CLPTM1L

Summary

CLPTM1L (CLPTM1 like, HGNC:24308) is a protein-coding gene on chromosome 5p15.33, encoding Lipid scramblase CLPTM1L (Q96KA5). Scramblase that mediates the translocation of glucosaminylphosphatidylinositol (alpha-D-GlcN-(1-6)-(1,2-diacyl-sn-glycero-3-phospho)-1D-myo-inositol, GlcN-PI) across the endoplasmic reticulum (ER) membrane, from the cytosolic leaflet to the luminal leaflet of the ER membrane, wh….

The protein encoded by this gene is a membrane protein whose overexpression in cisplatin-sensitive cells causes apoptosis. Polymorphisms in this gene have been reported to increase susceptibility to several cancers, including lung, pancreatic, and breast cancers.

Source: NCBI Gene 81037 — RefSeq curated summary.

At a glance

• GWAS associations: 43
• Clinical variants (ClinVar): 155 total — 1 pathogenic
• Druggable target: yes
• MANE Select transcript: NM_030782

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24308
Approved symbol	CLPTM1L
Name	CLPTM1 like
Location	5p15.33
Locus type	gene with protein product
Status	Approved
Aliases	FLJ14400, CRR9
Ensembl gene	ENSG00000049656
Ensembl biotype	protein_coding
OMIM	612585
Entrez	81037

Gene structure

Transcript identifiers

Ensembl transcripts: 27 — 14 protein_coding, 10 retained_intron, 3 protein_coding_CDS_not_defined

ENST00000320895, ENST00000503042, ENST00000503151, ENST00000503534, ENST00000505605, ENST00000505914, ENST00000506641, ENST00000507195, ENST00000507807, ENST00000508765, ENST00000511268, ENST00000511786, ENST00000512451, ENST00000513250, ENST00000515719, ENST00000630539, ENST00000879373, ENST00000924966, ENST00000924967, ENST00000924968, ENST00000924969, ENST00000924970, ENST00000966756, ENST00000966757, ENST00000966758, ENST00000966759, ENST00000966760

RefSeq mRNA: 1 — MANE Select: NM_030782 NM_030782

CCDS: CCDS3862

Canonical transcript exons

ENST00000320895 — 17 exons

Exon	Start	End
ENSE00001083946	1337904	1337982
ENSE00001083948	1338860	1339005
ENSE00001222336	1344351	1344451
ENSE00001222534	1341671	1341860
ENSE00001830316	1344680	1345099
ENSE00001951937	1317752	1318453
ENSE00003468492	1334289	1334383
ENSE00003507125	1330280	1330383
ENSE00003521257	1321635	1321679
ENSE00003523678	1331799	1331883
ENSE00003539907	1325751	1325816
ENSE00003589719	1335057	1335174
ENSE00003658112	1320616	1320731
ENSE00003682964	1322877	1322911
ENSE00003683498	1324763	1324813
ENSE00003686574	1321764	1321819
ENSE00003688659	1323787	1323869

Expression profiles

Bgee: expression breadth ubiquitous, 255 present calls, max score 99.37.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 23.1992 / max 204.9007, expressed in 1811 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
60773	16.7196	1804
60774	4.2617	1683
60772	2.0121	1261
60768	0.0818	24
60769	0.0557	19
60767	0.0311	9
60770	0.0233	9
60766	0.0139	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ileal mucosa	UBERON:0000331	99.37	gold quality
kidney epithelium	UBERON:0004819	99.27	gold quality
right lobe of thyroid gland	UBERON:0001119	98.64	gold quality
body of pancreas	UBERON:0001150	98.61	gold quality
left lobe of thyroid gland	UBERON:0001120	98.58	gold quality
oocyte	CL:0000023	98.55	gold quality
upper lobe of left lung	UBERON:0008952	98.51	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	98.48	gold quality
secondary oocyte	CL:0000655	98.46	gold quality
right lobe of liver	UBERON:0001114	98.45	gold quality
body of stomach	UBERON:0001161	98.44	gold quality
upper lobe of lung	UBERON:0008948	98.44	gold quality
right lung	UBERON:0002167	98.34	gold quality
minor salivary gland	UBERON:0001830	98.28	gold quality
stromal cell of endometrium	CL:0002255	98.19	gold quality
thyroid gland	UBERON:0002046	98.16	gold quality
skin of leg	UBERON:0001511	98.15	gold quality
small intestine Peyer’s patch	UBERON:0003454	98.14	gold quality
saliva-secreting gland	UBERON:0001044	98.08	gold quality
rectum	UBERON:0001052	98.05	gold quality
thymus	UBERON:0002370	98.05	gold quality
skin of abdomen	UBERON:0001416	97.99	gold quality
metanephros cortex	UBERON:0010533	97.94	gold quality
upper arm skin	UBERON:0004263	97.91	gold quality
spleen	UBERON:0002106	97.89	gold quality
pancreas	UBERON:0001264	97.86	gold quality
stomach	UBERON:0000945	97.84	gold quality
right testis	UBERON:0004534	97.79	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	97.79	gold quality
vermiform appendix	UBERON:0001154	97.77	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-HCAD-13	yes	91.75
E-MTAB-7249	yes	60.60
E-MTAB-9467	yes	51.84
E-ANND-3	yes	27.93
E-MTAB-10290	no	119.42

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

27 targeting CLPTM1L, 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-4282	99.99	75.36	6408
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-1271-5P	99.91	71.99	1972
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-1299	99.77	71.24	2389
HSA-MIR-494-3P	99.70	71.45	2795
HSA-MIR-5700	99.64	69.88	2280
HSA-MIR-875-3P	99.63	69.47	2548
HSA-MIR-372-5P	99.41	69.11	2299
HSA-MIR-4251	99.40	69.19	3363
HSA-MIR-196A-3P	99.19	67.34	1204
HSA-MIR-4528	99.18	69.77	1936
HSA-MIR-371A-5P	99.08	66.51	1914
HSA-MIR-2115-5P	98.66	68.07	1191
HSA-MIR-640	98.44	66.93	644
HSA-MIR-4691-5P	98.41	66.77	1343
HSA-MIR-6792-3P	98.41	66.86	1359
HSA-MIR-8078	98.32	65.73	361
HSA-MIR-12126	98.09	64.82	637
HSA-MIR-5088-5P	97.97	64.28	487
HSA-MIR-96-3P	97.47	68.03	839
HSA-MIR-8059	95.11	66.30	646
HSA-MIR-4471	95.11	66.84	755

Literature-anchored findings (GeneRIF, showing 40)

• The susceptibility region contains two genes, TERT and CLPTM1L, suggesting that one or both may have a role in lung cancer etiology. (PMID:18978790)
• Sequence variants at the TERT-CLPTM1L locus associate with many cancer types. (PMID:19151717)
• The observed associations between rs401681 and several cancers might be weaker than previously described. Lack of an association between the SNP and mean telomere length suggests association with cancer risk at this locus is not mediated through TERT. (PMID:20570912)
• Single nucleotide polymorphisms in CLPTM1L is associated with squamous cell carcinoma of the head and neck. (PMID:20802237)
• The absence of association of a single-nucleotide polymorphism in the TERT-CLPTM1L locus with age-related phenotypes was found in a large multicohort study. (PMID:21332924)
• variants in or near BAK1, DMRT1, TERT-CLPTM1L, and KITLG predispose to familial and bilateral TGCT. (PMID:21617256)
• the lung cancer susceptibility locus Tert-Clptm1l on chromosome 5p15.33 increases the risk for bronchial obstruction and emphysema. (PMID:21622582)
• Single-nucleotide polymorphisms in CLPTM1L is associated with lung cancer. (PMID:21771723)
• the TERT-CLPTM1L locus influences melanoma risk. (PMID:21993562)
• We identified a common risk variant for estrogen receptor-negative breast cancer at the TERT-CLPTM1L locus on chromosome 5p15: rs10069690 (PMID:22037553)
• We genotyped eleven SNPs in 2,892 women of African descent but were unable to detect any significant association between TERT-CLPTM1L SNPs and their predispositions for breast cancer risk. (PMID:22134622)
• haplotype G-T-A in CLPTM1L also confers a risk to glioma suggesting CLPTM1L is also involved in the etiology of glioma. (PMID:22213090)
• The CT genotype at rs401681 was more common and the TT genotype was rare in patients, and the differences were significant between lung adenocarcinoma patients and controls. This was also true for rs402710. Moreover, the frequency of the GGCTCT haplotype was higher and the TTTTTT frequency was lower in patients, especially those with lung adenocarcinoma. (PMID:22370939)
• This study implicates anti-apoptotic CLPTM1L function as a potential mechanism of susceptibility to lung tumorigenesis and resistance to chemotherapy. (PMID:22675468)
• TERT-CLPTM1L rs401681[C] allele is risk factor for basal cell carcinoma but not for squamous cell carcinoma. (PMID:22893025)
• Further molecular characterization by flow-FISH and quantitative RT-PCR suggest TERT and CLPTM1L as target genes of 5p15.33 rearrangements. (PMID:23137523)
• association between genetic polymorphism and cancer risk (PMID:23226346)
• CLPTM1L is a mitochondria protein that may be associated with an anti-apoptotic mechanism which affects drug-resistance in lung cancer cells. (PMID:23300716)
• results suggest that genetic variants in the TERT-CLPTM1L gene may predispose individuals to be susceptible to lung cancer, particularly non-small cell lung cancer, in the Chinese population (PMID:23359026)
• The 5p15.33 region containing telomerase reverse transcriptase gene (TERT) and cleft lip and palate transmembrane protein 1-like (CLPTM1L) gene showed significant association with lung cancer in Han Chinese. (PMID:23368278)
• Our results reiterate that genetic variants of TERT and CLPTM1L contribute to lung cancer susceptibility in Chinese population. (PMID:23433592)
• Longer telomere length in peripheral white blood cells is associated with risk of lung cancer and the rs2736100 (CLPTM1L-TERT) polymorphism. (PMID:23555636)
• The 5p15.33 locus involving CLPTM1L polymorphisms is significantly associated with lung cancer risk. (PMID:23653681)
• TERT-CLPTM1L genomic region was associated with increased risk of cancer. (PMID:23707794)
• Genetic variants in TERT and CLPTM1L may affect the susceptibility of lung cancer (PMID:23738012)
• Polymorphism in CLPTM1L gene is associated with lung cancer. (PMID:23908149)
• CLPTM1L SNPs (rs401681 and rs4975616) were not associated with non-small cell lung cancer in a non-smoking Han Chinese population. (PMID:24175795)
• A protumorigenic role for CLPTM1L that is critical for Ras-driven lung cancers, with potential implications for therapy and chemosensitization. (PMID:24366883)
• the role of TERT-CLPTM1L variants in the etiology of esophageal squamous cell carcinoma and lung cancer (PMID:24386361)
• CLPTM1L rs31489 was a potential biomarker for lung cancer risk in Caucasians (PMID:24535780)
• the T allele of rs401681 in CLPTM1L-TERT locus predisposes its carriers to pancreatic cancer. (PMID:24577890)
• CLPTM1L SNPs are associated with nasopharyngeal carcinoma risk. (PMID:24615621)
• our study indicated that the CLPTM1L - rs401681 (G>A) polymorphism was significantly associated with decreased lung cancer risk, especially among European populations. (PMID:24634236)
• Results suggest that CLPTM1L functions as a growth-promoting gene in the pancreas and that overexpression may lead to an abrogation of normal cytokinesis. (PMID:24648346)
• CLPTM1L-rs401681 polymorphism was not associated with lung cancer risk in Chinese males. (PMID:24861918)
• CLPTM1L polymorphisms rs402710 and rs401681 are risk-conferring factors for the development of lung cancer. [Meta-analysis] (PMID:24907075)
• Our meta-analysis provides supportive evidence that CRR9p polymorphism may influence a risk of lung cancer and non-small cell lung cancer in a protective model. (PMID:24957041)
• TERT-CLPTM1L rs401681 CT and CT/TT genotypes are associated with decreased risk of esophageal squamous cell carcinoma. (PMID:25007268)
• Six independent risk neoplasm loci marked by common single-nucleotide polymorphisms have been found: five in the TERT gene, and one in CLPTM1L gene, both on chromosome 5. (PMID:25027329)
• association of the CLPTM1L polymorphism and the risk of the lung cancer in non-smoking females in China (PMID:25037574)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	clptm1l	ENSDARG00000021048
mus_musculus	Clptm1l	ENSMUSG00000021610
rattus_norvegicus	Clptm1l	ENSRNOG00000016923
drosophila_melanogaster	CG4332	FBGN0030456
caenorhabditis_elegans		WBGENE00011761

Paralogs (1): CLPTM1 (ENSG00000104853)

Protein

Protein identifiers

Lipid scramblase CLPTM1L — Q96KA5 (reviewed: Q96KA5)

Alternative names: Cisplatin resistance-related protein 9, Cleft lip and palate transmembrane protein 1-like protein

All UniProt accessions (2): Q96KA5, G5E9Z2

UniProt curated annotations — full annotation on UniProt →

Function. Scramblase that mediates the translocation of glucosaminylphosphatidylinositol (alpha-D-GlcN-(1-6)-(1,2-diacyl-sn-glycero-3-phospho)-1D-myo-inositol, GlcN-PI) across the endoplasmic reticulum (ER) membrane, from the cytosolic leaflet to the luminal leaflet of the ER membrane, where it participates in the biosynthesis of glycosylphosphatidylinositol (GPI). GPI is a lipid glycoconjugate involved in post-translational modification of proteins. Can also translocate 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol) (phosphatidylinositol or PI), as well as several other phospholipids (1,2-diacyl-sn-glycero-3-phosphocholine, 1,2-diacyl-sn-glycero-3-phosphoethanolamine), and N-acetylglucosaminylphosphatidylinositol (GlcNAc-PI) in vitro.

Subcellular location. Endoplasmic reticulum membrane.

Tissue specificity. Ubiquitously expressed.

Induction. Up-regulated by cisplatin.

Similarity. Belongs to the CLPTM1 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q96KA5-1	1	yes
Q96KA5-2	2

RefSeq proteins (1): NP_110409* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008429	CLPTM1	Family

Pfam: PF05602

Catalyzed reactions (Rhea), 5 shown:

• a 1,2-diacyl-sn-glycero-3-phosphocholine(in) = a 1,2-diacyl-sn-glycero-3-phosphocholine(out) (RHEA:38571)
• a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol)(in) = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol)(out) (RHEA:38691)
• a 1,2-diacyl-sn-glycero-3-phosphoethanolamine(in) = a 1,2-diacyl-sn-glycero-3-phosphoethanolamine(out) (RHEA:38895)
• a 6-(alpha-D-glucosaminyl)-1-(1,2-diacyl-sn-glycero-3-phospho)-1D-myo-inositol(in) = a 6-(alpha-D-glucosaminyl)-1-(1,2-diacyl-sn-glycero-3-phospho)-1D-myo-inositol(out) (RHEA:71491)
• 6-(alpha-D-glucosaminyl)-(1-octadecanoyl,2-(9Z)-octadecenoyl-sn-glycero-3-phospho)-1D-myo-inositol(in) = 6-(alpha-D-glucosaminyl)-(1-octadecanoyl,2-(9Z)-octadecenoyl-sn-glycero-3-phospho)-1D-myo-inositol(out) (RHEA:71495)

UniProt features (20 total): topological domain 7, transmembrane region 6, glycosylation site 3, sequence variant 2, chain 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96KA5-F1	78.54	0.16

Functional residue map

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

Glycosylation sites (3): 91, 101, 229

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 124 (showing top): GSE45365_NK_CELL_VS_BCELL_UP, HONMA_DOCETAXEL_RESISTANCE, GOBP_PLASMA_MEMBRANE_ORGANIZATION, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, GOBP_REGULATION_OF_MEMBRANE_LIPID_DISTRIBUTION, PATIL_LIVER_CANCER, GOBP_ORGANOPHOSPHATE_ESTER_TRANSPORT, NIKOLSKY_BREAST_CANCER_5P15_AMPLICON, GOBP_ENDOMEMBRANE_SYSTEM_ORGANIZATION, GOBP_PHOSPHOLIPID_TRANSPORT, GOBP_MEMBRANE_ORGANIZATION, GOBP_LIPID_LOCALIZATION, SENESE_HDAC3_TARGETS_DN, GOCC_NUCLEAR_OUTER_MEMBRANE_ENDOPLASMIC_RETICULUM_MEMBRANE_NETWORK, GOCC_ORGANELLE_SUBCOMPARTMENT

GO Biological Process (3): apoptotic process (GO:0006915), lipid transport (GO:0006869), plasma membrane phospholipid scrambling (GO:0017121)

GO Molecular Function (2): phospholipid scramblase activity (GO:0017128), protein binding (GO:0005515)

GO Cellular Component (4): endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), endomembrane system (GO:0012505), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
transport	1
lipid localization	1
plasma membrane organization	1
phospholipid translocation	1
plasma membrane phospholipid scrambling	1
intramembrane lipid carrier activity	1
binding	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
vacuole	1
plasma membrane	1

Protein interactions and networks

STRING

1348 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CLPTM1L	TERT	O14746	924
CLPTM1L	NR5A2	O00482	723
CLPTM1L	DMRT1	Q9Y5R6	717
CLPTM1L	ATF7IP	Q6VMQ6	708
CLPTM1L	SLC6A18	Q96N87	690
CLPTM1L	ETNK1	Q9HBU6	630
CLPTM1L	CHRNA3	P32297	620
CLPTM1L	SLC45A2	Q9UMX9	591
CLPTM1L	CHRNA5	P30532	581
CLPTM1L	PLA2G6	O60733	579
CLPTM1L	LPCAT1	Q8NF37	577
CLPTM1L	HYKK	A2RU49	551
CLPTM1L	MC1R	Q01726	550
CLPTM1L	SOX5	P35711	497
CLPTM1L	MSH5	O43196	479

IntAct

94 interactions, top by confidence:

A	B	Type	Score
EMC7	EMC8	psi-mi:“MI:0914”(association)	0.790
VAPB	FAM83G	psi-mi:“MI:0914”(association)	0.730
GPC6	GPC4	psi-mi:“MI:0914”(association)	0.710
NIPAL1	ESYT2	psi-mi:“MI:0914”(association)	0.640
CLPTM1L	KCNF1	psi-mi:“MI:0915”(physical association)	0.560
SLC6A8	ILVBL	psi-mi:“MI:0914”(association)	0.530
UNC93B1	GPR89A	psi-mi:“MI:0914”(association)	0.530
sseJ	AGPS	psi-mi:“MI:0914”(association)	0.460
EFNA1	CLPTM1L	psi-mi:“MI:0915”(physical association)	0.400
CLPTM1L	ADRB2	psi-mi:“MI:0915”(physical association)	0.370
CLPTM1L	GK	psi-mi:“MI:0915”(physical association)	0.370
HSCB	RBP5	psi-mi:“MI:0914”(association)	0.350
ISG15	SURF4	psi-mi:“MI:0914”(association)	0.350
IFITM3	STX12	psi-mi:“MI:0914”(association)	0.350
P2RY6	ESYT2	psi-mi:“MI:0914”(association)	0.350
SLC15A3		psi-mi:“MI:0914”(association)	0.350
UNC93B1		psi-mi:“MI:0914”(association)	0.350
P2RY6	RAVER1	psi-mi:“MI:0914”(association)	0.350
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
NS3	C15orf61	psi-mi:“MI:0914”(association)	0.350
PA	ESYT2	psi-mi:“MI:0914”(association)	0.350
pipB2	PLOD2	psi-mi:“MI:0914”(association)	0.350
sseG	PSMD12	psi-mi:“MI:0914”(association)	0.350
POMK	ESYT2	psi-mi:“MI:0914”(association)	0.350
PIK3C3	USP11	psi-mi:“MI:0914”(association)	0.350
Npc1	ESYT2	psi-mi:“MI:0914”(association)	0.350
CANX	HLA-A	psi-mi:“MI:0914”(association)	0.350
CCDC47	ESYT2	psi-mi:“MI:0914”(association)	0.350

BioGRID (164): CLPTM1L (Affinity Capture-MS), CLPTM1L (Affinity Capture-MS), CLPTM1L (Proximity Label-MS), CLPTM1L (Proximity Label-MS), CLPTM1L (Affinity Capture-MS), CLPTM1L (Affinity Capture-MS), CLPTM1L (Affinity Capture-MS), CLPTM1L (Affinity Capture-MS), CLPTM1L (Affinity Capture-MS), CLPTM1L (Affinity Capture-MS), CLPTM1L (Affinity Capture-MS), CLPTM1L (Affinity Capture-MS), CLPTM1L (Affinity Capture-MS), CLPTM1L (Affinity Capture-MS), CLPTM1L (Affinity Capture-MS)

ESM2 similar proteins: A0JNC1, A2VE61, A7XZ53, B1H3H9, D3ZEH5, F4HXY7, O35052, O95674, P48651, P98191, Q00576, Q01685, Q0JR55, Q0VCK9, Q28CY9, Q28H54, Q2KHY9, Q5EA65, Q5N8Q3, Q5R7B1, Q5U239, Q5ZKD1, Q5ZKJ0, Q5ZM65, Q6AXM5, Q6DD44, Q6DED0, Q6I628, Q7ZYQ3, Q803C9, Q8BGS7, Q8BXA5, Q8CIF6, Q8NBJ9, Q91XU8, Q91ZQ0, Q92903, Q96KA5, Q99KU0, Q99L43

Diamond homologs: A2VE61, O96005, Q2NL17, Q54RJ1, Q5R7B1, Q5ZKJ0, Q6DEL2, Q6DHU1, Q8BXA5, Q8VBZ3, Q96KA5

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 127 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
amino acid transport	6	17.7×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	92
Likely benign	18
Benign	8

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1459245	NC_000005.9:g.(?218471)(1895829_?)del	Pathogenic

SpliceAI

3263 predictions. Top by Δscore:

Variant	Effect	Δscore
5:1320615:CCA:C	donor_gain	1.0000
5:1320729:AGCCT:A	acceptor_loss	1.0000
5:1320730:GC:G	acceptor_gain	1.0000
5:1320730:GCC:G	acceptor_loss	1.0000
5:1320731:CC:C	acceptor_gain	1.0000
5:1320732:C:A	acceptor_loss	1.0000
5:1320732:C:CC	acceptor_gain	1.0000
5:1320733:T:A	acceptor_loss	1.0000
5:1320741:C:CT	acceptor_gain	1.0000
5:1321630:CTCA:C	donor_loss	1.0000
5:1321632:CA:C	donor_loss	1.0000
5:1321633:A:AC	donor_gain	1.0000
5:1321634:C:CC	donor_gain	1.0000
5:1321634:CCTTG:C	donor_loss	1.0000
5:1321676:TCAA:T	acceptor_gain	1.0000
5:1321677:CAA:C	acceptor_gain	1.0000
5:1321677:CAAC:C	acceptor_gain	1.0000
5:1321678:AA:A	acceptor_gain	1.0000
5:1321679:ACTG:A	acceptor_loss	1.0000
5:1321680:C:CC	acceptor_gain	1.0000
5:1321680:CTGA:C	acceptor_loss	1.0000
5:1321681:T:G	acceptor_loss	1.0000
5:1321687:A:T	acceptor_gain	1.0000
5:1322908:CCAG:C	acceptor_gain	1.0000
5:1322909:CAGC:C	acceptor_gain	1.0000
5:1323786:CCT:C	donor_gain	1.0000
5:1323870:C:CC	acceptor_gain	1.0000
5:1324810:CAAA:C	acceptor_gain	1.0000
5:1324814:C:CC	acceptor_gain	1.0000
5:1325745:TCCTA:T	donor_loss	1.0000

AlphaMissense

3543 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:1320660:G:C	C496W	1.000
5:1320661:C:T	C496Y	1.000
5:1320700:G:T	A483D	1.000
5:1320702:A:C	F482L	1.000
5:1320702:A:T	F482L	1.000
5:1320704:A:G	F482L	1.000
5:1320708:G:C	D480E	1.000
5:1320708:G:T	D480E	1.000
5:1320709:T:A	D480V	1.000
5:1320709:T:C	D480G	1.000
5:1320709:T:G	D480A	1.000
5:1320710:C:G	D480H	1.000
5:1320712:T:A	D479V	1.000
5:1330341:A:G	L340P	1.000
5:1335081:C:G	A258P	1.000
5:1320639:A:C	F503L	0.999
5:1320639:A:T	F503L	0.999
5:1320640:A:G	F503S	0.999
5:1320641:A:G	F503L	0.999
5:1320650:C:G	D500H	0.999
5:1320651:G:C	D499E	0.999
5:1320651:G:T	D499E	0.999
5:1320652:T:A	D499V	0.999
5:1320652:T:G	D499A	0.999
5:1320653:C:G	D499H	0.999
5:1320655:C:G	R498P	0.999
5:1320662:A:G	C496R	0.999
5:1320664:G:T	A495D	0.999
5:1320670:C:G	R493P	0.999
5:1320674:G:C	H492D	0.999

dbSNP variants (sampled 300 via entrez): RS1000029949 (5:1342452 G>A), RS1000276948 (5:1343778 T>C), RS1000470723 (5:1324954 G>A), RS1000555357 (5:1323400 G>A), RS1000767871 (5:1320571 G>A,C), RS1000780123 (5:1330735 T>A,C,G), RS1000803023 (5:1331448 A>C), RS1000839853 (5:1335481 C>G,T), RS1000852663 (5:1329243 C>T), RS1000896156 (5:1319494 G>A,C), RS1000953994 (5:1335673 G>A,C), RS1001132331 (5:1331295 C>T), RS1001229181 (5:1345050 G>A,T), RS1001281415 (5:1344875 G>A,C), RS1001356355 (5:1324615 T>C)

Disease associations

OMIM: gene MIM:612585 | disease phenotypes: MIM:613135, MIM:613989

GenCC curated gene-disease

Mondo (4): parkinsonism-dystonia, infantile (MONDO:0013150), prostate cancer (MONDO:0008315), dyskeratosis congenita, autosomal dominant 2 (MONDO:0013521), idiopathic pulmonary fibrosis (MONDO:0800504)

Orphanet (3): Infantile dystonia-parkinsonism (Orphanet:238455), Familial prostate cancer (Orphanet:1331), Idiopathic pulmonary fibrosis (Orphanet:2032)

HPO phenotypes

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

GWAS associations

43 associations (top):

Study	Trait	p-value
GCST000256_1	Lung cancer	4.000000e-06
GCST000257_3	Lung cancer	8.000000e-09
GCST000318_1	Basal cell carcinoma	4.000000e-12
GCST000459_2	Lung cancer	3.000000e-09
GCST000506_3	Lung adenocarcinoma	2.000000e-10
GCST000574_3	Pancreatic cancer	7.000000e-07
GCST000701_4	Testicular germ cell cancer	1.000000e-23
GCST000761_1	Lung adenocarcinoma	2.000000e-22
GCST000842_9	Bladder cancer	5.000000e-07
GCST001267_5	Melanoma	3.000000e-08
GCST002022_7	Testicular germ cell tumor	5.000000e-24
GCST002299_3	Chronic lymphocytic leukemia	2.000000e-07
GCST002553_7	Pancreatic cancer	2.000000e-11
GCST002553_8	Pancreatic cancer	1.000000e-13
GCST002991_10	Pancreatic cancer	3.000000e-08
GCST003578_5	Nasopharyngeal carcinoma	3.000000e-14
GCST003726_10	Basal cell carcinoma	1.000000e-18
GCST003758_3	Pancreatic cancer	2.000000e-08
GCST003858_3	Oral cavity cancer	6.000000e-10
GCST004093_29	Prostate-specific antigen levels	9.000000e-13
GCST004661_1	Uveal melanoma	2.000000e-09
GCST004713_20	Testicular germ cell tumor	3.000000e-27
GCST004748_46	Lung cancer	2.000000e-32
GCST004749_103	Lung cancer in ever smokers	3.000000e-17
GCST004750_70	Squamous cell lung carcinoma	7.000000e-21
GCST005113_1	Nasopharyngeal carcinoma	6.000000e-13
GCST005113_8	Nasopharyngeal carcinoma	4.000000e-06
GCST005434_10	Pancreatic cancer	9.000000e-17
GCST005434_16	Pancreatic cancer	2.000000e-08
GCST005896_46	Non-melanoma skin cancer	2.000000e-18

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0009260	non-melanoma skin carcinoma
EFO:0008008	lower urinary tract symptom
EFO:0003924	hair color
EFO:0004632	nevus count
EFO:0007874	gut microbiome measurement

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D054990	Idiopathic Pulmonary Fibrosis	C08.381.483.652.500
D011471	Prostatic Neoplasms	C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750
C567730	Parkinsonism-Dystonia, Infantile (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067447 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.09	Kd	8.156	nM	CHEMBL3752910
8.09	ED50	8.156	nM	CHEMBL3752910

PubChem BioAssay actives

1 with measured affinity, of 2 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149840: Binding affinity to human CLPTM1L incubated for 45 mins by Kinobead based pull down assay	kd	0.0082	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases methylation, affects expression, increases expression	4
bisphenol A	affects expression, increases expression	2
bisphenol F	increases expression	1
propylparaben	increases expression	1
sodium arsenate	decreases expression	1
beta-lapachone	increases expression	1
arsenite	increases methylation	1
methylparaben	increases expression	1
sodium arsenite	decreases expression	1
cupric chloride	increases expression	1
diallyl trisulfide	increases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
CGP 52608	affects binding, increases reaction	1
bisphenol S	increases expression	1
Sunitinib	increases expression	1
Arsenic	affects methylation	1
Benzo(a)pyrene	affects methylation	1
Camptothecin	increases response to substance	1
Cisplatin	increases response to substance, decreases expression, decreases reaction	1
Dimethyl Sulfoxide	increases expression	1
Hydrogen Peroxide	affects expression	1
Ivermectin	decreases expression	1
Ribonucleotides	affects binding	1
Smoke	decreases expression	1
Tretinoin	decreases expression	1
Zinc	increases expression	1
1-Methyl-4-phenylpyridinium	decreases expression	1
Aflatoxin B1	increases methylation	1
Antirheumatic Agents	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652882	Binding	Binding affinity to human CLPTM1L incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00029224	PHASE4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00035997	PHASE4	COMPLETED	Open-label Trial on the Effect of I.V. Zoledronic Acid 4 mg on Bone Density in Hormone Sensitive Prostate Cancer Patients With Bone Metastasis
NCT00063609	PHASE4	COMPLETED	The Effect of Zoledronic Acid on Bone Loss in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy
NCT00103623	PHASE4	SUSPENDED	The Plenaxis® Experience Study
NCT00106392	PHASE4	COMPLETED	A Safety and Efficacy Study of Prograf in the Prevention of Erectile Dysfunction After Radical Prostatectomy
NCT00185029	PHASE4	UNKNOWN	MR-Lymphography and Lymph Node Staging in Prostate Cancer
NCT00199485	PHASE4	COMPLETED	Angelica Sinensis for the Treatment of Hot Flashes in Men Undergoing LHRH Therapy for Prostate Cancer
NCT00219219	PHASE4	COMPLETED	Zoledronic Acid in the Prevention of Skeletal-related Events in Hormone Refractory and Hormone-sensitive Prostate Cancer Patients With Bone Metastases
NCT00219271	PHASE4	COMPLETED	Effect Of Zoledronic Acid On Circulating And Bone Marrow-Residing Prostate Cancer Cells In Patients With Clinically Localized Prostate Cancer
NCT00237146	PHASE4	COMPLETED	Study to Evaluate Zoledronic Acid on Quality of Life and Skeletal-related Events as Adjuvant Treatment in Patients With Hormone-naïve Prostate Cancer and Bone Metastasis Who Have Undergone Orchiectomy
NCT00242554	PHASE4	COMPLETED	Open-label Phase IV Clinical Trial to Evaluate the Safety and Tolerability of Zoledronic Acid in Patients With Prostate Cancer and Bone Metastases
NCT00280098	PHASE4	COMPLETED	Docetaxel in the Treatment of Hormone Refractory Prostate Cancer
NCT00293696	PHASE4	COMPLETED	Casodex/Zoladex Biomarkers in Localised Prostate Cancer
NCT00334139	PHASE4	COMPLETED	Effect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer
NCT00375765	PHASE4	COMPLETED	Effects On Dihydrotestosterone Regulated Gene Expression In Benign Prostatic Hyperplasia Or Prostate Cancer
NCT00391690	PHASE4	COMPLETED	Evaluation of Bone Markers as Diagnostic Tools for Early Detection of Bone Metastases in Patients With High Risk Prostate Cancer
NCT00422708	PHASE4	COMPLETED	Local Anesthesia for Prostate Biopsy
NCT00526331	PHASE4	COMPLETED	Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
NCT00590213	PHASE4	COMPLETED	Compare the Value of Prophylactic Versus Therapeutic Breast Radiotherapy in CASODEX
NCT00629330	PHASE4	TERMINATED	Dissemination of Prostate Cancer Screening to PCP’s in African American Communities
NCT00771966	PHASE4	COMPLETED	Radical Prostatectomy and Perioperative Fluid Therapy
NCT00805701	PHASE4	COMPLETED	Study Assessing The Efficacy And Safety Of Avodart (Dutasteride) At Improving Urinary Symptoms In Men With Prostate Cancer Who Are Undergoing Seed Implantation
NCT00859027	PHASE4	COMPLETED	Effect Of Risedronate On Bone Mass In Older Men Receiving Neoadjuvant Therapy For Prostate Cancer
NCT00906269	PHASE4	UNKNOWN	Can Hyperbaric Oxygen Improve Erectile Function Following Surgery for Prostate Cancer
NCT00953277	PHASE4	COMPLETED	Study of Nerve Reconstruction Using AVANCE in Subjects Who Undergo Robotic Assisted Prostatectomy for Treatment of Prostate Cancer
NCT00982800	PHASE4	COMPLETED	Does Postoperative Gabapentin Reduce Pain, Opioid Consumption and Anxiety and Have a Positive Effect on Health Related Quality of Life After Radical Prostatectomy?
NCT01083199	PHASE4	COMPLETED	Global Performance Evaluation of the AMS CONTINUUM™ Device
NCT01136226	PHASE4	COMPLETED	Evaluate Recovery of Testosterone for Patients Using Eligard
NCT01161563	PHASE4	COMPLETED	Randomized Crossover Trial to Assess the Tolerability of Gonadotropin Releasing Hormone (GnRH) Analogue Administration
NCT01230905	PHASE4	COMPLETED	Study to Monitor the Effects of Androgen Suppression Treatment on the Heart
NCT01296672	PHASE4	COMPLETED	3 Month Finasteride Challenge Test Can Significantly Improve the Performance of Screening for Prostate Cancer
NCT01365143	PHASE4	TERMINATED	Prospective Randomized Trial Comparing Robotic Versus Open Radical Prostatectomy
NCT01379742	PHASE4	UNKNOWN	Comparison of Between ThinSeed™ and OncoSeed™ for Permanent Prostate Brachytherapy
NCT01486563	PHASE4	COMPLETED	Hydroxyethyl Starch and Renal Function After Radical Prostatectomy
NCT01511874	PHASE4	COMPLETED	Efficacy and Safety Study of ELIGARD 22.5mg With Prostate Cancer
NCT01512472	PHASE4	TERMINATED	Firmagon (Degarelix) Intermittent Therapy
NCT01547416	PHASE4	COMPLETED	The Effect of Combined General/Epidural Anesthesia Versus General Anesthesia on Diaphragmatic Function
NCT01571544	PHASE4	COMPLETED	The Use of Thermal Suits as Preventing Hypothermia During Surgery
NCT01581749	PHASE4	UNKNOWN	Evaluation of Truebeam for Low-Intermediate Risk Prostate Cancer
NCT01649635	PHASE4	COMPLETED	Study of Cabazitaxel Combined With Prednisone and Prophylaxis of Neutropenia Complications in the Treatment of Patients With Metastatic Castration-resistant Prostate Cancer