SEC14L4

Summary

SEC14L4 (SEC14 like lipid binding 4, HGNC:20627) is a protein-coding gene on chromosome 22q12.2, encoding SEC14-like protein 4 (Q9UDX3). 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. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 284904 — RefSeq curated summary.

At a glance

• GWAS associations: 12
• Clinical variants (ClinVar): 76 total
• Dosage sensitivity (ClinGen): haploinsufficiency dosage sensitivity unlikely, triplosensitivity no evidence
• MANE Select transcript: NM_174977

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20627
Approved symbol	SEC14L4
Name	SEC14 like lipid binding 4
Location	22q12.2
Locus type	gene with protein product
Status	Approved
Aliases	TAP3, dJ130H16.5
Ensembl gene	ENSG00000133488
Ensembl biotype	protein_coding
OMIM	612825
Entrez	284904

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 9 protein_coding, 2 nonsense_mediated_decay

ENST00000255858, ENST00000320982, ENST00000321205, ENST00000381982, ENST00000860139, ENST00000860140, ENST00000860141, ENST00000860142, ENST00000860143, ENST00000936336, ENST00000950086

RefSeq mRNA: 2 — MANE Select: NM_174977 NM_001161368, NM_174977

CCDS: CCDS13878, CCDS54517

Canonical transcript exons

ENST00000255858 — 12 exons

Exon	Start	End
ENSE00001320913	30505558	30505695
ENSE00003459407	30492474	30492557
ENSE00003479842	30494150	30494210
ENSE00003488859	30491573	30491742
ENSE00003504517	30495254	30495442
ENSE00003514521	30488902	30490246
ENSE00003541376	30494866	30494961
ENSE00003584690	30495583	30495642
ENSE00003588693	30503677	30503752
ENSE00003591111	30492049	30492155
ENSE00003670128	30495928	30495971
ENSE00003682412	30491834	30491973

Expression profiles

Bgee: expression breadth ubiquitous, 111 present calls, max score 88.80.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.4495 / max 101.4184, expressed in 111 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
193635	0.4495	111

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	88.80	gold quality
trabecular bone tissue	UBERON:0002483	87.81	gold quality
right lobe of liver	UBERON:0001114	85.55	gold quality
liver	UBERON:0002107	84.72	gold quality
lower lobe of lung	UBERON:0008949	79.83	gold quality
mammalian vulva	UBERON:0000997	78.76	gold quality
upper arm skin	UBERON:0004263	76.45	silver quality
upper leg skin	UBERON:0004262	74.38	gold quality
corpus epididymis	UBERON:0004359	72.87	gold quality
parotid gland	UBERON:0001831	72.73	gold quality
bone marrow	UBERON:0002371	72.45	gold quality
bronchial epithelial cell	CL:0002328	70.68	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	69.37	gold quality
triceps brachii	UBERON:0001509	68.84	gold quality
gluteal muscle	UBERON:0002000	68.73	gold quality
right testis	UBERON:0004534	67.74	gold quality
epithelium of bronchus	UBERON:0002031	67.29	silver quality
endothelial cell	CL:0000115	67.28	gold quality
cauda epididymis	UBERON:0004360	67.01	gold quality
bronchus	UBERON:0002185	66.97	silver quality
testis	UBERON:0000473	66.64	gold quality
nipple	UBERON:0002030	66.59	silver quality
left testis	UBERON:0004533	66.51	gold quality
upper lobe of lung	UBERON:0008948	66.09	gold quality
upper lobe of left lung	UBERON:0008952	65.40	gold quality
adult organism	UBERON:0007023	64.91	gold quality
mucosa of paranasal sinus	UBERON:0005030	64.44	gold quality
lung	UBERON:0002048	64.11	gold quality
cerebellar vermis	UBERON:0004720	63.94	gold quality
right lung	UBERON:0002167	63.38	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-CURD-119	yes	239.76
E-ANND-3	no	2.26

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ISL1, NEUROG3, RAX

miRNA regulators (miRDB)

42 targeting SEC14L4, 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-4455	100.00	65.48	1587
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-3059-5P	99.70	69.93	2491
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-143-3P	99.49	69.05	1457
HSA-MIR-4770	99.49	69.09	1451
HSA-MIR-766-3P	99.47	65.24	1811
HSA-MIR-501-3P	99.33	66.12	651
HSA-MIR-502-3P	99.33	66.12	651
HSA-MIR-504-3P	99.30	67.18	1745
HSA-MIR-6088	99.29	68.45	1284
HSA-MIR-3692-5P	99.29	67.04	1421
HSA-MIR-661	99.09	65.94	2062
HSA-MIR-6506-5P	99.04	65.66	1386
HSA-MIR-6889-3P	98.84	67.35	1198
HSA-MIR-330-5P	98.73	67.63	1788
HSA-MIR-6529-3P	98.68	66.76	1020
HSA-MIR-6728-3P	98.63	67.63	1534
HSA-MIR-767-3P	98.61	67.69	1192
HSA-MIR-619-5P	98.57	64.97	1988
HSA-MIR-6780A-3P	98.42	67.49	1518

Functional genomics

ClinGen dosage: haploinsufficiency 40 (dosage sensitivity unlikely), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 2)

• 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)
• The isolation of an alternatively spliced hTAP3 cDNA and a polymorphism within the coding region of the hTAP3/SEC14L4 gene, is reported. (PMID:20012369)

Cross-species orthologs

10 orthologs

Organism	Symbol	Gene ID
danio_rerio	sec14l8	ENSDARG00000059729
danio_rerio	sec14l7	ENSDARG00000099633
mus_musculus	Sec14l4	ENSMUSG00000019368
rattus_norvegicus	Sec14l4	ENSRNOG00000090249
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), SEC14L3 (ENSG00000100012), SEC14L5 (ENSG00000103184), SEC14L1 (ENSG00000129657), TTPA (ENSG00000137561), SEC14L6 (ENSG00000214491)

Protein

Protein identifiers

SEC14-like protein 4 — Q9UDX3 (reviewed: Q9UDX3)

Alternative names: Tocopherol-associated protein 3

All UniProt accessions (4): B2RMR2, Q9UDX3, D7F472, F8WEM2

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 (2)

UniProt ID	Names	Canonical?
Q9UDX3-1	1	yes
Q9UDX3-2	2

RefSeq proteins (2): NP_001154840, NP_777637* (*=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, PF03765

UniProt features (47 total): helix 18, strand 15, turn 6, sequence variant 4, domain 2, chain 1, splice variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
4TLG	X-RAY DIFFRACTION	1.77

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UDX3-F1	95.28	0.92

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 41 (showing top): GOMF_LIPID_BINDING, DODD_NASOPHARYNGEAL_CARCINOMA_DN, SHEDDEN_LUNG_CANCER_GOOD_SURVIVAL_A12, MIR8068, MIR3059_5P, MIR143_3P_MIR4770, MIR504_3P, MIR6780A_3P, MIR6088, MIR3179, MIR6742_3P, GSE13738_RESTING_VS_TCR_ACTIVATED_CD4_TCELL_UP, chr22q12, GSE15215_CD2_POS_VS_NEG_PDC_UP, GSE17721_CTRL_VS_GARDIQUIMOD_8H_BMDC_DN

GO Biological Process (0):

GO Molecular Function (2): lipid binding (GO:0008289), protein binding (GO:0005515)

GO Cellular Component (1): cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	2
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

526 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SEC14L4	TPM3	P06753	562
SEC14L4	TSPAN16	Q9UKR8	436
SEC14L4	CPSF4L	A6NMK7	404
SEC14L4	FAM185A	Q8N0U4	380
SEC14L4	TMEM82	A0PJX8	364
SEC14L4	C1orf162	Q8NEQ5	348
SEC14L4	SLC25A35	Q3KQZ1	339
SEC14L4	CFAP161	Q6P656	328
SEC14L4	C5orf63	A6NC05	321
SEC14L4	ZNF502	Q8TBZ5	317
SEC14L4	CNTN2	P78432	316
SEC14L4	AMZ1	Q400G9	313
SEC14L4	ZNF735	P0CB33	310
SEC14L4	CYB561D2	O14569	308
SEC14L4	ANKRD54	Q6NXT1	295

IntAct

69 interactions, top by confidence:

A	B	Type	Score
USHBP1	SEC14L4	psi-mi:“MI:0915”(physical association)	0.720
SEC14L4	USHBP1	psi-mi:“MI:0915”(physical association)	0.720
SEC14L4	TCF4	psi-mi:“MI:0915”(physical association)	0.560
REL	SEC14L4	psi-mi:“MI:0915”(physical association)	0.560
SEC14L4	INCA1	psi-mi:“MI:0915”(physical association)	0.560
BMF	SEC14L4	psi-mi:“MI:0915”(physical association)	0.560
SEC14L4	REL	psi-mi:“MI:0915”(physical association)	0.560
INCA1	SEC14L4	psi-mi:“MI:0915”(physical association)	0.560
TCF4	SEC14L4	psi-mi:“MI:0915”(physical association)	0.560
SEC14L4	BMF	psi-mi:“MI:0915”(physical association)	0.560
KRT34	SEC14L4	psi-mi:“MI:0915”(physical association)	0.560
PLEKHF2	SEC14L4	psi-mi:“MI:0915”(physical association)	0.560
CTAG1A	SEC14L4	psi-mi:“MI:0915”(physical association)	0.560
CRX	SEC14L4	psi-mi:“MI:0915”(physical association)	0.560
PAX6	SEC14L4	psi-mi:“MI:0915”(physical association)	0.560
TRIM54	SEC14L4	psi-mi:“MI:0915”(physical association)	0.560
MEOX1	SEC14L4	psi-mi:“MI:0915”(physical association)	0.560
KRT31	SEC14L4	psi-mi:“MI:0915”(physical association)	0.560
PAX5	SEC14L4	psi-mi:“MI:0915”(physical association)	0.560
HAO2	SEC14L4	psi-mi:“MI:0915”(physical association)	0.560
ZMYND12	SEC14L4	psi-mi:“MI:0915”(physical association)	0.560
TEPSIN	SEC14L4	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (28): SEC14L4 (Two-hybrid), SEC14L4 (Two-hybrid), SEC14L4 (Two-hybrid), SEC14L4 (Two-hybrid), INCA1 (Two-hybrid), SEC14L4 (Reconstituted Complex), SEC14L4 (Affinity Capture-MS), SEC14L4 (Two-hybrid), SEC14L4 (Two-hybrid), SEC14L4 (Two-hybrid), SEC14L4 (Two-hybrid), SEC14L4 (Two-hybrid), SEC14L4 (Two-hybrid), SEC14L4 (Two-hybrid), SEC14L4 (Two-hybrid)

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	65
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2376 predictions. Top by Δscore:

Variant	Effect	Δscore
22:30490107:T:TA	donor_gain	1.0000
22:30490109:A:AC	donor_gain	1.0000
22:30490110:C:CC	donor_gain	1.0000
22:30490244:CAT:C	acceptor_gain	1.0000
22:30490245:AT:A	acceptor_gain	1.0000
22:30490246:TCT:T	acceptor_loss	1.0000
22:30490247:C:CC	acceptor_gain	1.0000
22:30490247:CTGCA:C	acceptor_loss	1.0000
22:30490248:T:G	acceptor_loss	1.0000
22:30491571:A:AC	donor_gain	1.0000
22:30491572:C:CC	donor_gain	1.0000
22:30491572:CAGA:C	donor_gain	1.0000
22:30491830:CTACC:C	donor_loss	1.0000
22:30491831:TACCT:T	donor_loss	1.0000
22:30491974:C:CC	acceptor_gain	1.0000
22:30491975:T:C	acceptor_loss	1.0000
22:30492044:TGTA:T	donor_loss	1.0000
22:30492045:GTAC:G	donor_loss	1.0000
22:30492046:TACC:T	donor_loss	1.0000
22:30492047:ACC:A	donor_loss	1.0000
22:30492048:C:CA	donor_loss	1.0000
22:30492151:GTTGT:G	acceptor_gain	1.0000
22:30492152:TTGT:T	acceptor_gain	1.0000
22:30492153:TGT:T	acceptor_gain	1.0000
22:30492154:GT:G	acceptor_gain	1.0000
22:30492156:C:CC	acceptor_gain	1.0000
22:30492156:CT:C	acceptor_loss	1.0000
22:30492157:T:A	acceptor_loss	1.0000
22:30492553:TGGGG:T	acceptor_gain	1.0000
22:30492554:GGGG:G	acceptor_gain	1.0000

AlphaMissense

2678 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:30491741:A:G	W305R	0.990
22:30491741:A:T	W305R	0.990
22:30491733:A:C	F307L	0.984
22:30491733:A:T	F307L	0.984
22:30491735:A:G	F307L	0.984
22:30490234:A:G	F365S	0.979
22:30491706:A:C	F316L	0.978
22:30491706:A:T	F316L	0.978
22:30491708:A:G	F316L	0.978
22:30490233:G:C	F365L	0.976
22:30490233:G:T	F365L	0.976
22:30490235:A:G	F365L	0.976
22:30491734:A:G	F307S	0.976
22:30503686:A:G	W41R	0.971
22:30503686:A:T	W41R	0.971
22:30492536:G:T	A201D	0.967
22:30492110:A:G	L237P	0.964
22:30494930:A:T	V152E	0.962
22:30495345:A:G	L111P	0.959
22:30495629:C:G	R63P	0.959
22:30490227:G:C	N367K	0.958
22:30490227:G:T	N367K	0.958
22:30491954:A:T	V264E	0.958
22:30491573:A:C	Y361D	0.954
22:30491701:A:T	V318D	0.954
22:30491837:A:G	L303P	0.954
22:30490203:C:A	K375N	0.951
22:30490203:C:G	K375N	0.951
22:30494158:A:T	V191D	0.948
22:30495631:G:C	F62L	0.947

dbSNP variants (sampled 300 via entrez): RS1000181202 (22:30498207 C>T), RS1000451676 (22:30498402 G>A), RS1000457619 (22:30494494 A>C), RS1000475263 (22:30501290 C>G,T), RS1000487328 (22:30494772 C>A,T), RS1000847422 (22:30501086 C>A), RS1001185341 (22:30497363 A>G), RS1001280303 (22:30493447 G>A), RS1001615391 (22:30497785 A>T), RS1002104879 (22:30497784 T>C,G), RS1002238604 (22:30503975 G>A), RS1002562462 (22:30502700 G>A), RS1002592163 (22:30495753 G>A,C), RS1002670307 (22:30492339 G>A,T), RS1002743507 (22:30504940 T>G)

Disease associations

OMIM: gene MIM:612825 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

12 associations (top):

Study	Trait	p-value
GCST004621_178	Red cell distribution width	5.000000e-16
GCST006804_121	Red cell distribution width	3.000000e-16
GCST010703_155	Brain morphology (MOSTest)	3.000000e-09
GCST012134_3	hemolysis of donated blood (oxidative)	1.000000e-09
GCST90002386_492	High light scatter reticulocyte percentage of red cells	1.000000e-09
GCST90002397_597	Mean spheric corpuscular volume	2.000000e-11
GCST90002397_598	Mean spheric corpuscular volume	4.000000e-10
GCST90002404_591	Red cell distribution width	1.000000e-44
GCST90002405_415	Reticulocyte count	7.000000e-10
GCST90002405_416	Reticulocyte count	3.000000e-10
GCST90002406_568	Reticulocyte fraction of red cells	2.000000e-10
GCST90002406_569	Reticulocyte fraction of red cells	2.000000e-11

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0009188	Red cell distribution width
EFO:0004346	neuroimaging measurement
EFO:0009473	hemolysis
EFO:0007986	reticulocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Tetrachlorodibenzodioxin	affects cotreatment, increases expression, decreases expression	4
Benzo(a)pyrene	affects methylation, increases expression, increases methylation	3
aristolochic acid I	increases expression	1
dicrotophos	increases expression	1
pirinixic acid	affects binding, increases activity, increases expression	1
ethyl-p-hydroxybenzoate	decreases expression	1
sodium arsenite	decreases expression	1
3,4,3’,4’-tetrachlorobiphenyl	affects expression	1
2-ethyl-5-carboxypentyl phthalate	increases abundance, increases methylation	1
CGP 52608	affects binding, increases reaction	1
abrine	decreases expression	1
bisphenol S	decreases methylation	1
jinfukang	affects cotreatment, increases expression	1
Leflunomide	increases expression	1
Acetaminophen	decreases expression	1
Arsenic	affects methylation	1
Cisplatin	affects cotreatment, increases expression	1
Endosulfan	affects cotreatment, increases expression	1
Lead	decreases expression	1
Phthalic Acids	increases abundance, increases methylation	1
Silicon Dioxide	decreases expression	1
Smoke	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Urethane	decreases expression	1
Cyclosporine	decreases expression	1
Okadaic Acid	increases expression	1

Clinical trials (associated diseases)

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