TTPAL

Summary

TTPAL (alpha tocopherol transfer protein like, HGNC:16114) is a protein-coding gene on chromosome 20q13.12, encoding Alpha-tocopherol transfer protein-like (Q9BTX7). May act as a protein that binds a hydrophobic ligand.

Predicted to enable phosphatidylinositol bisphosphate binding activity. Located in membrane.

Source: NCBI Gene 79183 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 47 total
• MANE Select transcript: NM_001039199

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16114
Approved symbol	TTPAL
Name	alpha tocopherol transfer protein like
Location	20q13.12
Locus type	gene with protein product
Status	Approved
Aliases	dJ179M20.3
Ensembl gene	ENSG00000124120
Ensembl biotype	protein_coding
OMIM	621341
Entrez	79183

Gene structure

Transcript identifiers

Ensembl transcripts: 27 — 26 protein_coding, 1 retained_intron

ENST00000262605, ENST00000372904, ENST00000372906, ENST00000456317, ENST00000461134, ENST00000901707, ENST00000901708, ENST00000901709, ENST00000901710, ENST00000901711, ENST00000901712, ENST00000901713, ENST00000901714, ENST00000901715, ENST00000901716, ENST00000901717, ENST00000901718, ENST00000901719, ENST00000901720, ENST00000901721, ENST00000901722, ENST00000901723, ENST00000901724, ENST00000901725, ENST00000901726, ENST00000901727, ENST00000945911

RefSeq mRNA: 3 — MANE Select: NM_001039199 NM_001039199, NM_001261839, NM_024331

CCDS: CCDS13332

Canonical transcript exons

ENST00000262605 — 5 exons

Exon	Start	End
ENSE00000844868	44479985	44480444
ENSE00000844869	44484337	44484530
ENSE00000991517	44489263	44494603
ENSE00001126525	44486596	44486706
ENSE00001948495	44475874	44475991

Expression profiles

Bgee: expression breadth ubiquitous, 252 present calls, max score 93.73.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.4155 / max 145.2724, expressed in 1778 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
184724	6.0351	1725
184725	5.2911	1645
184728	0.0643	7
184727	0.0183	6
184729	0.0066	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
decidua	UBERON:0002450	93.73	gold quality
gingival epithelium	UBERON:0001949	88.37	gold quality
liver	UBERON:0002107	88.14	gold quality
right lobe of liver	UBERON:0001114	87.36	gold quality
tibia	UBERON:0000979	86.79	gold quality
esophagus squamous epithelium	UBERON:0006920	85.65	gold quality
gingiva	UBERON:0001828	85.51	gold quality
secondary oocyte	CL:0000655	84.18	gold quality
nipple	UBERON:0002030	83.93	gold quality
trabecular bone tissue	UBERON:0002483	83.78	gold quality
epithelium of esophagus	UBERON:0001976	83.19	gold quality
stromal cell of endometrium	CL:0002255	82.69	gold quality
endometrium	UBERON:0001295	82.05	gold quality
medial globus pallidus	UBERON:0002477	81.86	gold quality
epithelium of nasopharynx	UBERON:0001951	81.73	gold quality
islet of Langerhans	UBERON:0000006	81.52	gold quality
penis	UBERON:0000989	81.17	gold quality
middle temporal gyrus	UBERON:0002771	81.14	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	80.98	gold quality
corpus epididymis	UBERON:0004359	80.53	gold quality
globus pallidus	UBERON:0001875	80.48	gold quality
bone marrow	UBERON:0002371	80.34	gold quality
blood	UBERON:0000178	79.97	gold quality
tonsil	UBERON:0002372	79.52	gold quality
upper leg skin	UBERON:0004262	79.47	gold quality
pericardium	UBERON:0002407	79.43	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.41	gold quality
amniotic fluid	UBERON:0000173	79.41	gold quality
squamous epithelium	UBERON:0006914	79.29	gold quality
mammalian vulva	UBERON:0000997	79.24	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.86

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

198 targeting TTPAL, 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-1252-5P	100.00	69.80	2774
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-4713-3P	100.00	65.92	505
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-23B-5P	99.98	66.07	587
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-3912-5P	99.95	66.11	925
HSA-MIR-651-3P	99.94	73.48	5177

Literature-anchored findings (GeneRIF, showing 3)

• High TTPAL expression is associated with Colorectal Tumorigenesis. (PMID:31018940)
• TTPAL promotes gastric tumorigenesis by directly targeting NNMT to activate PI3K/AKT signaling. (PMID:34642500)
• Investigation of the expression levels of CDH1, FHIT, PTEN, and TTPAL genes in colorectal tumors. (PMID:36161592)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	ttpal	ENSDARG00000070644
mus_musculus	Ttpal	ENSMUSG00000017679
rattus_norvegicus	Ttpal	ENSRNOG00000009076
drosophila_melanogaster	CG10237	FBGN0032783

Paralogs (3): RLBP1 (ENSG00000140522), CLVS2 (ENSG00000146352), CLVS1 (ENSG00000177182)

Protein

Protein identifiers

Alpha-tocopherol transfer protein-like — Q9BTX7 (reviewed: Q9BTX7)

All UniProt accessions (3): A6PVK2, Q9BTX7, Q5QPC2

UniProt curated annotations — full annotation on UniProt →

Function. May act as a protein that binds a hydrophobic ligand.

RefSeq proteins (3): NP_001034288, NP_001248768, NP_077307 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001251	CRAL-TRIO_dom	Domain
IPR011074	CRAL/TRIO_N_dom	Domain
IPR036273	CRAL/TRIO_N_dom_sf	Homologous_superfamily
IPR036865	CRAL-TRIO_dom_sf	Homologous_superfamily

Pfam: PF00650, PF03765

UniProt features (5 total): chain 1, domain 1, region of interest 1, compositionally biased region 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BTX7-F1	86.11	0.79

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 147 (showing top): GSE45365_NK_CELL_VS_BCELL_UP, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, SP3_Q3, MONNIER_POSTRADIATION_TUMOR_ESCAPE_UP, GOCC_TRANS_GOLGI_NETWORK, RYTTCCTG_ETS2_B, GRADE_COLON_AND_RECTAL_CANCER_UP, GOCC_TRANS_GOLGI_NETWORK_MEMBRANE, SCGGAAGY_ELK1_02, GOCC_ORGANELLE_SUBCOMPARTMENT, GOMF_PHOSPHATIDYLINOSITOL_3_5_BISPHOSPHATE_BINDING, MGGAAGTG_GABP_B, GOMF_PHOSPHATIDYLINOSITOL_PHOSPHATE_BINDING, CCGNMNNTNACG_UNKNOWN

GO Biological Process (0):

GO Molecular Function (2): phosphatidylinositol-3,5-bisphosphate binding (GO:0080025), phosphatidylinositol bisphosphate binding (GO:1902936)

GO Cellular Component (2): membrane (GO:0016020), trans-Golgi network membrane (GO:0032588)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
phosphatidylinositol phosphate binding	1
phosphatidylinositol bisphosphate binding	1
anion binding	1
cellular anatomical structure	1
trans-Golgi network	1
organelle membrane	1

Protein interactions and networks

STRING

554 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TTPAL	OR9Q2	Q8NGE9	433
TTPAL	ZNF777	Q9ULD5	400
TTPAL	ZNF398	Q8TD17	387
TTPAL	FAM171B	Q6P995	380
TTPAL	PKIG	Q9Y2B9	369
TTPAL	A0A2R8YDH4	A0A2R8YDH4	364
TTPAL	CCDC149	Q6ZUS6	353
TTPAL	CHCHD1	Q96BP2	352
TTPAL	ZSWIM2	Q8NEG5	348
TTPAL	GRAMD4	Q6IC98	343
TTPAL	ERVMER34-1	Q9H9K5	308
TTPAL	ZFP3	Q96NJ6	305
TTPAL	TRUB2	O95900	305
TTPAL	CCDC186	Q7Z3E2	300
TTPAL	KRT82	Q9NSB4	293

IntAct

6 interactions, top by confidence:

A	B	Type	Score
ALB	F2	psi-mi:“MI:0914”(association)	0.350
DNAJC5	HIDE1	psi-mi:“MI:0914”(association)	0.350
TTPAL	HIDE1	psi-mi:“MI:0914”(association)	0.350
PLA2G5	MANBA	psi-mi:“MI:0914”(association)	0.350
NHLRC3	OGG1	psi-mi:“MI:0914”(association)	0.350

BioGRID (14): TTPAL (Synthetic Lethality), TTPAL (Affinity Capture-RNA), TTPAL (Affinity Capture-MS), RHOA (Affinity Capture-MS), MAPKAPK2 (Affinity Capture-MS), C19orf38 (Affinity Capture-MS), TTPAL (Affinity Capture-MS), TTPAL (Affinity Capture-MS), PTPN9 (Affinity Capture-MS), TTPAL (Proximity Label-MS), TTPAL (Positive Genetic), TTPAL (Proximity Label-MS), TTPAL (Affinity Capture-RNA), TTPAL (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: A6JFQ6, A6JUQ6, E1C1U1, P10123, P12271, P41034, P49638, Q19895, Q5M7E1, Q5RCA6, Q5RFR0, Q5SPP0, Q5SYC1, Q8BG92, Q8BWP5, Q8IUQ0, Q95KF7, Q9BTX7, Q9D3D0, Q9D4C9, Q9Z275, P53989, P49193, O76054, P45816, Q99J08, Q99MS0, Q8R0F9, Q9UDX3, O35239, P43378, Q641Z2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	39
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1406 predictions. Top by Δscore:

Variant	Effect	Δscore
20:44475987:GGCCG:G	donor_gain	1.0000
20:44475988:GCCGG:G	donor_gain	1.0000
20:44475989:CCGG:C	donor_loss	1.0000
20:44475993:T:G	donor_loss	1.0000
20:44486591:CACA:C	acceptor_loss	1.0000
20:44486592:ACAG:A	acceptor_gain	1.0000
20:44486593:CAGG:C	acceptor_loss	1.0000
20:44486594:A:AG	acceptor_gain	1.0000
20:44486594:A:G	acceptor_loss	1.0000
20:44486594:AG:A	acceptor_gain	1.0000
20:44486594:AGGAT:A	acceptor_gain	1.0000
20:44486595:G:GG	acceptor_gain	1.0000
20:44486595:GG:G	acceptor_gain	1.0000
20:44486595:GGAT:G	acceptor_gain	1.0000
20:44486595:GGATG:G	acceptor_gain	1.0000
20:44486702:ACAGA:A	donor_gain	1.0000
20:44486703:CAGA:C	donor_gain	1.0000
20:44486704:AGA:A	donor_gain	1.0000
20:44486704:AGAGT:A	donor_loss	1.0000
20:44486705:GA:G	donor_gain	1.0000
20:44486705:GAG:G	donor_gain	1.0000
20:44486707:G:GG	donor_gain	1.0000
20:44486707:GT:G	donor_loss	1.0000
20:44486708:TAAG:T	donor_loss	1.0000
20:44486709:A:AG	donor_loss	1.0000
20:44475988:GCCG:G	donor_gain	0.9900
20:44475992:G:GG	donor_gain	0.9900
20:44475994:GAGT:G	donor_loss	0.9900
20:44476052:G:T	donor_gain	0.9900
20:44484336:GACA:G	acceptor_gain	0.9900

AlphaMissense

2212 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:44480184:G:C	R62P	1.000
20:44480249:T:C	F84L	1.000
20:44480251:C:A	F84L	1.000
20:44480251:C:G	F84L	1.000
20:44480267:T:C	F90L	1.000
20:44480269:T:A	F90L	1.000
20:44480269:T:G	F90L	1.000
20:44480292:T:C	L98P	1.000
20:44484436:G:A	G182E	1.000
20:44484436:G:T	G182V	1.000
20:44480139:T:C	L47P	0.999
20:44480144:G:A	E49K	0.999
20:44480145:A:T	E49V	0.999
20:44480181:T:C	L61P	0.999
20:44480253:T:A	L85H	0.999
20:44480253:T:C	L85P	0.999
20:44480255:C:G	R86G	0.999
20:44480256:G:C	R86P	0.999
20:44480259:C:A	A87D	0.999
20:44480262:G:C	R88P	0.999
20:44480264:A:G	K89E	0.999
20:44480267:T:A	F90I	0.999
20:44480267:T:G	F90V	0.999
20:44480282:G:C	A95P	0.999
20:44480295:T:C	L99P	0.999
20:44480352:C:A	P118Q	0.999
20:44484342:T:A	W151R	0.999
20:44484342:T:C	W151R	0.999
20:44484428:G:C	Q179H	0.999
20:44484428:G:T	Q179H	0.999

dbSNP variants (sampled 300 via entrez): RS1000009529 (20:44477068 G>A,T), RS1000027553 (20:44474772 C>T), RS1000104577 (20:44485943 CCT>C), RS1001005752 (20:44490443 T>C), RS1001226701 (20:44476322 C>T), RS1001383292 (20:44481572 AAAGT>A), RS1002125462 (20:44490850 T>G), RS1002267759 (20:44491198 C>T), RS1002339113 (20:44484325 T>A,C,G), RS1002442007 (20:44478853 G>A,C), RS1002488385 (20:44492280 G>A,C), RS1002501124 (20:44494202 T>C), RS1002602838 (20:44489863 G>A), RS1002604471 (20:44492522 T>C), RS1002777669 (20:44479710 G>A)

Disease associations

OMIM: gene MIM:621341 | 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
GCST004131_41	Inflammatory bowel disease	1.000000e-17
GCST004133_4	Ulcerative colitis	4.000000e-30

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Cyclosporine	decreases expression	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
GSK-J4	decreases expression	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
2-butenal	decreases expression	1
sodium arsenite	decreases expression	1
ferrous chloride	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
pentabromodiphenyl ether	decreases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, increases expression	1
bisphenol S	affects cotreatment, decreases expression	1
Bortezomib	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Leflunomide	decreases expression	1
Acetaminophen	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	affects methylation	1
Atrazine	decreases expression	1
Vehicle Emissions	increases abundance, increases expression	1
Benzo(a)pyrene	increases methylation	1
Catechin	affects cotreatment, increases expression	1
Dexamethasone	affects cotreatment, decreases expression	1
Diazinon	increases methylation	1
Estradiol	affects cotreatment, increases expression	1
Gallic Acid	decreases expression	1
Indomethacin	decreases expression, affects cotreatment	1
Plant Extracts	affects cotreatment, increases expression	1
Silicon Dioxide	decreases expression	1

Clinical trials (associated diseases)

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