CEMIP2

Summary

CEMIP2 (cell migration inducing hyaluronidase 2, HGNC:11869) is a protein-coding gene on chromosome 9q21.13, encoding Cell surface hyaluronidase CEMIP2 (Q9UHN6). Cell surface hyaluronidase that mediates the initial cleavage of extracellular high-molecular-weight hyaluronan into intermediate-size hyaluronan of approximately 10-5 kDa fragments.

This gene encodes a type II transmembrane protein that belongs to the interferon-induced transmembrane (IFITM) protein superfamily. The encoded protein functions as a cell surface hyaluronidase that cleaves extracellular high molecular weight hyaluronan into intermediate size fragments before internalization and degradation in the lysosome. It also has an interferon-mediated antiviral function in humans through activation of the JAK STAT signaling pathway. The activation of this gene by transcription factor SOX4 in breast cancer cells has been shown to mediate the pathological effects of SOX4 on cancer progression. Naturally occurring mutations in this gene are associated with autosomal recessive non-syndromic hearing loss.

Source: NCBI Gene 23670 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 264 total — 3 pathogenic
• Phenotypes (HPO): 2
• MANE Select transcript: NM_013390

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11869
Approved symbol	CEMIP2
Name	cell migration inducing hyaluronidase 2
Location	9q21.13
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000135048
Ensembl biotype	protein_coding
OMIM	605835
Entrez	23670

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 10 protein_coding, 6 retained_intron, 1 nonsense_mediated_decay

ENST00000377043, ENST00000377044, ENST00000377055, ENST00000377057, ENST00000377066, ENST00000396272, ENST00000474495, ENST00000537329, ENST00000538669, ENST00000542935, ENST00000543165, ENST00000545719, ENST00000546219, ENST00000853336, ENST00000853337, ENST00000911423, ENST00000971297

RefSeq mRNA: 3 — MANE Select: NM_013390 NM_001135820, NM_001349784, NM_013390

CCDS: CCDS47979, CCDS6638

Canonical transcript exons

ENST00000377044 — 24 exons

Exon	Start	End
ENSE00000637471	71740063	71740232
ENSE00000706014	71730705	71730914
ENSE00000706015	71732351	71732520
ENSE00000706016	71734806	71734994
ENSE00000803709	71745018	71745579
ENSE00000803710	71746201	71746341
ENSE00001472646	71750043	71750385
ENSE00001816206	71683366	71685393
ENSE00001862023	71768357	71768513
ENSE00003473725	71694509	71694607
ENSE00003481448	71685743	71685846
ENSE00003485456	71709259	71709474
ENSE00003501624	71725581	71725709
ENSE00003503201	71722427	71722515
ENSE00003506140	71697985	71698204
ENSE00003564143	71714934	71715089
ENSE00003589020	71730048	71730253
ENSE00003615225	71704595	71704803
ENSE00003643245	71690092	71690246
ENSE00003655383	71700642	71700824
ENSE00003659182	71729845	71729914
ENSE00003668829	71717948	71718079
ENSE00003672666	71716517	71716552
ENSE00003692624	71712083	71712260

Expression profiles

Bgee: expression breadth ubiquitous, 251 present calls, max score 97.49.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 24.1520 / max 1530.3248, expressed in 1723 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
100929	24.1245	1723
100928	0.0275	17

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
upper lobe of left lung	UBERON:0008952	97.49	gold quality
upper lobe of lung	UBERON:0008948	96.93	gold quality
right lung	UBERON:0002167	96.51	gold quality
sural nerve	UBERON:0015488	96.28	gold quality
gall bladder	UBERON:0002110	96.23	gold quality
secondary oocyte	CL:0000655	95.91	gold quality
omental fat pad	UBERON:0010414	94.22	gold quality
placenta	UBERON:0001987	94.18	gold quality
peritoneum	UBERON:0002358	94.18	gold quality
tibial nerve	UBERON:0001323	93.96	gold quality
oocyte	CL:0000023	93.94	gold quality
right lobe of liver	UBERON:0001114	93.91	gold quality
mucosa of transverse colon	UBERON:0004991	93.70	gold quality
rectum	UBERON:0001052	93.67	gold quality
colonic epithelium	UBERON:0000397	93.64	gold quality
adipose tissue of abdominal region	UBERON:0007808	93.29	gold quality
lung	UBERON:0002048	92.82	gold quality
monocyte	CL:0000576	92.64	gold quality
leukocyte	CL:0000738	92.42	gold quality
liver	UBERON:0002107	92.42	gold quality
mononuclear cell	CL:0000842	92.37	gold quality
tendon of biceps brachii	UBERON:0008188	92.36	gold quality
body of stomach	UBERON:0001161	92.25	gold quality
stromal cell of endometrium	CL:0002255	92.21	gold quality
stomach	UBERON:0000945	92.03	gold quality
blood	UBERON:0000178	91.82	gold quality
small intestine Peyer’s patch	UBERON:0003454	91.76	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	91.67	gold quality
granulocyte	CL:0000094	91.50	gold quality
spleen	UBERON:0002106	91.44	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-CURD-122	yes	22.03
E-CURD-46	yes	16.50
E-ANND-3	yes	15.86
E-CURD-112	yes	12.02
E-GEOD-93593	yes	8.56
E-MTAB-9067	yes	6.96
E-GEOD-130148	yes	4.31
E-MTAB-6379	no	691.73

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

152 targeting CEMIP2, 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-8485	100.00	77.57	4731
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-3613-3P	100.00	76.36	7965
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-3662	99.99	73.82	5684
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-548N	99.98	71.94	4170
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-302C-5P	99.97	72.56	3642
HSA-MIR-548AN	99.97	70.91	2817

Literature-anchored findings (GeneRIF, showing 13)

• Results showed that missense mutations in transmembrane protein 2 p.Ser1254Asn, interferon alpha 2 p.Ala120Thr, its regulator NLR family member X1 p.Arg707Cys, and complement component 2 p.Glu318Asp were associated with chronic hepatitis B. (PMID:22610944)
• TMEM2 inhibits Hepatitis b virus infection in HepG2 and HepG2.2.15 by activating the JAK-STAT signaling pathway. (PMID:27253403)
• our findings lead us to propose that TMEM2 may not only mediate the pathologic effects of SOX4 on cancer progression but also potentially its contributions to embryonic development (PMID:27328729)
• 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)
• ectopic expression of human TMEM2 in C. elegans protected animals from endoplasmic reticulum stress and increased both longevity and pathogen resistance. (PMID:31761535)
• Transcriptome alterations in HepG2 cells induced by shRNA knockdown and overexpression of TMEM2 gene. (PMID:32326855)
• miR-518a-3p Suppresses Triple-Negative Breast Cancer Invasion and Migration Through Regulation of TMEM2. (PMID:33251982)
• TMEM2 expression is downregulated as bladder cancer invades the muscle layer. (PMID:35525055)
• Expression and regulation of recently discovered hyaluronidases, HYBID and TMEM2, in chondrocytes from knee osteoarthritic cartilage. (PMID:36241903)
• Concurrent Overexpression of Two Hyaluronidases, KIAA1199 and TMEM2, Strongly Predicts Shorter Survival After Resection in Pancreatic Ductal Adenocarcinoma. (PMID:36395406)
• Human TMEM2 is not a catalytic hyaluronidase, but a regulator of hyaluronan metabolism via HYBID (KIAA1199/CEMIP) and HAS2 expression. (PMID:37196767)
• TMEM2 is a bona fide hyaluronidase possessing intrinsic catalytic activity. (PMID:37527776)
• HRD1-induced TMEM2 ubiquitination promotes ER stress-mediated apoptosis through a non-canonical pathway in intestinal ischemia/reperfusion. (PMID:38378757)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	cemip2	ENSDARG00000061600
mus_musculus	Cemip2	ENSMUSG00000024754
rattus_norvegicus	Cemip2	ENSRNOG00000012782

Paralogs (1): CEMIP (ENSG00000103888)

Protein

Protein identifiers

Cell surface hyaluronidase CEMIP2 — Q9UHN6 (reviewed: Q9UHN6)

Alternative names: Cell migration-inducing hyaluronidase 2, Transmembrane protein 2

All UniProt accessions (6): B4E1B9, Q9UHN6, F5GZC1, F5H6B2, H3BLX9, H3BLY0

UniProt curated annotations — full annotation on UniProt →

Function. Cell surface hyaluronidase that mediates the initial cleavage of extracellular high-molecular-weight hyaluronan into intermediate-size hyaluronan of approximately 10-5 kDa fragments. Very specific to hyaluronan; not able to cleave chondroitin sulfate or dermatan sulfate. Has an essential function in systemic hyaluronan catabolism and turnover and regulates cell adhesion and migration via hyaluronan degradation at focal adhesion sites. Acts as a regulator of angiogenesis and heart morphogenesis by mediating degradation of extracellular hyaluronan, thereby regulating VEGF signaling.

Subcellular location. Cell membrane.

Tissue specificity. Widely expressed.

Induction. Up-regulated in by proinflammatory cytokines in normal human dermal fibroblasts (NHDF).

Similarity. Belongs to the CEMIP family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9UHN6-1	1	yes
Q9UHN6-2	2

RefSeq proteins (3): NP_001129292, NP_001336713, NP_037522* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011050	Pectin_lyase_fold/virulence	Homologous_superfamily
IPR019316	G8_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, PF15711, PF24605, PF24606

UniProt features (156 total): strand 96, helix 16, turn 15, sequence variant 9, glycosylation site 4, domain 3, repeat 3, topological domain 2, modified residue 2, sequence conflict 2, chain 1, region of interest 1, splice variant 1, transmembrane region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
8C6I	X-RAY DIFFRACTION	3.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UHN6-F1	89.66	0.77

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 (2): 10, 63

Glycosylation sites (4): 248, 292, 914, 1234

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 269 (showing top): GSE45365_NK_CELL_VS_CD11B_DC_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_HYALURONAN_CATABOLIC_PROCESS, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, GOBP_CARBOHYDRATE_DERIVATIVE_CATABOLIC_PROCESS, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, MCBRYAN_PUBERTAL_TGFB1_TARGETS_UP, RIZKI_TUMOR_INVASIVENESS_3D_DN, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_HYALURONAN_METABOLIC_PROCESS, GOBP_SPROUTING_ANGIOGENESIS, FOSTER_TOLERANT_MACROPHAGE_UP, MCBRYAN_PUBERTAL_BREAST_3_4WK_UP, PETRETTO_HEART_MASS_QTL_CIS_DN

GO Biological Process (3): angiogenesis (GO:0001525), hyaluronan catabolic process (GO:0030214), regulation of sprouting angiogenesis (GO:1903670)

GO Molecular Function (7): hyalurononglucosaminidase activity (GO:0004415), calcium ion binding (GO:0005509), carbohydrate binding (GO:0030246), cadherin binding (GO:0045296), hydrolase activity, hydrolyzing O-glycosyl compounds (GO:0004553), hydrolase activity (GO:0016787), hydrolase activity, acting on glycosyl bonds (GO:0016798)

GO Cellular Component (5): nucleolus (GO:0005730), cytosol (GO:0005829), plasma membrane (GO:0005886), membrane (GO:0016020), extracellular exosome (GO:0070062)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
blood vessel morphogenesis	1
anatomical structure formation involved in morphogenesis	1
glycosaminoglycan catabolic process	1
hyaluronan metabolic process	1
sprouting angiogenesis	1
regulation of angiogenesis	1
hexosaminidase activity	1
metal ion binding	1
binding	1
cell adhesion molecule binding	1
hydrolase activity, acting on glycosyl bonds	1
catalytic activity	1
hydrolase activity	1
nuclear lumen	1
intracellular membraneless organelle	1
cytoplasm	1
membrane	1
cell periphery	1
extracellular vesicle	1

Protein interactions and networks

STRING

584 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CEMIP2	LRRTM2	O43300	924
CEMIP2	NRXN2	Q9P2S2	671
CEMIP2	NRXN1	Q9ULB1	653
CEMIP2	HYAL2	Q12891	581
CEMIP2	HYAL1	Q12794	534
CEMIP2	C9orf85	Q96MD7	527
CEMIP2	SPAM1	P38567	525
CEMIP2	IGFALS	P35858	499
CEMIP2	NXN	Q6DKJ4	479
CEMIP2	C9orf57	Q5W0N0	448
CEMIP2	PKHD1L1	Q86WI1	423
CEMIP2	HAS2	Q92819	421
CEMIP2	PKHD1	P08F94	380
CEMIP2	TTC33	Q6PID6	368
CEMIP2	SLIT1	O75093	363

IntAct

98 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CD81	EGFR	psi-mi:“MI:0914”(association)	0.600
CD81	C2orf72	psi-mi:“MI:0914”(association)	0.530
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
CRP	QSOX1	psi-mi:“MI:0914”(association)	0.530
DEFA1	MANBA	psi-mi:“MI:0914”(association)	0.530
LGALS1	PODXL	psi-mi:“MI:0914”(association)	0.530
CLGN	NPC1	psi-mi:“MI:0914”(association)	0.530
INSL5	COCH	psi-mi:“MI:0914”(association)	0.530
C1QTNF9B	PLOD3	psi-mi:“MI:0914”(association)	0.530
CCT8L2	ACSL4	psi-mi:“MI:0914”(association)	0.530
ANKH	FAM234B	psi-mi:“MI:0914”(association)	0.530
NRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.480
CEMIP2	iglC2	psi-mi:“MI:0915”(physical association)	0.370
CD81	STX3	psi-mi:“MI:0914”(association)	0.350
CD81	PVR	psi-mi:“MI:0914”(association)	0.350
CD81	CD276	psi-mi:“MI:0914”(association)	0.350
rep	BMPR1B	psi-mi:“MI:0914”(association)	0.350
	SHTN1	psi-mi:“MI:0914”(association)	0.350
	TNFRSF10A	psi-mi:“MI:0914”(association)	0.350

BioGRID (173): TMEM2 (Affinity Capture-MS), TMEM2 (Affinity Capture-MS), TMEM2 (Affinity Capture-MS), TMEM2 (Proximity Label-MS), TMEM2 (Proximity Label-MS), TMEM2 (Affinity Capture-MS), TMEM2 (Proximity Label-MS), TMEM2 (Affinity Capture-MS), TMEM2 (Affinity Capture-MS), TMEM2 (Affinity Capture-MS), TMEM2 (Affinity Capture-MS), TMEM2 (Affinity Capture-MS), TMEM2 (Affinity Capture-MS), TMEM2 (Affinity Capture-MS), TMEM2 (Affinity Capture-MS)

ESM2 similar proteins: A2RSQ1, A3KPQ7, M9NDE3, O73798, O75339, P08069, P12890, P15127, P15208, P16098, P24062, P34501, P51559, P82993, Q00PJ8, Q07DV8, Q07DY1, Q07E01, Q07E24, Q07E48, Q09YH7, Q09YI9, Q09YK0, Q09YL1, Q0INM3, Q0IZZ8, Q108U6, Q2IBC0, Q2IBG7, Q2QL89, Q2QLC0, Q2QLG5, Q2QLH6, Q54YG8, Q5FWI3, Q60751, Q60HF6, Q66K08, Q75ZY9, Q765H6

Diamond homologs: A3KPQ7, Q5FWI3, Q8BI06, Q8WUJ3, Q9D309, Q9UHN6, Q54KF6, Q54YG8, E2RK30, Q80ZA4, Q07E01, Q86WI1, A5PKI3, B0BLS9, E9PZ36, P08F94, Q6GQC1, Q91VU0, Q92520

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
MARCHF9	“down-regulates quantity by destabilization”	CEMIP2	ubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 122 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Extracellular matrix organization	6	5.2×	8e-03
RAF/MAP kinase cascade	6	5.0×	1e-02

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	0
Uncertain significance	210
Likely benign	14
Benign	1

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
3391905	GRCh37/hg19 9q21.11-21.31(chr9:72100051-83444640)x1	Pathogenic
827846	NM_013390.3(CEMIP2):c.1358G>A (p.Cys453Tyr)	Pathogenic
827847	NM_013390.3(CEMIP2):c.3144G>A (p.Trp1048Ter)	Pathogenic

SpliceAI

4312 predictions. Top by Δscore:

Variant	Effect	Δscore
9:71683944:T:A	donor_gain	1.0000
9:71694500:GGTAC:G	donor_loss	1.0000
9:71694501:GTAC:G	donor_loss	1.0000
9:71694502:TAC:T	donor_loss	1.0000
9:71694503:ACTT:A	donor_loss	1.0000
9:71694504:CT:C	donor_loss	1.0000
9:71694505:T:TC	donor_loss	1.0000
9:71694506:TA:T	donor_loss	1.0000
9:71694507:A:AC	donor_gain	1.0000
9:71694507:ACA:A	donor_loss	1.0000
9:71694508:C:CC	donor_gain	1.0000
9:71694508:C:T	donor_loss	1.0000
9:71694508:CA:C	donor_gain	1.0000
9:71694508:CAG:C	donor_gain	1.0000
9:71694508:CAGA:C	donor_gain	1.0000
9:71694508:CAGAA:C	donor_gain	1.0000
9:71700619:ATTC:A	donor_gain	1.0000
9:71700622:C:A	donor_gain	1.0000
9:71700667:T:A	donor_gain	1.0000
9:71700683:T:A	donor_gain	1.0000
9:71704589:ACAT:A	donor_loss	1.0000
9:71704590:CAT:C	donor_loss	1.0000
9:71704591:ATA:A	donor_loss	1.0000
9:71704592:TAC:T	donor_loss	1.0000
9:71704593:A:AC	donor_gain	1.0000
9:71704593:A:T	donor_loss	1.0000
9:71704594:C:CT	donor_gain	1.0000
9:71704594:CTTG:C	donor_gain	1.0000
9:71709297:TAGAC:T	donor_gain	1.0000
9:71709298:AGACA:A	donor_gain	1.0000

AlphaMissense

9126 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:71730050:A:C	C659W	0.999
9:71718005:T:A	K781I	0.998
9:71730051:C:G	C659S	0.998
9:71730052:A:G	C659R	0.998
9:71730052:A:T	C659S	0.998
9:71730107:A:C	C640W	0.998
9:71730108:C:G	C640S	0.998
9:71730109:A:T	C640S	0.998
9:71734888:G:C	S437R	0.998
9:71734888:G:T	S437R	0.998
9:71734890:T:G	S437R	0.998
9:71704647:A:G	W1048R	0.997
9:71704647:A:T	W1048R	0.997
9:71717985:A:G	W788R	0.997
9:71717985:A:T	W788R	0.997
9:71729898:A:G	W666R	0.997
9:71729898:A:T	W666R	0.997
9:71730051:C:T	C659Y	0.997
9:71730109:A:G	C640R	0.997
9:71730215:A:C	C604W	0.997
9:71740225:A:G	W348R	0.997
9:71740225:A:T	W348R	0.997
9:71712226:C:A	G876W	0.996
9:71712228:T:A	D875V	0.996
9:71715020:G:C	S835R	0.996
9:71715020:G:T	S835R	0.996
9:71715022:T:G	S835R	0.996
9:71716529:A:G	L808P	0.996
9:71716540:A:C	N804K	0.996
9:71716540:A:T	N804K	0.996

dbSNP variants (sampled 300 via entrez): RS1000027792 (9:71702461 T>C), RS1000092378 (9:71751910 C>G), RS1000113205 (9:71707444 C>G), RS1000128102 (9:71708056 G>A), RS1000196147 (9:71711393 A>AT), RS1000244860 (9:71726571 A>C,G), RS1000270089 (9:71683234 G>A,C), RS1000272655 (9:71749716 AAAG>A), RS1000282173 (9:71769079 C>A,G,T), RS1000294193 (9:71738787 A>G), RS1000323040 (9:71682976 C>G), RS1000323694 (9:71762132 G>A), RS1000360613 (9:71720722 T>C), RS1000458214 (9:71702235 G>A), RS1000520744 (9:71750194 G>A,T)

Disease associations

OMIM: gene MIM:605835 | disease phenotypes: MIM:160700

GenCC curated gene-disease

Mondo (3): congenital heart disease (MONDO:0005453), myopia (MONDO:0001384), inherited retinal dystrophy (MONDO:0019118)

Orphanet (1): OBSOLETE: Inherited retinal disorder (Orphanet:71862)

HPO phenotypes

2 total (2 of 2 shown, HPO-id order):

HPO	Term
HP:0000545	Myopia
HP:0000556	Retinal dystrophy

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST006585_2653	Blood protein levels	4.000000e-07
GCST007326_81	Number of sexual partners	5.000000e-08
GCST007576_147	Chronotype	1.000000e-08
GCST009442_3	Age-related cognitive decline (executive function) (slope of z-scores)	6.000000e-06
GCST012095_27	Major depressive episode treated with electroconvulsive therapy	6.000000e-06

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0008328	chronotype measurement
EFO:0007710	cognitive decline measurement
EFO:0007634	major depressive episode

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D006330	Heart Defects, Congenital	C14.240.400; C14.280.400; C16.131.240.400
D009216	Myopia	C11.744.636
D058499	Retinal Dystrophies	C11.768.585.658

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases methylation, increases expression	7
trichostatin A	increases expression, affects cotreatment, decreases expression	4
Valproic Acid	affects cotreatment, decreases expression, increases expression	4
(+)-JQ1 compound	increases expression	3
Rotenone	decreases expression, increases expression	3
Cyclosporine	decreases expression, increases expression	3
sodium arsenite	decreases expression, increases expression	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression, decreases expression	2
Air Pollutants	affects cotreatment, increases abundance, increases expression, decreases expression	2
Estradiol	increases expression, increases reaction	2
Formaldehyde	decreases expression, increases expression	2
Nickel	increases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Particulate Matter	decreases expression, increases abundance, affects cotreatment, increases expression	2
FR900359	increases phosphorylation	1
methylmercuric chloride	decreases expression	1
alpha-pinene	affects cotreatment, increases expression, increases abundance	1
bisphenol A	affects cotreatment, decreases expression	1
deoxynivalenol	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
rutecarpine	increases expression	1
methacrylaldehyde	affects cotreatment, increases expression, increases abundance	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
pentabromodiphenyl ether	decreases expression	1
deguelin	decreases expression	1
scriptaid	increases expression	1
4-chloro-N-((4-(1,1-dimethylethyl)phenyl)methyl)-3-ethyl-1-methyl-1H-pyrazole-5-carboxamide	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_TS88	HAP1 TMEM2 (-) 1	Cancer cell line	Male
CVCL_XU45	HAP1 TMEM2 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00668824	PHASE4	UNKNOWN	Improved Diagnosis of Congenital Heart Disease by Magnetic Resonance Imaging Using Vasovist
NCT01368705	PHASE4	COMPLETED	Nitrogen Balance in Infants After Post Cardiothoracic Surgery
NCT01619982	PHASE4	COMPLETED	Pre-operative Prophylaxis With Vancomycin and Cefazolin in Pediatric Cardiovascular Surgery Patients
NCT02122679	PHASE4	WITHDRAWN	Tranexamic Acid Effect on Platelet Aggregation Following Infant Cardiopulmonary Bypass
NCT02527811	PHASE4	UNKNOWN	Ulinastatin Injection in in Pediatric Patients Undergoing Open Heart Surgery
NCT03014700	PHASE4	COMPLETED	Fibrinogen Concentrate vs Cryoprecipitate
NCT03408340	PHASE4	TERMINATED	Paravertebral Nerve Blocks in Neonates
NCT03630796	PHASE4	UNKNOWN	Effect of Sevoflurane in Postoperative Troponin I Levels in Children Undergoing Congenital Heart Defects Surgery
NCT03667703	PHASE4	COMPLETED	Stress Ulcer Prophylaxis Versus Placebo in Critically Ill Infants With Congenital Heart Disease
NCT04453761	PHASE4	UNKNOWN	Thiamine Influenced on Substrate Energy Effectiveness in Indonesian Children Undergoing Cardiopulmonary Bypass
NCT06668389	PHASE4	RECRUITING	Sodium-Glucose Cotransporter 2 Inhibitors for Repaired Tetralogy of Fallot Patients for Enhancement of Cardio-Pulmonary Status Trial
NCT07499154	PHASE4	NOT_YET_RECRUITING	Perioperative Lidocaine for Lung Protection in Infants Undergoing Cardiac Surgery
NCT00000470	PHASE3	COMPLETED	Infant Heart Surgery: Central Nervous System Sequelae of Circulatory Arrest
NCT00000494	PHASE3	COMPLETED	Management of Patent Ductus in Premature Infants
NCT01134302	PHASE3	UNKNOWN	Hybrid Versus Norwood Management Strategies in Infants Undergoing Single Ventricle Palliation
NCT01607983	PHASE3	WITHDRAWN	Effects of Pulmonary Vasodilation Upon VA Coupling in Fontan Patients
NCT01662011	PHASE3	UNKNOWN	Application of Neurally Adjusted Ventilatory Assist to Children After Congenital Cardiac Surgery
NCT02320669	PHASE3	COMPLETED	Phase 3 Triiodothyronine Supplementation for Infants After Cardiopulmonary Bypass
NCT02615262	PHASE3	COMPLETED	Intraoperative Dexamethasone in Pediatric Cardiac Surgery
NCT03153137	PHASE3	COMPLETED	Clinical Study Assessing the Efficacy and Safety of Macitentan in Fontan-palliated Subjects
NCT03154476	PHASE3	COMPLETED	Role of Sildenafil for Fontan Associated Liver Disease (SiFALD) Study
NCT04536194	PHASE3	COMPLETED	Dopamine Versus Norepinephrine Under General Anesthesia
NCT04702373	PHASE3	ACTIVE_NOT_RECRUITING	Training in Exercise Activities and Motion for Growth (TEAM 4 Growth) RCT
NCT05049590	PHASE3	COMPLETED	Acute Normovolemic Hemodilution in Complex Cardiac Surgery
NCT06406517	PHASE3	UNKNOWN	Comparative Effectiveness of Gadopiclenol for Evaluation of Adult Congenital Heart Anatomy and Hemodynamics
NCT06693674	PHASE3	RECRUITING	Effect of Sacubitril-Valsartan on Cardiac Structure and Function
NCT06955260	PHASE3	NOT_YET_RECRUITING	SGLT2 Inhibition With Empagliflozin in Fontan Circulatory Failure
NCT00115375	PHASE2	COMPLETED	Platelet Aggregation Inhibition in Children on Clopidogrel (PICOLO)
NCT00350220	PHASE2	COMPLETED	Transfusion Strategies in Pediatric Cardiothoracic Surgery
NCT00374088	PHASE2	COMPLETED	N-Acetylcysteine in Neonatal Congenital Heart Surgery (INACT Study)
NCT00538785	PHASE2	COMPLETED	A Study to Evaluate MEDI-524 In Children With Hemodynamically Significant Congenital Heart Disease
NCT00770705	PHASE2	WITHDRAWN	Parenteral Phenoxybenzamine During Congenital Heart Disease Surgery
NCT00919945	PHASE2	TERMINATED	Impact of Early Enteral Feeding on Splanchnic Blood Flow After Surgery for Critical Heart Disease in the Newborn
NCT01063712	PHASE2	COMPLETED	Safety and Effectiveness of the Device Nit-Occlud® PDA-R
NCT01069510	PHASE2	COMPLETED	Spironolactone in Adult Congenital Heart Disease
NCT01189981	PHASE2	COMPLETED	Effect of eHealth Encouragements to Intensive Exercise in Adolescents With Congenital Heart Disease
NCT01330433	PHASE2	COMPLETED	Effects of CoSeal on Bleeding & Adhesions in Pediatric Heart Surgery
NCT01662037	PHASE2	COMPLETED	Bosentan Therapy in Children With Functional Single Ventricle
NCT01668264	PHASE2	UNKNOWN	Imaging Assessment of Diastolic Function
NCT01827059	PHASE2	UNKNOWN	Bosentan In Exercise Induced Pulmonary Arterial Hypertension in CongenitaL Heart diseasE