GALNT11

Summary

GALNT11 (polypeptide N-acetylgalactosaminyltransferase 11, HGNC:19875) is a protein-coding gene on chromosome 7q36.1, encoding Polypeptide N-acetylgalactosaminyltransferase 11 (Q8NCW6). Polypeptide N-acetylgalactosaminyltransferase that catalyzes the initiation of protein O-linked glycosylation and is involved in left/right asymmetry by mediating O-glycosylation of NOTCH1.

Enables Notch binding activity and polypeptide N-acetylgalactosaminyltransferase activity. Involved in protein O-linked glycosylation via threonine. Predicted to be located in Golgi membrane. Predicted to be active in Golgi apparatus.

Source: NCBI Gene 63917 — RefSeq curated summary.

At a glance

• GWAS associations: 12
• Clinical variants (ClinVar): 127 total — 2 pathogenic
• MANE Select transcript: NM_022087

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19875
Approved symbol	GALNT11
Name	polypeptide N-acetylgalactosaminyltransferase 11
Location	7q36.1
Locus type	gene with protein product
Status	Approved
Aliases	GalNAc-T11
Ensembl gene	ENSG00000178234
Ensembl biotype	protein_coding
OMIM	615130
Entrez	63917

Gene structure

Transcript identifiers

Ensembl transcripts: 56 — 52 protein_coding, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000415421, ENST00000419245, ENST00000422997, ENST00000423337, ENST00000430044, ENST00000431668, ENST00000431940, ENST00000434507, ENST00000446096, ENST00000447778, ENST00000447796, ENST00000482812, ENST00000491061, ENST00000880711, ENST00000880712, ENST00000880713, ENST00000880714, ENST00000880715, ENST00000880716, ENST00000880717, ENST00000880718, ENST00000880719, ENST00000880720, ENST00000880721, ENST00000880722, ENST00000880723, ENST00000880724, ENST00000880725, ENST00000880726, ENST00000880727, ENST00000880728, ENST00000880729, ENST00000880730, ENST00000880731, ENST00000880732, ENST00000880733, ENST00000880734, ENST00000880735, ENST00000923096, ENST00000923097, ENST00000923098, ENST00000923099, ENST00000923100, ENST00000923101, ENST00000923102, ENST00000923103, ENST00000923104, ENST00000923105, ENST00000966854, ENST00000966855, ENST00000966856, ENST00000966857, ENST00000966858, ENST00000966859, ENST00000966860, ENST00000966861

RefSeq mRNA: 20 — MANE Select: NM_022087 NM_001304514, NM_001371458, NM_001371459, NM_001371460, NM_001371461, NM_001371462, NM_001371463, NM_001371464, NM_001371465, NM_001371466, NM_001371467, NM_001371468, NM_001371469, NM_001371470, NM_001371471, NM_001371472, NM_001371473, NM_001371474, NM_001371475, NM_022087

CCDS: CCDS5930, CCDS94237

Canonical transcript exons

ENST00000430044 — 12 exons

Exon	Start	End
ENSE00000730486	152120831	152120968
ENSE00000730487	152118678	152118782
ENSE00000730499	152100798	152100921
ENSE00001641239	152121546	152122340
ENSE00001848491	152025674	152025884
ENSE00003507309	152108038	152108287
ENSE00003526817	152113246	152113398
ENSE00003570503	152105245	152105370
ENSE00003574564	152117157	152117375
ENSE00003651887	152110528	152110645
ENSE00003683982	152103112	152103278
ENSE00003799741	152094190	152094522

Expression profiles

Bgee: expression breadth ubiquitous, 286 present calls, max score 99.14.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 25.3875 / max 248.2244, expressed in 1801 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
82120	24.9510	1801
82123	0.1764	19
82133	0.0621	5
82132	0.0362	4
82129	0.0339	4
82124	0.0316	9
82125	0.0293	10
82131	0.0245	4
82127	0.0193	9
82126	0.0104	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
choroid plexus epithelium	UBERON:0003911	99.14	gold quality
renal medulla	UBERON:0000362	98.88	gold quality
nephron tubule	UBERON:0001231	98.87	gold quality
pigmented layer of retina	UBERON:0001782	98.43	gold quality
kidney epithelium	UBERON:0004819	98.38	gold quality
Brodmann (1909) area 23	UBERON:0013554	98.10	gold quality
renal glomerulus	UBERON:0000074	97.82	gold quality
middle temporal gyrus	UBERON:0002771	97.64	gold quality
metanephric glomerulus	UBERON:0004736	97.59	gold quality
lateral nuclear group of thalamus	UBERON:0002736	97.56	gold quality
tibia	UBERON:0000979	97.48	gold quality
visceral pleura	UBERON:0002401	97.29	gold quality
cervix squamous epithelium	UBERON:0006922	97.23	gold quality
adult organism	UBERON:0007023	97.04	gold quality
parietal pleura	UBERON:0002400	96.98	gold quality
esophagus squamous epithelium	UBERON:0006920	96.88	gold quality
hair follicle	UBERON:0002073	96.84	gold quality
kidney	UBERON:0002113	96.57	gold quality
squamous epithelium	UBERON:0006914	96.38	gold quality
tendon of biceps brachii	UBERON:0008188	96.32	gold quality
cortex of kidney	UBERON:0001225	96.21	gold quality
adult mammalian kidney	UBERON:0000082	96.16	gold quality
cerebellar vermis	UBERON:0004720	96.09	gold quality
pleura	UBERON:0000977	95.99	gold quality
superior vestibular nucleus	UBERON:0007227	95.69	gold quality
substantia nigra pars compacta	UBERON:0001965	95.50	gold quality
cardia of stomach	UBERON:0001162	95.41	gold quality
ventral tegmental area	UBERON:0002691	95.33	gold quality
endothelial cell	CL:0000115	95.31	gold quality
pons	UBERON:0000988	95.31	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	12.37
E-MTAB-7606	no	200.63

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

48 targeting GALNT11, 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-5692A	100.00	74.40	6850
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-4320	99.75	65.80	793
HSA-MIR-12124	99.68	69.17	2700
HSA-MIR-4328	99.57	71.06	4094
HSA-MIR-5695	99.41	67.48	1047
HSA-MIR-4318	99.38	66.94	1505
HSA-MIR-4427	99.34	70.33	1854

Literature-anchored findings (GeneRIF, showing 4)

• GALNT11, the human ortholog to Drosophila melanogaster pgant35A, was shown not to support rescue of the l(2)35Aa lethality during Drosophila embryogenesis. (PMID:20422447)
• Single nucleiotide polymorphism in the GALNT11 genes were investigated to assess allele frequencies in different populations. This SNP would be useful marker for forensic individualization, in particular, as ancestry-informative markers. (PMID:20547088)
• evidence suggests that CLL patient samples harbor aberrant O-glycosylation highlighted by Tn antigen expression and that the over-expression of GALNT11 constitutes a new molecular marker for CLL (PMID:24076351)
• possible role in the deterioration of kidney function [meta-analysis] (PMID:25493955)

Cross-species orthologs

15 orthologs

Organism	Symbol	Gene ID
mus_musculus	Galnt11	ENSMUSG00000038072
rattus_norvegicus	Galnt11	ENSRNOG00000008117
drosophila_melanogaster	Pgant7	FBGN0030930
drosophila_melanogaster	Pgant5	FBGN0031681
drosophila_melanogaster	Pgant6	FBGN0035375
drosophila_melanogaster	CG7304	FBGN0036527
drosophila_melanogaster	CG7579	FBGN0036528
drosophila_melanogaster	Pgant8	FBGN0036529
drosophila_melanogaster	Pgant9	FBGN0050463
drosophila_melanogaster	CG31776	FBGN0051776
drosophila_melanogaster	Pgant4	FBGN0051956
caenorhabditis_elegans		WBGENE00001628
caenorhabditis_elegans		WBGENE00001630
caenorhabditis_elegans		WBGENE00001632
caenorhabditis_elegans		WBGENE00001635

Paralogs (19): GALNT16 (ENSG00000100626), GALNTL5 (ENSG00000106648), GALNT7 (ENSG00000109586), GALNT18 (ENSG00000110328), GALNT3 (ENSG00000115339), GALNT12 (ENSG00000119514), GALNT8 (ENSG00000130035), GALNT15 (ENSG00000131386), GALNT5 (ENSG00000136542), GALNT6 (ENSG00000139629), GALNT1 (ENSG00000141429), GALNT2 (ENSG00000143641), GALNT13 (ENSG00000144278), GALNT14 (ENSG00000158089), GALNT10 (ENSG00000164574), GALNTL6 (ENSG00000174473), GALNT9 (ENSG00000182870), GALNT17 (ENSG00000185274), GALNT4 (ENSG00000257594)

Protein

Protein identifiers

Polypeptide N-acetylgalactosaminyltransferase 11 — Q8NCW6 (reviewed: Q8NCW6)

Alternative names: Polypeptide GalNAc transferase 11, Protein-UDP acetylgalactosaminyltransferase 11, UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase 11

All UniProt accessions (9): Q8NCW6, A0A090N7X6, B7Z3L9, C9J111, C9J8A7, C9JMT8, C9JPR8, C9K0N9, H7BZL5

UniProt curated annotations — full annotation on UniProt →

Function. Polypeptide N-acetylgalactosaminyltransferase that catalyzes the initiation of protein O-linked glycosylation and is involved in left/right asymmetry by mediating O-glycosylation of NOTCH1. O-glycosylation of NOTCH1 promotes activation of NOTCH1, modulating the balance between motile and immotile (sensory) cilia at the left-right organiser (LRO). Polypeptide N-acetylgalactosaminyltransferases catalyze the transfer of an N-acetyl-D-galactosamine residue to a serine or threonine residue on the protein receptor. Displays the same enzyme activity toward MUC1, MUC4, and EA2 than GALNT1. Not involved in glycosylation of erythropoietin (EPO).

Subunit / interactions. Interacts with NOTCH1.

Subcellular location. Golgi apparatus membrane.

Tissue specificity. Highly expressed in kidney. Expressed at intermediate level in brain, heart and skeletal muscle. Weakly expressed other tissues. In kidney, it is strongly expressed in tubules but not expressed in glomeruli.

Disease relevance. Defects in GALNT11 may be a cause of heterotaxy, a congenital heart disease resulting from abnormalities in left-right (LR) body patterning.

Domain organisation. There are two conserved domains in the glycosyltransferase region: the N-terminal domain (domain A, also called GT1 motif), which is probably involved in manganese coordination and substrate binding and the C-terminal domain (domain B, also called Gal/GalNAc-T motif), which is probably involved in catalytic reaction and UDP-Gal binding. The ricin B-type lectin domain binds to GalNAc and contributes to the glycopeptide specificity.

Pathway. Protein modification; protein glycosylation.

Similarity. Belongs to the glycosyltransferase 2 family. GalNAc-T subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8NCW6-1	1	yes
Q8NCW6-2	2

RefSeq proteins (20): NP_001291443, NP_001358387, NP_001358388, NP_001358389, NP_001358390, NP_001358391, NP_001358392, NP_001358393, NP_001358394, NP_001358395, NP_001358396, NP_001358397, NP_001358398, NP_001358399, NP_001358400, NP_001358401, NP_001358402, NP_001358403, NP_001358404, NP_071370* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000772	Ricin_B_lectin	Domain
IPR001173	Glyco_trans_2-like	Domain
IPR029044	Nucleotide-diphossugar_trans	Homologous_superfamily
IPR035992	Ricin_B-like_lectins	Homologous_superfamily
IPR045885	GalNAc-T	Domain

Pfam: PF00535, PF00652

Enzyme classification (BRENDA):

• EC 2.4.1.41 — polypeptide N-acetylgalactosaminyltransferase (BRENDA: 21 organisms, 537 substrates, 86 inhibitors, 206 Km, 52 kcat entries)

Substrate kinetics (BRENDA)

71 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
UDP-GALNAC	0.0017–16	32
UDP-N-ACETYL-D-GALACTOSAMINE	0.008–0.081	11
PTTDSTTPAPTTK	0.042–1.02	7
GTTPSPVPTTSTTSAP	0.0259–0.344	5
MUC5AC-13	0.018–0.77	5
MUC5AC-3	0.033–0.107	5
STPSTPSTPSTPSTP	0.2–0.65	5
CPPTPSATTPAPPSSSAPPETTAA	0.01–0.48	4
DSTTPAPTTK	0.07–2.19	4
GTTPSPVPTTST[GALNAC]TSAP	0.115–0.46	4
GT[GALNAC]TPSPVPTTSTTSAP	0.035–0.332	4
UDP-GAL	0.027–0.041	4
GVVPTVVPG	1.74–17.6	3
IGA HINGE	0.01–0.02	3
IGA HINGE-4GALNAC	0.12–0.81	3

Catalyzed reactions (Rhea), 2 shown:

• L-seryl-[protein] + UDP-N-acetyl-alpha-D-galactosamine = a 3-O-[N-acetyl-alpha-D-galactosaminyl]-L-seryl-[protein] + UDP + H(+) (RHEA:23956)
• L-threonyl-[protein] + UDP-N-acetyl-alpha-D-galactosamine = a 3-O-[N-acetyl-alpha-D-galactosaminyl]-L-threonyl-[protein] + UDP + H(+) (RHEA:52424)

UniProt features (31 total): binding site 9, disulfide bond 5, sequence conflict 3, topological domain 2, splice variant 2, sequence variant 2, region of interest 2, chain 1, modified residue 1, glycosylation site 1, transmembrane region 1, mutagenesis site 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NCW6-F1	85.38	0.71

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (9): 246; 247; 350; 378; 381; 386; 191; 222; 245

Post-translational modifications (1): 95

Disulfide bonds (5): 141–373, 364–441, 493–512, 536–553, 578–596

Glycosylation sites (1): 428

Mutagenesis-validated functional residues (1):

Position	Phenotype
247	abolishes glycosyltransferase activity and ability to rescue left-right patterning defects induced by galnt11 knockdown

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-913709	O-linked glycosylation of mucins

MSigDB gene sets: 173 (showing top): GOBP_NOTCH_RECEPTOR_PROCESSING, ROVERSI_GLIOMA_COPY_NUMBER_UP, MOLENAAR_TARGETS_OF_CCND1_AND_CDK4_UP, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_SPECIFICATION_OF_SYMMETRY, MARTINEZ_RB1_TARGETS_DN, SHEDDEN_LUNG_CANCER_GOOD_SURVIVAL_A4, GOBP_CARBOHYDRATE_DERIVATIVE_BIOSYNTHETIC_PROCESS, GOBP_CILIUM_ORGANIZATION, WAGNER_APO2_SENSITIVITY, COATES_MACROPHAGE_M1_VS_M2_UP, GOBP_ORGANELLE_ASSEMBLY, GOBP_REGULATION_OF_NOTCH_SIGNALING_PATHWAY, DODD_NASOPHARYNGEAL_CARCINOMA_UP, GOBP_CELL_PROJECTION_ORGANIZATION

GO Biological Process (10): protein O-linked glycosylation (GO:0006493), Notch receptor processing (GO:0007220), determination of left/right symmetry (GO:0007368), regulation of Notch signaling pathway (GO:0008593), protein O-linked glycosylation via N-acetylgalactosamine (GO:0016266), cilium assembly (GO:0060271), Notch signaling involved in heart development (GO:0061314), obsolete protein glycosylation (GO:0006486), Notch signaling pathway (GO:0007219), obsolete protein O-linked glycosylation via threonine (GO:0018243)

GO Molecular Function (7): polypeptide N-acetylgalactosaminyltransferase activity (GO:0004653), Notch binding (GO:0005112), carbohydrate binding (GO:0030246), metal ion binding (GO:0046872), protein binding (GO:0005515), transferase activity (GO:0016740), glycosyltransferase activity (GO:0016757)

GO Cellular Component (3): Golgi membrane (GO:0000139), Golgi apparatus (GO:0005794), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
O-linked glycosylation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
Notch signaling pathway	2
binding	2
glycoprotein biosynthetic process	1
protein metabolic process	1
determination of bilateral symmetry	1
left/right pattern formation	1
regulation of signal transduction	1
protein O-linked glycosylation	1
axoneme assembly	1
intraciliary transport involved in cilium assembly	1
cilium organization	1
protein localization to cilium	1
organelle assembly	1
trans-Golgi to periciliary membrane compartment transport	1
plasma membrane bounded cell projection assembly	1
ciliary transition zone assembly	1
heart development	1
cell surface receptor signaling pathway involved in heart development	1
cell surface receptor signaling pathway	1
acetylgalactosaminyltransferase activity	1
catalytic activity, acting on a protein	1
signaling receptor binding	1
cation binding	1
catalytic activity	1
transferase activity	1
Golgi apparatus	1
bounding membrane of organelle	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

688 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GALNT11	NUP188	Q5SRE5	495
GALNT11	ST3GAL1	Q11201	492
GALNT11	C1GALT1	Q9NS00	490
GALNT11	ACTR3B	Q9P1U1	487
GALNT11	DAND5	Q8N907	477
GALNT11	C1GALT1C1	Q96EU7	470
GALNT11	B4GALT5	O43286	458
GALNT11	EDEM2	Q9BV94	435
GALNT11	DNAH9	Q9NYC9	428
GALNT11	EPS8L2	Q9H6S3	422
GALNT11	ARL13B	Q3SXY8	407
GALNT11	GGN	Q86UU5	399
GALNT11	C1GALT1C1L	P0DN25	391
GALNT11	SLC5A12	Q1EHB4	371
GALNT11	MAN2A2	P49641	367

IntAct

45 interactions, top by confidence:

A	B	Type	Score
SUCLG2	SUCLG1	psi-mi:“MI:0914”(association)	0.690
TOR1AIP2	TMEM223	psi-mi:“MI:0914”(association)	0.530
SDF4	GTPBP6	psi-mi:“MI:0914”(association)	0.530
HLA-DPA1	TYW5	psi-mi:“MI:0914”(association)	0.530
PDCD1	RTL8C	psi-mi:“MI:0914”(association)	0.530
ARMC6	SLC27A2	psi-mi:“MI:0914”(association)	0.530
MMP26	SLC25A20	psi-mi:“MI:0914”(association)	0.530
DHRS9	MFSD4B	psi-mi:“MI:0914”(association)	0.530
GALNT11	MATR3	psi-mi:“MI:0915”(physical association)	0.400
PDCD1	TMEM223	psi-mi:“MI:0914”(association)	0.350
HLA-DPA1	GXYLT2	psi-mi:“MI:0914”(association)	0.350
KLK11	DENND11	psi-mi:“MI:0914”(association)	0.350
TMPRSS11B		psi-mi:“MI:0914”(association)	0.350
NRG1	HS6ST1	psi-mi:“MI:0914”(association)	0.350
ARMC6	SLC27A2	psi-mi:“MI:0914”(association)	0.350
P2RX2	C1QL1	psi-mi:“MI:0914”(association)	0.350
FNDC4	MT-ND2	psi-mi:“MI:0914”(association)	0.350
DHRS9	ATP2B2	psi-mi:“MI:0914”(association)	0.350
CLEC2D	TMEM120B	psi-mi:“MI:0914”(association)	0.350
KLRC1	METTL15	psi-mi:“MI:0914”(association)	0.350
MAGEA8	METTL15	psi-mi:“MI:0914”(association)	0.350
FCGR3A	RTL8C	psi-mi:“MI:0914”(association)	0.350
CST9L	QSOX1	psi-mi:“MI:0914”(association)	0.350
TMPRSS11B	ADAM10	psi-mi:“MI:0914”(association)	0.350

BioGRID (60): GALNT11 (Affinity Capture-MS), GALNT11 (Affinity Capture-MS), GALNT11 (Affinity Capture-MS), GALNT11 (Affinity Capture-MS), GALNT11 (Affinity Capture-MS), GALNT11 (Affinity Capture-MS), GALNT11 (Affinity Capture-MS), GALNT11 (Affinity Capture-MS), GALNT11 (Affinity Capture-MS), GALNT11 (Affinity Capture-MS), GALNT11 (Affinity Capture-MS), GALNT11 (Affinity Capture-MS), GALNT11 (Affinity Capture-MS), GALNT11 (Affinity Capture-MS), GALNT11 (Affinity Capture-MS)

ESM2 similar proteins: A0A2C9JXL4, E9Q649, O95395, P0DN25, P97402, Q08BL3, Q0VC84, Q18515, Q24342, Q3SX46, Q499P3, Q5F3G7, Q5HZL5, Q5U258, Q5XJP0, Q5YB40, Q66GS2, Q6A1G2, Q6DE15, Q6DJR8, Q6GNL1, Q6P3P5, Q6P6V1, Q6WV16, Q6Y288, Q7K237, Q7SYI5, Q7T3S5, Q7Z1Z1, Q864U8, Q866Z5, Q8BGY6, Q8BHT6, Q8L7M1, Q8LPF8, Q8N0V5, Q8NCW6, Q96EU7, Q99NB2, Q9BYG0

Diamond homologs: A8Y236, H0ZAB5, O08832, O08912, O45293, O45947, O61394, O61397, O88422, P34678, P70419, Q07537, Q10471, Q10472, Q10473, Q14435, Q29121, Q49A17, Q5EA41, Q5RFJ6, Q6DJR8, Q6IS24, Q6P6V1, Q6P9A2, Q6P9S7, Q6PB93, Q6UE39, Q6WV16, Q6WV17, Q6WV19, Q6WV20, Q7K755, Q7TT15, Q7Z4T8, Q7Z7M9, Q80VA0, Q86SF2, Q86SR1, Q8BGT9, Q8BVG5

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 58 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
Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell	5	12.1×	5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	96
Likely benign	10
Benign	2

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
1342507	NC_000007.14:g.152052676_152295696del	Pathogenic
687627	GRCh37/hg19 7q36.1(chr7:151768932-152145034)x3	Pathogenic

SpliceAI

2746 predictions. Top by Δscore:

Variant	Effect	Δscore
7:152025880:AGGCG:A	donor_gain	1.0000
7:152025881:GGCG:G	donor_gain	1.0000
7:152025881:GGCGG:G	donor_gain	1.0000
7:152025882:GCG:G	donor_gain	1.0000
7:152025882:GCGG:G	donor_gain	1.0000
7:152025885:G:GG	donor_gain	1.0000
7:152025886:T:A	donor_loss	1.0000
7:152094312:A:AG	acceptor_gain	1.0000
7:152094518:ATTAG:A	donor_gain	1.0000
7:152094519:TTAG:T	donor_gain	1.0000
7:152094520:TAG:T	donor_gain	1.0000
7:152094521:AG:A	donor_gain	1.0000
7:152094522:GG:G	donor_gain	1.0000
7:152094523:G:GG	donor_gain	1.0000
7:152094523:GT:G	donor_loss	1.0000
7:152100913:G:GT	donor_gain	1.0000
7:152100914:A:T	donor_gain	1.0000
7:152100917:GCAGC:G	donor_gain	1.0000
7:152100920:GC:G	donor_gain	1.0000
7:152100922:G:GG	donor_gain	1.0000
7:152102115:T:TA	acceptor_gain	1.0000
7:152103110:A:AG	acceptor_gain	1.0000
7:152103111:G:GG	acceptor_gain	1.0000
7:152103111:GAT:G	acceptor_gain	1.0000
7:152108035:CA:C	acceptor_loss	1.0000
7:152108036:A:AC	acceptor_loss	1.0000
7:152108036:A:AG	acceptor_gain	1.0000
7:152108036:AG:A	acceptor_gain	1.0000
7:152108037:G:GA	acceptor_gain	1.0000
7:152108037:GG:G	acceptor_gain	1.0000

AlphaMissense

3995 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:152108223:T:C	F300L	1.000
7:152108225:C:A	F300L	1.000
7:152108225:C:G	F300L	1.000
7:152108229:T:A	W302R	1.000
7:152108229:T:C	W302R	1.000
7:152108231:G:C	W302C	1.000
7:152108231:G:T	W302C	1.000
7:152110613:T:A	W350R	1.000
7:152110613:T:C	W350R	1.000
7:152110615:G:C	W350C	1.000
7:152110615:G:T	W350C	1.000
7:152110617:G:A	G351E	1.000
7:152110623:A:T	E353V	1.000
7:152110627:T:A	N354K	1.000
7:152110627:T:G	N354K	1.000
7:152113297:C:G	H378D	1.000
7:152113299:C:A	H378Q	1.000
7:152113299:C:G	H378Q	1.000
7:152113303:T:C	F380L	1.000
7:152113304:T:G	F380C	1.000
7:152113305:C:A	F380L	1.000
7:152113305:C:G	F380L	1.000
7:152113359:C:A	N398K	1.000
7:152113359:C:G	N398K	1.000
7:152120957:T:A	W562R	1.000
7:152120957:T:C	W562R	1.000
7:152094285:T:A	W20R	0.999
7:152094285:T:C	W20R	0.999
7:152105328:G:A	G224R	0.999
7:152105328:G:C	G224R	0.999

dbSNP variants (sampled 300 via entrez): RS1000037351 (7:152063792 T>G), RS1000069493 (7:152110966 C>T), RS1000077446 (7:152101336 A>G,T), RS1000086517 (7:152075752 C>T), RS1000087725 (7:152104518 A>C,T), RS1000115744 (7:152080711 C>T), RS1000126626 (7:152058969 T>C,G), RS1000221223 (7:152098697 G>C), RS1000232888 (7:152090654 A>C,G), RS1000244157 (7:152099425 G>A), RS1000250943 (7:152099213 A>G), RS1000272146 (7:152073766 T>C), RS1000279379 (7:152116692 C>T), RS1000319178 (7:152046061 G>A), RS1000350175 (7:152045838 T>C)

Disease associations

OMIM: gene MIM:615130 | disease phenotypes: MIM:617768

GenCC curated gene-disease

Mondo (3): Kleefstra syndrome 2 (MONDO:0054701), intellectual disability (MONDO:0001071), megacolon (MONDO:0001273)

Orphanet (1): NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

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

GWAS associations

12 associations (top):

Study	Trait	p-value
GCST002720_4	Kidney function decline traits	2.000000e-07
GCST003264_1046	Post bronchodilator FEV1/FVC ratio	3.000000e-06
GCST003264_1047	Post bronchodilator FEV1/FVC ratio	3.000000e-06
GCST003264_1081	Post bronchodilator FEV1/FVC ratio	4.000000e-06
GCST003264_125	Post bronchodilator FEV1/FVC ratio	2.000000e-06
GCST003264_149	Post bronchodilator FEV1/FVC ratio	2.000000e-06
GCST003264_214	Post bronchodilator FEV1/FVC ratio	4.000000e-06
GCST003264_237	Post bronchodilator FEV1/FVC ratio	4.000000e-06
GCST003264_500	Post bronchodilator FEV1/FVC ratio	3.000000e-06
GCST003264_85	Post bronchodilator FEV1/FVC ratio	2.000000e-06
GCST003264_940	Post bronchodilator FEV1/FVC ratio	5.000000e-06
GCST003264_962	Post bronchodilator FEV1/FVC ratio	5.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0006836	rapid kidney function decline
EFO:0004713	FEV/FVC ratio

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D008531	Megacolon	C06.405.469.158.701

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases expression, increases methylation	3
Cyclosporine	decreases expression, increases expression	2
Particulate Matter	affects cotreatment, decreases expression, increases abundance, increases expression	2
bisphenol F	affects cotreatment, decreases expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
sodium arsenite	increases expression	1
butyraldehyde	decreases expression	1
nickel chloride	decreases expression	1
ochratoxin A	increases acetylation	1
isobutyl alcohol	affects cotreatment, decreases expression, increases abundance	1
beta-methylcholine	affects expression	1
perfluoro-n-nonanoic acid	decreases expression	1
enzalutamide	affects expression	1
jinfukang	affects cotreatment, increases expression	1
Zoledronic Acid	decreases expression	1
Acetaminophen	increases expression	1
Cisplatin	affects cotreatment, increases expression	1
Dexamethasone	affects cotreatment, decreases expression	1
Doxorubicin	decreases expression	1
Fluoxetine	increases expression	1
Gasoline	affects cotreatment, decreases expression, increases abundance	1
Indomethacin	affects cotreatment, decreases expression	1
Lead	affects expression	1
Methyl Methanesulfonate	increases expression	1
Phenobarbital	affects expression	1
Polycyclic Aromatic Hydrocarbons	affects cotreatment, decreases expression, increases abundance	1
Quercetin	affects expression	1
Valproic Acid	affects expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, decreases expression	1
Aflatoxin B1	increases methylation	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT03479476	PHASE2/PHASE3	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome
NCT02616796	PHASE1/PHASE2	COMPLETED	Effects of Social Gaze Training on Brain and Behavior in Fragile X Syndrome
NCT06860672	EARLY_PHASE1	RECRUITING	Clinical Trial of the Dual Vector Base Editor for the Treatment of the CHD3-R1025W Mutation
NCT00597948	Not specified	COMPLETED	Healthy Lifestyles for People With Intellectual Disabilities
NCT01087320	Not specified	RECRUITING	Genome Medical Sequencing for Gene Discovery
NCT01652963	Not specified	UNKNOWN	Picture-based Computerised Assessment and Training of Cognitive Behaviour Therapy Skills
NCT01695395	Not specified	COMPLETED	Mental Health Care Provision for Adults With Intellectual Disability and a Mental Disorder
NCT01867554	Not specified	COMPLETED	Research and Characterization of New Genes Involved in Intellectual Disability
NCT01915381	Not specified	COMPLETED	Improving Adherence Healthy Lifestyle With a Smartphone Application Based on Adults With Intellectual Disabilities
NCT01988623	Not specified	COMPLETED	Pivotal Response Treatment for Individuals With Intellectual Disabilities
NCT02099773	Not specified	COMPLETED	Support Staff-client Interactions With Augmentative and Alternative Communication
NCT02136849	Not specified	COMPLETED	Inter-regional Project of the Great Western Exploration Approach for Exome Molecular Causes Severe Intellectual Disability Isolated or Syndromic
NCT02225041	Not specified	COMPLETED	Sedation Strategy and Cognitive Outcome After Critical Illness in Early Childhood
NCT02414438	Not specified	COMPLETED	Establishing the Clinical Utility of First StepDx PLUS and NextStepDx PLUS Study
NCT02451761	Not specified	COMPLETED	Apparently Balanced Chromosomal Translocation/ Next-generation Sequencing/ Intellectual Disability
NCT02461420	Not specified	ACTIVE_NOT_RECRUITING	Mapping the Genotype, Phenotype, and Natural History of Phelan-McDermid Syndrome
NCT02461459	Not specified	ACTIVE_NOT_RECRUITING	Autism Spectrum Disorder (ASD) and Intellectual Disability (ID) Determinants in Tuberous Sclerosis Complex (TSC)
NCT02486081	Not specified	COMPLETED	Development and Application-Smart Football for Movement Evaluation and Training in the Special Education Population
NCT02504502	Not specified	COMPLETED	Enhancing Genomic Laboratory Reports to Enhance Communication and Empower Patients
NCT02513277	Not specified	COMPLETED	Diabetes Screening & Prevention for People With Learning (Intellectual) Disabilities:STOP Diabetes Study
NCT02561754	Not specified	COMPLETED	Weight Management for Adolescents With IDD
NCT02591446	Not specified	COMPLETED	Transcranial Magnetic Stimulation Studies in Autism Spectrum Disorders
NCT02714868	Not specified	COMPLETED	Evaluation of Project TEAM (Teens Making Environmental and Activity Modifications)
NCT02721394	Not specified	UNKNOWN	FCT With Young Children With ID in the UK: A Feasibility Project V.1
NCT02746614	Not specified	COMPLETED	Psychomotor Therapy Effects in Adaptive Behavior and Motor Proficiency in Intellectual Disability
NCT02836405	Not specified	COMPLETED	TMS for the Investigation of Brain Plasticity in Autism Spectrum Disorders