TULP2

Summary

TULP2 (TUB like protein 2, HGNC:12424) is a protein-coding gene on chromosome 19q13.33, encoding Tubby-related protein 2 (O00295).

TULP2 is a member of a family of tubby-like genes (TULPs) that encode proteins of unknown function. Members of this family have been identified in plants, vertebrates, and invertebrates. The TULP proteins share a conserved C-terminal region of approximately 200 amino acid residues.

Source: NCBI Gene 7288 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 95 total
• MANE Select transcript: NM_003323

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12424
Approved symbol	TULP2
Name	TUB like protein 2
Location	19q13.33
Locus type	gene with protein product
Status	Approved
Aliases	TUBL2, CT65
Ensembl gene	ENSG00000104804
Ensembl biotype	protein_coding
OMIM	602309
Entrez	7288

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 6 protein_coding, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000221399, ENST00000518572, ENST00000520977, ENST00000522229, ENST00000522945, ENST00000706741, ENST00000706742, ENST00000706743, ENST00000706744

RefSeq mRNA: 1 — MANE Select: NM_003323 NM_003323

CCDS: CCDS12739

Canonical transcript exons

ENST00000221399 — 13 exons

Exon	Start	End
ENSE00000718395	48889510	48889631
ENSE00000718402	48894998	48895162
ENSE00000718409	48895366	48895503
ENSE00000853369	48896430	48896556
ENSE00000853370	48897345	48897396
ENSE00000853371	48897837	48897869
ENSE00001342189	48898590	48898744
ENSE00002501941	48887950	48888261
ENSE00003996821	48880967	48881126
ENSE00003996823	48885448	48885560
ENSE00003996829	48882032	48882203
ENSE00003996832	48883754	48883852
ENSE00003996833	48883932	48884046

Expression profiles

Bgee: expression breadth ubiquitous, 159 present calls, max score 95.82.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0115 / max 10.3750, expressed in 3 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
181953	0.0074	3
181952	0.0041	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	95.82	gold quality
male germ cell	CL:0000015	93.31	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	89.93	gold quality
right testis	UBERON:0004534	89.92	gold quality
left testis	UBERON:0004533	89.85	gold quality
testis	UBERON:0000473	87.19	gold quality
granulocyte	CL:0000094	82.08	gold quality
mucosa of stomach	UBERON:0001199	79.70	gold quality
adult organism	UBERON:0007023	77.20	gold quality
bone marrow cell	CL:0002092	74.04	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	65.20	gold quality
right ovary	UBERON:0002118	63.85	gold quality
spleen	UBERON:0002106	63.50	gold quality
left uterine tube	UBERON:0001303	63.14	gold quality
left ovary	UBERON:0002119	62.60	gold quality
lower esophagus muscularis layer	UBERON:0035833	62.47	gold quality
right frontal lobe	UBERON:0002810	62.43	gold quality
lower esophagus	UBERON:0013473	62.39	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	62.18	gold quality
prefrontal cortex	UBERON:0000451	61.71	gold quality
Brodmann (1909) area 9	UBERON:0013540	61.44	gold quality
cingulate cortex	UBERON:0003027	59.88	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	59.60	gold quality
anterior cingulate cortex	UBERON:0009835	59.58	gold quality
gall bladder	UBERON:0002110	59.38	gold quality
ovary	UBERON:0000992	59.07	gold quality
body of uterus	UBERON:0009853	58.83	gold quality
muscle layer of sigmoid colon	UBERON:0035805	58.29	gold quality
frontal cortex	UBERON:0001870	58.17	gold quality
cerebellar hemisphere	UBERON:0002245	58.13	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	11.00
E-CURD-10	no	37.13

Regulation

Is transcription factor: no

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	si:dkey-220f10.4	ENSDARG00000062902
mus_musculus	Tulp2	ENSMUSG00000023467
rattus_norvegicus	Tulp2	ENSRNOG00000020927
drosophila_melanogaster	ktub	FBGN0015721

Paralogs (5): TULP3 (ENSG00000078246), TULP1 (ENSG00000112041), WDR35 (ENSG00000118965), TULP4 (ENSG00000130338), TUB (ENSG00000166402)

Protein

Protein identifiers

Tubby-related protein 2 — O00295 (reviewed: O00295)

Alternative names: Cancer/testis antigen 65, Tubby-like protein 2

All UniProt accessions (6): A0A9L9PX91, A0A9L9PXV8, E5RH05, E5RHR0, E5RIF7, O00295

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Cytoplasm. Secreted.

Tissue specificity. Strongly expressed in testis. Also expressed in retina. Expressed in cancer cell lines.

Similarity. Belongs to the TUB family.

RefSeq proteins (1): NP_003314* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000007	Tubby_C	Domain
IPR005398	Tubby_N	Domain
IPR018066	Tubby_C_CS	Conserved_site
IPR025659	Tubby-like_C	Homologous_superfamily

Pfam: PF01167, PF16322

UniProt features (12 total): sequence variant 5, compositionally biased region 2, modified residue 2, chain 1, region of interest 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O00295-F1	67.08	0.33

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (2): 135, 190

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 86 (showing top): RNGTGGGC_UNKNOWN, GOBP_PROTEIN_LOCALIZATION_TO_CILIUM, GOBP_SENSORY_PERCEPTION_OF_LIGHT_STIMULUS, MODULE_99, GOBP_PROTEIN_LOCALIZATION_TO_ORGANELLE, GOBP_SENSORY_PERCEPTION, WEBER_METHYLATED_HCP_IN_FIBROBLAST_DN, GOCC_CILIUM, WEBER_METHYLATED_HCP_IN_SPERM_DN, MODULE_248, SWEET_LUNG_CANCER_KRAS_UP, MIKKELSEN_ES_ICP_WITH_H3K4ME3, MODULE_129, PANGAS_TUMOR_SUPPRESSION_BY_SMAD1_AND_SMAD5_DN, PURBEY_TARGETS_OF_CTBP1_NOT_SATB1_DN

GO Biological Process (2): visual perception (GO:0007601), protein localization to cilium (GO:0061512)

GO Molecular Function (1): protein-containing complex binding (GO:0044877)

GO Cellular Component (3): extracellular region (GO:0005576), cytoplasm (GO:0005737), cilium (GO:0005929)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
sensory perception of light stimulus	1
protein localization to organelle	1
binding	1
intracellular anatomical structure	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1

Protein interactions and networks

STRING

650 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TULP2	SPATA31G1	Q5VYM1	627
TULP2	REDIC1	Q86WS4	595
TULP2	C9orf43	Q8TAL5	575
TULP2	GARIN2	Q8N9W8	565
TULP2	FAM209A	Q5JX71	564
TULP2	MAGEB16	A2A368	532
TULP2	TMCO5A	Q8N6Q1	507
TULP2	TTC21B	Q7Z4L5	501
TULP2	TTC9B	Q8N6N2	498
TULP2	ZFAND4	Q86XD8	497
TULP2	WBP2NL	Q6ICG8	490
TULP2	IRGQ	Q8WZA9	486
TULP2	PKDREJ	Q9NTG1	480
TULP2	EPPIN	O95925	478
TULP2	RAB23	Q9ULC3	470

IntAct

9 interactions, top by confidence:

A	B	Type	Score
TULP2	LONP1	psi-mi:“MI:0914”(association)	0.530
SRPK1	TULP2	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
EWSR1	TULP2	psi-mi:“MI:0915”(physical association)	0.370
MEOX2	TULP2	psi-mi:“MI:0915”(physical association)	0.370
TULP2	ZSWIM8	psi-mi:“MI:0914”(association)	0.350
TULP2	DDAH2	psi-mi:“MI:0914”(association)	0.350

BioGRID (62): TULP2 (Two-hybrid), TULP2 (Two-hybrid), TULP2 (Two-hybrid), CTR9 (Affinity Capture-MS), HDAC6 (Affinity Capture-MS), PAF1 (Affinity Capture-MS), LEO1 (Affinity Capture-MS), ZSWIM8 (Affinity Capture-MS), MAPK8IP2 (Affinity Capture-MS), IFT122 (Affinity Capture-MS), WDR19 (Affinity Capture-MS), SIK2 (Affinity Capture-MS), IFT140 (Affinity Capture-MS), CDC73 (Affinity Capture-MS), WDR35 (Affinity Capture-MS)

ESM2 similar proteins: A0A1W2PPD8, A2A3K4, A4Q9E5, A4Q9F0, A4Q9F1, A6PVC2, A7E379, B2GUB3, D3YWQ0, F1MAB7, O00295, O15021, O75912, O89084, O94953, O94966, P03177, P15304, P46686, P54748, Q08493, Q0P4M4, Q14999, Q1ECV4, Q1HVD1, Q28969, Q3KSQ2, Q3ULB5, Q4G017, Q5R8Z4, Q5R978, Q5RCJ3, Q5TKR9, Q6EEF3, Q6EMB2, Q6J1Y9, Q6NZK8, Q6X4W1, Q6ZT98, Q7TNN8

Diamond homologs: A8WN62, B0WI30, B0XFQ9, B3MDU3, B3NJY0, B4H4X0, B4I7J9, B4J6R7, B4KNA9, B4LMR9, B4MKC7, B4P9H8, B4QFM2, O00294, O00295, O75386, O88413, O88808, P46686, P50586, P50607, Q09306, Q0WPY0, Q10LG8, Q16IR1, Q16KI5, Q28X18, Q2QXB2, Q53PP5, Q5QM27, Q688Y7, Q68Y48, Q69U54, Q6NPQ1, Q6Z2G9, Q75HX5, Q7PZK5, Q7XSV4, Q86PC9, Q8GVE5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	78
Likely benign	7
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2194 predictions. Top by Δscore:

Variant	Effect	Δscore
19:48883973:T:TA	donor_gain	1.0000
19:48884053:C:CT	acceptor_gain	1.0000
19:48884054:A:T	acceptor_gain	1.0000
19:48884063:A:AC	acceptor_gain	1.0000
19:48885559:CG:C	acceptor_gain	1.0000
19:48885561:C:CC	acceptor_gain	1.0000
19:48887943:A:AC	donor_gain	1.0000
19:48887944:C:CC	donor_gain	1.0000
19:48887944:CTGCA:C	donor_gain	1.0000
19:48889504:TCCTA:T	donor_loss	1.0000
19:48889505:CCTAC:C	donor_loss	1.0000
19:48889506:CTA:C	donor_loss	1.0000
19:48889507:TAC:T	donor_loss	1.0000
19:48889508:A:AG	donor_loss	1.0000
19:48889628:GTCC:G	acceptor_gain	1.0000
19:48889629:TCC:T	acceptor_gain	1.0000
19:48889630:CC:C	acceptor_gain	1.0000
19:48889630:CCC:C	acceptor_gain	1.0000
19:48889631:CC:C	acceptor_gain	1.0000
19:48889632:C:A	acceptor_loss	1.0000
19:48889632:C:CC	acceptor_gain	1.0000
19:48889635:A:AC	acceptor_gain	1.0000
19:48889635:A:C	acceptor_gain	1.0000
19:48889637:G:GC	acceptor_gain	1.0000
19:48896595:C:CT	acceptor_gain	1.0000
19:48882012:A:C	donor_gain	0.9900
19:48882030:A:AC	donor_gain	0.9900
19:48882031:C:CC	donor_gain	0.9900
19:48882204:C:CA	acceptor_loss	0.9900
19:48882204:C:CC	acceptor_gain	0.9900

AlphaMissense

3414 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:48881080:G:C	F498L	0.983
19:48881080:G:T	F498L	0.983
19:48881082:A:G	F498L	0.983
19:48881104:G:C	F490L	0.980
19:48881104:G:T	F490L	0.980
19:48881106:A:G	F490L	0.980
19:48884022:G:C	F362L	0.980
19:48884022:G:T	F362L	0.980
19:48884024:A:G	F362L	0.980
19:48882054:G:C	F475L	0.977
19:48882054:G:T	F475L	0.977
19:48882056:A:G	F475L	0.977
19:48882057:G:C	N474K	0.971
19:48882057:G:T	N474K	0.971
19:48881053:G:C	S507R	0.964
19:48881053:G:T	S507R	0.964
19:48881055:T:G	S507R	0.964
19:48881035:G:C	S513R	0.963
19:48881035:G:T	S513R	0.963
19:48881037:T:G	S513R	0.963
19:48881038:G:C	F512L	0.961
19:48881038:G:T	F512L	0.961
19:48881040:A:G	F512L	0.961
19:48882090:G:C	F463L	0.960
19:48882090:G:T	F463L	0.960
19:48882092:A:G	F463L	0.960
19:48882055:A:G	F475S	0.956
19:48881068:G:C	F502L	0.953
19:48881068:G:T	F502L	0.953
19:48881070:A:G	F502L	0.953

dbSNP variants (sampled 300 via entrez): RS1000028104 (19:48897360 C>A), RS1000113043 (19:48889569 T>C), RS1000307076 (19:48883724 A>G), RS1000446799 (19:48888349 C>T), RS1000618476 (19:48882215 A>G), RS1000674338 (19:48882793 C>T), RS1000678771 (19:48883538 C>T), RS1000857859 (19:48898791 G>A), RS1000892066 (19:48898978 A>C), RS1000923926 (19:48885929 G>A), RS1000991612 (19:48892506 T>G), RS1001189129 (19:48890895 G>C), RS1001396289 (19:48885042 A>G,T), RS1001472879 (19:48893906 G>A), RS1001575211 (19:48894720 T>A)

Disease associations

OMIM: gene MIM:602309 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

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

11 total (human), top 11 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
sodium arsenite	increases expression	1
2-palmitoylglycerol	increases expression	1
licochalcone B	increases expression	1
Leflunomide	increases expression	1
Arsenic	affects methylation	1
Atrazine	increases expression	1
Methotrexate	decreases expression	1
Tetrachlorodibenzodioxin	increases expression	1
Thiram	increases expression	1
Tobacco Smoke Pollution	affects expression	1

Clinical trials (associated diseases)

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