CMTM2

Summary

CMTM2 (CKLF like MARVEL transmembrane domain containing 2, HGNC:19173) is a protein-coding gene on chromosome 16q21, encoding CKLF-like MARVEL transmembrane domain-containing protein 2 (Q8TAZ6).

This gene belongs to the chemokine-like factor gene superfamily, a novel family that links the chemokine and the transmembrane 4 superfamilies of signaling molecules. The protein encoded by this gene may play an important role in testicular development.

Source: NCBI Gene 146225 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 45 total
• MANE Select transcript: NM_144673

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19173
Approved symbol	CMTM2
Name	CKLF like MARVEL transmembrane domain containing 2
Location	16q21
Locus type	gene with protein product
Status	Approved
Aliases	MGC39436, FLJ25732
Ensembl gene	ENSG00000140932
Ensembl biotype	protein_coding
OMIM	607885
Entrez	146225

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 2 protein_coding, 1 retained_intron, 1 nonsense_mediated_decay

ENST00000268595, ENST00000379486, ENST00000532362, ENST00000569316

RefSeq mRNA: 2 — MANE Select: NM_144673 NM_001199317, NM_144673

CCDS: CCDS10814, CCDS56001

Canonical transcript exons

ENST00000268595 — 4 exons

Exon	Start	End
ENSE00000945630	66580026	66580184
ENSE00001840252	66579463	66579892
ENSE00003580305	66586997	66587098
ENSE00003598864	66587919	66588275

Expression profiles

Bgee: expression breadth ubiquitous, 161 present calls, max score 99.84.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 3.0421 / max 1078.5442, expressed in 87 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
154522	1.8589	75
154518	0.6641	4
154519	0.3612	5
154521	0.1527	18
154520	0.0052	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	99.84	gold quality
left testis	UBERON:0004533	99.38	gold quality
right testis	UBERON:0004534	99.34	gold quality
adult organism	UBERON:0007023	99.09	gold quality
blood	UBERON:0000178	97.82	gold quality
testis	UBERON:0000473	97.03	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	91.64	gold quality
granulocyte	CL:0000094	90.10	gold quality
trabecular bone tissue	UBERON:0002483	89.80	gold quality
bone marrow	UBERON:0002371	88.07	gold quality
spleen	UBERON:0002106	86.35	gold quality
leukocyte	CL:0000738	86.06	gold quality
monocyte	CL:0000576	85.17	gold quality
bone marrow cell	CL:0002092	80.77	gold quality
right lung	UBERON:0002167	80.31	gold quality
vermiform appendix	UBERON:0001154	77.11	gold quality
upper lobe of left lung	UBERON:0008952	74.67	gold quality
upper lobe of lung	UBERON:0008948	72.03	gold quality
palpebral conjunctiva	UBERON:0001812	71.00	silver quality
gall bladder	UBERON:0002110	70.38	gold quality
pancreatic ductal cell	CL:0002079	69.45	silver quality
caecum	UBERON:0001153	69.21	gold quality
ileal mucosa	UBERON:0000331	68.98	silver quality
lung	UBERON:0002048	66.56	gold quality
nasal cavity epithelium	UBERON:0005384	66.21	silver quality
adipose tissue of abdominal region	UBERON:0007808	65.87	gold quality
left uterine tube	UBERON:0001303	65.66	gold quality
omental fat pad	UBERON:0010414	65.46	gold quality
peritoneum	UBERON:0002358	65.40	gold quality
smooth muscle tissue	UBERON:0001135	65.26	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-134144	yes	2914.14
E-ANND-3	yes	3.63

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

14 targeting CMTM2, 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-6077	99.99	68.04	2299
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-4694-3P	99.79	69.53	2640
HSA-MIR-494-3P	99.70	71.45	2795
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-147B-5P	99.45	70.62	2432
HSA-MIR-6830-5P	99.01	68.73	1884
HSA-MIR-1537-5P	98.70	68.33	999
HSA-MIR-12116	97.94	68.91	595
HSA-MIR-1279	97.83	67.50	1898

Literature-anchored findings (GeneRIF, showing 8)

• 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)
• novel evidence that the final intron/exon region of the CKLFSF1 gene contains a novel eukaryotic promoter capable of directing expression of the downstream gene, CKLFSF2 (PMID:15778092)
• CKLFSF2 was specifically expressed in meiotic and post-meiotic germ cells, which were localized to the endoplasmic reticulum (ER) near the Golgi apparatus. (PMID:17334588)
• Intracellular CMTM2 can negatively regulate HIV-1 transcription, at least in part, by targeting the AP-1 and CREB pathways. (PMID:21034562)
• Aberrant DNA methylation of CMTM2 gene is associated with colorectal cancer. (PMID:22901147)
• he expression of CMTM2 in the male reproductive system of the adult human exhibits cell- and region-specific patterns, which suggests that they may play an important role in spermatogenesis and sperm-egg fusion (PMID:28816268)
• CMTM2 is downregulated in hepatocellular carcinoma tissues and correlated with the prognosis of hepatocellular carcinoma patients, suggesting a potential tumor suppressor role of CMTM2 in hepatocellular carcinoma progression. (PMID:31990600)
• Identification of Serum CMTM2 as a Potential Biomarker for HBV-Related Disorders. (PMID:33101541)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
mus_musculus	Cmtm2b	ENSMUSG00000035785
mus_musculus	Cmtm2a	ENSMUSG00000074127
rattus_norvegicus	Cmtm2a	ENSRNOG00000025420
rattus_norvegicus	Cmtm2b	ENSRNOG00000057998
caenorhabditis_elegans	F28H1.4	WBGENE00017909
caenorhabditis_elegans	F47B3.3	WBGENE00018527

Paralogs (14): CMTM1 (ENSG00000089505), CMTM6 (ENSG00000091317), PLP2 (ENSG00000102007), PLLP (ENSG00000102934), CMTM3 (ENSG00000140931), 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 2 — Q8TAZ6 (reviewed: Q8TAZ6)

Alternative names: Chemokine-like factor superfamily member 2

All UniProt accessions (2): Q8TAZ6, H3BMC0

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Membrane.

Tissue specificity. Highly expressed in testis.

Similarity. Belongs to the chemokine-like factor family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8TAZ6-1	1	yes
Q8TAZ6-2	2

RefSeq proteins (2): NP_001186246, NP_653274* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008253	Marvel	Domain
IPR050578	MARVEL-CKLF_proteins	Family

UniProt features (13 total): transmembrane region 3, compositionally biased region 3, region of interest 2, chain 1, splice variant 1, sequence variant 1, sequence conflict 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TAZ6-F1	66.74	0.25

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 65 (showing top): BENPORATH_ES_WITH_H3K27ME3, GOBP_TAXIS, chr16q21, GOMF_CYTOKINE_ACTIVITY, GOMF_SIGNALING_RECEPTOR_BINDING, WEBER_METHYLATED_HCP_IN_FIBROBLAST_DN, OSMAN_BLADDER_CANCER_DN, ACEVEDO_LIVER_CANCER_WITH_H3K27ME3_DN, WEBER_METHYLATED_HCP_IN_SPERM_DN, GOMF_SIGNALING_RECEPTOR_REGULATOR_ACTIVITY, HATADA_METHYLATED_IN_LUNG_CANCER_UP, MARTENS_TRETINOIN_RESPONSE_UP, HECKER_IFNB1_TARGETS, MIR4694_3P, MIR6077

GO Biological Process (2): 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
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

426 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CMTM2	CKLF	Q9UBR5	968
CMTM2	CMTM3	Q96MX0	968
CMTM2	CMTM4	Q8IZR5	963
CMTM2	CMTM7	Q96FZ5	946
CMTM2	CMTM5	Q96DZ9	841
CMTM2	CMTM6	Q9NX76	756
CMTM2	CMTM8	Q8IZV2	740
CMTM2	CMTM1	Q8IZ96	520
CMTM2	CCL17	Q92583	475
CMTM2	CX3CL1	P78423	468
CMTM2	CCL22	O00626	452
CMTM2	TSPAN1	O60635	447
CMTM2	MOB3C	Q70IA8	409
CMTM2	MYADML2	A6NDP7	391
CMTM2	PLLP	Q9Y342	352

IntAct

37 interactions, top by confidence:

A	B	Type	Score
CMTM2	YIPF1	psi-mi:“MI:0915”(physical association)	0.560
TM4SF4	CMTM2	psi-mi:“MI:0915”(physical association)	0.560
CMTM2	MANBAL	psi-mi:“MI:0915”(physical association)	0.560
STRIT1	CMTM2	psi-mi:“MI:0915”(physical association)	0.560
ARL6IP6	CMTM2	psi-mi:“MI:0915”(physical association)	0.560
FAM180B	CMTM2	psi-mi:“MI:0915”(physical association)	0.560
CDW52	CMTM2	psi-mi:“MI:0915”(physical association)	0.560
SLC7A1	CMTM2	psi-mi:“MI:0915”(physical association)	0.560
CYB561	CMTM2	psi-mi:“MI:0915”(physical association)	0.560
NIPAL4	CMTM2	psi-mi:“MI:0915”(physical association)	0.560
CMTM2	TIMMDC1	psi-mi:“MI:0915”(physical association)	0.560
CMTM2	UBE2A	psi-mi:“MI:0915”(physical association)	0.370
GSK3B	CMTM2	psi-mi:“MI:0915”(physical association)	0.370
CMTM2	GAPDHS	psi-mi:“MI:0914”(association)	0.350
YIPF1	CMTM2	psi-mi:“MI:0915”(physical association)	0.000
TM4SF4	CMTM2	psi-mi:“MI:0915”(physical association)	0.000
MANBAL	CMTM2	psi-mi:“MI:0915”(physical association)	0.000
CYB561	CMTM2	psi-mi:“MI:0915”(physical association)	0.000
NIPAL4	CMTM2	psi-mi:“MI:0915”(physical association)	0.000
CMTM2	MANBAL	psi-mi:“MI:0915”(physical association)	0.000
STRIT1	CMTM2	psi-mi:“MI:0915”(physical association)	0.000
ARL6IP6	CMTM2	psi-mi:“MI:0915”(physical association)	0.000
FAM180B	CMTM2	psi-mi:“MI:0915”(physical association)	0.000
CDW52	CMTM2	psi-mi:“MI:0915”(physical association)	0.000
SLC7A1	CMTM2	psi-mi:“MI:0915”(physical association)	0.000
CMTM2	TIMMDC1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (19): CMTM2 (Reconstituted Complex), CMTM2 (Two-hybrid), CMTM2 (Two-hybrid), CMTM2 (Two-hybrid), CMTM2 (Two-hybrid), CMTM2 (Two-hybrid), CD52 (Two-hybrid), TM4SF4 (Two-hybrid), NIPAL4 (Two-hybrid), ARL6IP6 (Two-hybrid), FAM180B (Two-hybrid), LOC100507537 (Two-hybrid), CMTM2 (Two-hybrid), PRADC1 (Affinity Capture-MS), GAPDHS (Affinity Capture-MS)

ESM2 similar proteins: A4GG66, A4GVD1, D3Z8X7, E9QA62, O60308, O95772, P08247, P20488, P28228, P28229, P36381, P36383, P48165, Q0IHQ3, Q0VAK6, Q0VG18, Q14738, Q148L1, Q1LUC3, Q28653, Q28EW0, Q2HJ66, Q2TBG9, Q5F3A1, Q5R4Q3, Q5VW38, Q6NZH5, Q6P6V6, Q6PYT3, Q6R4A8, Q7ZU80, Q7ZXS7, Q80V31, Q8BU14, Q8BXN9, Q8C5W4, Q8CH18, Q8TAZ6, Q91049, Q91WD0

Diamond homologs: Q8IZ96, Q8TAZ6, Q9DAC0, Q9DAR1, Q9UBR5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	37
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

378 predictions. Top by Δscore:

Variant	Effect	Δscore
16:66579888:GTTTG:G	donor_gain	1.0000
16:66586991:CTTCA:C	acceptor_loss	1.0000
16:66586992:TTCA:T	acceptor_loss	1.0000
16:66586993:TCAG:T	acceptor_loss	1.0000
16:66586994:CA:C	acceptor_loss	1.0000
16:66586995:A:AG	acceptor_gain	1.0000
16:66586996:G:A	acceptor_loss	1.0000
16:66586996:G:GG	acceptor_gain	1.0000
16:66586996:GGAC:G	acceptor_gain	1.0000
16:66587094:CTGTG:C	donor_gain	1.0000
16:66587096:GTG:G	donor_gain	1.0000
16:66587096:GTGGT:G	donor_loss	1.0000
16:66587098:GGT:G	donor_loss	1.0000
16:66587099:G:A	donor_loss	1.0000
16:66587099:G:GG	donor_gain	1.0000
16:66587100:T:A	donor_loss	1.0000
16:66587101:GAGTC:G	donor_loss	1.0000
16:66579788:G:GT	donor_gain	0.9900
16:66579889:T:G	donor_gain	0.9900
16:66579893:G:GG	donor_gain	0.9900
16:66579893:GT:G	donor_loss	0.9900
16:66579894:T:G	donor_loss	0.9900
16:66586995:AG:A	acceptor_gain	0.9900
16:66586996:GG:G	acceptor_gain	0.9900
16:66586996:GGA:G	acceptor_gain	0.9900
16:66587034:T:TA	acceptor_gain	0.9900
16:66587097:TG:T	donor_gain	0.9900
16:66587098:GG:G	donor_gain	0.9900
16:66579895:G:GG	donor_loss	0.9800
16:66579898:C:G	donor_gain	0.9800

AlphaMissense

1623 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:66579851:T:C	F82L	0.976
16:66579853:C:A	F82L	0.976
16:66579853:C:G	F82L	0.976
16:66580137:A:C	S133R	0.961
16:66580139:C:A	S133R	0.961
16:66580139:C:G	S133R	0.961
16:66580116:A:C	S126R	0.951
16:66580118:C:A	S126R	0.951
16:66580118:C:G	S126R	0.951
16:66580164:T:C	F142L	0.946
16:66580166:C:A	F142L	0.946
16:66580166:C:G	F142L	0.946
16:66580173:T:A	W145R	0.945
16:66580173:T:C	W145R	0.945
16:66587027:T:C	F159L	0.944
16:66587029:C:A	F159L	0.944
16:66587029:C:G	F159L	0.944
16:66580175:G:C	W145C	0.904
16:66580175:G:T	W145C	0.904
16:66587048:T:C	F166L	0.903
16:66587050:T:A	F166L	0.903
16:66587050:T:G	F166L	0.903
16:66587928:G:C	G186R	0.894
16:66579880:G:C	K91N	0.884
16:66579880:G:T	K91N	0.884
16:66587937:G:A	G189R	0.881
16:66587937:G:C	G189R	0.881
16:66587929:G:A	G186D	0.877
16:66587052:C:A	A167D	0.875
16:66587011:C:A	D153E	0.873

dbSNP variants (sampled 300 via entrez): RS1000101533 (16:66588766 C>T), RS1000987075 (16:66587243 G>A), RS1001062668 (16:66583811 C>A), RS1001536600 (16:66587472 G>A), RS1001661934 (16:66588424 G>T), RS1001717115 (16:66581552 A>G), RS1001810473 (16:66581801 T>C), RS1002050665 (16:66583082 C>A,T), RS1002144318 (16:66583352 C>G,T), RS1002397583 (16:66588025 G>A), RS1002723323 (16:66580035 A>G), RS1003288802 (16:66578641 C>A,G), RS1004034371 (16:66580547 C>A,G), RS1004173515 (16:66580878 C>T), RS1004520575 (16:66580957 G>A)

Disease associations

OMIM: gene MIM:607885 | 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

14 total (human), top 14 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
triphenyl phosphate	affects expression	1
sodium arsenite	increases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	increases reaction, affects binding	1
theaflavin-3,3’-digallate	affects expression	1
Acetaminophen	decreases expression	1
Air Pollutants	affects expression, increases abundance	1
Benzo(a)pyrene	increases methylation	1
Ozone	affects expression, increases abundance	1
Smoke	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Antirheumatic Agents	decreases expression	1
Cadmium Chloride	decreases expression	1

Clinical trials (associated diseases)

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