CEMIP

Summary

CEMIP (cell migration inducing hyaluronidase 1, HGNC:29213) is a protein-coding gene on chromosome 15q25.1, encoding Cell migration-inducing and hyaluronan-binding protein (Q8WUJ3). Mediates depolymerization of hyaluronic acid (HA) via the cell membrane-associated clathrin-coated pit endocytic pathway.

Enables several functions, including clathrin heavy chain binding activity; hyaluronic acid binding activity; and hyalurononglucosaminidase activity. Involved in several processes, including hyaluronan catabolic process; positive regulation of protein phosphorylation; and positive regulation of protein targeting to membrane. Located in several cellular components, including clathrin-coated endocytic vesicle; endoplasmic reticulum; and nucleus.

Source: NCBI Gene 57214 — RefSeq curated summary.

At a glance

• Gene–disease (curated): nonsyndromic genetic hearing loss (Disputed, ClinGen)
• GWAS associations: 7
• Clinical variants (ClinVar): 263 total
• MANE Select transcript: NM_001293298

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29213
Approved symbol	CEMIP
Name	cell migration inducing hyaluronidase 1
Location	15q25.1
Locus type	gene with protein product
Status	Approved
Aliases	IR2155535, TMEM2L, HYBID, CEMIP1
Ensembl gene	ENSG00000103888
Ensembl biotype	protein_coding
OMIM	608366
Entrez	57214

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 5 protein_coding, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000220244, ENST00000356249, ENST00000394685, ENST00000495041, ENST00000559966, ENST00000560027, ENST00000954074

RefSeq mRNA: 3 — MANE Select: NM_001293298 NM_001293298, NM_001293304, NM_018689

CCDS: CCDS10315

Canonical transcript exons

ENST00000394685 — 30 exons

Exon	Start	End
ENSE00000700021	80906663	80906838
ENSE00000700023	80909097	80909306
ENSE00000700060	80946965	80947065
ENSE00000924478	80894990	80895122
ENSE00000924479	80895869	80896060
ENSE00000924480	80920094	80920299
ENSE00000924481	80921032	80921101
ENSE00000924482	80922009	80922137
ENSE00000924483	80924621	80924706
ENSE00000924484	80925624	80925755
ENSE00000924485	80928902	80928937
ENSE00000924486	80929019	80929174
ENSE00000924487	80931859	80932039
ENSE00000924489	80936674	80936885
ENSE00000924490	80937794	80937979
ENSE00000924491	80941849	80942053
ENSE00000924493	80942945	80943102
ENSE00001104271	80873864	80873973
ENSE00001104278	80887694	80887764
ENSE00001104281	80888701	80888796
ENSE00001104286	80879716	80879854
ENSE00001104291	80884175	80884354
ENSE00001104293	80878721	80878867
ENSE00001104296	80880900	80881136
ENSE00001266705	80933245	80933460
ENSE00001266786	80889471	80889592
ENSE00001519199	80873538	80873696
ENSE00003607097	80942251	80942337
ENSE00003846673	80779370	80779614
ENSE00003850583	80948797	80951771

Expression profiles

Bgee: expression breadth ubiquitous, 211 present calls, max score 95.71.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 87.8437 / max 5335.4967, expressed in 1190 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
148023	86.9795	1184
148036	0.2111	83
148047	0.1130	53
148044	0.1053	51
148042	0.0819	37
148049	0.0729	33
148048	0.0677	29
148043	0.0513	26
148041	0.0507	21
148032	0.0491	29

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
choroid plexus epithelium	UBERON:0003911	95.71	gold quality
trigeminal ganglion	UBERON:0001675	95.00	gold quality
stromal cell of endometrium	CL:0002255	94.92	gold quality
tibia	UBERON:0000979	91.10	gold quality
pericardium	UBERON:0002407	90.86	gold quality
cartilage tissue	UBERON:0002418	84.38	silver quality
olfactory bulb	UBERON:0002264	83.05	silver quality
lymph node	UBERON:0000029	81.03	gold quality
lower esophagus mucosa	UBERON:0035834	80.86	gold quality
right lobe of thyroid gland	UBERON:0001119	80.64	gold quality
left lobe of thyroid gland	UBERON:0001120	80.41	gold quality
decidua	UBERON:0002450	79.95	gold quality
epithelium of nasopharynx	UBERON:0001951	79.86	silver quality
upper lobe of left lung	UBERON:0008952	79.78	gold quality
visceral pleura	UBERON:0002401	79.56	silver quality
thyroid gland	UBERON:0002046	78.51	gold quality
upper lobe of lung	UBERON:0008948	78.51	gold quality
left ovary	UBERON:0002119	78.43	gold quality
vermiform appendix	UBERON:0001154	78.39	gold quality
right uterine tube	UBERON:0001302	77.89	gold quality
left uterine tube	UBERON:0001303	77.83	gold quality
right ovary	UBERON:0002118	77.21	gold quality
endocervix	UBERON:0000458	76.92	gold quality
esophagus mucosa	UBERON:0002469	76.44	gold quality
ectocervix	UBERON:0012249	76.39	gold quality
right lung	UBERON:0002167	76.11	gold quality
right hemisphere of cerebellum	UBERON:0014890	75.67	gold quality
body of uterus	UBERON:0009853	75.66	gold quality
adenohypophysis	UBERON:0002196	75.47	gold quality
pituitary gland	UBERON:0000007	75.23	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-HCAD-35	yes	4431.25
E-MTAB-8530	yes	4197.70
E-GEOD-124858	no	2870.97
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

129 targeting CEMIP, 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-4283	100.00	66.42	2097
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-23B-5P	99.98	66.07	587
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-146A-5P	99.96	68.93	988
HSA-MIR-146B-5P	99.96	69.13	977
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-7153-5P	99.94	68.89	1006
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-3065-3P	99.87	70.25	1407
HSA-LET-7A-2-3P	99.87	70.53	1921
HSA-MIR-369-3P	99.85	70.52	2264
HSA-LET-7G-3P	99.85	70.43	1929

Literature-anchored findings (GeneRIF, showing 40)

• three possibly disease-causing point mutations (PMID:14577002)
• KIAA1199 was highly expressed in gastric cancer, and was associated with prognosis and lymph node metastasis in multivariate analyses. Taken together, KIAA1199 may be a novel gene that plays an important role in progression of gastric cancer. (PMID:19434458)
• KIAA1199 is upregulated in gastric adenocarcinoma and is associated with tumor progression. (PMID:21443102)
• KIAA1199 transcript and protein are highly expressed in the majority of CRCs. KIAA1199 probably participates in Wnt-signalling, affecting cell proliferation, motility, adhesion. Also, KIAA1199 has a clinical correlation to outcome in stage-II CRC patients (PMID:21772334)
• KIAA1199 is differentially expressed in neoplastic tissues and KIAA1199 transcripts are more abundant in the plasma of patients with either cancer or adenoma compared to controls. (PMID:22276102)
• KIAA1199 is a new hyaluronan binding protein involved in hyaluronan depolymerization. (PMID:23509262)
• proteins that might interact with KIAA1199 and molecular pathways in which it might play roles, were identified. (PMID:23936024)
• KIAA1199 serves as a novel cell migration-promoting gene and plays a critical role in maintaining cancer mesenchymal status. (PMID:23990668)
• Results suggest that the N-terminal portion of KIAA1199 functions as a cleavable signal sequence required for proper KIAA1199 translocation and KIAA1199-mediated HAhyaluronan depolymerization. (PMID:24269685)
• KIAA1199 influences the proliferation, adhesion, motility, invasiveness and epithelial-to-mesenchymal transition of cancer cells, is a likely target gene of the Wnt/beta-catenin signalling pathway[review] (PMID:24573670)
• Findings indicate that KIAA1199 may play an important role in breast tumor growth and invasiveness. (PMID:24628760)
• KIAA1199 plays an important role in glycogen breakdown and cancer cell survival (PMID:25051373)
• oncogenic protein induced by HPV infection and constitutive NF-kappaB activity that transmits pro-survival and invasive signals through EGFR signalling (PMID:25366117)
• Results provide insight into the upregulation of CEMIP within cancer and can lead to novel treatment strategies targeting this cancer cell migration-promoting gene. (PMID:26009875)
• We present evidence that high expression of KIAA1199 is associated with tumor invasion depth, TNM stage, and poor prognosis in colorectal cancer (PMID:26045799)
• CEMIP directly facilitates colon tumor growth, and high CEMIP expression correlates with poor outcome in stage III and in stages II+III combined cohorts. (PMID:26437221)
• Regulation of Hyaluronan (HA) Metabolism Mediated by HYBID (Hyaluronan-binding Protein Involved in HA Depolymerization, KIAA1199) and HA Synthases in Growth Factor-stimulated Fibroblasts. (PMID:26518873)
• KIAA1199 is overexpressed in pancreatic intraepithelial neoplasia. (PMID:27922049)
• Overexpression of KIAA1199 may contribute to increased migration of pancreatic ductal adenocarcinoma cells and predict shorter survival after surgical resection. (PMID:28012880)
• Results suggest a possible link between inflammation, induced KIAA1199 expression, and enhanced migration during pancreatic ductal adenocarcinoma (PDAC) progression. (PMID:28179576)
• Elevated KIAA1199 protein expression is associated with tumor invasion and metastasis in colorectal cancer. (PMID:28213952)
• KIAA1199 promotes migration and invasion by Wnt/beta-catenin pathway and matrix metalloproteinase-mediated epithelial-mesenchymal transition progression, and serves as a poor prognosis marker in gastric cancer. (PMID:28422983)
• Our findings revealed that KIAA1199 protein could be applied in predicting nonsmall cell lung cancer patient’s outcome (PMID:28901311)
• the in-vitro anti-proliferative and pro-apoptotic effects in colorectal cancer cells that were induced by silencing cell migration inducing hyaluronan binding protein may be associated with GRP78 repression and UPR attenuation (PMID:29024602)
• CEMIP showed a diagnostic yield of 86.1% (68/79) in CA 19-9 negative pancreatic cancer. (PMID:29467409)
• Upregulation of CEMIP promotes migration and invasion in anoikis-resistant prostate cancer cells by enhancing PDK4-associated metabolic reprogramming. (PMID:29505302)
• CEMIP expression was increased in retinoblastoma tissues and cells. miR-140-5p inhibited CEMIP expression possibly by targeting the 3’-UTR. (PMID:29808799)
• expression of KIAA1199 is up-regulated in primary hepatocellular carcinoma, which is significantly correlated with the clinicopathological features and prognosis, high expression of KIAA1199 increased the risk of death in patients with primary hepatocellular carcinom (PMID:29886655)
• Here, we demonstrate that BRAF(V600E) -mutated colorectal cancers acquire resistance to MEK1 inhibition by inducing expression of the scaffold protein CEMIP through a beta-catenin- and FRA-1-dependent pathway (PMID:29915160)
• High HYBID expression is associated with osteoarthritis. (PMID:29935163)
• CEMIP expression in lung fibroblasts (FB) was downregulated in a glioma-associated oncogene homologue-dependent manner and CEMIP silencing in idiopathic pulmonary fibrosis FB reduced collagen production and attenuated cell proliferation and migration. (PMID:30166321)
• study reveals that KIAA1199 promotes metastasis of colorectal cancer cells via microtubule destabilization regulated by a PP2A/stathmin pathway, and suggests that KIAA1199 may be a promising target for preventing metastasis in colorectal cancer. (PMID:30202098)
• Findings indicate that hyaluronan-binding protein (HYBID) is indispensable for KIAA1199 (CEMIP)-mediated hyaluronan-B (HA) depolymerization in skin fibroblasts, but transmembrane protein 2 (TMEM2) is not involved in the HYBID-mediated process as a catalytic hyaluronidase. (PMID:30241936)
• KIAA1199 overexpression is an independent prognostic marker in non-small-cell lung cancer (NSCLC). KIAA1199 expression directly influences the expression of epithelial-mesenchymal transition (EMT) markers. KIAA1199 promotes invasion and migration in NSCLC via PI3K-Akt mediated EMT. (PMID:30478628)
• KIAA1199 is a mobilizing factor that interacts with P38 and Wnt signaling, and induces changes in actin cytoskeleton, as a mechanism mediating recruitment of hMSC to bone formation sites. (PMID:30755597)
• CEMIP may promote the development of ovarian cancer by regulating PI3K/AKT signaling. (PMID:30925458)
• Studies showed that KIAA1199 promoted the migration, invasion, and metastasis of sorafenib-resistant HCC cells. Mechanistically, KIAA1199 is required for EGF-induced epithelial-mesenchymal transition (EMT) in sorafenib-resistant HCC cells by aiding in EGFR phosphorylation. (PMID:30980868)
• CASC19 expression was upregulated in colorectal cancer (CRC) tissues and CRC cell lines. Higher CASC19 expression was associated with poorer prognoses. CASC19 positively regulates CEMIP expression through targeting miR-140-5p. CASC19 may regulate the proliferation, epithelial-mesenchymal transition, and metastasizing ability of CRC cells by regulating microRNA-140-5p, as well as cell migration by inducing CEMIP. (PMID:31011255)
• Expression of KIAA1199 was highly upregulated in osteoarthritic cartilage. KIAA1199 knockdown exerted anti-catabolic and anti-inflammatory effects on IL-1beta-induced human chondrocytes via regulation of the Wnt/beta-catenin signaling pathway. Therefore, pharmacological inhibition of KIAA1199 may represent a promising therapeutic target for osteoarthritis. (PMID:31103876)
• The miR-486-5p/KIAA1199/epithelial-mesenchymal transition axis might play a critical role in Papillary Thyroid Cancer invasion and metastasis. (PMID:31501407)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	cemip	ENSDARG00000039881
mus_musculus	Cemip	ENSMUSG00000052353
rattus_norvegicus	Cemip	ENSRNOG00000012442

Paralogs (1): CEMIP2 (ENSG00000135048)

Protein

Protein identifiers

Cell migration-inducing and hyaluronan-binding protein — Q8WUJ3 (reviewed: Q8WUJ3)

Alternative names: Hyaluronan binding protein involved in hyaluronan depolymerization

All UniProt accessions (3): H0YCE1, H0YL56, Q8WUJ3

UniProt curated annotations — full annotation on UniProt →

Function. Mediates depolymerization of hyaluronic acid (HA) via the cell membrane-associated clathrin-coated pit endocytic pathway. Binds to hyaluronic acid. Hydrolyzes high molecular weight hyaluronic acid to produce an intermediate-sized product, a process that may occur through rapid vesicle endocytosis and recycling without intracytoplasmic accumulation or digestion in lysosomes. Involved in hyaluronan catabolism in the dermis of the skin and arthritic synovium. Positively regulates epithelial-mesenchymal transition (EMT), and hence tumor cell growth, invasion and cancer dissemination. In collaboration with HSPA5/BIP, promotes cancer cell migration in a calcium and PKC-dependent manner. May be involved in hearing.

Subunit / interactions. Interacts with EPHA2 and ITPR3. Interacts with HSPA5/BIP; the interaction induces calcium leakage from the endoplasmic reticulum and cell migration. Interacts with clathrin heavy chain/CLTC.

Subcellular location. Nucleus. Cytoplasm. Endoplasmic reticulum. Cell membrane. Membrane. Clathrin-coated pit. Secreted.

Tissue specificity. Expressed in dermal and in synovial fibroblasts. Strongly expressed in gastric cancers compared with the paired normal tissues. Strongly expressed in both ductal carcinoma and invasive breast cancer cells compared with benign epithelial cells (at protein level). Strongly expressed in brain, placenta, prostate, breast, lung and testis. Expressed in fibroblasts, epithelial cells and cancer cells. In ear, it is specifically expressed in inner ear. Expressed in cochlea and vestibule tissues. Strongly expressed in gastric cancers compared with the paired normal tissues. Strongly expressed in colon adenocarcinomas compared with normal colonic mucosas. Strongly expressed in breast cancer as compared to normal breast tissue.

Post-translational modifications. N-glycosylated; glycosylation is not necessary for HA-binding.

Activity regulation. Activity is up-regulated by histamine.

Domain organisation. The signal sequence is essential in mediating its proper translocation, hyaluronic acid (HA) degradation activity and secretion.

Induction. Up-regulated by histamine. Up-regulated by the adapter protein complex 1 (AP-1) and NF-kappaB/RELA. Down-regulated by transforming growth factor TGFB1.

Similarity. Belongs to the CEMIP family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8WUJ3-1	1	yes
Q8WUJ3-2	2

RefSeq proteins (3): NP_001280227, NP_001280233, NP_061159 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011050	Pectin_lyase_fold/virulence	Homologous_superfamily
IPR019316	G8_domain	Domain
IPR025155	WxxW_domain	Domain
IPR039473	TMEM2_PANDER-like	Domain
IPR039477	ILEI/PANDER_dom	Domain
IPR052252	CEMIP/CEMIP2	Family
IPR055400	CEMIP_X	Domain
IPR055401	CEMIP_beta-hel_dom	Domain

Pfam: PF10162, PF13330, PF15711, PF24605, PF24606

UniProt features (27 total): glycosylation site 7, sequence variant 6, repeat 4, domain 3, splice variant 2, sequence conflict 2, signal peptide 1, chain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8WUJ3-F1	90.69	0.75

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 (7): 119, 165, 312, 370, 420, 889, 921

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-2160916	Hyaluronan degradation
R-HSA-1430728	Metabolism
R-HSA-1630316	Glycosaminoglycan metabolism
R-HSA-2142845	Hyaluronan metabolism
R-HSA-2142850
R-HSA-71387	Metabolism of carbohydrates and carbohydrate derivatives

MSigDB gene sets: 298 (showing top): AHRARNT_01, GOBP_POSITIVE_REGULATION_OF_CALCIUM_ION_TRANSPORT, TGGTGCT_MIR29A_MIR29B_MIR29C, BENPORATH_ES_WITH_H3K27ME3, GOBP_REGULATION_OF_PHOSPHORYLATION, GOBP_SENSORY_PERCEPTION_OF_MECHANICAL_STIMULUS, PEREZ_TP63_TARGETS, GOZGIT_ESR1_TARGETS_DN, GOBP_HYALURONAN_CATABOLIC_PROCESS, GOBP_PROTEIN_TARGETING, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_CATABOLIC_PROCESS, TATTATA_MIR374, AREB6_01, GAUSSMANN_MLL_AF4_FUSION_TARGETS_E_UP

GO Biological Process (9): sensory perception of sound (GO:0007605), positive regulation of peptidyl-threonine phosphorylation (GO:0010800), hyaluronan catabolic process (GO:0030214), positive regulation of cell migration (GO:0030335), positive regulation of release of sequestered calcium ion into cytosol (GO:0051281), positive regulation of protein targeting to membrane (GO:0090314), positive regulation of protein kinase C activity (GO:1900020), hyaluronan metabolic process (GO:0030212), hyaluronan biosynthetic process (GO:0030213)

GO Molecular Function (8): hyalurononglucosaminidase activity (GO:0004415), hyaluronic acid binding (GO:0005540), carbohydrate binding (GO:0030246), clathrin heavy chain binding (GO:0032050), ER lumen protein retrieval receptor activity (GO:0046923), protein binding (GO:0005515), hydrolase activity (GO:0016787), hydrolase activity, acting on glycosyl bonds (GO:0016798)

GO Cellular Component (11): fibrillar center (GO:0001650), extracellular region (GO:0005576), cytoplasm (GO:0005737), endoplasmic reticulum (GO:0005783), plasma membrane (GO:0005886), clathrin-coated pit (GO:0005905), clathrin-coated vesicle membrane (GO:0030665), nuclear membrane (GO:0031965), clathrin-coated endocytic vesicle (GO:0045334), nucleus (GO:0005634), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Hyaluronan metabolism	1
Metabolism of carbohydrates and carbohydrate derivatives	1
Glycosaminoglycan metabolism	1
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
hyaluronan metabolic process	2
binding	2
endomembrane system	2
intracellular membrane-bounded organelle	2
membrane	2
clathrin-coated vesicle	2
sensory perception of mechanical stimulus	1
positive regulation of protein phosphorylation	1
regulation of peptidyl-threonine phosphorylation	1
peptidyl-threonine phosphorylation	1
glycosaminoglycan catabolic process	1
cell migration	1
regulation of cell migration	1
positive regulation of cell motility	1
release of sequestered calcium ion into cytosol	1
regulation of release of sequestered calcium ion into cytosol	1
positive regulation of calcium ion transmembrane transport	1
protein targeting to membrane	1
positive regulation of cellular process	1
regulation of protein targeting to membrane	1
positive regulation of establishment of protein localization	1
diacylglycerol-dependent serine/threonine kinase activity	1
positive regulation of protein serine/threonine kinase activity	1
regulation of protein kinase C activity	1
glycosaminoglycan metabolic process	1
glycosaminoglycan biosynthetic process	1
hexosaminidase activity	1
carboxylic acid binding	1
clathrin binding	1
signal sequence receptor activity	1
catalytic activity	1
hydrolase activity	1
nucleolus	1
intracellular anatomical structure	1
cytoplasm	1
cell periphery	1
coated vesicle membrane	1
nucleus	1
nuclear envelope	1

Protein interactions and networks

STRING

656 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CEMIP	HYAL1	Q12794	623
CEMIP	SPAM1	P38567	622
CEMIP	HYAL2	Q12891	601
CEMIP	HAS2	Q92819	542
CEMIP	PHKB	Q93100	538
CEMIP	PLXNA2	O75051	509
CEMIP	VWA2	Q5GFL6	484
CEMIP	PYGB	P11216	482
CEMIP	PYGM	P11217	480
CEMIP	PYGL	P06737	471
CEMIP	HAS3	O00219	438
CEMIP	HAS1	Q92839	404
CEMIP	IMPG2	Q9BZV3	392
CEMIP	CCN2	P29279	356
CEMIP	CD44	P16070	348

IntAct

17 interactions, top by confidence:

A	B	Type	Score
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
CEMIP	COPA	psi-mi:“MI:0914”(association)	0.500
CEMIP	COPA	psi-mi:“MI:0915”(physical association)	0.500
CEMIP	PHKB	psi-mi:“MI:0915”(physical association)	0.500
CEMIP	HSPA8	psi-mi:“MI:0915”(physical association)	0.400
CEMIP	PYGB	psi-mi:“MI:0915”(physical association)	0.400
SDC1	ILVBL	psi-mi:“MI:0915”(physical association)	0.400
PLXNA2	CEMIP	psi-mi:“MI:0915”(physical association)	0.370
DCUN1D1	RGSL1	psi-mi:“MI:0914”(association)	0.350
	PLXNB2	psi-mi:“MI:0914”(association)	0.350
BTNL2	TMEM131L	psi-mi:“MI:0914”(association)	0.350
DNAJB9	POTEF	psi-mi:“MI:0914”(association)	0.350
CFC1	POTEF	psi-mi:“MI:0914”(association)	0.350
MFAP4	QSOX1	psi-mi:“MI:0914”(association)	0.350
DNASE1L1	QSOX1	psi-mi:“MI:0914”(association)	0.350
CBLN4	AGRN	psi-mi:“MI:0914”(association)	0.350

BioGRID (77): CEMIP (Proximity Label-MS), CEMIP (Affinity Capture-MS), CEMIP (Affinity Capture-MS), CEMIP (Affinity Capture-MS), CEMIP (Affinity Capture-MS), CEMIP (Affinity Capture-MS), CEMIP (Affinity Capture-MS), CEMIP (Affinity Capture-MS), CEMIP (Affinity Capture-MS), ARHGAP26 (Affinity Capture-Western), CEMIP (Affinity Capture-Western), CEMIP (Co-localization), MIB1 (Affinity Capture-Western), CEMIP (Affinity Capture-Western), MIB1 (Co-localization)

ESM2 similar proteins: A0A0P0XM10, A7YY53, F4HTM3, F4JZJ0, F4JZJ2, H2DF88, O00469, O02791, O18823, O65355, O95497, O95498, P28039, P48980, P54803, P54804, P54818, P57681, P70665, Q0J290, Q0VA39, Q14CN2, Q1L8D2, Q28017, Q28262, Q3LIE5, Q498K0, Q5M886, Q5R748, Q5SNX7, Q6NQ66, Q75HQ3, Q811A3, Q8BI06, Q8GX69, Q8K1B9, Q8RY23, Q8WUJ3, Q95KC9, Q99KS6

Diamond homologs: A3KPQ7, Q5FWI3, Q8BI06, Q8WUJ3, Q9D309, Q9UHN6, A5PKI3, B0BLS9, P58499, P97805, P98173, Q5R5C3, Q6GQC1, Q7ZYY4, Q810F4, Q91VU0, Q92520, Q96BQ1, Q9D8T0, E2RK30, E9PZ36, P08F94, Q54KF6, Q54YG8, Q54IW5, Q54L52, Q54LY1, Q54XG9, Q557B8, Q80ZA4, Q86WI1

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	177
Likely benign	26
Benign	57

Top pathogenic / likely-pathogenic (0)

SpliceAI

5264 predictions. Top by Δscore:

Variant	Effect	Δscore
15:80873858:TTTCA:T	acceptor_loss	1.0000
15:80873859:TTCA:T	acceptor_loss	1.0000
15:80873860:TCA:T	acceptor_loss	1.0000
15:80873861:CA:C	acceptor_loss	1.0000
15:80873861:CAGGG:C	acceptor_gain	1.0000
15:80873862:A:AG	acceptor_gain	1.0000
15:80873862:A:C	acceptor_loss	1.0000
15:80873862:AG:A	acceptor_gain	1.0000
15:80873862:AGG:A	acceptor_gain	1.0000
15:80873862:AGGGA:A	acceptor_gain	1.0000
15:80873863:G:GA	acceptor_loss	1.0000
15:80873863:G:GG	acceptor_gain	1.0000
15:80873863:GG:G	acceptor_gain	1.0000
15:80873863:GGG:G	acceptor_gain	1.0000
15:80873863:GGGA:G	acceptor_gain	1.0000
15:80873863:GGGAG:G	acceptor_gain	1.0000
15:80878719:A:AG	acceptor_gain	1.0000
15:80878719:AGT:A	acceptor_gain	1.0000
15:80878720:G:GG	acceptor_gain	1.0000
15:80878720:GT:G	acceptor_gain	1.0000
15:80878720:GTG:G	acceptor_gain	1.0000
15:80878863:GGGAG:G	donor_gain	1.0000
15:80878864:GGAGG:G	donor_gain	1.0000
15:80879700:A:AG	acceptor_gain	1.0000
15:80879700:AAT:A	acceptor_gain	1.0000
15:80879803:G:GT	donor_gain	1.0000
15:80879852:AAGG:A	donor_loss	1.0000
15:80879853:AGGT:A	donor_loss	1.0000
15:80879855:GTGC:G	donor_loss	1.0000
15:80879856:T:A	donor_loss	1.0000

AlphaMissense

9064 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:80920132:C:G	C612W	1.000
15:80920224:G:C	R643P	1.000
15:80895976:A:C	S443R	0.999
15:80895978:T:A	S443R	0.999
15:80895978:T:G	S443R	0.999
15:80909274:T:C	C589R	0.999
15:80909276:C:G	C589W	0.999
15:80920124:G:C	G610R	0.999
15:80920125:G:A	G610D	0.999
15:80920125:G:T	G610V	0.999
15:80920128:A:G	H611R	0.999
15:80920130:T:C	C612R	0.999
15:80920131:G:A	C612Y	0.999
15:80920145:G:C	D617H	0.999
15:80920148:G:T	G618W	0.999
15:80920165:C:A	N623K	0.999
15:80920165:C:G	N623K	0.999
15:80920180:T:G	C628W	0.999
15:80920220:G:C	D642H	0.999
15:80920238:T:A	C648S	0.999
15:80920238:T:C	C648R	0.999
15:80920239:G:A	C648Y	0.999
15:80920239:G:C	C648S	0.999
15:80920240:C:G	C648W	0.999
15:80920295:T:A	C667S	0.999
15:80920295:T:C	C667R	0.999
15:80920296:G:A	C667Y	0.999
15:80920296:G:C	C667S	0.999
15:80920297:C:G	C667W	0.999
15:80921040:C:A	S671Y	0.999

dbSNP variants (sampled 300 via entrez): RS1000010184 (15:80900877 A>C), RS1000031278 (15:80855373 T>C), RS1000064083 (15:80833169 G>A), RS1000074872 (15:80879467 C>T), RS1000100968 (15:80945068 C>T), RS1000101264 (15:80797761 G>A), RS1000103554 (15:80934893 C>A), RS1000124357 (15:80814368 C>G,T), RS1000131538 (15:80872369 A>G), RS1000132060 (15:80831695 T>C), RS1000157275 (15:80814641 T>C), RS1000173121 (15:80801242 A>G), RS1000183617 (15:80792295 G>A,C), RS1000228816 (15:80809893 C>A), RS1000236133 (15:80876302 T>C)

Disease associations

OMIM: gene MIM:608366 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
nonsyndromic genetic hearing loss	Disputed Evidence	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
nonsyndromic genetic hearing loss	Disputed	AR

Mondo (1): nonsyndromic genetic hearing loss (MONDO:0019497)

Orphanet (0):

HPO phenotypes

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

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST002675_5	Response to statins (LDL cholesterol change)	3.000000e-07
GCST005951_10	Body mass index	2.000000e-08
GCST005984_65	Glomerular filtration rate	1.000000e-08
GCST005985_13	Creatinine levels	2.000000e-08
GCST007344_92	Estimated glomerular filtration rate	8.000000e-09
GCST010796_4773	Electrocardiogram morphology (amplitude at temporal datapoints)	4.000000e-08
GCST011743_63	HDL cholesterol levels in HIV infection	8.000000e-06

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004340	body mass index
EFO:0004327	electrocardiography
EFO:0004612	high density lipoprotein cholesterol measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C580334	Nonsyndromic Deafness (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, decreases methylation, increases expression, increases methylation	4
Tetrachlorodibenzodioxin	increases expression	4
sodium arsenite	increases expression, decreases expression	3
Copper	affects cotreatment, decreases expression, affects binding, increases expression	3
Estradiol	decreases expression, decreases reaction, increases expression	3
propionaldehyde	increases expression	2
bisphenol A	affects cotreatment, increases methylation, decreases methylation, decreases expression	2
pentanal	increases expression	2
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression, increases expression	2
(+)-JQ1 compound	decreases expression, increases expression	2
Resveratrol	affects cotreatment, decreases expression	2
Acetaminophen	increases expression	2
Calcitriol	decreases expression	2
Dexamethasone	affects cotreatment, decreases expression	2
Tobacco Smoke Pollution	decreases expression, increases expression	2
Aflatoxin B1	increases expression, increases methylation	2
aristolochic acid I	increases expression	1
GSK-J4	increases expression	1
3,19-(2-bromobenzylidene)andrographolide	decreases response to substance, increases expression	1
CBP30 compound	decreases reaction, increases expression	1
dicrotophos	increases expression	1
methyleugenol	decreases expression	1
triphenyl phosphate	affects expression	1
sodium arsenate	decreases expression, increases abundance	1
2-methyl-4-isothiazolin-3-one	increases expression	1
hydroxyhydroquinone	increases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
2,4,5,2’,4’,5’-hexachlorobiphenyl	increases expression	1
mono-(2-ethylhexyl)phthalate	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E1K1	HyCyte HCT 116 KO-hCEMIP	Cancer cell line	Male
CVCL_E1KN	HyCyte HeLa KO-hCEMIP	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01802190	Not specified	TERMINATED	Prevalence of POU4F3 and SLC17A8 Mutations