T	acceptor_loss	0.9800
7:143702977:GCA:G	acceptor_loss	0.9800
7:143702979:A:C	acceptor_loss	0.9800
7:143702980:G:GA	acceptor_loss	0.9800
7:143703238:G:GG	donor_gain	0.9800

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000196077 (7:143730658 A>C), RS1000197200 (7:143632485 C>T), RS1000252547 (7:143727187 AC>A), RS1000275212 (7:143701836 G>A,T), RS1000283750 (7:143725905 C>G,T), RS1000526715 (7:143633483 A>G), RS1000589963 (7:143724400 G>A), RS1000620969 (7:143721676 T>A,C,G), RS1001577349 (7:143637656 C>T), RS1001652302 (7:143634336 A>C), RS1001807489 (7:143728090 G>A,T), RS1002071010 (7:143725189 T>A), RS1002549283 (7:143724767 T>A,C), RS1002580062 (7:143650267 C>T), RS1002653784 (7:143648165 C>T)

Disease associations

OMIM: gene MIM:616252 | 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
GCST004749_16	Lung cancer in ever smokers	5.000000e-06
GCST008114_13	Type 2 diabetes	8.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

33 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
epigallocatechin gallate	affects cotreatment, increases expression	2
Acetaminophen	decreases expression, increases expression	2
aristolochic acid I	decreases expression	1
sotorasib	decreases expression, affects cotreatment	1
bisphenol A	decreases expression	1
decabromobiphenyl ether	increases expression	1
sodium arsenite	decreases expression	1
butyraldehyde	increases expression	1
tetrabromobisphenol A	increases expression	1
potassium chromate(VI)	affects cotreatment, increases expression	1
maleic acid	increases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, increases expression	1
pentabrominated diphenyl ether 100	increases expression	1
bisphenol S	decreases expression	1
trametinib	affects cotreatment, decreases expression	1
NVP-BKM120	affects cotreatment, decreases expression	1
theaflavin-3,3’-digallate	affects expression	1
Catechin	affects cotreatment, increases expression	1
Diethylhexyl Phthalate	increases expression	1
Gasoline	affects cotreatment, decreases expression, increases abundance	1
N-Nitrosopyrrolidine	increases expression	1
Polycyclic Aromatic Hydrocarbons	affects cotreatment, decreases expression, increases abundance	1
Silicon Dioxide	decreases expression	1
Smoke	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Valproic Acid	decreases methylation	1
Aflatoxin B1	increases expression	1
Asbestos, Crocidolite	decreases expression	1
Sodium Selenite	decreases expression	1
Cadmium Chloride	increases expression	1

Clinical trials (associated diseases)

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