CMTM6

Summary

CMTM6 (CKLF like MARVEL transmembrane domain containing 6, HGNC:19177) is a protein-coding gene on chromosome 3p22.3, encoding CKLF-like MARVEL transmembrane domain-containing protein 6 (Q9NX76). Master regulator of recycling and plasma membrane expression of PD-L1/CD274, an immune inhibitory ligand critical for immune tolerance to self and antitumor immunity.

This gene belongs to the chemokine-like factor gene superfamily, a novel family that is similar to the chemokine and transmembrane 4 superfamilies. This gene is one of several chemokine-like factor genes located in a cluster on chromosome 3. This gene is widely expressed in many tissues, but the exact function of the encoded protein is unknown.

Source: NCBI Gene 54918 — RefSeq curated summary.

At a glance

• GWAS associations: 10
• Clinical variants (ClinVar): 22 total — 1 likely-pathogenic
• MANE Select transcript: NM_017801

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19177
Approved symbol	CMTM6
Name	CKLF like MARVEL transmembrane domain containing 6
Location	3p22.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ20396
Ensembl gene	ENSG00000091317
Ensembl biotype	protein_coding
OMIM	607889
Entrez	54918

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 6 protein_coding, 2 retained_intron

ENST00000205636, ENST00000478886, ENST00000495177, ENST00000855852, ENST00000855853, ENST00000855854, ENST00000855855, ENST00000935841

RefSeq mRNA: 1 — MANE Select: NM_017801 NM_017801

CCDS: CCDS2653

Canonical transcript exons

ENST00000205636 — 4 exons

Exon	Start	End
ENSE00000758826	32487938	32488036
ENSE00001328818	32481312	32484097
ENSE00001873793	32502608	32502852
ENSE00003624861	32491710	32491886

Expression profiles

Bgee: expression breadth ubiquitous, 289 present calls, max score 99.40.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 45.8693 / max 909.2950, expressed in 1811 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
41598	45.1756	1810
41594	0.4348	215
41597	0.2589	98

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
bronchial epithelial cell	CL:0002328	99.40	gold quality
epithelium of bronchus	UBERON:0002031	99.29	gold quality
bronchus	UBERON:0002185	99.23	gold quality
trabecular bone tissue	UBERON:0002483	99.17	gold quality
upper leg skin	UBERON:0004262	98.73	gold quality
mucosa of paranasal sinus	UBERON:0005030	98.54	gold quality
nipple	UBERON:0002030	98.52	gold quality
mononuclear cell	CL:0000842	98.41	gold quality
monocyte	CL:0000576	98.40	gold quality
secondary oocyte	CL:0000655	98.32	gold quality
leukocyte	CL:0000738	98.31	gold quality
mammary duct	UBERON:0001765	98.28	gold quality
epithelium of nasopharynx	UBERON:0001951	98.24	gold quality
nasopharynx	UBERON:0001728	98.22	gold quality
lower lobe of lung	UBERON:0008949	98.16	gold quality
epithelium of mammary gland	UBERON:0003244	98.15	gold quality
nasal cavity epithelium	UBERON:0005384	98.15	gold quality
skin of hip	UBERON:0001554	98.08	gold quality
palpebral conjunctiva	UBERON:0001812	98.05	gold quality
caput epididymis	UBERON:0004358	97.97	gold quality
mammalian vulva	UBERON:0000997	97.90	gold quality
upper arm skin	UBERON:0004263	97.89	gold quality
mucosa of sigmoid colon	UBERON:0004993	97.85	gold quality
bone element	UBERON:0001474	97.78	gold quality
hair follicle	UBERON:0002073	97.77	gold quality
esophagus squamous epithelium	UBERON:0006920	97.76	gold quality
oocyte	CL:0000023	97.75	gold quality
decidua	UBERON:0002450	97.74	gold quality
adult organism	UBERON:0007023	97.73	gold quality
bone marrow	UBERON:0002371	97.67	gold quality

Single-cell (SCXA)

Detected in 9 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-MTAB-8142	yes	74.25
E-HCAD-4	yes	58.20
E-MTAB-10287	yes	51.66
E-HCAD-10	yes	16.17
E-MTAB-9067	yes	11.33
E-MTAB-8498	yes	9.15
E-CURD-84	no	879.52
E-CURD-95	no	424.06
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

125 targeting CMTM6, 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-3163	100.00	77.23	8605
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-4775	99.98	75.00	6394
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-7152-3P	99.97	67.47	849
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-146A-5P	99.96	68.93	988
HSA-MIR-146B-5P	99.96	69.13	977
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-651-3P	99.94	73.48	5177

Literature-anchored findings (GeneRIF, showing 34)

• Bioinformatics based on CKLF2 cDNA and protein sequences in combination with experimental validation identified CKLFSF1-8 gene clusters, between the SCY and the TM4SF gene families. The 8 family members were cloned and characterized. (PMID:12782130)
• CMTM6 is present at the cell surface, associates with the PD-L1 protein, reduces its ubiquitination and increases PD-L1 protein half-life; CMTM6 enhances the ability of PD-L1-expressing tumour cells to inhibit T cells; collectively, our data reveal that PD-L1 relies on CMTM6/4 to efficiently carry out its inhibitory function, and suggest potential new avenues to block this pathway (PMID:28813410)
• CMTM6 depletion, via the reduction of PD-L1, significantly alleviates the suppression of tumour-specific T cell activity in vitro and in vivo; findings provide insights into the biology of PD-L1 regulation, identify a previously unrecognized master regulator of this critical immune checkpoint and highlight a potential therapeutic target to overcome immune evasion by tumour cells (PMID:28813417)
• CMTM6 plays an important role in regulating T cell activation and antitumor responses. (PMID:30131308)
• Downregulation of CMTM6 is related to HCC metastasis and the prognosis of HCC patients. (PMID:30562063)
• Quantitative Assessment of CMTM6 in the Tumor Microenvironment and Association with Response to PD-1 Pathway Blockade in Advanced-Stage Non-Small Cell Lung Cancer. (PMID:31605795)
• Targeting CMTM6 Suppresses Stem Cell-Like Properties and Enhances Antitumor Immunity in Head and Neck Squamous Cell Carcinoma. (PMID:31771985)
• CMTM5/7 are biomarkers and prognostic factors in human breast carcinoma. (PMID:32568178)
• Coexpression of CMTM6 and PD-L1 as a predictor of poor prognosis in macrotrabecular-massive hepatocellular carcinoma. (PMID:32770259)
• CMTM6 is positively correlated with PD-L1 expression and immune cells infiltration in lung squamous carcinoma. (PMID:32866782)
• OSCC cell-secreted exosomal CMTM6 induced M2-like macrophages polarization via ERK1/2 signaling pathway. (PMID:33104837)
• CMTM6 drives cisplatin resistance by regulating Wnt signaling through the ENO-1/AKT/GSK3beta axis. (PMID:33434185)
• CMTM6 Stabilizes PD-L1 Expression and Is a New Prognostic Impact Factor in Hepatocellular Carcinoma. (PMID:33553979)
• CMTM6 and PD-L1 coexpression is associated with an active immune microenvironment and a favorable prognosis in colorectal cancer. (PMID:33579737)
• HuR up-regulates cell surface PD-L1 via stabilizing CMTM6 transcript in cancer. (PMID:33649535)
• The association between the expression of PD-L1 and CMTM6 in undifferentiated pleomorphic sarcoma. (PMID:33811537)
• CMTM6 expression in M2 macrophages is a potential predictor of PD-1/PD-L1 inhibitor response in colorectal cancer. (PMID:33818637)
• CMTM6 and PD-1/PD-L1 overexpression is associated with the clinical characteristics of malignancy in oral squamous cell carcinoma. (PMID:34034998)
• High membrane expression of CMTM6 in hepatocellular carcinoma is associated with tumor recurrence. (PMID:34080242)
• The clinical and prognostic significance of CMTM6/PD-L1 in oncology. (PMID:35278198)
• The predictive value and correlation of beta-catenin, CMTM6, and PD-L1 expression in colorectal cancer. (PMID:35293763)
• CMTM6 as a master regulator of PD-L1. (PMID:35294592)
• CMTM6 and CMTM4 as two novel regulators of PD-L1 modulate the tumor microenvironment. (PMID:35958549)
• Analysis of CMTM6 and CMTM4 expression as potential regulators of the PD-L1 protein and its association with prognosis in glioma cancer. (PMID:35983975)
• CMTM6 attenuates cisplatin-induced cell death in OSCC by regulating AKT/c-Myc-driven ribosome biogenesis. (PMID:36165231)
• CMTM6 overexpression confers trastuzumab resistance in HER2-positive breast cancer. (PMID:36627608)
• CMTM6 is highly expressed in lung adenocarcinoma and can be used as a biomarker of a poor diagnosis. (PMID:36643629)
• CMTM6 recruits T cells within the endocervical adenocarcinoma microenvironment and suppresses cell proliferation via the p53 pathway. (PMID:36815510)
• From patient tissue correlates to molecular mechanisms of cancer immune evasion: the emerging role of CD58 and PD-L1 co-regulation via CMTM6. (PMID:38082156)
• Bioinformatics analysis of CMTM family in pan-cancer and preliminary exploration of CMTM6 in bladder cancer. (PMID:38113979)
• Transmembrane Protein CMTM6 Alleviates Ocular Inflammatory Response and Improves Corneal Epithelial Barrier Function in Experimental Dry Eye. (PMID:38165704)
• CMTM 6 promotes the development of thyroid cancer by inhibiting NIS activity through activating the MAPK signaling pathway. (PMID:38221563)
• Autophagy-related CMTM6 promotes glioblastoma progression by activating Wnt/beta-catenin pathway and acts as an onco-immunological biomarker. (PMID:38686653)
• CMTM6 mediates the Warburg effect and promotes the liver metastasis of colorectal cancer. (PMID:39218981)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	cmtm6	ENSDARG00000099631
mus_musculus	Cmtm6	ENSMUSG00000032434
rattus_norvegicus	Cmtm6	ENSRNOG00000010951
caenorhabditis_elegans	F28H1.4	WBGENE00017909
caenorhabditis_elegans	F47B3.3	WBGENE00018527

Paralogs (14): CMTM1 (ENSG00000089505), PLP2 (ENSG00000102007), PLLP (ENSG00000102934), CMTM3 (ENSG00000140931), CMTM2 (ENSG00000140932), MALL (ENSG00000144063), MAL2 (ENSG00000147676), CMTM7 (ENSG00000153551), MARVELD1 (ENSG00000155254), CMTM5 (ENSG00000166091), CMTM8 (ENSG00000170293), MAL (ENSG00000172005), CMTM4 (ENSG00000183723), CKLF (ENSG00000217555)

Protein

Protein identifiers

CKLF-like MARVEL transmembrane domain-containing protein 6 — Q9NX76 (reviewed: Q9NX76)

Alternative names: Chemokine-like factor superfamily member 6

All UniProt accessions (1): Q9NX76

UniProt curated annotations — full annotation on UniProt →

Function. Master regulator of recycling and plasma membrane expression of PD-L1/CD274, an immune inhibitory ligand critical for immune tolerance to self and antitumor immunity. Associates with both constitutive and IFNG-induced PD-L1/CD274 at recycling endosomes, where it protects PD-L1/CD274 from being targeted for lysosomal degradation, likely by preventing its STUB1-mediated ubiquitination. May stabilize PD-L1/CD274 expression on antigen presenting cells and potentiates inhibitory signaling by PDCD1/CD279, its receptor on T-cells, ultimately triggering T-cell anergy.

Subunit / interactions. Interacts with PD-L1/CD274 (via transmembrane domain); the interaction is direct. Interacts with CMTM4. Interacts with CD58, ARG1, ENO1 and TMPO.

Subcellular location. Cell membrane. Early endosome membrane. Recycling endosome membrane.

Tissue specificity. Expressed in the leukocytes, placenta and testis.

Similarity. Belongs to the chemokine-like factor family.

RefSeq proteins (1): NP_060271* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008253	Marvel	Domain
IPR050578	MARVEL-CKLF_proteins	Family

Pfam: PF01284

UniProt features (15 total): topological domain 5, transmembrane region 4, modified residue 3, chain 1, domain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NX76-F1	77.53	0.25

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 (3): 1, 8, 171

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-6798695	Neutrophil degranulation

MSigDB gene sets: 255 (showing top): REACTOME_INNATE_IMMUNE_SYSTEM, LU_IL4_SIGNALING, MODULE_255, RORA1_01, GOCC_VACUOLAR_MEMBRANE, GOCC_SECRETORY_GRANULE, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, MODULE_317, GOBP_VESICLE_MEDIATED_TRANSPORT, GNF2_LYN, GNF2_MCL1, FOSTER_TOLERANT_MACROPHAGE_UP, BLALOCK_ALZHEIMERS_DISEASE_UP, GATA6_01, GNF2_MYD88

GO Biological Process (3): protein transport (GO:0015031), regulation of protein stability (GO:0031647), endocytic recycling (GO:0032456)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (7): plasma membrane (GO:0005886), membrane (GO:0016020), early endosome membrane (GO:0031901), azurophil granule membrane (GO:0035577), specific granule membrane (GO:0035579), recycling endosome membrane (GO:0055038), endosome (GO:0005768)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Innate Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
endosome membrane	2
secretory granule membrane	2
transport	1
intracellular protein localization	1
establishment of protein localization	1
regulation of biological quality	1
endosomal transport	1
vesicle-mediated transport to the plasma membrane	1
binding	1
membrane	1
cell periphery	1
cellular anatomical structure	1
early endosome	1
lysosomal membrane	1
azurophil granule	1
specific granule	1
recycling endosome	1
endomembrane system	1
cytoplasmic vesicle	1

Protein interactions and networks

STRING

654 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CMTM6	CMTM8	Q8IZV2	972
CMTM6	CMTM7	Q96FZ5	960
CMTM6	CKLF	Q9UBR5	959
CMTM6	CMTM1	Q8IZ96	817
CMTM6	CMTM2	Q8TAZ6	756
CMTM6	CMTM3	Q96MX0	750
CMTM6	CD274	Q9NZQ7	746
CMTM6	CMTM5	Q96DZ9	736
CMTM6	PLLP	Q9Y342	635
CMTM6	HIP1R	O75146	499
CMTM6	STOM	P27105	430
CMTM6	CMTM4	Q8IZR5	427
CMTM6	SPOP	O43791	420
CMTM6	COPS5	Q92905	420
CMTM6	PDCD1LG2	Q9BQ51	410

IntAct

140 interactions, top by confidence:

A	B	Type	Score
CD274	PDCD1LG2	psi-mi:“MI:0914”(association)	0.740
CD274	CMTM6	psi-mi:“MI:0915”(physical association)	0.690
CMTM6	CD274	psi-mi:“MI:0915”(physical association)	0.690
CMTM6	CD274	psi-mi:“MI:0403”(colocalization)	0.690
CD40	CMTM6	psi-mi:“MI:0915”(physical association)	0.670
CD27	TCAF2	psi-mi:“MI:0914”(association)	0.640
CIAO2A	CMTM6	psi-mi:“MI:0915”(physical association)	0.560
SNRPB2	CMTM6	psi-mi:“MI:0915”(physical association)	0.560
CD160	CMTM6	psi-mi:“MI:0915”(physical association)	0.560
EHHADH	CMTM6	psi-mi:“MI:0915”(physical association)	0.560
CMTM6	SPG21	psi-mi:“MI:0915”(physical association)	0.560
APOA5	CMTM6	psi-mi:“MI:0915”(physical association)	0.560
BPIFA2	CMTM6	psi-mi:“MI:0915”(physical association)	0.560
RUSC1	CMTM6	psi-mi:“MI:0915”(physical association)	0.560
COQ8A	CMTM6	psi-mi:“MI:0915”(physical association)	0.560
RBMX	CMTM6	psi-mi:“MI:0915”(physical association)	0.560
TCEA2	CMTM6	psi-mi:“MI:0915”(physical association)	0.560
TMED8	CMTM6	psi-mi:“MI:0915”(physical association)	0.560
RBFA	CMTM6	psi-mi:“MI:0915”(physical association)	0.560
ECPAS	CMTM6	psi-mi:“MI:0915”(physical association)	0.560
MIEF1	CMTM6	psi-mi:“MI:0915”(physical association)	0.560
GLIPR1	ALOXE3	psi-mi:“MI:0914”(association)	0.560
STK16	UNC119B	psi-mi:“MI:0914”(association)	0.530

BioGRID (102): FAM9B (Two-hybrid), CMTM6 (Affinity Capture-MS), CMTM6 (Affinity Capture-MS), CMTM6 (Affinity Capture-MS), CMTM6 (Affinity Capture-MS), CMTM6 (Affinity Capture-MS), CMTM6 (Affinity Capture-MS), CMTM6 (Affinity Capture-MS), CMTM6 (Affinity Capture-MS), CMTM6 (Affinity Capture-MS), CMTM6 (Affinity Capture-MS), CD274 (Affinity Capture-Western), CMTM6 (Affinity Capture-Western), CMTM6 (Co-localization), CMTM6 (Two-hybrid)

ESM2 similar proteins: A2VE58, A3KQ86, A3LPS1, A6H7B0, A7E3W5, A8MWL6, A9SEY7, B2RZ87, O43759, O43760, O43761, O54980, O55100, O55101, O75508, O95473, P0DI72, P0DI73, P22831, P47987, Q08AU7, Q08DL4, Q13021, Q28597, Q2YDD6, Q3MHK4, Q4R3L1, Q5APC0, Q5BLB7, Q5R703, Q5REK8, Q5RFC1, Q5XGR0, Q60771, Q62876, Q63ZU3, Q6DFR5, Q7TQJ1, Q8BGN8, Q8R191

Diamond homologs: Q5RFC1, Q8CJ61, Q8IZR5, Q9CZ69, Q9NX76, A6H7B0, Q96FZ5, Q9ESD6, Q9R1Q7

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
CMTM6	“up-regulates quantity by stabilization”	CD274	stabilization

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	17
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1527002	GRCh37/hg19 3p24.2-22.3(chr3:25045365-32691140)	Likely pathogenic

SpliceAI

800 predictions. Top by Δscore:

Variant	Effect	Δscore
3:32484628:T:TA	donor_gain	1.0000
3:32487936:A:AC	donor_gain	1.0000
3:32487937:C:CG	donor_gain	1.0000
3:32487937:CA:C	donor_gain	1.0000
3:32487937:CAA:C	donor_gain	1.0000
3:32488047:A:C	acceptor_gain	1.0000
3:32502607:CCAG:C	donor_gain	1.0000
3:32484625:A:AC	donor_gain	0.9900
3:32484625:ACTT:A	donor_gain	0.9900
3:32484626:C:CC	donor_gain	0.9900
3:32484626:CTTC:C	donor_gain	0.9900
3:32484647:T:TA	donor_gain	0.9900
3:32487933:C:G	donor_loss	0.9900
3:32487937:CAAT:C	donor_gain	0.9900
3:32487937:CAATT:C	donor_gain	0.9900
3:32488036:CCTA:C	acceptor_gain	0.9900
3:32488037:CTATG:C	acceptor_loss	0.9900
3:32488038:T:G	acceptor_loss	0.9900
3:32488039:A:C	acceptor_gain	0.9900
3:32488043:A:C	acceptor_gain	0.9900
3:32488046:CA:C	acceptor_gain	0.9900
3:32488047:A:AC	acceptor_gain	0.9900
3:32488498:T:TA	donor_gain	0.9900
3:32488521:T:A	donor_gain	0.9900
3:32491805:CAAA:C	donor_gain	0.9900
3:32491887:C:CC	acceptor_gain	0.9900
3:32502602:ACT:A	donor_loss	0.9900
3:32502603:CTC:C	donor_loss	0.9900
3:32502604:T:TA	donor_loss	0.9900
3:32502605:CACCA:C	donor_loss	0.9900

AlphaMissense

1175 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:32484077:A:C	S145R	0.998
3:32484077:A:T	S145R	0.998
3:32484079:T:G	S145R	0.998
3:32491800:G:C	S75R	0.998
3:32491800:G:T	S75R	0.998
3:32491802:T:G	S75R	0.998
3:32491794:A:C	S77R	0.996
3:32491794:A:T	S77R	0.996
3:32491796:T:G	S77R	0.996
3:32484090:C:T	G141E	0.995
3:32484091:C:G	G141R	0.993
3:32484091:C:T	G141R	0.993
3:32487993:G:T	A120E	0.993
3:32491779:A:C	S82R	0.991
3:32491779:A:T	S82R	0.991
3:32491781:T:G	S82R	0.991
3:32487942:G:T	A137E	0.990
3:32484068:G:C	F148L	0.989
3:32484068:G:T	F148L	0.989
3:32484070:A:G	F148L	0.989
3:32491799:A:G	C76R	0.988
3:32491809:C:A	E72D	0.988
3:32491809:C:G	E72D	0.988
3:32491812:A:C	F71L	0.988
3:32491812:A:T	F71L	0.988
3:32491814:A:G	F71L	0.988
3:32488012:C:G	G114R	0.987
3:32488012:C:T	G114R	0.987
3:32484081:G:T	A144E	0.986
3:32491831:C:T	C65Y	0.986

dbSNP variants (sampled 300 via entrez): RS1000017925 (3:32484287 T>A), RS1000047242 (3:32501115 G>A,T), RS1000234027 (3:32481160 A>G), RS1000239822 (3:32481721 C>T), RS1000286400 (3:32481409 A>C), RS1000322557 (3:32488308 G>A), RS1000408181 (3:32487139 A>T), RS1000520105 (3:32502300 T>C), RS1000620601 (3:32482961 C>G,T), RS1000766099 (3:32496410 C>T), RS1000800088 (3:32489134 G>A,C), RS1000862308 (3:32487363 TTTC>T), RS1000974541 (3:32482492 C>G,T), RS1001637430 (3:32482883 T>C), RS1001956624 (3:32503187 A>C)

Disease associations

OMIM: gene MIM:607889 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST002221_15	Cholesterol, total	2.000000e-08
GCST002222_25	LDL cholesterol	1.000000e-08
GCST004233_61	LDL cholesterol levels	7.000000e-08
GCST004235_50	Total cholesterol levels	4.000000e-08
GCST006612_73	LDL cholesterol	4.000000e-16
GCST006614_68	Total cholesterol levels	2.000000e-16
GCST010204_86	Low density lipoprotein cholesterol levels	2.000000e-19
GCST010243_36	Apolipoprotein B levels	3.000000e-18
GCST010245_153	LDL cholesterol levels	1.000000e-18
GCST010923_7	Beta blocker survival benefit in heart failure with reduced ejection fraction (time to all cause mortality x beta blocker interaction)	5.000000e-06

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004574	total cholesterol measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004615	apolipoprotein B measurement
EFO:0004352	mortality
EFO:0007766	response to beta blocker

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	2
Tretinoin	increases expression	2
Valproic Acid	increases expression, increases methylation	2
Cyclosporine	decreases expression	2
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
perfluorooctane sulfonic acid	decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Arsenic Trioxide	increases expression	1
Air Pollutants	affects expression, increases abundance	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Benzo(a)pyrene	increases methylation	1
Cadmium	increases abundance, increases expression	1
Caffeine	decreases phosphorylation	1
Calcium Chloride	increases expression	1
Hydrogen Peroxide	affects expression	1
Ivermectin	decreases expression	1
Manganese	increases expression, affects cotreatment, increases abundance	1
Ozone	affects expression, increases abundance	1
Phenobarbital	affects expression	1
Smoke	decreases expression	1
Testosterone	decreases expression	1
Tetrachlorodibenzodioxin	increases expression	1
Tunicamycin	decreases expression	1
Urethane	increases expression	1
Mifepristone	increases expression	1
Antirheumatic Agents	decreases expression	1
Cadmium Chloride	increases abundance, increases expression	1

Cellosaurus cell lines

7 cell lines: 7 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B7WR	Abcam Raji CMTM6 KO	Cancer cell line	Male
CVCL_B9XA	Abcam THP-1 CMTM6 KO	Cancer cell line	Male
CVCL_C6Z7	Abcam PC-3 CMTM6 KO	Cancer cell line	Male
CVCL_D6B2	HyCyte Daudi KO-hCMTM6	Cancer cell line	Male
CVCL_D6CC	HyCyte Raji KO-hCMTM6	Cancer cell line	Male
CVCL_E1U0	HAP1 CMTM6 (-) 2	Cancer cell line	Male
CVCL_XM89	HAP1 CMTM6 (-) 1	Cancer cell line	Male

Clinical trials (associated diseases)

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