C1GALT1C1

Summary

C1GALT1C1 (C1GALT1 specific chaperone 1, HGNC:24338) is a protein-coding gene on chromosome Xq24, encoding C1GALT1-specific chaperone 1 (Q96EU7). Probable chaperone required for the generation of 1 O-glycan Gal-beta1-3GalNAc-alpha1-Ser/Thr (T antigen), which is a precursor for many extended O-glycans in glycoproteins.

This gene encodes a type II transmembrane protein that is similar to the core 1 beta1,3-galactosyltransferase 1, which catalyzes the synthesis of the core-1 structure, also known as Thomsen-Friedenreich antigen, on O-linked glycans. This gene product lacks the galactosyltransferase activity itself, but instead acts as a molecular chaperone required for the folding, stability and full activity of the core 1 beta1,3-galactosyltransferase 1. Mutations in this gene have been associated with Tn syndrome. Alternatively spliced transcript variants encoding the same protein have been identified.

Source: NCBI Gene 29071 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hemolytic uremic syndrome, atypical, 8, with rhizomelic short stature (Limited, ClinGen)
• GWAS associations: 1
• Clinical variants (ClinVar): 75 total — 7 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 32
• MANE Select transcript: NM_001011551

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24338
Approved symbol	C1GALT1C1
Name	C1GALT1 specific chaperone 1
Location	Xq24
Locus type	gene with protein product
Status	Approved
Aliases	COSMC, C1GALT2
Ensembl gene	ENSG00000171155
Ensembl biotype	protein_coding
OMIM	300611
Entrez	29071

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000304661, ENST00000371313, ENST00000899457, ENST00000963053

RefSeq mRNA: 2 — MANE Select: NM_001011551 NM_001011551, NM_152692

CCDS: CCDS14602

Canonical transcript exons

ENST00000304661 — 2 exons

Exon	Start	End
ENSE00001454924	120625674	120627171
ENSE00001454926	120629917	120630054

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 94.91.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 33.5097 / max 448.7356, expressed in 1810 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
200379	26.6695	1799
200378	6.8401	1693

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
islet of Langerhans	UBERON:0000006	94.91	gold quality
calcaneal tendon	UBERON:0003701	92.53	gold quality
rectum	UBERON:0001052	92.27	gold quality
stromal cell of endometrium	CL:0002255	92.22	gold quality
adenohypophysis	UBERON:0002196	91.66	gold quality
endometrium	UBERON:0001295	91.64	gold quality
pituitary gland	UBERON:0000007	91.42	gold quality
right adrenal gland	UBERON:0001233	91.09	gold quality
left adrenal gland	UBERON:0001234	91.07	gold quality
left adrenal gland cortex	UBERON:0035825	90.93	gold quality
adrenal gland	UBERON:0002369	90.26	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	89.95	gold quality
right adrenal gland cortex	UBERON:0035827	89.91	gold quality
mucosa of transverse colon	UBERON:0004991	89.73	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	89.44	gold quality
smooth muscle tissue	UBERON:0001135	89.41	gold quality
monocyte	CL:0000576	89.13	gold quality
leukocyte	CL:0000738	89.02	gold quality
pancreas	UBERON:0001264	88.65	gold quality
duodenum	UBERON:0002114	88.44	gold quality
thoracic aorta	UBERON:0001515	88.13	gold quality
descending thoracic aorta	UBERON:0002345	88.05	gold quality
ascending aorta	UBERON:0001496	88.00	gold quality
placenta	UBERON:0001987	87.97	gold quality
gall bladder	UBERON:0002110	87.76	gold quality
fallopian tube	UBERON:0003889	87.49	gold quality
vermiform appendix	UBERON:0001154	87.47	gold quality
lymph node	UBERON:0000029	87.26	gold quality
saliva-secreting gland	UBERON:0001044	87.25	gold quality
endocervix	UBERON:0000458	87.18	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	12.37

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

41 targeting C1GALT1C1, 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-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-3617-3P	99.98	67.86	918
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-4715-3P	99.98	66.03	670
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-552-5P	99.93	68.56	1583
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-576-5P	99.84	70.46	2582
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-448	99.79	72.37	2103
HSA-MIR-3680-3P	99.75	72.51	3095
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-12129	99.72	67.45	1311
HSA-MIR-5003-5P	99.61	69.13	1624
HSA-MIR-32-3P	99.36	68.20	2517
HSA-MIR-6853-3P	99.36	70.79	1558
HSA-MIR-1206	99.30	69.32	1016
HSA-MIR-4758-3P	99.12	63.96	869
HSA-MIR-6770-5P	98.97	66.76	1853
HSA-MIR-374A-3P	98.87	67.82	1531
HSA-MIR-16-1-3P	98.70	69.23	1538
HSA-MIR-3613-5P	98.40	68.91	604

Literature-anchored findings (GeneRIF, showing 35)

• molecular cloning and characterization; C1Gal-T2 is the second candidate for core 1 synthase that plays an important role in synthesizing O-glycans in digestive organs (PMID:12361956)
• Tn syndrome is associated with a somatic mutation in Cosmc, a gene on the X chromosome that encodes a molecular ‘chaperone’ that is required for the proper folding and hence full activity of T-synthase (PMID:16251947)
• These results suggest that the intracellular dynamics of C1GalT is controlled by its specific molecular chaperon, Cosmc, in association with core 1 synthase activity. (PMID:18061573)
• The tumor-specific antigen caused by mutant COSMC seems to be rare and is not potentially a therapeutic target candidate in breast and colon cancers. (PMID:18321367)
• Colon cancer and melanoma-derived cells lines expressed Tn and STn antigen due to loss-of-function mutations in Cosmc. Cervical cancer specimens that showed expression of the Tn/STn antigens were also found to have mutations in Cosmc. (PMID:18339842)
• a novel inactivating mutations (Glu152Lys, Ser193Pro and Met1Ile) in the coding sequence of C1GALT1C1 (PMID:18537974)
• Cosmc is an endoplasmic reticulum (ER)-localized adenosine triphosphate binding chaperone that binds directly to human T-synthase. (PMID:18695044)
• Although decreased C1GALT1 activity has been implicated in IgAN pathogenesis and cosmc chaperone mutations can cause autoimmune disease, our data provide no evidence for a role of cosmc gene mutations in European patients with sporadic or familial IgAN. (PMID:18840896)
• The c.-347-190G>A polymorphism and the somatic mutation of encoding region of C1GALT1C1 gene were not significantly related to the genetic susceptibility to IgAN in Northern Chinese population (PMID:19778426)
• Cosmc represents the first endoplasmic reticulum chaperone identified to be required for folding of a glycosyltransferase (PMID:19923218)
• Study results suggest that C1GALT1C1 may play a key role in the regulation of IgA1 O-glycosylation. (PMID:20144270)
• The transmembrane domain of the molecular chaperone Cosmc directs its localization to the endoplasmic reticulum (PMID:21262965)
• Results indicate that Cosmc mediates the co-translational activation of C1GalT and that it may prevent the unfavorable aggregation of C1GalT. (PMID:21496458)
• The mRNA expression level of Cosmc gene in IgA nephropathy patients was significantly lower than that of controls. De-methylation modification up regulated the Cosmc gene expression significantly. (PMID:22332537)
• Results show that soluble Cosmc directly interacts in a specific manner with denatured, but not native, T-synthase to form a noncovalent and reversible complex that results in the acquisition of T-synthase catalytic activity. (PMID:22416136)
• overexpression of Cosmc is associated with colorectal cancer. (PMID:23390052)
• COSMC is a novel regulator for VEGFR2 signaling in endothelial cells and dysregulation of COSMC expression may contribute to the pathogenesis of hemangioma (PMID:23424651)
• Data indicate that cytotoxin associated gene A protein (CagA) promoted the underglycosylation of IgA1, which at least partly attributed to the downregulation of beta1,3-galactosyltransferase (C1GALT1) and its chaperone Cosmc. (PMID:24462875)
• CBRT is a unique recognition motif for Cosmc to promote its regulation and formation of active T-synthase and represents the first sequence-specific chaperone recognition system in the ER/Golgi required for normal protein O-glycosylation (PMID:24616093)
• hypermethylation of Cosmc promoter region could be a key mechanism for the reduction of Cosmc mRNA expression in IgAN lymphocytes with associated increase in aberrantly glycosylated IgA1 (PMID:25647400)
• the impact of COSMC mediated Tn antigen expression in two human pancreatic ductal adenocarcinoma cell lines on cellular oncogenic properties, were investigated. (PMID:26021314)
• These results indicate that Tn antigens expression and T-synthase inactivity in HT-29-Tn+ cells can be related to the absence of the Cosmc gene coding sequence in Cosmc active alleles (PMID:26045765)
• Cosmc and T-synthase are transcriptionally regulated at a basal level by the specificity protein/Kruppel-like transcription factor family of members. (PMID:26063800)
• Data suggest that patients with IgA nephropathy exhibit higher microRNA-374b in B cells compared to controls; microRNA-374b appears to target PTEN (phosphatase and tensin homolog) and Cosmc (C1GALT1 specific chaperone 1) proteins. (PMID:26545495)
• mutations c.393T>A and c.72A>G in the exon region of Cosmc gene in children with Henoch-Schonlein purpura (HSP) are not associated with the onset of Henoch-Schonlein purpura (PMID:27412546)
• elevated Tn levels in cancer and inflammation may be commonly regulated by the cytokine (TNFa and IL6)-Cosmc signaling axis (PMID:27542280)
• The terminal glycosylation of secreted IgA1 was altered in response to TGFbeta1. TGFbeta1 stimulation significantly decreased the mRNA levels of C1GalT1 and Cosmc. TGFbeta1 may be key in controlling the glycosylation of IgA1, in part via the downregulation of C1GalT1 and Cosmc. (PMID:28035353)
• Data indicate that mRNA levels of both core 1 synthase, glycoprotein-N-acetylgalactosamine 3-beta-galactosyltransferase, 1 (C1GALT1) and C1GALT1-specific chaperone 1 protein (C1GALT1C1) determine the rate of secretion of galactose-deficient IgA1 (Gd-IgA1) in IgA1-producing cells. (PMID:28187132)
• results provide new structure-function insight to Cosmc, indicate that Cosmc behaves as a modular protein and suggests points of modulation or regulation of in vivo chaperone function (PMID:28665962)
• The data suggest that hypermethylation of the Cosmc promoter may induce the expression of Tn antigen in activated T cells. (PMID:28708980)
• In addition, we found that Tn-expressing colorectal cancers (CRC) cell lines had either loss-of-function mutations in Cosmc or reversible Tn antigen expression, which was not caused by the deficiency of T-synthase activity (PMID:30115016)
• C1GALT1C1/COSMC is a novel prognostic biomarker for hepatocellular carcinoma. (PMID:31471227)
• Cosmc overexpression enhances malignancies in human colon cancer. (PMID:31633299)
• MicroRNA196b targets COSMC in pediatric IgA nephropathy. (PMID:32186752)
• Cosmc transfection decreases malignant behavior of Tn(+) cells and enhances sensitivity to apoptosis when induced by Apo2L/TRAIL via alteration of O-glycan structure. (PMID:34644263)

Cross-species orthologs

16 orthologs

Organism	Symbol	Gene ID
danio_rerio	c1galt1c1	ENSDARG00000036335
mus_musculus	C1galt1c1	ENSMUSG00000048970
rattus_norvegicus		ENSRNOG00000067336
rattus_norvegicus	C1galt1c1	ENSRNOG00000069353
drosophila_melanogaster	tgy	FBGN0030984
drosophila_melanogaster	CG18558	FBGN0031469
drosophila_melanogaster	CG2983	FBGN0031472
drosophila_melanogaster	CG34057	FBGN0054057
caenorhabditis_elegans	E03H4.3	WBGENE00008471
caenorhabditis_elegans	F56H6.1	WBGENE00010162
caenorhabditis_elegans		WBGENE00015361
caenorhabditis_elegans		WBGENE00015861
caenorhabditis_elegans		WBGENE00015871
caenorhabditis_elegans		WBGENE00021403
caenorhabditis_elegans		WBGENE00021407
caenorhabditis_elegans		WBGENE00044620

Paralogs (2): C1GALT1 (ENSG00000106392), C1GALT1C1L (ENSG00000223658)

Protein

Protein identifiers

C1GALT1-specific chaperone 1 — Q96EU7 (reviewed: Q96EU7)

Alternative names: C38H2-like protein 1, Core 1 beta1,3-galactosyltransferase 2, Core 1 beta3-galactosyltransferase-specific molecular chaperone

All UniProt accessions (1): Q96EU7

UniProt curated annotations — full annotation on UniProt →

Function. Probable chaperone required for the generation of 1 O-glycan Gal-beta1-3GalNAc-alpha1-Ser/Thr (T antigen), which is a precursor for many extended O-glycans in glycoproteins. Probably acts as a specific molecular chaperone assisting the folding/stability of core 1 beta-3-galactosyltransferase (C1GALT1).

Subunit / interactions. Associates with core 1 beta-3-galactosyltransferase (C1GALT1), probably not with the soluble active form.

Subcellular location. Membrane.

Tissue specificity. Ubiquitously expressed. Abundantly expressed in salivary gland, stomach, small intestine, kidney, and testis and at intermediate levels in whole brain, cerebellum, spinal cord, thymus, spleen, trachea, lung, pancreas, ovary, and uterus.

Disease relevance. Tn polyagglutination syndrome (TNPS) [MIM:300622] A clonal disorder characterized by the polyagglutination of red blood cells by naturally occurring anti-Tn antibodies following exposure of the Tn antigen on the surface of erythrocytes. Only a subset of red cells express the antigen, which can also be expressed on platelets and leukocytes. This condition may occur in healthy individuals who manifest asymptomatic anemia, leukopenia, or thrombocytopenia. However, there is also an association between the Tn antigen and leukemia or myelodysplastic disorders. The disease is caused by variants affecting the gene represented in this entry. Hemolytic uremic syndrome, atypical, 8, with rhizomelic short stature (AHUS8) [MIM:301110] An X-linked, atypical form of hemolytic uremic syndrome, characterized by microangiopathic hemolytic anemia, thrombocytopenia, renal failure and absence of episodes of enterocolitis and diarrhea. In contrast to typical hemolytic uremic syndrome, atypical forms have a poorer prognosis, with higher death rates and frequent progression to end-stage renal disease. AHUS8 patients have short stature with short limbs, in addition to acute renal dysfunction with proteinuria, thrombotic microangiopathy, anemia, thrombocytopenia, increased serum lactate dehydrogenase, and schistocytes on peripheral blood smear. More variable features include immunodeficiency with recurrent infections, developmental delay, and dysmorphic features. The age at onset of renal symptoms is variable, ranging from infancy to the early twenties. Female carriers may be mildly affected. The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous. Defects in C1GALT1C1 in Ag104A cell line create a tumor-specific glycopeptidic neo-epitope. This epitope induces a high-affinity, highly specific, syngeneic monoclonal antibody. This is caused by the abolition of function of a glycosyltransferase, disrupting O-glycan Core 1 synthesis.

Similarity. Belongs to the glycosyltransferase 31 family. Beta3-Gal-T subfamily.

RefSeq proteins (2): NP_001011551, NP_689905 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026050	C1GALT1/C1GALT1_chp1	Family

Enzyme classification (BRENDA):

• EC 2.4.1.122 — N-acetylgalactosaminide beta-1,3-galactosyltransferase (BRENDA: 10 organisms, 63 substrates, 10 inhibitors, 10 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

6 substrates with measured Km, best-characterized 6. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
UDP-GALACTOSE	0.02–0.63	3
ASIALO-MUCIN OF COWPER’S GLAND	0.0003–0.09	2
A-P-(N-ACETYL-D-GALACTOSAMINYL)T-S-S-A	0.55	1
ASIALO OVINE SUBMAXILLARY MUCIN	5	1
N-ACETYL-ALPHA-D-GALACTOSAMINYL-BENZYL	1.7	1
N-ACETYL-ALPHA-D-GALACTOSAMINYL-PHENYL	0.76	1

UniProt features (14 total): sequence variant 7, sequence conflict 3, topological domain 2, chain 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96EU7-F1	87.21	0.62

Function

Pathways and Gene Ontology

Reactome pathways

9 pathways

ID	Pathway
R-HSA-5083632	Defective C1GALT1C1 causes TNPS
R-HSA-913709	O-linked glycosylation of mucins
R-HSA-1643685	Disease
R-HSA-3781865	Diseases of glycosylation
R-HSA-3906995	Diseases associated with O-glycosylation of proteins
R-HSA-392499	Metabolism of proteins
R-HSA-5173105	O-linked glycosylation
R-HSA-5668914	Diseases of metabolism
R-HSA-597592	Post-translational protein modification

MSigDB gene sets: 200 (showing top): GCANCTGNY_MYOD_Q6, GOBP_PLATELET_ACTIVATION, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, CHIANG_LIVER_CANCER_SUBCLASS_UNANNOTATED_DN, ACEVEDO_LIVER_CANCER_WITH_H3K27ME3_UP, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_WOUND_HEALING, GOBP_PLATELET_MORPHOGENESIS, GOBP_CARBOHYDRATE_DERIVATIVE_BIOSYNTHETIC_PROCESS, SCHAEFFER_PROSTATE_DEVELOPMENT_6HR_UP, GOBP_HEMOSTASIS, E12_Q6, CUI_TCF21_TARGETS_2_DN, CART1_01, MILI_PSEUDOPODIA_CHEMOTAXIS_DN

GO Biological Process (3): protein O-linked glycosylation (GO:0006493), platelet activation (GO:0030168), platelet morphogenesis (GO:0036344)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (3): Golgi membrane (GO:0000139), extracellular exosome (GO:0070062), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-7 pathways:

Category	Pathways
Diseases associated with O-glycosylation of proteins	1
O-linked glycosylation	1
Diseases of metabolism	1
Diseases of glycosylation	1
Post-translational protein modification	1
Disease	1
Metabolism of proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
glycoprotein biosynthetic process	1
cell activation	1
blood coagulation	1
cell morphogenesis	1
binding	1
Golgi apparatus	1
bounding membrane of organelle	1
extracellular vesicle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

714 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
C1GALT1C1	ST6GALNAC1	Q9NSC7	743
C1GALT1C1	EEF1A2	P54266	722
C1GALT1C1	ST6GALNAC2	Q9UJ37	720
C1GALT1C1	B3GNT6	Q6ZMB0	711
C1GALT1C1	FCRL4	Q96PJ5	671
C1GALT1C1	ST3GAL1	Q11201	655
C1GALT1C1	GCNT1	Q02742	654
C1GALT1C1	C1GALT1	Q9NS00	585
C1GALT1C1	GCNT3	O95395	582
C1GALT1C1	GALNT2	Q10471	575
C1GALT1C1	GALNT12	Q8IXK2	555
C1GALT1C1	GALNT1	Q10472	550
C1GALT1C1	MUC1	P13931	540
C1GALT1C1	GALNT3	Q14435	532
C1GALT1C1	GALNT6	Q8NCL4	507

IntAct

44 interactions, top by confidence:

A	B	Type	Score
CD27	TCAF2	psi-mi:“MI:0914”(association)	0.640
SLC39A5	TMEM223	psi-mi:“MI:0914”(association)	0.530
FUT1	GOLIM4	psi-mi:“MI:0914”(association)	0.530
SLC6A8	ILVBL	psi-mi:“MI:0914”(association)	0.530
C1GALT1	C1GALT1C1	psi-mi:“MI:0407”(direct interaction)	0.440
C1GALT1C1	C1GALT1	psi-mi:“MI:0407”(direct interaction)	0.440
RNF41	CLEC16A	psi-mi:“MI:0914”(association)	0.350
ADPGK	TOR1B	psi-mi:“MI:0914”(association)	0.350
HTR3A	GPAA1	psi-mi:“MI:0914”(association)	0.350
TOR1A	CLEC3A	psi-mi:“MI:0914”(association)	0.350
SLC39A8	VAPB	psi-mi:“MI:0914”(association)	0.350
B3GNT2	NDUFA10	psi-mi:“MI:0914”(association)	0.350
ST3GAL4	MANEAL	psi-mi:“MI:0914”(association)	0.350
CANX	HLA-A	psi-mi:“MI:0914”(association)	0.350
CHRNA4	TMEM223	psi-mi:“MI:0914”(association)	0.350
PDGFRA	GXYLT2	psi-mi:“MI:0914”(association)	0.350
CLEC12B	GXYLT2	psi-mi:“MI:0914”(association)	0.350
KLRC1	METTL15	psi-mi:“MI:0914”(association)	0.350
ST14	LIPT2	psi-mi:“MI:0914”(association)	0.350
CX3CL1	FAM171A2	psi-mi:“MI:0914”(association)	0.350
SLC39A8	GOLIM4	psi-mi:“MI:0914”(association)	0.350
CSPG5	TCAF2	psi-mi:“MI:0914”(association)	0.350
ST3GAL4	NDUFA4	psi-mi:“MI:0914”(association)	0.350
TMPRSS13	TOR1A	psi-mi:“MI:0914”(association)	0.350
HPN	TOR1A	psi-mi:“MI:0914”(association)	0.350
HTR3A	EXTL3	psi-mi:“MI:0914”(association)	0.350

BioGRID (48): C1GALT1C1 (Affinity Capture-MS), C1GALT1C1 (Affinity Capture-MS), C1GALT1C1 (Affinity Capture-MS), C1GALT1C1 (Affinity Capture-MS), C1GALT1C1 (Affinity Capture-MS), C1GALT1C1 (Affinity Capture-MS), C1GALT1C1 (Affinity Capture-MS), C1GALT1C1 (Affinity Capture-MS), C1GALT1C1 (Affinity Capture-MS), C1GALT1C1 (Affinity Capture-MS), C1GALT1C1 (Affinity Capture-MS), C1GALT1C1 (Affinity Capture-MS), C1GALT1C1 (Affinity Capture-MS), C1GALT1C1 (Affinity Capture-MS), C1GALT1C1 (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: P0DN25, Q3SX46, Q499P3, Q96EU7, Q9JMG2, A0A2C9JXL4, Q08BL3, Q0VC84, Q18515, Q5F3G7, Q66GS2, Q6GNL1, Q7K237, Q7SYI5, Q9JJ05, Q9JJ06, Q9NS00, Q7Z1Z1, Q6ZQ11, Q86X52

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	7
Likely pathogenic	2
Uncertain significance	35
Likely benign	12
Benign	3

Top pathogenic / likely-pathogenic (9)

Variant ID	HGVS	Classification
10791	NM_001011551.3(C1GALT1C1):c.202C>T (p.Arg68Ter)	Pathogenic
10793	NM_001011551.3(C1GALT1C1):c.454G>A (p.Glu152Lys)	Pathogenic
2506572	NM_001011551.3(C1GALT1C1):c.266C>T (p.Thr89Ile)	Pathogenic
253389	GRCh37/hg19 Xp22.33-q28(chrX:71267-155234036)x2	Pathogenic
39573	NM_001011551.3(C1GALT1C1):c.577T>C (p.Ser193Pro)	Pathogenic
39574	NM_001011551.3(C1GALT1C1):c.3G>C (p.Met1Ile)	Pathogenic
873539	NM_001011551.3(C1GALT1C1):c.540T>G (p.Tyr180Ter)	Pathogenic
1675199	NM_001011551.3(C1GALT1C1):c.59C>A (p.Ala20Asp)	Likely pathogenic
3376970	NM_001011551.3(C1GALT1C1):c.553G>A (p.Gly185Arg)	Likely pathogenic

SpliceAI

275 predictions. Top by Δscore:

Variant	Effect	Δscore
X:120629912:CTCA:C	donor_loss	1.0000
X:120629914:CACC:C	donor_loss	1.0000
X:120629915:A:AC	donor_gain	1.0000
X:120629915:AC:A	donor_gain	1.0000
X:120629916:C:CC	donor_gain	1.0000
X:120629916:CC:C	donor_gain	1.0000
X:120629916:CCCG:C	donor_gain	1.0000
X:120627168:TTTCC:T	acceptor_loss	0.9900
X:120627170:TCCTA:T	acceptor_loss	0.9900
X:120627172:C:A	acceptor_loss	0.9900
X:120627173:T:G	acceptor_loss	0.9900
X:120629909:CCACT:C	donor_loss	0.9900
X:120629910:CACTC:C	donor_loss	0.9900
X:120629915:ACC:A	donor_gain	0.9900
X:120629915:ACCCG:A	donor_gain	0.9900
X:120629916:CCC:C	donor_gain	0.9900
X:120629916:CCCGC:C	donor_gain	0.9900
X:120627172:C:CC	acceptor_gain	0.9800
X:120629975:G:C	donor_gain	0.9700
X:120629966:T:TA	donor_gain	0.9600
X:120629969:T:TA	donor_gain	0.9600
X:120627168:TTTC:T	acceptor_gain	0.9500
X:120629998:T:A	donor_gain	0.9500
X:120627167:TTTTC:T	acceptor_gain	0.9400
X:120627170:TC:T	acceptor_gain	0.9100
X:120627171:CC:C	acceptor_gain	0.9100
X:120627182:GAAAA:G	acceptor_loss	0.8900
X:120627183:AAAAA:A	acceptor_loss	0.8900
X:120627445:ACCCT:A	acceptor_gain	0.8900
X:120627446:CCCTT:C	acceptor_gain	0.8900

AlphaMissense

2152 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:120626597:A:C	S190R	0.996
X:120626597:A:T	S190R	0.996
X:120626599:T:G	S190R	0.996
X:120626899:A:G	W90R	0.996
X:120626899:A:T	W90R	0.996
X:120626954:A:C	C71W	0.996
X:120626604:A:T	V188D	0.995
X:120626897:C:A	W90C	0.995
X:120626897:C:G	W90C	0.995
X:120626955:C:T	C71Y	0.995
X:120626487:A:G	L227P	0.994
X:120626706:A:G	L154P	0.994
X:120626708:G:C	N153K	0.993
X:120626708:G:T	N153K	0.993
X:120626723:A:C	F148L	0.993
X:120626723:A:T	F148L	0.993
X:120626725:A:G	F148L	0.993
X:120626956:A:G	C71R	0.993
X:120626429:A:C	F246L	0.991
X:120626429:A:T	F246L	0.991
X:120626431:A:G	F246L	0.991
X:120626598:C:A	S190I	0.991
X:120626712:T:A	E152V	0.991
X:120626721:G:T	A149D	0.991
X:120626752:A:G	W139R	0.991
X:120626752:A:T	W139R	0.991
X:120626886:C:T	C94Y	0.991
X:120626430:A:G	F246S	0.990
X:120626491:A:G	C226R	0.990
X:120626577:A:G	L197P	0.990

dbSNP variants (sampled 300 via entrez): RS1000665883 (X:120628826 C>T), RS1000733907 (X:120625593 T>A,C), RS1002396306 (X:120631135 T>C), RS1002587847 (X:120629674 G>A), RS1002659027 (X:120631428 G>A,T), RS1003071195 (X:120629244 G>A,C), RS1004296289 (X:120630943 T>C), RS1004336111 (X:120626783 G>A), RS1006786689 (X:120630101 G>A,C), RS1008102633 (X:120629935 G>T), RS1008407120 (X:120628593 T>C), RS1009160460 (X:120625843 T>C), RS1009230579 (X:120626079 TGGTTATACCAGTGC>T), RS1009369224 (X:120629664 T>C), RS1010898075 (X:120630781 T>C)

Disease associations

OMIM: gene MIM:300611 | disease phenotypes: MIM:300622, MIM:301110, MIM:300676

GenCC curated gene-disease

Disease	Classification	Inheritance
hemolytic uremic syndrome, atypical, 8, with rhizomelic short stature	Limited	X-linked

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
hemolytic uremic syndrome, atypical, 8, with rhizomelic short stature	Limited	XL

Mondo (4): Tn polyagglutination syndrome (MONDO:0010381), hemolytic uremic syndrome, atypical, 8, with rhizomelic short stature (MONDO:0957495), syndromic X-linked intellectual disability 14 (MONDO:0010398), atypical hemolytic-uremic syndrome (MONDO:0016244)

Orphanet (2): Lujan-Fryns syndrome (Orphanet:776), Atypical hemolytic uremic syndrome (Orphanet:2134)

HPO phenotypes

32 total (30 of 32 shown, HPO-id order):

HPO	Term
HP:0000093	Proteinuria
HP:0000278	Retrognathia
HP:0000322	Short philtrum
HP:0000348	High forehead
HP:0000358	Posteriorly rotated ears
HP:0000431	Wide nasal bridge
HP:0000527	Long eyelashes
HP:0001263	Global developmental delay
HP:0001419	X-linked recessive inheritance
HP:0001442	Typified by somatic mosaicism
HP:0001873	Thrombocytopenia
HP:0001875	Decreased total neutrophil count
HP:0001877	Abnormal erythrocyte morphology
HP:0001878	Hemolytic anemia
HP:0001882	Decreased total leukocyte count
HP:0001888	Decreased total lymphocyte count
HP:0001903	Anemia
HP:0001981	Schistocytosis
HP:0002197	Generalized-onset seizure
HP:0002714	Downturned corners of mouth
HP:0002719	Recurrent infections
HP:0002960	Autoimmunity
HP:0003026	Short long bone
HP:0003259	Elevated circulating creatinine concentration
HP:0003498	Disproportionate short stature
HP:0003593	Infantile onset
HP:0004719	Hyperechogenic kidneys
HP:0004798	Recurrent infection of the gastrointestinal tract
HP:0005272	Prominent nasolabial fold
HP:0005575	Hemolytic-uremic syndrome

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST004159_2	Serum galactose-deficient IgA1 levels	5.000000e-06

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D065766	Atypical Hemolytic Uremic Syndrome	C12.050.351.968.419.936.463.500; C12.200.777.419.936.463.500; C12.950.419.936.463.500; C15.378.050.141.610.500; C15.378.140.855.925.500.500; C15.378.243.937.925.500.500
C567063	Mental Retardation, X-Linked, Syndromic 14 (supp.)
C562719	Tn Syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	3
perfluorooctane sulfonic acid	decreases expression	2
Air Pollutants	affects expression, increases abundance, decreases expression	2
Arsenic	affects methylation, decreases methylation, increases expression	2
Cisplatin	increases expression, decreases expression, affects cotreatment	2
Dexamethasone	increases expression, affects cotreatment	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
aristolochic acid I	decreases expression	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression, affects cotreatment	1
trichostatin A	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cobaltous chloride	decreases expression	1
benzo(e)pyrene	increases methylation	1
potassium chromate(VI)	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	affects cotreatment, increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Acetaminophen	decreases expression	1
Vehicle Emissions	increases abundance, increases expression	1
Benzo(a)pyrene	affects methylation, decreases methylation, increases methylation	1
Diethylstilbestrol	decreases expression	1
Ethyl Methanesulfonate	decreases expression	1
Indomethacin	increases expression, affects cotreatment	1
Ketoconazole	decreases expression	1
Lead	increases expression	1
Methapyrilene	increases methylation	1

Cellosaurus cell lines

17 cell lines: 15 cancer cell line, 1 spontaneously immortalized cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_EI09	Hep-G2 SimpleCell O-GalNAc KO GalNAc-T1	Cancer cell line	Male
CVCL_EI10	Hep-G2 SimpleCell O-GalNAc KO GalNAc-T2	Cancer cell line	Male
CVCL_EI11	Hep-G2 SimpleCell O-GalNAc KI GalNAc-T3	Cancer cell line	Male
CVCL_S022	Capan-1 SimpleCell O-GalNAc	Cancer cell line	Male
CVCL_S023	COLO 205 SimpleCell O-GalNAc	Cancer cell line	Male
CVCL_S024	HaCaT SimpleCell O-GalNAc	Spontaneously immortalized cell line	Male
CVCL_S025	HEK293 SimpleCell O-GalNAc	Transformed cell line	Female
CVCL_S027	Hep-G2 SimpleCell O-GalNAc	Cancer cell line	Male
CVCL_S028	IMR-32 SimpleCell O-GalNAc	Cancer cell line	Male
CVCL_S029	K-562 SimpleCell O-GalNAc	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02574403	PHASE4	COMPLETED	Study Assessing an Algorithm-based Strategy of Eculizumab Discontinuation in Children and Adults With aHUS
NCT07308574	PHASE4	RECRUITING	Post-Marketing Clinical Study of Ravulizumab in Participants With Clinical aHUS
NCT02949128	PHASE3	COMPLETED	Study of ALXN1210 in Complement Inhibitor Treatment-Naïve Adult and Adolescent Participants With Atypical Hemolytic Uremic Syndrome (aHUS)
NCT03131219	PHASE3	COMPLETED	Study of Ravulizumab in Children and Adolescents With Atypical Hemolytic Uremic Syndrome (aHUS)
NCT03205995	PHASE3	TERMINATED	Safety and Efficacy Study of OMS721 in Patients With Atypical Hemolytic Uremic Syndrome
NCT04861259	PHASE3	ACTIVE_NOT_RECRUITING	A Study Evaluating the Efficacy, Safety, Pharmacokinetics and Pharmacodynamics of Crovalimab in Adult and Adolescent Participants With Atypical Hemolytic Uremic Syndrome (aHUS)
NCT04889430	PHASE3	COMPLETED	Efficacy and Safety of Iptacopan (LNP023) in Adult Patients With Atypical Hemolytic Uremic Syndrome Naive to Complement Inhibitor Therapy
NCT04958265	PHASE3	ACTIVE_NOT_RECRUITING	A Study Evaluating the Efficacy, Safety, Pharmacokinetics and Pharmacodynamics of Crovalimab in Pediatric Participants With Atypical Hemolytic Uremic Syndrome (aHUS)
NCT05795140	PHASE3	RECRUITING	Evaluate Long-term Safety, Tolerability and Efficacy of Iptacopan in Study Participants With aHUS
NCT05935215	PHASE3	RECRUITING	Efficacy and Safety of Switching From Anti-C5 Antibody Treatment to Iptacopan Treatment in Study Participants With Atypical Hemolytic Uremic Syndrome (aHUS)
NCT00838513	PHASE2	COMPLETED	Open Label Controlled Trial of Eculizumab in Adult Patients With Plasma Therapy-sensitive Atypical Hemolytic Uremic Syndrome (aHUS)
NCT00844428	PHASE2	COMPLETED	Open Label Controlled Trial of Eculizumab in Adolescent Patients With Plasma Therapy-Sensitive aHUS
NCT00844545	PHASE2	COMPLETED	Open Label Controlled Trial of Eculizumab in Adult Patients With Plasma Therapy-Resistant aHUS
NCT00844844	PHASE2	COMPLETED	Open Label Controlled Trial of Eculizumab in Adolescent Patients With Plasma Therapy-Resistant aHUS
NCT01193348	PHASE2	COMPLETED	An Open-Label, Multi-Center Clinical Trial of Eculizumab in Pediatric Patients With Atypical Hemolytic-Uremic Syndrome
NCT01194973	PHASE2	COMPLETED	An Open-label, Multi-center Clinical Trial of Eculizumab in Adult Patients With Atypical Hemolytic-uremic Syndrome
NCT01757431	PHASE2	COMPLETED	The Safety and Efficacy of Eculizumab in Japanese Patients With Atypical Hemolytic Uremic Syndrome (aHUS)
NCT02464891	PHASE2	TERMINATED	Complement Inhibition in aHUS Dialysis Patients
NCT03303313	PHASE2	WITHDRAWN	A Study of an Investigational Drug, Cemdisiran (ALN-CC5), in Patients With Atypical Hemolytic Uremic Syndrome
NCT03518203	PHASE2	COMPLETED	Eculizumab to Treat Thrombotic Microangiopathy/Atypical Hemolytic Uremic Syndrome -Associated Multiple Organ Dysfunction Syndrome in Hematopoietic Stem Cell Transplant Recipients
NCT03999840	PHASE2	WITHDRAWN	Eculizumab to Cemdisiran Switch in aHUS
NCT04725812	PHASE2	TERMINATED	Complement Regulation to Undo Systemic Harm in Preeclampsia
NCT01522170	Not specified	TERMINATED	aHUS Observational Long Term Follow-Up
NCT01522183	Not specified	RECRUITING	Atypical Hemolytic-Uremic Syndrome (aHUS) Registry
NCT01755429	Not specified	COMPLETED	To Characterize the Safety and Tolerability of Eculizumab in Two Japanese aHUS Patients
NCT01770951	Not specified	COMPLETED	A Retrospective, Observational, Non-interventional Trial to Assess Eculizumab Treatment Effect in Patients With Atypical Hemolytic Uremic Syndrome (aHUS)
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
NCT02614898	Not specified	TERMINATED	Evaluation of Potential Predictors of Disease Progression in Participants With Atypical Hemolytic Uremic Syndrome (aHUS) Including Genetics, Biomarkers, and Treatment
NCT02626663	Not specified	WITHDRAWN	The Role of Microparticles as a Biomarker
NCT03574506	Not specified	UNKNOWN	Eculizumab Use in the Postpartum Period for the Treatment of Pregnancy Associated aHUS: A Case Series
NCT03605511	Not specified	UNKNOWN	TTP and aHUS in Complicated Pregnancies
NCT04749810	Not specified	COMPLETED	Observational Study of Elizaria® in aHUS Patients
NCT05405777	Not specified	COMPLETED	A Retrospective Study to Evaluate the Clinical Outcome According to Treatment in aHUS Patients in South Korea
NCT05805202	Not specified	RECRUITING	Functional Implications of Rare Gene Mutations in aHUS Open the Door to Personalized Therapy
NCT05996731	Not specified	RECRUITING	Developing a Pipeline to Employ RNA-Seq as a Complementary Diagnostic Tool in Rare Diseases
NCT06065852	Not specified	RECRUITING	National Registry of Rare Kidney Diseases
NCT06099236	Not specified	ACTIVE_NOT_RECRUITING	A Prospective, Non-interventional, Observational Study of Presentation, Treatment Patterns and Outcomes in Atypical Hemolytic Uremic Syndrome Patients
NCT06312644	Not specified	RECRUITING	Study of Ultomiris® (Ravulizumab) Safety in Pregnancy
NCT07218536	Not specified	RECRUITING	The Burden of Atypical Hemolytic Uremic Syndrome and The Clinical Characteristics of Patients in Egyptian Hospitals A Multicenter, Observational, Retrospective Cohort Study in Egypt
NCT07399730	Not specified	NOT_YET_RECRUITING	Ravulizumab Outcomes in Polish Patients With aHUS