CSGALNACT1

Summary

CSGALNACT1 (chondroitin sulfate N-acetylgalactosaminyltransferase 1, HGNC:24290) is a protein-coding gene on chromosome 8p21.3, encoding Chondroitin sulfate N-acetylgalactosaminyltransferase 1 (Q8TDX6). Transfers 1,4-N-acetylgalactosamine (GalNAc) from UDP-GalNAc to the non-reducing end of glucuronic acid (GlcUA).

This gene encodes an enzyme that transfers N-acetylglucosamine (GalNAc) to the core tetrasaccharide linker and to elongating chondroitin sulfate chains in proteoglycans. Knockout of the orthologous mouse gene indicates that the protein is necessary for normal cartilage development and aggrecan metabolism. Mutations in this gene are associated with multiple sclerosis progression, and with mild skeletal dysplasia and joint laxity.

Source: NCBI Gene 55790 — RefSeq curated summary.

At a glance

• Gene–disease (curated): skeletal dysplasia, mild, with joint laxity and advanced bone age (Strong, GenCC)
• GWAS associations: 12
• Clinical variants (ClinVar): 411 total — 15 pathogenic, 6 likely-pathogenic
• Phenotypes (HPO): 71
• Druggable target: yes
• MANE Select transcript: NM_001354483

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24290
Approved symbol	CSGALNACT1
Name	chondroitin sulfate N-acetylgalactosaminyltransferase 1
Location	8p21.3
Locus type	gene with protein product
Status	Approved
Aliases	CSGalNAcT-1, FLJ11264, ChGn
Ensembl gene	ENSG00000147408
Ensembl biotype	protein_coding
OMIM	616615
Entrez	55790

Gene structure

Transcript identifiers

Ensembl transcripts: 92 — 81 protein_coding, 7 protein_coding_CDS_not_defined, 4 nonsense_mediated_decay

ENST00000332246, ENST00000397998, ENST00000454498, ENST00000517494, ENST00000517651, ENST00000518542, ENST00000519222, ENST00000520003, ENST00000522573, ENST00000522732, ENST00000522854, ENST00000523227, ENST00000523262, ENST00000523919, ENST00000524112, ENST00000524213, ENST00000692225, ENST00000695892, ENST00000695893, ENST00000695894, ENST00000695895, ENST00000695896, ENST00000695897, ENST00000695898, ENST00000695899, ENST00000695900, ENST00000895854, ENST00000895855, ENST00000895856, ENST00000895857, ENST00000895858, ENST00000895859, ENST00000895860, ENST00000895861, ENST00000895862, ENST00000895863, ENST00000895864, ENST00000895865, ENST00000895866, ENST00000895867, ENST00000895868, ENST00000895869, ENST00000950513, ENST00000950514, ENST00000950515, ENST00000950516, ENST00000950517, ENST00000950518, ENST00000950519, ENST00000950520, ENST00000950521, ENST00000950522, ENST00000950523, ENST00000950524, ENST00000950525, ENST00000950526, ENST00000950527, ENST00000950528, ENST00000950529, ENST00000950530, ENST00000950531, ENST00000950532, ENST00000950533, ENST00000950534, ENST00000950535, ENST00000950536, ENST00000950537, ENST00000950538, ENST00000950539, ENST00000950540, ENST00000950541, ENST00000950542, ENST00000950543, ENST00000950544, ENST00000950545, ENST00000950546, ENST00000950547, ENST00000950548, ENST00000950549, ENST00000950550, ENST00000950551, ENST00000950552, ENST00000950553, ENST00000950554, ENST00000950555, ENST00000950556, ENST00000950557, ENST00000950558, ENST00000950559, ENST00000950560, ENST00000950561, ENST00000950562

RefSeq mRNA: 22 — MANE Select: NM_001354483 NM_001130518, NM_001354475, NM_001354476, NM_001354477, NM_001354480, NM_001354481, NM_001354483, NM_001354484, NM_001354485, NM_001354487, NM_001354488, NM_001354489, NM_001354490, NM_001354491, NM_001354492, NM_001354494, NM_001354495, NM_001354496, NM_001354497, NM_001354498, NM_001354499, NM_018371

CCDS: CCDS6010

Canonical transcript exons

ENST00000692225 — 9 exons

Exon	Start	End
ENSE00001376899	19601771	19601865
ENSE00001391788	19505201	19506130
ENSE00003461177	19458426	19458642
ENSE00003472723	19439830	19439931
ENSE00003531719	19418656	19418750
ENSE00003593461	19420340	19420518
ENSE00003595388	19404161	19406069
ENSE00003683029	19408613	19408694
ENSE00003932322	19757186	19757277

Expression profiles

Bgee: expression breadth ubiquitous, 280 present calls, max score 97.86.

FANTOM5 (CAGE): breadth broad, TPM avg 6.8606 / max 177.4451, expressed in 865 samples.

FANTOM5 promoters (17 alternative TSS)

Promoter ID	TPM avg	Samples expressed
92137	2.1746	612
92122	1.6329	300
92142	1.2643	456
92136	0.2865	150
92130	0.2746	67
92138	0.2563	133
92124	0.2080	115
92125	0.2010	108
92140	0.1388	62
92123	0.1263	86

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cartilage tissue	UBERON:0002418	97.86	gold quality
cardiac muscle of right atrium	UBERON:0003379	97.47	gold quality
synovial joint	UBERON:0002217	96.36	gold quality
tibia	UBERON:0000979	95.89	gold quality
layer of synovial tissue	UBERON:0007616	95.83	gold quality
left ventricle myocardium	UBERON:0006566	95.82	gold quality
placenta	UBERON:0001987	95.34	gold quality
myocardium	UBERON:0002349	95.34	gold quality
vena cava	UBERON:0004087	95.24	gold quality
saphenous vein	UBERON:0007318	95.17	gold quality
endothelial cell	CL:0000115	95.16	silver quality
bone marrow cell	CL:0002092	94.53	gold quality
urethra	UBERON:0000057	94.28	gold quality
mucosa of urinary bladder	UBERON:0001259	93.58	gold quality
heart right ventricle	UBERON:0002080	93.46	gold quality
superficial temporal artery	UBERON:0001614	92.57	gold quality
orbitofrontal cortex	UBERON:0004167	92.45	gold quality
thyroid gland	UBERON:0002046	92.38	gold quality
CA1 field of hippocampus	UBERON:0003881	92.37	gold quality
bone marrow	UBERON:0002371	92.33	gold quality
postcentral gyrus	UBERON:0002581	92.27	gold quality
calcaneal tendon	UBERON:0003701	92.13	gold quality
dorsal root ganglion	UBERON:0000044	91.97	gold quality
cardiac atrium	UBERON:0002081	91.87	gold quality
parietal pleura	UBERON:0002400	91.87	gold quality
trabecular bone tissue	UBERON:0002483	91.82	gold quality
superior frontal gyrus	UBERON:0002661	91.70	gold quality
left lobe of thyroid gland	UBERON:0001120	91.65	gold quality
parietal lobe	UBERON:0001872	91.53	gold quality
sural nerve	UBERON:0015488	91.40	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-HCAD-35	yes	63.73
E-CURD-119	yes	28.27
E-GEOD-81608	yes	14.74
E-HCAD-25	yes	14.22
E-ENAD-27	yes	7.88
E-MTAB-9801	yes	7.60
E-ANND-3	yes	6.80

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

96 targeting CSGALNACT1, 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-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-7152-3P	99.97	67.47	849
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-10523-5P	99.91	69.22	2038
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-526B-3P	99.88	74.06	2587
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-20B-5P	99.88	74.01	2621
HSA-MIR-519D-3P	99.88	73.97	2607
HSA-MIR-93-5P	99.88	73.98	2606
HSA-MIR-12119	99.87	68.35	1653
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917

Literature-anchored findings (GeneRIF, showing 8)

• These results suggest that this enzyme has N-acetylgalactosaminyltransferase activity in both the elongation and initiation of chondroitin sulfate synthesis. (PMID:12163485)
• plays a role in the initiation and elongation in the synthesis of chondroitin sulfate (PMID:12446672)
• higher expression in the fetal skin than in adult skin (PMID:19701759)
• CSGALNACT1 missense mutations are associated with neuropathies. (PMID:21160489)
• CSGalNAcT-1 exhibited higher enzymatic efficiency toward monosulfated trisaccharides substituted at C4 or C6 position of Gal1, and at C6 of Gal2 compared with the unsulfated oligosaccharide. (PMID:22156920)
• CSGalNAcT-1 and Hapln-1 may play important roles in the pathogenesis of Kashin-Beck disease and osteoarthritis. (PMID:23748413)
• In men, patients who had multiple sclerosis (MS) with S126L had a slower disease progression. This cSNP might be associated with the sex differences in clinical course of MS. (PMID:26806424)
• CSGALNACT1-congenital disorder of glycosylation: A mild skeletal dysplasia with advanced bone age. (PMID:31705726)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	csgalnact1a	ENSDARG00000040535
danio_rerio	csgalnact1b	ENSDARG00000089233
mus_musculus	Csgalnact1	ENSMUSG00000036356
rattus_norvegicus	Csgalnact1	ENSRNOG00000013024
drosophila_melanogaster	Csgalnact	FBGN0033500

Paralogs (7): CHPF2 (ENSG00000033100), CHPF (ENSG00000123989), CHSY1 (ENSG00000131873), B4GALNT3 (ENSG00000139044), CSGALNACT2 (ENSG00000169826), B4GALNT4 (ENSG00000182272), CHSY3 (ENSG00000198108)

Protein

Protein identifiers

Chondroitin sulfate N-acetylgalactosaminyltransferase 1 — Q8TDX6 (reviewed: Q8TDX6)

Alternative names: Chondroitin beta-1,4-N-acetylgalactosaminyltransferase 1

All UniProt accessions (6): Q8TDX6, A0A8Q3WKU9, E5RGB2, E5RGK2, E5RJB6, E5RK93

UniProt curated annotations — full annotation on UniProt →

Function. Transfers 1,4-N-acetylgalactosamine (GalNAc) from UDP-GalNAc to the non-reducing end of glucuronic acid (GlcUA). Required for addition of the first GalNAc to the core tetrasaccharide linker and for elongation of chondroitin chains. Important role in chondroitin chain biosynthesis in cartilage formation and subsequent endochondral ossification. Moreover, is involved in the metabolism of aggrecan.

Subcellular location. Golgi apparatus. Golgi stack membrane.

Tissue specificity. Ubiquitous, with the highest levels in placenta, thyroid, bladder, prostate and adrenal gland. Detected at low levels in the other tissues examined.

Post-translational modifications. N-glycosylated.

Disease relevance. Skeletal dysplasia, mild, with joint laxity and advanced bone age (SDJLABA) [MIM:618870] An autosomal recessive disorder characterized by skeletal dysplasia, short stature, short long bones, advanced bone age, joint laxity, and facial dysmorphism. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the chondroitin N-acetylgalactosaminyltransferase family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q8TDX6-1	1	yes
Q8TDX6-2	2
Q8TDX6-3	3

RefSeq proteins (22): NP_001123990, NP_001341404, NP_001341405, NP_001341406, NP_001341409, NP_001341410, NP_001341412, NP_001341413, NP_001341414, NP_001341416, NP_001341417, NP_001341418, NP_001341419, NP_001341420, NP_001341421, NP_001341423, NP_001341424, NP_001341425, NP_001341426, NP_001341427, NP_001341428, NP_060841 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008428	Chond_GalNAc	Family
IPR029044	Nucleotide-diphossugar_trans	Homologous_superfamily
IPR051227	CS_glycosyltransferase	Family

Pfam: PF05679

Enzyme classification (BRENDA):

• EC 2.4.1.174 — glucuronylgalactosylproteoglycan 4-beta-N-acetylgalactosaminyltransferase (BRENDA: 5 organisms, 22 substrates, 39 inhibitors, 0 Km, 0 kcat entries)
• EC 2.4.1.175 — glucuronosyl-N-acetylgalactosaminyl-proteoglycan 4-beta-N-acetylgalactosaminyltransferase (BRENDA: 8 organisms, 92 substrates, 7 inhibitors, 8 Km, 1 kcat entries)

Substrate kinetics (BRENDA)

4 substrates with measured Km, best-characterized 4. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
UDP-N-ACETYL-BETA-D-GALACTOSAMINE	0.0059–0.05	3
UDP-GALNAC	0.221–9.275	2
CHONDROITIN SULFATE CS-11	0.36	1
UDP-N-ACETYL-ALPHA-D-GLUCOSAMINE	0.0059	1

Catalyzed reactions (Rhea), 1 shown:

• 3-O-(beta-D-GlcA-(1->3)-beta-D-Gal-(1->3)-beta-D-Gal-(1->4)-beta-D-Xyl)-L-seryl-[protein] + UDP-N-acetyl-alpha-D-galactosamine = 3-O-(beta-D-GalNAc-(1->4)-beta-D-GlcA-(1->3)-beta-D-Gal-(1->3)-beta-D-Gal-(1->4)-beta-D-Xyl)-L-seryl-[protein] + UDP + H(+) (RHEA:23464)

UniProt features (23 total): sequence variant 8, splice variant 3, sequence conflict 3, topological domain 2, binding site 2, glycosylation site 2, chain 1, transmembrane region 1, coiled-coil region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TDX6-F1	87.71	0.65

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 (2): 360; 477

Glycosylation sites (2): 315, 324

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-2022870	CS-GAG biosynthesis

MSigDB gene sets: 458 (showing top): GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_DN, VERHAAK_AML_WITH_NPM1_MUTATED_DN, GOBP_CARTILAGE_DEVELOPMENT, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GAUSSMANN_MLL_AF4_FUSION_TARGETS_A_UP, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_REPLACEMENT_OSSIFICATION, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, GOBP_CHONDROITIN_SULFATE_PROTEOGLYCAN_BIOSYNTHETIC_PROCESS, GOBP_ANIMAL_ORGAN_MORPHOGENESIS, GOBP_BONE_DEVELOPMENT, chr8p21, WOO_LIVER_CANCER_RECURRENCE_UP, GOBP_HEPARAN_SULFATE_PROTEOGLYCAN_METABOLIC_PROCESS

GO Biological Process (11): endochondral ossification (GO:0001958), heparan sulfate proteoglycan biosynthetic process (GO:0015012), UDP-N-acetylgalactosamine metabolic process (GO:0019276), proteoglycan biosynthetic process (GO:0030166), extracellular matrix organization (GO:0030198), heparin proteoglycan biosynthetic process (GO:0030210), UDP-glucuronate metabolic process (GO:0046398), chondroitin sulfate proteoglycan biosynthetic process (GO:0050650), dermatan sulfate proteoglycan biosynthetic process (GO:0050651), cartilage development (GO:0051216), chondroitin sulfate proteoglycan metabolic process (GO:0050654)

GO Molecular Function (10): acetylgalactosaminyltransferase activity (GO:0008376), peptidoglycan glycosyltransferase activity (GO:0008955), glucuronosyltransferase activity (GO:0015020), metal ion binding (GO:0046872), glucuronylgalactosylproteoglycan 4-beta-N-acetylgalactosaminyltransferase activity (GO:0047237), glucuronosyl-N-acetylgalactosaminyl-proteoglycan 4-beta-N-acetylgalactosaminyltransferase activity (GO:0047238), protein binding (GO:0005515), UDP-glycosyltransferase activity (GO:0008194), transferase activity (GO:0016740), hexosyltransferase activity (GO:0016758)

GO Cellular Component (4): Golgi membrane (GO:0000139), Golgi cisterna membrane (GO:0032580), Golgi apparatus (GO:0005794), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Chondroitin sulfate/dermatan sulfate metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein O-linked glycosylation via xylose	4
proteoglycan biosynthetic process	3
hexosyltransferase activity	3
nucleotide-sugar metabolic process	2
proteoglycan metabolic process	2
UDP-glycosyltransferase activity	2
acetylgalactosaminyltransferase activity	2
glycosyltransferase activity	2
replacement ossification	1
endochondral bone morphogenesis	1
heparan sulfate proteoglycan metabolic process	1
amino sugar metabolic process	1
glycoprotein biosynthetic process	1
extracellular structure organization	1
external encapsulating structure organization	1
heparin proteoglycan metabolic process	1
carboxylic acid metabolic process	1
chondroitin sulfate proteoglycan metabolic process	1
dermatan sulfate proteoglycan metabolic process	1
skeletal system development	1
animal organ development	1
connective tissue development	1
cation binding	1
binding	1
catalytic activity	1
Golgi apparatus	1
bounding membrane of organelle	1
organelle membrane	1
Golgi cisterna	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

840 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CSGALNACT1	CHST7	Q9NS84	666
CSGALNACT1	B4GALT7	Q9UBV7	665
CSGALNACT1	CHST12	Q9NRB3	665
CSGALNACT1	CHST11	Q9NPF2	661
CSGALNACT1	CHST15	Q7LFX5	660
CSGALNACT1	XYLT1	Q86Y38	632
CSGALNACT1	B3GAT3	O94766	630
CSGALNACT1	CHPF	Q8IZ52	610
CSGALNACT1	CHST13	Q8NET6	608
CSGALNACT1	CHST3	Q7LGC8	608
CSGALNACT1	CHST14	Q8NCH0	600
CSGALNACT1	EXTL2	Q9UBQ6	598
CSGALNACT1	EXTL3	O43909	591
CSGALNACT1	HS2ST1	Q7LGA3	584
CSGALNACT1	XYLT2	Q9H1B5	566

IntAct

8 interactions, top by confidence:

A	B	Type	Score
PB2		psi-mi:“MI:0914”(association)	0.350
CSGALNACT1	ATP2B3	psi-mi:“MI:0914”(association)	0.350
	TMEM223	psi-mi:“MI:0914”(association)	0.350
CSGALNACT1	FAM234B	psi-mi:“MI:0914”(association)	0.350
CSGALNACT1	CTSV	psi-mi:“MI:0914”(association)	0.350
CSGALNACT2	GOSR2	psi-mi:“MI:0914”(association)	0.350
SLC39A7	ESYT2	psi-mi:“MI:0914”(association)	0.350

BioGRID (84): CSGALNACT2 (Affinity Capture-MS), SLC30A1 (Affinity Capture-MS), GPRC5B (Affinity Capture-MS), ARFGEF1 (Affinity Capture-MS), ARFGEF2 (Affinity Capture-MS), TMEM214 (Affinity Capture-MS), KIAA1467 (Affinity Capture-MS), ATP2B3 (Affinity Capture-MS), TMUB1 (Affinity Capture-MS), TMX4 (Affinity Capture-MS), TIMELESS (Affinity Capture-MS), CSGALNACT2 (Affinity Capture-MS), SLC30A1 (Affinity Capture-MS), ARFGEF1 (Affinity Capture-MS), TMEM214 (Affinity Capture-MS)

ESM2 similar proteins: A0A0D3QS98, A0A0D3QS99, A4D0V7, C5H5C4, F6Q1T7, O70309, O75354, P17405, P18084, P18424, P22413, P50747, P52850, P58242, P61642, P80747, Q04519, Q0VBD0, Q0VD19, Q13219, Q52KP5, Q58CQ9, Q5QQ51, Q5STE3, Q64687, Q6DFZ6, Q6KFX9, Q6MZW2, Q6P988, Q6UWX4, Q6YGZ1, Q6ZXD2, Q71RP1, Q812F8, Q8BJQ9, Q8C1F4, Q8C419, Q8N5D6, Q8N6G5, Q8R116

Diamond homologs: Q0VC84, Q5DTK1, Q6ZQ11, Q70JA7, Q7Z1Z1, Q86X52, Q8BJQ9, Q8C1F4, Q8N6G5, Q8TDX6, Q76KP1, Q9JJ05, Q9JJ06, Q9NS00, Q18515

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	15
Likely pathogenic	6
Uncertain significance	208
Likely benign	128
Benign	31

Top pathogenic / likely-pathogenic (21)

Variant ID	HGVS	Classification
1376713	NM_001354483.2(CSGALNACT1):c.76_77del (p.Ile26fs)	Pathogenic
1451730	NM_001354483.2(CSGALNACT1):c.272_276del (p.Glu91fs)	Pathogenic
1452382	NM_001354483.2(CSGALNACT1):c.490dup (p.Thr164fs)	Pathogenic
1709216	NM_001354483.2(CSGALNACT1):c.472C>T (p.Gln158Ter)	Pathogenic
2080858	NM_001354483.2(CSGALNACT1):c.229del (p.Arg77fs)	Pathogenic
2161347	NM_001354483.2(CSGALNACT1):c.184C>T (p.Gln62Ter)	Pathogenic
2423790	NC_000008.10:g.(?19276147)(19316173_?)del	Pathogenic
2879714	NM_001354483.2(CSGALNACT1):c.703G>T (p.Glu235Ter)	Pathogenic
3696202	NM_001354483.2(CSGALNACT1):c.338dup (p.Glu114fs)	Pathogenic
4770051	NM_001354483.2(CSGALNACT1):c.168dup (p.Tyr57fs)	Pathogenic
4780307	NM_001354483.2(CSGALNACT1):c.1043dup (p.Ser350fs)	Pathogenic
4849108	NC_000008.10:g.(19316154_19362711)_(19363642_19448670)del	Pathogenic
870476	NC_000008.11:g.19411890_19467180del	Pathogenic
870478	NM_001354483.2(CSGALNACT1):c.372del (p.His125fs)	Pathogenic
870479	NC_000008.10:g.19340642_19425619delinsA	Pathogenic
1503160	NC_000008.10:g.(?19263291)(19297462_?)del	Likely pathogenic
2506476	NM_001354483.2(CSGALNACT1):c.632_634del (p.Glu211del)	Likely pathogenic
4075424	NM_001354483.2(CSGALNACT1):c.868C>T (p.Gln290Ter)	Likely pathogenic
4812190	NM_001354483.2(CSGALNACT1):c.1228-6_1230del	Likely pathogenic
870480	NM_001354483.2(CSGALNACT1):c.1294G>T (p.Asp432Tyr)	Likely pathogenic
992625	NM_001354483.2(CSGALNACT1):c.791A>G (p.Asn264Ser)	Likely pathogenic

SpliceAI

3289 predictions. Top by Δscore:

Variant	Effect	Δscore
8:19406065:CCCAC:C	acceptor_gain	1.0000
8:19406066:CCAC:C	acceptor_gain	1.0000
8:19406066:CCACC:C	acceptor_gain	1.0000
8:19406067:CAC:C	acceptor_gain	1.0000
8:19406067:CACC:C	acceptor_gain	1.0000
8:19406069:CCTG:C	acceptor_loss	1.0000
8:19420339:CCTGG:C	donor_gain	1.0000
8:19439828:A:AC	donor_gain	1.0000
8:19439829:C:CA	donor_gain	1.0000
8:19457708:G:C	donor_gain	1.0000
8:19458422:CAAC:C	donor_loss	1.0000
8:19458423:AAC:A	donor_loss	1.0000
8:19458425:C:G	donor_loss	1.0000
8:19458453:TTGTC:T	donor_gain	1.0000
8:19458454:TGTCC:T	donor_gain	1.0000
8:19458638:GATCC:G	acceptor_gain	1.0000
8:19458639:ATCC:A	acceptor_gain	1.0000
8:19458640:TCC:T	acceptor_gain	1.0000
8:19458641:CC:C	acceptor_gain	1.0000
8:19458641:CCC:C	acceptor_gain	1.0000
8:19458642:CC:C	acceptor_gain	1.0000
8:19458643:C:CA	acceptor_loss	1.0000
8:19458643:C:CC	acceptor_gain	1.0000
8:19458643:C:T	acceptor_gain	1.0000
8:19458646:T:C	acceptor_gain	1.0000
8:19458646:T:TC	acceptor_gain	1.0000
8:19505196:CTAA:C	donor_loss	1.0000
8:19505197:TAACC:T	donor_loss	1.0000
8:19505198:AACCT:A	donor_loss	1.0000
8:19505199:ACC:A	donor_loss	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000003229 (8:19572581 A>G), RS1000005334 (8:19595766 A>C), RS1000014054 (8:19458588 C>G,T), RS1000025838 (8:19656543 G>A), RS1000036800 (8:19458770 C>A,G,T), RS1000040666 (8:19556912 C>T), RS1000063811 (8:19432112 C>A), RS1000067512 (8:19618084 G>A,C), RS1000068002 (8:19675553 C>T), RS1000068986 (8:19647234 G>C), RS1000084529 (8:19756788 G>A), RS1000086087 (8:19422133 T>A,C), RS1000087320 (8:19629524 T>A), RS1000093992 (8:19712370 C>T), RS1000098376 (8:19685330 A>C)

Disease associations

OMIM: gene MIM:616615 | disease phenotypes: MIM:618870

GenCC curated gene-disease

Disease	Classification	Inheritance
skeletal dysplasia, mild, with joint laxity and advanced bone age	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
skeletal dysplasia, mild, with joint laxity and advanced bone age	Moderate	AR

Mondo (1): skeletal dysplasia, mild, with joint laxity and advanced bone age (MONDO:0030029)

Orphanet (0):

HPO phenotypes

71 total (30 of 71 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000256	Macrocephaly
HP:0000308	Microretrognathia
HP:0000311	Round face
HP:0000343	Long philtrum
HP:0000358	Posteriorly rotated ears
HP:0000444	Convex nasal ridge
HP:0000463	Anteverted nares
HP:0000470	Short neck
HP:0000494	Downslanted palpebral fissures
HP:0000499	Abnormal eyelash morphology
HP:0000501	Glaucoma
HP:0000520	Proptosis
HP:0000540	Hypermetropia
HP:0000592	Blue sclerae
HP:0000767	Pectus excavatum
HP:0000944	Abnormal metaphysis morphology
HP:0000954	Single transverse palmar crease
HP:0001156	Brachydactyly
HP:0001249	Intellectual disability
HP:0001252	Hypotonia
HP:0001270	Motor delay
HP:0001331	Absent septum pellucidum
HP:0001373	Joint dislocation
HP:0001377	Limited elbow extension
HP:0001382	Joint hypermobility
HP:0001591	Bell-shaped thorax
HP:0001629	Ventricular septal defect
HP:0001631	Atrial septal defect
HP:0001643	Patent ductus arteriosus

GWAS associations

12 associations (top):

Study	Trait	p-value
GCST002046_2	Response to antidepressant treatment (citalopram)	2.000000e-07
GCST003081_3	Glucocorticoid-induced osteonecrosis (age 10 years and older)	2.000000e-06
GCST003615_3	Persistent hepatitis B virus infection	3.000000e-12
GCST003859_11	Oropharynx cancer	3.000000e-06
GCST004372_8	Language performance in older adults (adjusted for episodic memory)	4.000000e-06
GCST007059_4	Response to antidepressants (symptom improvement)	4.000000e-06
GCST008663_3	Lung function in never smokers (low FEV1 vs average FEV1)	4.000000e-07
GCST008839_195	Height	4.000000e-16
GCST010173_50	Triglyceride levels	9.000000e-35
GCST010204_101	Low density lipoprotein cholesterol levels	3.000000e-28
GCST011359_2	Venous thromboembolism	1.000000e-27
GCST90000025_323	Appendicular lean mass	9.000000e-10

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0004874	memory performance
EFO:0007710	cognitive decline measurement
EFO:0007797	language measurement
EFO:0004314	forced expiratory volume
EFO:0004530	triglyceride measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004980	appendicular lean mass

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2040705 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, decreases methylation	7
Benzo(a)pyrene	affects methylation, decreases expression, increases expression, increases methylation	4
Aflatoxin B1	increases expression, increases methylation, decreases methylation	3
bisphenol A	decreases methylation, decreases expression, affects cotreatment	2
sodium arsenite	increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Silicon Dioxide	increases expression, decreases expression	2
Tretinoin	increases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	affects expression, decreases expression	2
Particulate Matter	decreases expression	2
triphenyl phosphate	affects expression	1
2,5,2’,5’-tetrachlorobiphenyl	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
cobaltous chloride	decreases expression	1
butyraldehyde	decreases expression	1
pyrvinium	decreases expression, decreases reaction	1
hydroquinone	increases expression	1
2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
di-n-butylphosphoric acid	affects expression	1
cylindrospermopsin	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	1
abrine	increases expression	1
quinocetone	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
enzalutamide	decreases expression	1
jinfukang	affects cotreatment, decreases expression	1
(+)-JQ1 compound	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Temozolomide	affects response to substance	1

ChEMBL screening assays

9 unique, capped per target: 9 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2045265	Binding	Inhibition of human DGAT1 assessed as conversion of [14C]-oleoyl-CoA to [14C]-triglyceride at 1 uM after 10 mins by scintillation counting	Synthesis and biological evaluation of isoxazole, oxazole, and oxadiazole containing heteroaryl analogs of biaryl ureas as DGAT1 inhibitors. — Eur J Med Chem

Clinical trials (associated diseases)

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