RECK

Summary

RECK (reversion inducing cysteine rich protein with kazal motifs, HGNC:11345) is a protein-coding gene on chromosome 9p13.3, encoding Reversion-inducing cysteine-rich protein with Kazal motifs (O95980). Functions together with ADGRA2 to enable brain endothelial cells to selectively respond to Wnt7 signals (WNT7A or WNT7B).

The protein encoded by this gene is a cysteine-rich, extracellular protein with protease inhibitor-like domains whose expression is suppressed strongly in many tumors and cells transformed by various kinds of oncogenes. In normal cells, this membrane-anchored glycoprotein may serve as a negative regulator for matrix metalloproteinase-9, a key enzyme involved in tumor invasion and metastasis. Several transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 8434 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 129 total
• MANE Select transcript: NM_021111

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11345
Approved symbol	RECK
Name	reversion inducing cysteine rich protein with kazal motifs
Location	9p13.3
Locus type	gene with protein product
Status	Approved
Aliases	hRECK
Ensembl gene	ENSG00000122707
Ensembl biotype	protein_coding
OMIM	605227
Entrez	8434

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 8 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000377966, ENST00000475774, ENST00000479053, ENST00000905832, ENST00000905833, ENST00000905834, ENST00000929594, ENST00000929595, ENST00000943608, ENST00000943609

RefSeq mRNA: 5 — MANE Select: NM_021111 NM_001316345, NM_001316346, NM_001316347, NM_001316348, NM_021111

CCDS: CCDS6597

Canonical transcript exons

ENST00000377966 — 21 exons

Exon	Start	End
ENSE00000699599	36121533	36121688
ENSE00000699603	36120663	36120736
ENSE00000699607	36118757	36118967
ENSE00000699611	36116985	36117177
ENSE00000699615	36112305	36112476
ENSE00000699617	36109957	36110079
ENSE00000699619	36107976	36108164
ENSE00000699621	36105143	36105283
ENSE00000699623	36102094	36102230
ENSE00000699625	36100331	36100543
ENSE00000699627	36091164	36091343
ENSE00000699629	36087694	36087961
ENSE00000833079	36122824	36124455
ENSE00001944711	36036913	36037098
ENSE00003522385	36058827	36058901
ENSE00003534420	36052265	36052323
ENSE00003590883	36063795	36063880
ENSE00003643648	36065577	36065624
ENSE00003649436	36060119	36060155
ENSE00003677085	36083365	36083562
ENSE00003684764	36080605	36080638

Expression profiles

Bgee: expression breadth ubiquitous, 268 present calls, max score 95.68.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 25.4954 / max 650.6378, expressed in 1657 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
96650	25.4515	1657
96649	0.0439	13

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
skin of hip	UBERON:0001554	95.68	gold quality
parietal pleura	UBERON:0002400	94.18	gold quality
upper leg skin	UBERON:0004262	93.49	gold quality
germinal epithelium of ovary	UBERON:0001304	93.48	gold quality
pleura	UBERON:0000977	93.24	gold quality
tibia	UBERON:0000979	92.50	gold quality
stromal cell of endometrium	CL:0002255	92.26	gold quality
visceral pleura	UBERON:0002401	92.15	gold quality
mammary duct	UBERON:0001765	91.45	gold quality
synovial joint	UBERON:0002217	91.10	gold quality
calcaneal tendon	UBERON:0003701	90.94	gold quality
pericardium	UBERON:0002407	90.77	gold quality
lower lobe of lung	UBERON:0008949	90.16	gold quality
epithelium of mammary gland	UBERON:0003244	89.42	gold quality
thoracic mammary gland	UBERON:0005200	89.41	gold quality
mammary gland	UBERON:0001911	89.05	gold quality
urethra	UBERON:0000057	88.63	gold quality
blood vessel layer	UBERON:0004797	88.40	gold quality
renal glomerulus	UBERON:0000074	87.95	gold quality
superficial temporal artery	UBERON:0001614	87.78	gold quality
descending thoracic aorta	UBERON:0002345	87.72	gold quality
thoracic aorta	UBERON:0001515	87.60	gold quality
ascending aorta	UBERON:0001496	87.57	gold quality
metanephric glomerulus	UBERON:0004736	87.41	gold quality
choroid plexus epithelium	UBERON:0003911	87.11	gold quality
mucosa of stomach	UBERON:0001199	86.83	gold quality
right coronary artery	UBERON:0001625	86.49	gold quality
aorta	UBERON:0000947	86.47	gold quality
gall bladder	UBERON:0002110	86.25	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.83	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-4850	no	480.90
E-MTAB-10290	no	254.46
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): DNMT1, DNMT3B, HDAC1, HDAC4, HIF1A, MYOD1, NR1H4, PAX3, SP1, SP3, STAT3

miRNA regulators (miRDB)

133 targeting RECK, 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-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-10401-5P	99.99	65.79	948
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-607	99.97	73.62	5593
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-548J-3P	99.94	72.61	4881

Literature-anchored findings (GeneRIF, showing 40)

• Four SNPs were identified in the coding region of the gene (exons 1, 9, 13 and 15), and the remaining nine in introns 5, 8, 10, 12, 15 and 17. (PMID:12438739)
• High RECK protein is associated with invasiveness of pancreatic cancer by MMP-2 activation (PMID:12738734)
• Histone deacetylase inhibition increases RECK expression which inhibits MMP activation and cancer cell invasion. Trichostatin A up-regulated RECK via transcriptional activation in CL-1 human lung cancer cells. This attenuated MMP-2 activity. (PMID:12810630)
• RECK suppresses tumor angiogenesis/ (PMID:15328199)
• Findings indicate that glycosylation mediates RECK suppression of tumor cell invasion by multiple mechanisms such as suppressing MMP-9 secretion and inhibiting MMP-2 activation. (PMID:16103099)
• HER-2/neu induces the binding of Sp proteins and HDAC1 to the RECK promoter to inhibit RECK expression and to promote cell invasion (PMID:16377629)
• RECK gene could inhibit the expression of MMP-9 in hilar cholangiocarcinomas. (PMID:16463672)
• RECK downregulation is critical for the invasiveness process in glioma (PMID:16791855)
• RAS oncogene induces RECK gene silencing through DNMT3b-mediated promoter methylation which may be useful in treatment of cancer metastasis (PMID:16951151)
• The TC heterozygotes of the RECK-420 T/C SNP showed a better survival compared to the TT homozygotes (P=0.02 in all cases and P=0.03 in lymph node negative cases) (PMID:17033924)
• downregulation of the metastasis suppressor RECK is caused by promoter methylation in non-small cell lung cancer (PMID:17233834)
• RECK plays an important role in the invasiveness of osteosarcoma (PMID:17262820)
• Tgat oncoprotein is the functional inhibitor of RECK (PMID:17328864)
• RECK protein interacts with MT1-MMP and CD13/aminopeptidase N and modulates their endocytic pathways (PMID:17329256)
• epigenetic down-regulation of the metastasis suppressor RECK in colon cancer is associated with promoter methylation (PMID:17443689)
• The expression of RECK at RNA and protein levels appears to decrease in prostate cancer specimens. (PMID:17583418)
• Decreased RECK expression in tumor compared with non-malignant prostate tissue. (PMID:17628776)
• suppression of RECK expression is involved in the progression of adenocarcinoma of the lung (PMID:17714826)
• The K23 motifs of RECK protein can inhibit MMP-9 secretion and activity and attenuate metastasis of lung cancer cells. (PMID:18194466)
• Data suggest that radiation post-transciptionally enhances RECK protein levels in Panc-1 cells, at least in part, via TGF-beta signaling, and that irradiation increases Panc-1 invasiveness via a mechanism that may not be linked to MMP-2 activity. (PMID:18319621)
• in colorectal neoplasms, MMP-2 expression correlates with the depth of invasion, venous invasion and liver metastasis; MMP-9 and RECK expression correlate with venous invasion (PMID:18425389)
• Data suggest that RECK protein is inversely correlated with tissue damage and MMP-9 secretion in systemic lupus erythematosus. (PMID:18652766)
• RECK is cleaved by MMP-2 and MMP-7 and competitively inhibits MMP-7-catalyzed cleavage of fibronectin (PMID:19022775)
• Motility, adhesion, homing, and mobilization of human hematopoietic progenitor cells are regulated in a cell-autonomous manner by dynamic and opposite changes in MT1-MMP and RECK expression. (PMID:19197139)
• RECK is a glycosylphosphatidylinositol-anchored glycoprotein that inhibits the enzymatic activities of matrix metalloproteinases (MMP), thereby suppressing fibrosarcoma metastasis. (PMID:19208844)
• It regulates Notch signaling and its polarity mediated by ectodomain shedding of ADM10-activity-dependent DSL ligand. (review) (PMID:19827606)
• Low or no RECK expression and increased MMP-2 expression may be associated with negative clinical findings in ameloblastoma (PMID:19995435)
• There are differences in expression between histological types of NSCLC (SCC, adenocarcinoma). There is a higher expression of RECK in stage IA in comparison with stages IB-IIIA. (PMID:20032402)
• This work has associated RECK tumor-suppressing activity with the inhibition of motility and invasion in this glioblastoma multiforme model. (PMID:20127710)
• Aberrant methylation of RECK gene may provide useful information for the early diagnosis and treatment of peritoneal metastasis of gastric cancer. (PMID:20143471)
• Hypoxia and RAS-signaling pathways converge on, and cooperatively downregulate, the RECK tumor-suppressor protein through microRNAs. (PMID:20154725)
• Data show that RECK is up-regulated in human osteoarthritic cartilage and suggest that RECK plays a role in chondrocyte cloning through suppression and promotion of chondrocyte migration and proliferation, respectively. (PMID:20395433)
• RECK has a role in the development of vascular endothelial cells under physiologic and pathologic (tumor angiogenesis) conditions, mainly by use of RNA interference techniques. (PMID:20407016)
• miR-21 expression has a key role in regulating cellular processes in osteosarcoma, likely through regulating RECK (PMID:20480266)
• The abnormal expression levels of RECK and MMP-2 may play an important role in carcinogenesis of esophageal squamous carcinoma. (PMID:20510080)
• RECK and MMP-14 proteins may serve as markers in the estimation of the extent of metastasis and dissemination of the neuroblastoma. (PMID:20579139)
• RECK expression is low in colorectal cancer, while MMP-9 and VEGF-C expressions are high. (PMID:20878580)
• multivariate analysis confirmed that reduced RECK expression was an independent and significant factor to predict a poor prognosis in osteosarcoma. (PMID:20973064)
• RECK functions as a metastasis suppressor in cholangiocarcinoma (PMID:21076843)
• The expressions of RECK and RAGE in nasopharyngeal carcinoma were down-regulated. (PMID:21254649)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	reck	ENSDARG00000090039
mus_musculus	Reck	ENSMUSG00000028476
rattus_norvegicus	Reck	ENSRNOG00000014863
drosophila_melanogaster	Reck	FBGN0036463

Protein

Protein identifiers

Reversion-inducing cysteine-rich protein with Kazal motifs — O95980 (reviewed: O95980)

Alternative names: Suppressor of tumorigenicity 15 protein

All UniProt accessions (1): O95980

UniProt curated annotations — full annotation on UniProt →

Function. Functions together with ADGRA2 to enable brain endothelial cells to selectively respond to Wnt7 signals (WNT7A or WNT7B). Plays a key role in Wnt7-specific responses: required for central nervous system (CNS) angiogenesis and blood-brain barrier regulation. Acts as a Wnt7-specific coactivator of canonical Wnt signaling by decoding Wnt ligands: acts by interacting specifically with the disordered linker region of Wnt7, thereby conferring ligand selectivity for Wnt7. ADGRA2 is then required to deliver RECK-bound Wnt7 to frizzled by assembling a higher-order RECK-ADGRA2-Fzd-LRP5-LRP6 complex. Also acts as a serine protease inhibitor: negatively regulates matrix metalloproteinase-9 (MMP9) by suppressing MMP9 secretion and by direct inhibition of its enzymatic activity. Also inhibits metalloproteinase activity of MMP2 and MMP14 (MT1-MMP).

Subunit / interactions. Interacts (via knot repeats) with WNT7A (via disordered linker region); the interaction is direct. Interacts (via knot repeats) with WNT7B (via disordered linker region); the interaction is direct. Interacts with ADGRA2; the interaction is direct. Interacts with MMP9.

Subcellular location. Cell membrane.

Tissue specificity. Expressed in various tissues and untransformed cells. It is undetectable in tumor-derived cell lines and oncogenically transformed cells.

Post-translational modifications. N-glycosylated.

Domain organisation. The Kazal-like domains mediate the serine protease inhibitor activity.

Similarity. Belongs to the RECK family.

RefSeq proteins (2): NP_001303274, NP_066934* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002350	Kazal_dom	Domain
IPR036058	Kazal_dom_sf	Homologous_superfamily
IPR039016	RECK	Family
IPR055110	RECK-like_N	Domain
IPR055134	EGF2_RECK_dom	Domain
IPR056976	EGF1_RECK	Domain
IPR056977	FnI_RECK	Domain
IPR056978	CC4_RECK	Domain
IPR056979	FZ_RECK	Domain

Pfam: PF07648, PF22955, PF22961, PF23298, PF23332, PF25027, PF25028

UniProt features (30 total): disulfide bond 6, glycosylation site 5, repeat 5, helix 4, domain 3, signal peptide 1, chain 1, region of interest 1, lipid moiety-binding region 1, propeptide 1, sequence variant 1, mutagenesis site 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
8TZP	ELECTRON MICROSCOPY	3.23

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95980-F1	81.43	0.36

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 (1): 942

Disulfide bonds (6): 633–658, 635–654, 643–671, 716–735, 724–750, 761–787

Glycosylation sites (5): 39, 86, 200, 297, 352

Mutagenesis-validated functional residues (1):

Position	Phenotype
225–272	abolished interaction with wnt7a.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-163125	Post-translational modification: synthesis of GPI-anchored proteins

MSigDB gene sets: 314 (showing top): CHIARADONNA_NEOPLASTIC_TRANSFORMATION_KRAS_DN, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GOLDRATH_IMMUNE_MEMORY, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_RESPONSE_TO_MC_AND_SERUM_DEPRIVATION_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_REGULATION_OF_WNT_SIGNALING_PATHWAY, GOBP_FORELIMB_MORPHOGENESIS, BONCI_TARGETS_OF_MIR15A_AND_MIR16_1, YY1_Q6, GOBP_REGULATION_OF_EXTRACELLULAR_MATRIX_ORGANIZATION, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION, PUJANA_CHEK2_PCC_NETWORK, MAHAJAN_RESPONSE_TO_IL1A_DN, GOBP_ANATOMICAL_STRUCTURE_MATURATION

GO Biological Process (15): blood vessel maturation (GO:0001955), sprouting angiogenesis (GO:0002040), embryo implantation (GO:0007566), negative regulation of extracellular matrix disassembly (GO:0010716), extracellular matrix organization (GO:0030198), negative regulation of cell migration (GO:0030336), embryonic forelimb morphogenesis (GO:0035115), regulation of angiogenesis (GO:0045765), canonical Wnt signaling pathway (GO:0060070), regulation of canonical Wnt signaling pathway (GO:0060828), regulation of establishment of blood-brain barrier (GO:0090210), positive regulation of canonical Wnt signaling pathway (GO:0090263), regulation of extracellular matrix organization (GO:1903053), Wnt signaling pathway (GO:0016055), obsolete negative regulation of metalloendopeptidase activity (GO:1904684)

GO Molecular Function (7): endopeptidase inhibitor activity (GO:0004866), serine-type endopeptidase inhibitor activity (GO:0004867), metalloendopeptidase inhibitor activity (GO:0008191), coreceptor activity (GO:0015026), Wnt-protein binding (GO:0017147), protein binding (GO:0005515), peptidase inhibitor activity (GO:0030414)

GO Cellular Component (5): extracellular region (GO:0005576), plasma membrane (GO:0005886), membrane (GO:0016020), side of membrane (GO:0098552), Wnt signalosome (GO:1990909)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Post-translational protein modification	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
angiogenesis	2
canonical Wnt signaling pathway	2
endopeptidase inhibitor activity	2
membrane	2
blood vessel development	1
anatomical structure maturation	1
multicellular organism development	1
female pregnancy	1
reproductive process	1
regulation of extracellular matrix disassembly	1
extracellular matrix disassembly	1
negative regulation of extracellular matrix organization	1
extracellular structure organization	1
external encapsulating structure organization	1
cell migration	1
regulation of cell migration	1
negative regulation of cell motility	1
embryonic limb morphogenesis	1
forelimb morphogenesis	1
regulation of anatomical structure morphogenesis	1
regulation of vasculature development	1
Wnt signaling pathway	1
regulation of Wnt signaling pathway	1
regulation of cell development	1
establishment of blood-brain barrier	1
positive regulation of Wnt signaling pathway	1
regulation of canonical Wnt signaling pathway	1
extracellular matrix organization	1
regulation of cellular component organization	1
cell surface receptor signaling pathway	1
endopeptidase activity	1
peptidase inhibitor activity	1
endopeptidase regulator activity	1
serine-type endopeptidase activity	1
metalloendopeptidase activity	1
signaling receptor activity	1
protein binding	1
binding	1
enzyme inhibitor activity	1

Protein interactions and networks

STRING

910 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RECK	MMP14	P50281	892
RECK	PDCD4	Q53EL6	793
RECK	MMP2	P08253	769
RECK	MMP9	P14780	759
RECK	SPARC	P09486	755
RECK	TIMP3	P35625	732
RECK	TIMP2	P16035	663
RECK	PTEN	P60484	622
RECK	ADGRA2	Q96PE1	562
RECK	WNT7A	O00755	546
RECK	PLAUR	Q03405	525
RECK	TIMP1	P01033	524
RECK	LATS2	Q9NRM7	521
RECK	ADAMTS10	Q9H324	517
RECK	TPM1	P09493	513

IntAct

13 interactions, top by confidence:

A	B	Type	Score
ERBB2	RECK	psi-mi:“MI:0403”(colocalization)	0.560
ERBB2	RECK	psi-mi:“MI:0915”(physical association)	0.560
RECK	IFNA4	psi-mi:“MI:0914”(association)	0.530
RECK	TXN2	psi-mi:“MI:0915”(physical association)	0.400
RECK	TEKT4	psi-mi:“MI:0915”(physical association)	0.370
TRIM69	RECK	psi-mi:“MI:0915”(physical association)	0.370
RECK	MTNR1B	psi-mi:“MI:0915”(physical association)	0.000
	RECK	psi-mi:“MI:0915”(physical association)	0.000
DYRK1A	RECK	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (67): RECK (Two-hybrid), RECK (Two-hybrid), RECK (Two-hybrid), RECK (Two-hybrid), KEAP1 (Two-hybrid), TRIM39 (Two-hybrid), USHBP1 (Two-hybrid), KRT40 (Two-hybrid), TRIM69 (Two-hybrid), TEKT4 (Two-hybrid), NOTCH2NL (Two-hybrid), RECK (Two-hybrid), RECK (Two-hybrid), MCCC2 (Affinity Capture-MS), IFNA4 (Affinity Capture-MS)

ESM2 similar proteins: A0A1D5PUP4, A5YT95, O35757, O62650, O75882, O95980, P07225, P09858, P10669, P17247, P19883, P21214, P21674, P26012, P26013, P27090, P30371, P31514, P31515, P47931, P49767, P50291, P61811, P61812, P97299, P97953, Q07257, Q0VBD0, Q17QD6, Q38L25, Q5RA73, Q6NW40, Q6V9H4, Q6ZQ11, Q863H1, Q86X52, Q8BFR2, Q8CI19, Q8JG54, Q8N475

Diamond homologs: A0A0R4IKU3, A0A1D5PUP4, O95980, Q9Z0J1, A2ASQ1, P25304, A0JP86, A3KN33, A5YT95, E9Q7X7, G4V4G1, G5ECE3, O00468, O00634, O09118, O15230, O62650, O75094, O75445, O88280, O94813, O95631, O95633, P02468, P02469, P07942, P0DKM7, P0DKM8, P0DKM9, P10184, P10669, P11046, P11047, P15215, P15800, P16895, P19883, P21674, P31514, P31515

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	99
Likely benign	8
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

3453 predictions. Top by Δscore:

Variant	Effect	Δscore
9:36066739:AT:A	acceptor_gain	1.0000
9:36066740:T:G	acceptor_gain	1.0000
9:36083363:A:AG	acceptor_gain	1.0000
9:36083363:AGT:A	acceptor_gain	1.0000
9:36083364:G:GG	acceptor_gain	1.0000
9:36083364:GTG:G	acceptor_gain	1.0000
9:36083558:GGATA:G	donor_gain	1.0000
9:36083559:GATAG:G	donor_gain	1.0000
9:36083563:G:GG	donor_gain	1.0000
9:36091162:AG:A	acceptor_gain	1.0000
9:36091162:AGG:A	acceptor_gain	1.0000
9:36091163:GG:G	acceptor_gain	1.0000
9:36091163:GGG:G	acceptor_gain	1.0000
9:36100408:G:GT	donor_gain	1.0000
9:36102091:A:AG	acceptor_gain	1.0000
9:36102092:A:G	acceptor_gain	1.0000
9:36102093:G:GA	acceptor_gain	1.0000
9:36102093:GATCA:G	acceptor_gain	1.0000
9:36102226:CCTCA:C	donor_gain	1.0000
9:36102227:CTCA:C	donor_gain	1.0000
9:36102228:TCA:T	donor_gain	1.0000
9:36102229:CA:C	donor_gain	1.0000
9:36102229:CAG:C	donor_loss	1.0000
9:36102230:AGT:A	donor_loss	1.0000
9:36102231:GTA:G	donor_loss	1.0000
9:36102231:GTAA:G	donor_gain	1.0000
9:36102232:TAA:T	donor_loss	1.0000
9:36105139:TCAG:T	acceptor_loss	1.0000
9:36105140:CA:C	acceptor_loss	1.0000
9:36105141:A:AG	acceptor_gain	1.0000

AlphaMissense

6425 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:36063820:G:C	W99C	1.000
9:36063820:G:T	W99C	1.000
9:36063833:T:C	C104R	1.000
9:36083376:T:C	C151R	1.000
9:36083419:G:A	C165Y	1.000
9:36083420:T:G	C165W	1.000
9:36087705:T:A	C217S	1.000
9:36087706:G:A	C217Y	1.000
9:36087706:G:C	C217S	1.000
9:36087741:T:A	C229S	1.000
9:36087741:T:C	C229R	1.000
9:36087742:G:A	C229Y	1.000
9:36087742:G:C	C229S	1.000
9:36087793:T:C	L246P	1.000
9:36087837:T:A	W261R	1.000
9:36087837:T:C	W261R	1.000
9:36087839:G:C	W261C	1.000
9:36087839:G:T	W261C	1.000
9:36091326:T:G	C356W	1.000
9:36100400:G:C	W385C	1.000
9:36100400:G:T	W385C	1.000
9:36100475:G:C	W410C	1.000
9:36100475:G:T	W410C	1.000
9:36060130:G:C	W82C	0.999
9:36060130:G:T	W82C	0.999
9:36063818:T:A	W99R	0.999
9:36063818:T:C	W99R	0.999
9:36063833:T:A	C104S	0.999
9:36063834:G:A	C104Y	0.999
9:36063834:G:C	C104S	0.999

dbSNP variants (sampled 300 via entrez): RS1000008795 (9:36083830 G>T), RS1000012615 (9:36098243 A>G), RS1000036547 (9:36076884 C>A), RS1000071334 (9:36036568 C>G,T), RS1000089801 (9:36111533 G>A), RS1000183889 (9:36110672 T>C,G), RS1000219911 (9:36054275 T>C), RS1000250830 (9:36054014 A>C,G), RS1000293938 (9:36103156 T>A), RS1000366812 (9:36069892 G>A,T), RS1000386993 (9:36117117 C>T), RS1000444405 (9:36062387 C>T), RS1000483134 (9:36062225 A>G), RS1000488680 (9:36108811 T>G), RS1000499830 (9:36056582 A>G)

Disease associations

OMIM: gene MIM:605227 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST001848_261	IgG glycosylation	1.000000e-06
GCST001848_35	IgG glycosylation	4.000000e-08
GCST001848_494	IgG glycosylation	6.000000e-06
GCST001848_531	IgG glycosylation	6.000000e-07
GCST002815_5	Bipolar disorder (inflammation and infection response interaction)	6.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0005193	serum IgG glycosylation measurement
EFO:0007050	HSV1 seropositivity

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, increases expression	4
Decitabine	affects expression, affects methylation, decreases expression, decreases reaction	3
bisphenol A	affects cotreatment, decreases methylation, increases expression	2
trichostatin A	affects expression, increases expression	2
Folic Acid	affects expression, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Tetrachlorodibenzodioxin	decreases expression	2
Tobacco Smoke Pollution	decreases expression	2
Cyclosporine	decreases expression	2
Particulate Matter	decreases expression, increases abundance	2
aristolochic acid I	decreases expression	1
bisphenol F	affects cotreatment, increases expression	1
ursonic acid	affects expression	1
tomatidine	increases expression	1
triphenyl phosphate	affects expression	1
solasodine	increases expression	1
zinc chloride	decreases reaction, increases expression	1
sodium arsenite	decreases expression, decreases reaction, increases methylation	1
nickel chloride	decreases reaction, increases expression, decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
nickel sulfate	decreases expression	1
hydroquinone	decreases expression	1
epigallocatechin gallate	decreases expression, affects cotreatment	1
perfluorooctane sulfonic acid	decreases expression	1
4-((3-bromophenyl)amino)-6,7-dimethoxyquinazoline	decreases expression, decreases reaction	1
perfluoro-n-nonanoic acid	decreases expression	1
U 0126	decreases expression, decreases reaction	1
entinostat	increases expression	1
3-(4-methylphenylsulfonyl)-2-propenenitrile	decreases expression, decreases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1

Clinical trials (associated diseases)

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