CMTM1

Summary

CMTM1 (CKLF like MARVEL transmembrane domain containing 1, HGNC:19172) is a protein-coding gene on chromosome 16q21, encoding CKLF-like MARVEL transmembrane domain-containing protein 1 (Q8IZ96).

This gene belongs to the chemokine-like factor gene superfamily, a novel family that is similar to the chemokine and the transmembrane 4 superfamilies of signaling molecules. The protein encoded by this gene may play an important role in testicular development. Alternatively spliced transcript variants encoding different isoforms have been identified. Naturally occurring read-through transcription occurs between this locus and the neighboring locus CKLF (chemokine-like factor).

Source: NCBI Gene 113540 — RefSeq curated summary.

At a glance

• MANE Select transcript: NM_052999

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19172
Approved symbol	CMTM1
Name	CKLF like MARVEL transmembrane domain containing 1
Location	16q21
Locus type	gene with protein product
Status	Approved
Aliases	CKLFH1a, CKLFH
Ensembl gene	ENSG00000089505
Ensembl biotype	protein_coding
OMIM	607884
Entrez	113540

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 10 protein_coding, 10 nonsense_mediated_decay

ENST00000328020, ENST00000332695, ENST00000333001, ENST00000336328, ENST00000379500, ENST00000457188, ENST00000465057, ENST00000479381, ENST00000528324, ENST00000528441, ENST00000528484, ENST00000529386, ENST00000529506, ENST00000530141, ENST00000531885, ENST00000533078, ENST00000533666, ENST00000533915, ENST00000533953, ENST00000534143

RefSeq mRNA: 8 — MANE Select: NM_052999 NM_052999, NM_181268, NM_181269, NM_181270, NM_181271, NM_181272, NM_181283, NM_181296

CCDS: CCDS10810, CCDS10811, CCDS10812, CCDS45503, CCDS45504, CCDS54019, CCDS54020, CCDS54021

Canonical transcript exons

ENST00000379500 — 4 exons

Exon	Start	End
ENSE00001104129	66569936	66570094
ENSE00001361838	66566439	66566945
ENSE00003483951	66577104	66577202
ENSE00003704458	66578831	66579135

Expression profiles

Bgee: expression breadth ubiquitous, 131 present calls, max score 93.29.

FANTOM5 (CAGE): breadth broad, TPM avg 1.0235 / max 171.8634, expressed in 448 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
154517	0.6984	345
154515	0.2697	26
154516	0.0553	13

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	93.29	gold quality
testis	UBERON:0000473	92.95	gold quality
right testis	UBERON:0004534	92.76	gold quality
blood	UBERON:0000178	85.37	gold quality
ventricular zone	UBERON:0003053	78.27	gold quality
leukocyte	CL:0000738	75.09	gold quality
monocyte	CL:0000576	75.02	gold quality
cortical plate	UBERON:0005343	74.17	gold quality
ganglionic eminence	UBERON:0004023	74.06	gold quality
stromal cell of endometrium	CL:0002255	73.87	gold quality
granulocyte	CL:0000094	72.40	gold quality
cerebellum	UBERON:0002037	71.89	gold quality
cerebellar cortex	UBERON:0002129	71.83	gold quality
cerebellar hemisphere	UBERON:0002245	71.77	gold quality
right hemisphere of cerebellum	UBERON:0014890	71.11	gold quality
prefrontal cortex	UBERON:0000451	70.83	gold quality
superior frontal gyrus	UBERON:0002661	69.75	gold quality
vermiform appendix	UBERON:0001154	69.05	gold quality
frontal cortex	UBERON:0001870	68.76	gold quality
primary visual cortex	UBERON:0002436	68.72	gold quality
spleen	UBERON:0002106	68.51	gold quality
Brodmann (1909) area 9	UBERON:0013540	67.94	gold quality
cerebral cortex	UBERON:0000956	67.13	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	66.85	gold quality
placenta	UBERON:0001987	66.50	gold quality
brain	UBERON:0000955	65.99	gold quality
cortex of kidney	UBERON:0001225	65.92	gold quality
duodenum	UBERON:0002114	65.91	gold quality
anterior cingulate cortex	UBERON:0009835	65.69	gold quality
lymph node	UBERON:0000029	65.57	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-GEOD-99795	no	3.19
E-ANND-3	no	1.21

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

6 targeting CMTM1, 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-5587-5P	99.07	68.58	838
HSA-MIR-4478	99.07	65.16	2320
HSA-MIR-3652	97.71	65.43	1890
HSA-MIR-4430	97.47	65.61	1813
HSA-MIR-584-5P	95.82	68.05	848
HSA-MIR-885-3P	95.14	63.08	448

Literature-anchored findings (GeneRIF, showing 6)

• 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)
• gene structure, mapping to chromsome 16, identification of altenative transcription start sites, expression in spermatocyte and testes (PMID:15147728)
• 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)
• Study shows that CMTM1_v17 is highly expressed in human testis and many human tumor tissues and cell lines and seems to enhance cell proliferation and resistance to tumor necrosis factor-alpha (TNF-alpha)-induced apoptosis in MDA-MB-231 breast cancer cells. (PMID:25175386)
• CMTM1 and 3 are priority targets in glioblastomas. First insights into signalling of these two genes that might be conveyed by growth factor receptor, Src family kinase and WNT activation was presented. (PMID:25931111)
• High CMTM1_v17 expression was associated with chemotherapy resistance in lung cancer. (PMID:28129775)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Cmtm1	ENSMUSG00000110430
rattus_norvegicus	Cmtm1	ENSRNOG00000057711
caenorhabditis_elegans	F28H1.4	WBGENE00017909
caenorhabditis_elegans	F47B3.3	WBGENE00018527

Paralogs (14): CMTM6 (ENSG00000091317), 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 1 — Q8IZ96 (reviewed: Q8IZ96)

Alternative names: Chemokine-like factor superfamily member 1

All UniProt accessions (5): Q8IZ96, A0A0A0MTE4, E9PAX0, E9PIL3, H0YEC2

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 (17)

UniProt ID	Names	Canonical?
Q8IZ96-1	1	yes
Q8IZ96-2	1a, 17
Q8IZ96-3	1b
Q8IZ96-4	2
Q8IZ96-5	3
Q8IZ96-6	4
Q8IZ96-7	5
Q8IZ96-8	6, 7
Q8IZ96-9	8, 9
Q8IZ96-10	10
Q8IZ96-11	11
Q8IZ96-12	12
Q8IZ96-13	13
Q8IZ96-14	14, 15
Q8IZ96-15	16
Q8IZ96-16	19, 20,21,22,23
Q8IZ96-17	24

RefSeq proteins (8): NP_443725, NP_851785, NP_851786, NP_851787, NP_851788, NP_851789, NP_851800, NP_851813 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008253	Marvel	Domain
IPR050578	MARVEL-CKLF_proteins	Family

UniProt features (32 total): splice variant 25, transmembrane region 4, chain 1, sequence variant 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IZ96-F1	66.68	0.00

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 18 (showing top): GOBP_TAXIS, chr16q21, GOMF_CYTOKINE_ACTIVITY, GOMF_SIGNALING_RECEPTOR_BINDING, GOMF_SIGNALING_RECEPTOR_REGULATOR_ACTIVITY, TOYOTA_TARGETS_OF_MIR34B_AND_MIR34C, STK33_SKM_UP, STK33_UP, MIR6840_3P, GOBP_LOCOMOTION, NUYTTEN_EZH2_TARGETS_UP, GOMF_MOLECULAR_FUNCTION_ACTIVATOR_ACTIVITY, GSE7400_CTRL_VS_CSF3_IN_VIVO_TREATED_PBMC_DN, GSE2770_UNTREATED_VS_ACT_CD4_TCELL_48H_DN, GSE2770_TGFB_AND_IL4_VS_IL12_TREATED_ACT_CD4_TCELL_2H_DN

GO Biological Process (2): chemotaxis (GO:0006935), signal transduction (GO:0007165)

GO Molecular Function (1): cytokine activity (GO:0005125)

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
cellular anatomical structure	1

Protein interactions and networks

STRING

210 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CMTM1	CMTM3	Q96MX0	975
CMTM1	CMTM4	Q8IZR5	968
CMTM1	CMTM7	Q96FZ5	946
CMTM1	CMTM5	Q96DZ9	849
CMTM1	CMTM6	Q9NX76	817
CMTM1	CMTM8	Q8IZV2	755
CMTM1	MTM1	Q13496	578
CMTM1	TSPAN1	O60635	570
CMTM1	CMTM2	Q8TAZ6	520
CMTM1	CCL17	Q92583	509
CMTM1	CX3CL1	P78423	486
CMTM1	CCL22	O00626	467
CMTM1	WDR25	Q64LD2	433
CMTM1	PLLP	Q9Y342	418
CMTM1	CKLF	Q9UBR5	407

IntAct

3 interactions, top by confidence:

A	B	Type	Score
CMTM1	E6	psi-mi:“MI:0915”(physical association)	0.370
NEK4	E2F8	psi-mi:“MI:0914”(association)	0.350

BioGRID (4): CMTM1 (Affinity Capture-MS), CMTM1 (Affinity Capture-MS), CMTM1 (Two-hybrid), CMTM1 (Affinity Capture-Luminescence)

ESM2 similar proteins: A2VE13, A4K2N5, A4K2W1, B8BPI2, E1BY51, O09117, O09198, O35682, O62646, O88662, O89104, P21145, Q04941, Q10EJ2, Q16563, Q1RMQ3, Q28296, Q3URJ8, Q3ZBY0, Q5R6H1, Q5RAI2, Q5VXT5, Q64349, Q6DHB5, Q6GPN9, Q6P0C6, Q6P742, Q6VBQ5, Q6Y1E2, Q78S06, Q86TG1, Q86UW1, Q8BI08, Q8CJ61, Q8IZ96, Q8IZR5, Q8N2H4, Q8N8D7, Q91WN2, Q95MN6

Diamond homologs: Q8IZ96, Q9DAS1, Q9JK79, Q9UBR5, Q8TAZ6, Q9DAC0, Q9DAR1

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

729 predictions. Top by Δscore:

Variant	Effect	Δscore
16:66577101:CAGG:C	acceptor_loss	1.0000
16:66577102:A:AG	acceptor_gain	1.0000
16:66577102:AG:A	acceptor_gain	1.0000
16:66577102:AGG:A	acceptor_loss	1.0000
16:66577103:G:GG	acceptor_gain	1.0000
16:66577103:GG:G	acceptor_gain	1.0000
16:66577103:GGAT:G	acceptor_gain	1.0000
16:66577198:GGGGG:G	donor_gain	1.0000
16:66577199:GGGG:G	donor_gain	1.0000
16:66577199:GGGGG:G	donor_gain	1.0000
16:66577200:GGG:G	donor_gain	1.0000
16:66577200:GGGG:G	donor_gain	1.0000
16:66577201:GG:G	donor_gain	1.0000
16:66577201:GGG:G	donor_gain	1.0000
16:66577201:GGGT:G	donor_loss	1.0000
16:66577202:GG:G	donor_gain	1.0000
16:66577202:GGT:G	donor_loss	1.0000
16:66577202:GGTA:G	donor_loss	1.0000
16:66577203:G:GC	donor_loss	1.0000
16:66577204:TAA:T	donor_loss	1.0000
16:66577205:AAG:A	donor_loss	1.0000
16:66566751:A:T	donor_gain	0.9900
16:66575591:T:G	donor_gain	0.9900
16:66577103:GGATC:G	acceptor_gain	0.9900
16:66577177:G:GT	donor_gain	0.9900
16:66577203:G:GG	donor_gain	0.9900
16:66578810:ATAT:A	acceptor_gain	0.9900
16:66578811:T:G	acceptor_gain	0.9900
16:66578813:T:TA	acceptor_gain	0.9900
16:66578829:A:AG	acceptor_gain	0.9900

AlphaMissense

1835 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:66570085:G:C	W77C	0.994
16:66570085:G:T	W77C	0.994
16:66570083:T:A	W77R	0.991
16:66570083:T:C	W77R	0.991
16:66577116:A:C	S85R	0.988
16:66577118:T:A	S85R	0.988
16:66577118:T:G	S85R	0.988
16:66577134:T:C	F91L	0.988
16:66577136:C:A	F91L	0.988
16:66577136:C:G	F91L	0.988
16:66570012:A:T	E53V	0.986
16:66577115:C:A	N84K	0.986
16:66577115:C:G	N84K	0.986
16:66578837:T:C	C116R	0.986
16:66569963:T:C	F37L	0.983
16:66569965:C:A	F37L	0.983
16:66569965:C:G	F37L	0.983
16:66577200:G:A	G113R	0.983
16:66577200:G:C	G113R	0.983
16:66577106:T:A	D81E	0.982
16:66577106:T:G	D81E	0.982
16:66577197:G:A	G112R	0.981
16:66577197:G:C	G112R	0.981
16:66577201:G:A	G113E	0.981
16:66577108:T:C	L82P	0.980
16:66577126:C:T	T88I	0.980
16:66570017:T:C	C55R	0.979
16:66577105:A:C	D81A	0.979
16:66577197:G:T	G112W	0.979
16:66578861:T:C	C124R	0.979

dbSNP variants (sampled 300 via entrez): RS1000154538 (16:66574882 C>G,T), RS1000211221 (16:66567241 G>A), RS1000214068 (16:66573258 T>A), RS1000334257 (16:66575867 TC>T), RS1000418669 (16:66574576 G>A,C), RS1000720125 (16:66577023 T>A,G), RS1000815160 (16:66577369 C>A), RS1001273436 (16:66575307 T>A), RS1001286237 (16:66569600 T>A), RS1001785545 (16:66567517 T>C), RS1002636033 (16:66576637 A>C), RS1003288802 (16:66578641 C>A,G), RS1003301697 (16:66573054 G>A), RS1003309979 (16:66567796 A>G), RS1003359164 (16:66567504 G>A,T)

Disease associations

OMIM: gene MIM:607884 | 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

21 total (human), top 21 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Vorinostat	affects cotreatment, increases expression	2
Benzo(a)pyrene	decreases methylation, increases expression	2
aristolochic acid I	increases expression	1
decabromobiphenyl ether	affects expression	1
perfluorooctanoic acid	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment, decreases expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
perfluoro-n-nonanoic acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	1
perfluorohexanesulfonic acid	decreases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	increases expression	1
Vehicle Emissions	decreases methylation, increases expression	1
Cisplatin	decreases expression	1
Lipopolysaccharides	decreases expression, affects response to substance, increases expression, affects cotreatment	1
Pesticides	affects methylation	1
Phthalic Acids	decreases methylation	1
Thiram	decreases expression	1
tert-Butylhydroperoxide	decreases methylation	1

Clinical trials (associated diseases)

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