CMTM7

Summary

CMTM7 (CKLF like MARVEL transmembrane domain containing 7, HGNC:19178) is a protein-coding gene on chromosome 3p22.3, encoding CKLF-like MARVEL transmembrane domain-containing protein 7 (Q96FZ5).

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 acts as a tumor suppressor that regulates G1/S transition in the cell cycle, and epidermal growth factor receptor/protein kinase B signaling during tumor pathogenesis. Alternative splicing results in multiple transcript variants encoding different isoforms.

Source: NCBI Gene 112616 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 31 total
• MANE Select transcript: NM_138410

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19178
Approved symbol	CMTM7
Name	CKLF like MARVEL transmembrane domain containing 7
Location	3p22.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ30992
Ensembl gene	ENSG00000153551
Ensembl biotype	protein_coding
OMIM	607890
Entrez	112616

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 7 protein_coding, 2 nonsense_mediated_decay, 1 retained_intron

ENST00000334983, ENST00000349718, ENST00000454304, ENST00000464689, ENST00000465248, ENST00000487007, ENST00000875110, ENST00000875111, ENST00000929477, ENST00000929478

RefSeq mRNA: 2 — MANE Select: NM_138410 NM_138410, NM_181472

CCDS: CCDS33730, CCDS33731

Canonical transcript exons

ENST00000334983 — 5 exons

Exon	Start	End
ENSE00001011368	32452392	32452473
ENSE00001011370	32449454	32449552
ENSE00001075736	32441840	32442013
ENSE00001358259	32391853	32392065
ENSE00001902389	32454241	32455528

Expression profiles

Bgee: expression breadth ubiquitous, 219 present calls, max score 95.55.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 41.2397 / max 310.2784, expressed in 1679 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
35880	27.5812	1623
35879	8.3102	1539
35877	4.9581	1182
35878	0.3902	233

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	95.55	gold quality
blood	UBERON:0000178	94.14	gold quality
epithelial cell of pancreas	CL:0000083	93.80	silver quality
leukocyte	CL:0000738	93.80	gold quality
spleen	UBERON:0002106	93.70	gold quality
ileal mucosa	UBERON:0000331	93.65	gold quality
right lung	UBERON:0002167	93.58	gold quality
monocyte	CL:0000576	93.57	gold quality
right uterine tube	UBERON:0001302	93.22	gold quality
bone marrow	UBERON:0002371	92.25	gold quality
upper lobe of left lung	UBERON:0008952	92.01	gold quality
lymph node	UBERON:0000029	91.86	gold quality
upper lobe of lung	UBERON:0008948	91.76	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	91.75	gold quality
vermiform appendix	UBERON:0001154	91.55	gold quality
bone marrow cell	CL:0002092	90.97	gold quality
epithelium of nasopharynx	UBERON:0001951	90.91	gold quality
epithelium of mammary gland	UBERON:0003244	90.08	gold quality
nasal cavity epithelium	UBERON:0005384	90.07	gold quality
mammary duct	UBERON:0001765	90.01	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	89.42	gold quality
caput epididymis	UBERON:0004358	89.31	gold quality
cartilage tissue	UBERON:0002418	89.16	gold quality
nasal cavity mucosa	UBERON:0001826	88.96	gold quality
tibialis anterior	UBERON:0001385	88.88	silver quality
lung	UBERON:0002048	88.72	gold quality
fallopian tube	UBERON:0003889	88.71	gold quality
trabecular bone tissue	UBERON:0002483	88.45	gold quality
omental fat pad	UBERON:0010414	88.41	gold quality
peritoneum	UBERON:0002358	88.39	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-HCAD-4	yes	65.56
E-HCAD-6	yes	51.34
E-MTAB-5061	yes	26.54
E-MTAB-9067	yes	15.93
E-CURD-122	yes	6.78
E-MTAB-6142	no	131.94
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

27 targeting CMTM7, 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-4534	99.99	66.58	1907
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-8082	99.95	67.27	1170
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-577	99.78	69.13	2479
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-3714	99.71	70.74	2671
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-182-3P	99.57	67.57	825
HSA-MIR-766-5P	99.47	67.91	2225
HSA-MIR-6165	99.44	67.12	1389
HSA-MIR-16-2-3P	99.29	70.60	1954
HSA-MIR-195-3P	99.29	70.61	1954
HSA-MIR-6731-5P	99.28	67.42	2375
HSA-MIR-8085	99.28	67.56	2362
HSA-MIR-544B	99.18	67.41	1632
HSA-MIR-3675-3P	99.09	67.70	968
HSA-MIR-3154	98.94	66.55	1455
HSA-MIR-873-5P	98.84	66.90	1348
HSA-MIR-1910-3P	98.44	67.51	1695
HSA-MIR-6511A-5P	98.13	67.47	1770

Literature-anchored findings (GeneRIF, showing 12)

• 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)
• CMTM7 functions to link sIgM and BLNK in the plasma membrane. (PMID:22363743)
• Loss of CMTM7 by promoter CpG methylation is associated with neoplasms. (PMID:23893243)
• The CMTM7 expression may be related to survival of patients with non-smallcell lung cancer and a unique prognostic factor. CMTM7 may play an important role in NSCLC development. (PMID:23981602)
• Findings indicate the role of CMTM7 protein in the regulation of epidermal growth factor receptor (EGFR)-AKT proto-oncogene protein signaling in tumor cells, and as a molecule related to Rab5 GTP-binding protein activation. (PMID:26528697)
• SOX10 can regulate the proliferation and tumor formation of gastric cancer by regulating the expression of CMTM7. (PMID:30392914)
• CMTM7 functions as a tumor suppressor in liver cancer through suppression of cell cycle progression. (PMID:30903681)
• Interaction of the CMTM7 rs347134 Polymorphism with Dietary Patterns and the Risk of Obesity in Han Chinese Male Children. (PMID:32111069)
• CMTM5/7 are biomarkers and prognostic factors in human breast carcinoma. (PMID:32568178)
• CMTM7 as a novel molecule of ATG14L-Beclin1-VPS34 complex enhances autophagy by Rab5 to regulate tumorigenicity. (PMID:34281589)
• Breast cancer cell-derived extracellular vesicles transfer miR-182-5p and promote breast carcinogenesis via the CMTM7/EGFR/AKT axis. (PMID:34294040)
• CMTM7 inhibits breast cancer progression by regulating Wnt/beta-catenin signaling. (PMID:36829181)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	cmtm7	ENSDARG00000010032
mus_musculus	Cmtm7	ENSMUSG00000032436
rattus_norvegicus	Cmtm7	ENSRNOG00000067317

Paralogs (14): CMTM1 (ENSG00000089505), CMTM6 (ENSG00000091317), PLP2 (ENSG00000102007), PLLP (ENSG00000102934), CMTM3 (ENSG00000140931), CMTM2 (ENSG00000140932), MALL (ENSG00000144063), MAL2 (ENSG00000147676), MARVELD1 (ENSG00000155254), CMTM5 (ENSG00000166091), CMTM8 (ENSG00000170293), MAL (ENSG00000172005), CMTM4 (ENSG00000183723), CKLF (ENSG00000217555)

Protein

Protein identifiers

CKLF-like MARVEL transmembrane domain-containing protein 7 — Q96FZ5 (reviewed: Q96FZ5)

Alternative names: Chemokine-like factor superfamily member 7

All UniProt accessions (4): Q96FZ5, F8WDZ3, H0YFU6, H0YGW1

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Membrane.

Tissue specificity. Highly expressed in leukocytes.

Similarity. Belongs to the chemokine-like factor family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q96FZ5-1	1	yes
Q96FZ5-2	2

RefSeq proteins (2): NP_612419, NP_852137 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008253	Marvel	Domain
IPR050578	MARVEL-CKLF_proteins	Family

Pfam: PF01284

UniProt features (7 total): transmembrane region 4, chain 1, domain 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96FZ5-F1	70.28	0.06

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 166 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_UP, GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_UP, GOBP_B_CELL_ACTIVATION, GOBP_TAXIS, chr3p22, GOMF_CYTOKINE_ACTIVITY, DOUGLAS_BMI1_TARGETS_UP, GOBP_MATURE_B_CELL_DIFFERENTIATION, GOMF_SIGNALING_RECEPTOR_BINDING, IVANOVA_HEMATOPOIESIS_EARLY_PROGENITOR, NAKAMURA_TUMOR_ZONE_PERIPHERAL_VS_CENTRAL_UP, MARSON_BOUND_BY_FOXP3_STIMULATED, GOBP_LYMPHOCYTE_DIFFERENTIATION, GOMF_SIGNALING_RECEPTOR_REGULATOR_ACTIVITY, MEISSNER_NPC_HCP_WITH_H3_UNMETHYLATED

GO Biological Process (3): B-1a B cell differentiation (GO:0002337), chemotaxis (GO:0006935), signal transduction (GO:0007165)

GO Molecular Function (2): cytokine activity (GO:0005125), protein binding (GO:0005515)

GO Cellular Component (2): obsolete extracellular space (GO:0005615), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
B-1 B cell differentiation	1
response to chemical	1
taxis	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
receptor ligand activity	1
binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

368 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CMTM7	CMTM8	Q8IZV2	977
CMTM7	CKLF	Q9UBR5	964
CMTM7	CMTM6	Q9NX76	960
CMTM7	CMTM2	Q8TAZ6	946
CMTM7	CMTM1	Q8IZ96	946
CMTM7	CMTM3	Q96MX0	887
CMTM7	CMTM5	Q96DZ9	771
CMTM7	PLLP	Q9Y342	587
CMTM7	CX3CL1	P78423	437
CMTM7	CCL17	Q92583	435
CMTM7	CNOT10	Q9H9A5	435
CMTM7	TNFSF4	P23510	432
CMTM7	CCL22	O00626	429
CMTM7	CMTM4	Q8IZR5	427
CMTM7	GLB1	P16278	404

IntAct

143 interactions, top by confidence:

A	B	Type	Score
TMEM174	CMTM7	psi-mi:“MI:0915”(physical association)	0.600
CMTM7	GORAB	psi-mi:“MI:0915”(physical association)	0.560
CMTM7	PAGE1	psi-mi:“MI:0915”(physical association)	0.560
CMTM7	HAS3	psi-mi:“MI:0915”(physical association)	0.560
CMTM7	TEX29	psi-mi:“MI:0915”(physical association)	0.560
CMTM7	THAP4	psi-mi:“MI:0915”(physical association)	0.560
CMTM7	SHISA3	psi-mi:“MI:0915”(physical association)	0.560
CMTM7	LHFPL5	psi-mi:“MI:0915”(physical association)	0.560
CMTM7	HSD17B13	psi-mi:“MI:0915”(physical association)	0.560
CMTM7	TNFRSF17	psi-mi:“MI:0915”(physical association)	0.560
CMTM7	ADTRP	psi-mi:“MI:0915”(physical association)	0.560
CMTM7	PIANP	psi-mi:“MI:0915”(physical association)	0.560
CMTM7	DNAJC1	psi-mi:“MI:0915”(physical association)	0.560
CMTM7	ARL13B	psi-mi:“MI:0915”(physical association)	0.560
CMTM7	TMX2	psi-mi:“MI:0915”(physical association)	0.560
LDLRAD1	CMTM7	psi-mi:“MI:0915”(physical association)	0.560
CMTM7	DAGLA	psi-mi:“MI:0915”(physical association)	0.560
SDC3	CMTM7	psi-mi:“MI:0915”(physical association)	0.560
CMTM7	MS4A4A	psi-mi:“MI:0915”(physical association)	0.560
CD74	CMTM7	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (50): CMTM7 (Two-hybrid), CMTM7 (Two-hybrid), CMTM7 (Two-hybrid), CMTM7 (Two-hybrid), CMTM7 (Two-hybrid), CMTM7 (Two-hybrid), CMTM7 (Two-hybrid), CMTM7 (Two-hybrid), CMTM7 (Two-hybrid), CMTM7 (Two-hybrid), CMTM7 (Two-hybrid), CMTM7 (Two-hybrid), CMTM7 (Two-hybrid), CMTM7 (Two-hybrid), CMTM7 (Two-hybrid)

ESM2 similar proteins: A1A4P6, A1A5B4, A5PK40, A6NDV4, A6NFX1, A6NGC4, A6QL84, A6QLK4, B1AWJ5, B6ID01, E1BY51, P58749, Q2TA01, Q2YDG0, Q32PG7, Q3T9M1, Q4R7X9, Q5HZE5, Q5JZQ7, Q5R6H1, Q5RBY7, Q60HE8, Q6AY05, Q6AYM9, Q6PHN7, Q6TCG5, Q6UX01, Q6UXD7, Q7RTT9, Q7Z403, Q80ZE4, Q8CE47, Q8R139, Q8TBR7, Q96FZ5, Q96HE8, Q96S97, Q9BSA9, Q9BZW5, Q9CQC4

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

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	22
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

942 predictions. Top by Δscore:

Variant	Effect	Δscore
3:32392064:TGG:T	donor_loss	1.0000
3:32392065:GGTA:G	donor_loss	1.0000
3:32392067:T:G	donor_loss	1.0000
3:32441831:ATGT:A	acceptor_gain	1.0000
3:32441834:T:TA	acceptor_gain	1.0000
3:32441835:G:A	acceptor_gain	1.0000
3:32442010:GTCG:G	donor_gain	1.0000
3:32442012:CGG:C	donor_loss	1.0000
3:32442014:G:GA	donor_loss	1.0000
3:32442014:G:GG	donor_gain	1.0000
3:32442015:T:G	donor_loss	1.0000
3:32449558:G:GT	donor_gain	1.0000
3:32449568:G:T	donor_gain	1.0000
3:32392062:AATG:A	donor_gain	0.9900
3:32392063:ATG:A	donor_gain	0.9900
3:32392064:TG:T	donor_gain	0.9900
3:32392065:GG:G	donor_gain	0.9900
3:32392066:G:GG	donor_gain	0.9900
3:32441831:A:AG	acceptor_gain	0.9900
3:32441831:AT:A	acceptor_gain	0.9900
3:32441831:ATGTG:A	acceptor_gain	0.9900
3:32441832:T:G	acceptor_gain	0.9900
3:32441832:T:TA	acceptor_gain	0.9900
3:32441834:TGGCA:T	acceptor_loss	0.9900
3:32441835:GGCA:G	acceptor_loss	0.9900
3:32441836:GCA:G	acceptor_loss	0.9900
3:32441837:CAGGT:C	acceptor_loss	0.9900
3:32441838:A:AG	acceptor_gain	0.9900
3:32441838:A:G	acceptor_loss	0.9900
3:32441839:G:GA	acceptor_gain	0.9900

AlphaMissense

1125 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:32442002:T:A	W108R	0.991
3:32442002:T:C	W108R	0.991
3:32452399:G:A	G147D	0.989
3:32442004:G:C	W108C	0.982
3:32442004:G:T	W108C	0.982
3:32452398:G:C	G147R	0.982
3:32449497:C:A	A126D	0.979
3:32441919:T:A	V80D	0.978
3:32392053:A:C	K49N	0.977
3:32392053:A:T	K49N	0.977
3:32449475:G:C	G119R	0.974
3:32452428:A:C	S157R	0.973
3:32452430:C:A	S157R	0.973
3:32452430:C:G	S157R	0.973
3:32449476:G:A	G119D	0.972
3:32392062:A:C	Q52H	0.971
3:32392062:A:T	Q52H	0.971
3:32449548:G:A	G143E	0.971
3:32449463:C:G	H115D	0.970
3:32441909:T:C	F77L	0.967
3:32441911:T:A	F77L	0.967
3:32441911:T:G	F77L	0.967
3:32452395:T:C	F146L	0.965
3:32452397:T:A	F146L	0.965
3:32452397:T:G	F146L	0.965
3:32441856:C:A	A59D	0.964
3:32441927:T:C	C83R	0.964
3:32449547:G:A	G143R	0.964
3:32449547:G:C	G143R	0.964
3:32452419:T:C	C154R	0.964

dbSNP variants (sampled 300 via entrez): RS1000021787 (3:32393625 T>C), RS1000053077 (3:32393313 A>T), RS1000057839 (3:32442276 T>C), RS1000115037 (3:32418964 C>T), RS1000136696 (3:32435523 G>C), RS1000187655 (3:32443125 G>A,T), RS1000207394 (3:32451872 G>A,C), RS1000222303 (3:32423258 A>G), RS1000263390 (3:32393319 G>A), RS1000264292 (3:32435934 C>T), RS1000334445 (3:32406171 G>A,C), RS1000396863 (3:32448247 G>T), RS1000418804 (3:32449007 C>T), RS1000440866 (3:32399981 CTA>C), RS1000539822 (3:32401753 C>T)

Disease associations

OMIM: gene MIM:607890 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST000661_2	Mortality in heart failure	3.000000e-07
GCST002938_3	Copper levels	4.000000e-07
GCST004068_57	Venous thromboembolism adjusted for sickle cell variant rs77121243-T	3.000000e-06
GCST008575_6	IgM levels	1.000000e-14
GCST009391_1128	Metabolite levels	4.000000e-06
GCST009846_5	Hallux valgus	4.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004352	mortality
EFO:0010456	allantoin measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	4
trichostatin A	affects cotreatment, increases expression	3
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	2
Arsenic	increases abundance, increases expression, affects cotreatment	2
Estradiol	affects expression, increases expression	2
Nickel	increases expression	2
triphenyl phosphate	affects expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
sodium arsenate	increases expression, increases abundance	1
2-butenal	decreases expression	1
beta-lapachone	increases expression	1
mono-(2-ethylhexyl)phthalate	increases expression	1
cobaltous chloride	decreases expression	1
2-ethylhexyldiphenylphosphate	decreases expression	1
tetrabromobisphenol A	decreases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
tri-o-cresyl phosphate	decreases expression	1
avobenzone	increases expression	1
perfluorooctane sulfonic acid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
2,2’,4,4’,5-brominated diphenyl ether	decreases expression	1
abrine	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	affects cotreatment, increases expression	1
NSC 689534	affects binding, decreases expression	1
(+)-JQ1 compound	decreases expression	1
Temozolomide	increases expression	1
Fulvestrant	decreases methylation	1
Amiodarone	increases expression	1

Clinical trials (associated diseases)

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