SEC14L3

Summary

SEC14L3 (SEC14 like lipid binding 3, HGNC:18655) is a protein-coding gene on chromosome 22q12.2, encoding SEC14-like protein 3 (Q9UDX4). Probable hydrophobic ligand-binding protein; may play a role in the transport of hydrophobic ligands like tocopherol, squalene and phospholipids.

The protein encoded by this gene is highly similar to the protein encoded by the Saccharomyces cerevisiae SEC14 gene. The SEC14 protein is a phophatidylinositol transfer protein that is essential for biogenesis of Golgi-derived transport vesicles, and thus is required for the export of yeast secretory proteins from the Golgi complex. The specific function of this protein has not yet been determined. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene.

Source: NCBI Gene 266629 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 70 total
• Phenotypes (HPO): 12
• MANE Select transcript: NM_174975

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18655
Approved symbol	SEC14L3
Name	SEC14 like lipid binding 3
Location	22q12.2
Locus type	gene with protein product
Status	Approved
Aliases	TAP2
Ensembl gene	ENSG00000100012
Ensembl biotype	protein_coding
OMIM	612824
Entrez	266629

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 7 protein_coding, 1 nonsense_mediated_decay

ENST00000215812, ENST00000401751, ENST00000402286, ENST00000403066, ENST00000434642, ENST00000435069, ENST00000540910, ENST00000859021

RefSeq mRNA: 5 — MANE Select: NM_174975 NM_001257378, NM_001257379, NM_001257382, NM_001376914, NM_174975

CCDS: CCDS13877, CCDS58800, CCDS58801, CCDS93145

Canonical transcript exons

ENST00000215812 — 12 exons

Exon	Start	End
ENSE00001317700	30459229	30460142
ENSE00001837132	30471905	30472017
ENSE00003479726	30461310	30461479
ENSE00003491400	30462086	30462192
ENSE00003521524	30466334	30466394
ENSE00003539557	30468508	30468696
ENSE00003609547	30464820	30464903
ENSE00003611859	30461555	30461694
ENSE00003629653	30470019	30470078
ENSE00003639563	30470507	30470582
ENSE00003652013	30470212	30470255
ENSE00003655343	30466982	30467077

Expression profiles

Bgee: expression breadth broad, 59 present calls, max score 91.77.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
olfactory segment of nasal mucosa	UBERON:0005386	91.77	gold quality
bronchial epithelial cell	CL:0002328	89.19	gold quality
epithelium of bronchus	UBERON:0002031	88.22	gold quality
bronchus	UBERON:0002185	86.54	gold quality
mucosa of paranasal sinus	UBERON:0005030	81.59	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	76.92	gold quality
nasal cavity mucosa	UBERON:0001826	68.05	gold quality
nasal cavity epithelium	UBERON:0005384	65.00	silver quality
right lobe of liver	UBERON:0001114	63.70	gold quality
lower esophagus mucosa	UBERON:0035834	63.07	gold quality
buccal mucosa cell	CL:0002336	58.16	gold quality
liver	UBERON:0002107	57.97	gold quality
monocyte	CL:0000576	55.98	gold quality
mononuclear cell	CL:0000842	55.92	gold quality
blood	UBERON:0000178	55.42	gold quality
leukocyte	CL:0000738	53.39	gold quality
myocardium	UBERON:0002349	51.72	gold quality
bone marrow	UBERON:0002371	51.49	gold quality
left ventricle myocardium	UBERON:0006566	51.17	gold quality
cardiac muscle of right atrium	UBERON:0003379	51.07	gold quality
bone marrow cell	CL:0002092	50.62	gold quality
epithelial cell of pancreas	CL:0000083	50.52	gold quality
upper arm skin	UBERON:0004263	50.47	gold quality
quadriceps femoris	UBERON:0001377	50.37	gold quality
vastus lateralis	UBERON:0001379	50.12	gold quality
Brodmann (1909) area 46	UBERON:0006483	49.30	gold quality
blood vessel layer	UBERON:0004797	49.29	gold quality
cervix squamous epithelium	UBERON:0006922	49.20	gold quality
hair follicle	UBERON:0002073	49.18	gold quality
olfactory bulb	UBERON:0002264	48.92	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.39

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

44 targeting SEC14L3, 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-6129	100.00	66.46	2080
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-6755-5P	99.95	65.59	464
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-5004-5P	99.68	66.63	1294
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-1249-5P	99.61	66.55	2049
HSA-MIR-6797-5P	99.61	66.55	2084
HSA-MIR-516B-5P	99.56	66.33	1495
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-4251	99.40	69.19	3363
HSA-MIR-593-3P	99.22	67.28	1327
HSA-MIR-146A-3P	99.13	68.99	1881
HSA-MIR-4270	99.02	66.26	1987
HSA-MIR-6761-5P	98.71	68.03	1504
HSA-MIR-6754-5P	98.60	65.54	1627
HSA-MIR-1178-3P	98.57	67.09	890
HSA-MIR-541-5P	98.24	67.77	1181
HSA-MIR-3680-5P	98.06	66.20	394
HSA-MIR-3921	97.81	67.45	1431

Literature-anchored findings (GeneRIF, showing 7)

• Discusses cloning of rat SEC14-like protein 3 and mentions three human SPF-related genes, known as SEC14-like protein 1, 2 and 3. (PMID:15033454)
• we report a human SPF/TAP homology SEC14L3 with 2082 base pairs in length and contains an open reading frame encoding a 400 amino acids protein. Analysis shows that SEC14L3 is mapped to 22q12 and expresses only in the liver (PMID:15040456)
• Creb1/Crtc1-3 and Sec14l3 could be important for early responses of the bronchial epithelium to Th2-stimuli. (PMID:28383034)
• Here, the authors report that the zebrafish/human phosphatidylinositol transfer protein Sec14l3/SEC14L2 act as GTPase proteins to transduce Wnt signals from Frizzled to phospholipase C (PLC). (PMID:28463110)
• Genome-wide DNA methylation profiling in nonalcoholic fatty liver reveals predictive aberrant methylation in PRKCE and SEC14L3 promoters. (PMID:34108094)
• SEC14L3 plays a tumor-suppressive role in breast cancer through a Wnt/beta-catenin-related way. (PMID:35447102)
• SEC14L3 knockdown inhibited clear cell renal cell carcinoma proliferation, metastasis and sunitinib resistance through an SEC14L3/RPS3/NFkappaB positive feedback loop. (PMID:39425205)

Cross-species orthologs

10 orthologs

Organism	Symbol	Gene ID
danio_rerio	sec14l8	ENSDARG00000059729
danio_rerio	sec14l7	ENSDARG00000099633
mus_musculus	Sec14l3	ENSMUSG00000054986
rattus_norvegicus	Sec14l3	ENSRNOG00000004555
drosophila_melanogaster	retm	FBGN0031814
drosophila_melanogaster	CG13893	FBGN0035146
caenorhabditis_elegans		WBGENE00007925
caenorhabditis_elegans		WBGENE00009241
caenorhabditis_elegans	ctg-1	WBGENE00010370
caenorhabditis_elegans		WBGENE00011962

Paralogs (6): SEC14L2 (ENSG00000100003), SEC14L5 (ENSG00000103184), SEC14L1 (ENSG00000129657), SEC14L4 (ENSG00000133488), TTPA (ENSG00000137561), SEC14L6 (ENSG00000214491)

Protein

Protein identifiers

SEC14-like protein 3 — Q9UDX4 (reviewed: Q9UDX4)

Alternative names: Tocopherol-associated protein 2

All UniProt accessions (4): Q9UDX4, B5MC44, F8WB08, H7C1Y0

UniProt curated annotations — full annotation on UniProt →

Function. Probable hydrophobic ligand-binding protein; may play a role in the transport of hydrophobic ligands like tocopherol, squalene and phospholipids.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9UDX4-1	1	yes
Q9UDX4-2	2
Q9UDX4-3	3

RefSeq proteins (5): NP_001244307, NP_001244308, NP_001244311, NP_001363843, NP_777635* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001251	CRAL-TRIO_dom	Domain
IPR009038	GOLD_dom	Domain
IPR011074	CRAL/TRIO_N_dom	Domain
IPR036273	CRAL/TRIO_N_dom_sf	Homologous_superfamily
IPR036598	GOLD_dom_sf	Homologous_superfamily
IPR036865	CRAL-TRIO_dom_sf	Homologous_superfamily
IPR051064

Pfam: PF00650

UniProt features (48 total): helix 20, strand 16, sequence variant 4, turn 3, domain 2, splice variant 2, chain 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
4UYB	X-RAY DIFFRACTION	1.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UDX4-F1	96.96	0.96

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 374 (showing top): RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, WALLACE_PROSTATE_CANCER_RACE_UP, GOBP_POSITIVE_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_ANTIGEN_PRESENTATION_FOLDING_ASSEMBLY_AND_PEPTIDE_LOADING_OF_CLASS_I_MHC, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, GOBP_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_RESPONSE_TO_MC_AND_SERUM_DEPRIVATION_UP, GOBP_LEUKOCYTE_MEDIATED_CYTOTOXICITY, GOBP_ANTIGEN_PROCESSING_AND_PRESENTATION_VIA_MHC_CLASS_IB, GOBP_ANTIGEN_PROCESSING_AND_PRESENTATION_OF_PEPTIDE_ANTIGEN, GOBP_LEUKOCYTE_MEDIATED_IMMUNITY, KEGG_ABC_TRANSPORTERS, GOBP_POSITIVE_REGULATION_OF_T_CELL_MEDIATED_CYTOTOXICITY

GO Biological Process (0):

GO Molecular Function (1): lipid binding (GO:0008289)

GO Cellular Component (2): cytoplasm (GO:0005737), extracellular exosome (GO:0070062)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	1
intracellular anatomical structure	1
cellular anatomical structure	1
extracellular vesicle	1

Protein interactions and networks

STRING

528 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SEC14L3	SPHK2	Q9NRA0	377
SEC14L3	TSNAXIP1	Q2TAA8	364
SEC14L3	CANX	P27824	362
SEC14L3	PITPNB	P48739	359
SEC14L3	LHFPL7	Q6ICI0	358
SEC14L3	N4BP3	O15049	356
SEC14L3	RPS11	P04643	351
SEC14L3	MSLNL	Q96KJ4	351
SEC14L3	SPEF1	Q9Y4P9	349
SEC14L3	SVOPL	Q8N434	336
SEC14L3	GRAMD1C	Q8IYS0	335
SEC14L3	SCGB1C1	Q8TD33	329
SEC14L3	SCGB1C2	P0DMR2	328
SEC14L3	TTC9	Q92623	316
SEC14L3	CNGA4	Q8IV77	313

IntAct

4 interactions, top by confidence:

A	B	Type	Score
SEC14L3	SEC14L2	psi-mi:“MI:0914”(association)	0.530
DLG1	SEC14L3	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (7): SEC14L3 (Synthetic Lethality), SEC14L4 (Affinity Capture-MS), SEC14L2 (Affinity Capture-MS), SEC14L3 (Affinity Capture-MS), SEC14L3 (Affinity Capture-MS), SEC14L2 (Affinity Capture-MS), SEC14L4 (Affinity Capture-MS)

ESM2 similar proteins: A7T167, B3MZN7, B4PYH5, B5MCN3, F4JYJ3, O17907, O35239, O76054, P24280, P24859, P34913, P34914, P43378, P49193, P53989, P56523, P58875, P80299, Q03606, Q16KN5, Q16P87, Q29JQ0, Q2TAF8, Q4V8Q1, Q5RFR0, Q641Z2, Q653S9, Q6IPT4, Q6J756, Q6Q2C2, Q75DK1, Q78EJ9, Q8L7L1, Q8R0F9, Q91VA3, Q99J08, Q99MS0, Q9BTX7, Q9D3D0, Q9FKS0

Diamond homologs: A8Y5H7, B5MCN3, F4IHJ0, F4J7S8, F4JLE5, F4JVA6, F4JVA9, F4JYJ3, F4K6D3, O43304, O76054, P49193, P58875, Q03606, Q0V9N0, Q16KN5, Q29JQ0, Q7PWB1, Q8GXC6, Q8R0F9, Q92503, Q93ZE9, Q94A34, Q99J08, Q99MS0, Q9SI13, Q9SIW3, Q9UDX3, Q9UDX4, Q9VMD6, Q9Z1J8, Q10137, F4HP88, P24280, P24859, P33324, P45816, P46250, P53989, Q501H5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	67
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3449 predictions. Top by Δscore:

Variant	Effect	Δscore
22:30461304:ACTTA:A	donor_loss	1.0000
22:30461305:CT:C	donor_loss	1.0000
22:30461306:TT:T	donor_loss	1.0000
22:30461307:TAC:T	donor_loss	1.0000
22:30461308:A:AC	donor_gain	1.0000
22:30461308:ACA:A	donor_loss	1.0000
22:30461309:C:A	donor_loss	1.0000
22:30461309:C:CA	donor_gain	1.0000
22:30461309:CA:C	donor_gain	1.0000
22:30461309:CAG:C	donor_gain	1.0000
22:30461309:CAGA:C	donor_gain	1.0000
22:30461476:CCAC:C	acceptor_gain	1.0000
22:30461477:CAC:C	acceptor_gain	1.0000
22:30461477:CACC:C	acceptor_gain	1.0000
22:30461478:AC:A	acceptor_gain	1.0000
22:30461479:CC:C	acceptor_gain	1.0000
22:30461479:CCTG:C	acceptor_loss	1.0000
22:30461480:C:CA	acceptor_loss	1.0000
22:30461480:C:CC	acceptor_gain	1.0000
22:30461484:C:CT	acceptor_gain	1.0000
22:30461485:A:T	acceptor_gain	1.0000
22:30461565:AG:A	donor_gain	1.0000
22:30461691:TAAT:T	acceptor_gain	1.0000
22:30461692:AATC:A	acceptor_loss	1.0000
22:30461695:C:CA	acceptor_loss	1.0000
22:30461695:C:CC	acceptor_gain	1.0000
22:30461696:T:A	acceptor_loss	1.0000
22:30464815:CTT:C	donor_loss	1.0000
22:30464816:TTA:T	donor_loss	1.0000
22:30464817:TA:T	donor_loss	1.0000

AlphaMissense

2640 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:30460123:G:C	N367K	0.999
22:30460123:G:T	N367K	0.999
22:30460130:A:G	F365S	0.999
22:30461471:A:G	F307S	0.999
22:30461478:A:G	W305R	0.999
22:30461478:A:T	W305R	0.999
22:30461443:G:C	F316L	0.998
22:30461443:G:T	F316L	0.998
22:30461445:A:G	F316L	0.998
22:30461470:G:C	F307L	0.998
22:30461470:G:T	F307L	0.998
22:30461472:A:G	F307L	0.998
22:30468603:C:A	G110W	0.998
22:30460094:A:T	V377D	0.997
22:30460099:C:A	K375N	0.997
22:30460099:C:G	K375N	0.997
22:30460129:G:C	F365L	0.997
22:30460129:G:T	F365L	0.997
22:30460131:A:G	F365L	0.997
22:30460133:C:G	R364P	0.997
22:30461438:A:T	V318D	0.997
22:30464882:C:T	G201D	0.997
22:30467046:A:T	I152K	0.997
22:30468603:C:G	G110R	0.997
22:30468603:C:T	G110R	0.997
22:30470516:A:G	W41R	0.997
22:30470516:A:T	W41R	0.997
22:30460114:G:C	S370R	0.996
22:30460114:G:T	S370R	0.996
22:30460116:T:G	S370R	0.996

dbSNP variants (sampled 300 via entrez): RS1000098988 (22:30471545 G>A,C,T), RS1000264399 (22:30465619 A>G), RS1000298700 (22:30470048 C>G), RS1000370524 (22:30458063 G>A), RS1000398569 (22:30459076 A>G), RS1000523570 (22:30452672 C>T), RS1000698362 (22:30465352 A>G), RS1000956529 (22:30452392 C>A,T), RS1001055679 (22:30470278 T>C), RS1001178310 (22:30455800 G>A), RS1001355438 (22:30449573 T>C), RS1001690273 (22:30463273 G>A), RS1001787158 (22:30449203 C>T), RS1001804075 (22:30473159 C>T), RS1001809287 (22:30469767 T>A,G)

Disease associations

OMIM: gene MIM:612824 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

12 total (12 of 12 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0002110	Bronchiectasis
HP:0002205	Recurrent respiratory infections
HP:0002257	Chronic rhinitis
HP:0004429	Recurrent viral infections
HP:0004469	Chronic bronchitis
HP:0004798	Recurrent infection of the gastrointestinal tract
HP:0011109	Chronic sinusitis
HP:0011463	Childhood onset
HP:0031691	Severe viral infection
HP:0032230	Cytoplasmic antineutrophil antibody positivity
HP:0100582	Nasal polyposis

GWAS associations

0 associations (top):

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
Resveratrol	decreases expression, affects cotreatment	2
Benzo(a)pyrene	affects methylation, decreases methylation, increases expression	2
tebuconazole	decreases expression	1
Arsenicals	decreases expression	1
Copper	decreases expression, affects cotreatment	1
Diazinon	increases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Cadmium Chloride	decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B2QD	Abcam A-549 TAP2 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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