CHST11

Summary

CHST11 (carbohydrate sulfotransferase 11, HGNC:17422) is a protein-coding gene on chromosome 12q23.3, encoding Carbohydrate sulfotransferase 11 (Q9NPF2). Catalyzes the transfer of sulfate to position 4 of the N-acetylgalactosamine (GalNAc) residue of chondroitin.

The protein encoded by this gene belongs to the sulfotransferase 2 family. It is localized to the golgi membrane, and catalyzes the transfer of sulfate to position 4 of the N-acetylgalactosamine (GalNAc) residue of chondroitin. Chondroitin sulfate constitutes the predominant proteoglycan present in cartilage, and is distributed on the surfaces of many cells and extracellular matrices. A chromosomal translocation involving this gene and IgH, t(12;14)(q23;q32), has been reported in a patient with B-cell chronic lymphocytic leukemia. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 50515 — RefSeq curated summary.

At a glance

• Gene–disease (curated): osteochondrodysplasia, brachydactyly, and overlapping malformed digits (Strong, GenCC)
• GWAS associations: 9
• Clinical variants (ClinVar): 50 total
• Phenotypes (HPO): 22
• MANE Select transcript: NM_018413

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17422
Approved symbol	CHST11
Name	carbohydrate sulfotransferase 11
Location	12q23.3
Locus type	gene with protein product
Status	Approved
Aliases	C4ST1, C4St-1, C4ST, HSA269537
Ensembl gene	ENSG00000171310
Ensembl biotype	protein_coding
OMIM	610128
Entrez	50515

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 5 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000303694, ENST00000546689, ENST00000547956, ENST00000549016, ENST00000549260, ENST00000550711

RefSeq mRNA: 2 — MANE Select: NM_018413 NM_001173982, NM_018413

CCDS: CCDS55878, CCDS9099

Canonical transcript exons

ENST00000303694 — 3 exons

Exon	Start	End
ENSE00001165922	104756949	104762014
ENSE00002378684	104456948	104457529
ENSE00003479244	104601906	104601991

Expression profiles

Bgee: expression breadth ubiquitous, 243 present calls, max score 97.52.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 26.5512 / max 1164.2137, expressed in 1747 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
127761	7.7565	1206
127760	7.3847	1372
127759	5.5928	1243
127758	3.6446	1434
127762	0.6290	369
127764	0.5968	271
127771	0.4912	145
127772	0.3384	111
127773	0.0663	41
127770	0.0509	23

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tibia	UBERON:0000979	97.52	gold quality
blood	UBERON:0000178	92.85	gold quality
cartilage tissue	UBERON:0002418	92.22	gold quality
cortical plate	UBERON:0005343	91.89	gold quality
monocyte	CL:0000576	89.85	gold quality
leukocyte	CL:0000738	89.74	gold quality
mononuclear cell	CL:0000842	89.66	gold quality
bone marrow cell	CL:0002092	89.10	gold quality
bone marrow	UBERON:0002371	88.62	gold quality
ventricular zone	UBERON:0003053	87.72	gold quality
granulocyte	CL:0000094	86.85	gold quality
amniotic fluid	UBERON:0000173	86.75	gold quality
trabecular bone tissue	UBERON:0002483	85.96	gold quality
medial globus pallidus	UBERON:0002477	83.97	gold quality
vermiform appendix	UBERON:0001154	83.57	gold quality
lymph node	UBERON:0000029	83.46	gold quality
visceral pleura	UBERON:0002401	83.31	gold quality
placenta	UBERON:0001987	82.95	gold quality
left adrenal gland cortex	UBERON:0035825	82.82	gold quality
left adrenal gland	UBERON:0001234	82.54	gold quality
corpus epididymis	UBERON:0004359	82.22	gold quality
right adrenal gland	UBERON:0001233	82.11	gold quality
nucleus accumbens	UBERON:0001882	81.94	gold quality
adrenal cortex	UBERON:0001235	81.55	gold quality
caudate nucleus	UBERON:0001873	81.53	gold quality
adrenal gland	UBERON:0002369	81.34	gold quality
ganglionic eminence	UBERON:0004023	81.26	gold quality
globus pallidus	UBERON:0001875	81.16	gold quality
right adrenal gland cortex	UBERON:0035827	81.16	gold quality
gall bladder	UBERON:0002110	81.13	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-GEOD-180759	yes	2324.89
E-HCAD-35	yes	1841.77
E-GEOD-131882	yes	1206.62
E-CURD-119	yes	976.37
E-HCAD-25	yes	23.05
E-ANND-3	yes	8.10

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TAL1

miRNA regulators (miRDB)

143 targeting CHST11, 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-6867-5P	100.00	82.21	3464
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4715-3P	99.98	66.03	670
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-8082	99.95	67.27	1170
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-6845-3P	99.94	66.88	1439
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-4728-5P	99.85	69.39	4718

Literature-anchored findings (GeneRIF, showing 20)

• human D4ST-1, C4ST-1, and S4ST-2 have differential roles in dermatan sulfate biosynthesis (PMID:12847091)
• C4ST-1 and C6ST-1 differ from each other in the recognition of uronic acid residues adjacent to the targeted GalNAc residue (PMID:15324304)
• identified TGFbeta- responsive regulatory modules that can function in a cell type-specific fashion. Taken together, our results identify TGFbeta-dependent and -independent cis-regulatory modules of the C4ST-1 gene (PMID:19937589)
• Forced expression of C4ST-1 in L-Wnt-3a cells inhibited diffusion of Wnt-3a due to structural alterations in CS chains mediated by C4ST-1. (PMID:21123170)
• Cell surface P-selectin binding depends on CHST11 gene expression. CSPG4 serves as a P-selectin ligand through its CS chain and participates in P-selectin binding to the highly metastatic breast cancer cells. (PMID:21658254)
• reduced C4ST-1 expression and chondroitin sulfation imbalance mediating the effects of oncogenic HRAS signaling in the pathogenesis of Costello syndrome. (PMID:22317973)
• Silencing Wnt9A increased the expression of CHST11 in the colonic epithelial cells, and chromatin immunoprecipitation assay demonstrated enhancing effects of Wnt9A siRNA and exogenous BMP4 on the CHST11 promoter (PMID:25511584)
• CHST11 may play a direct role in progression of breast cancer and that its expression is controlled by DNA methylation. Therefore, in addition to CHST11 mRNA levels, the methylation status of this gene also has potential as a prognostic biomarker. (PMID:25586191)
• We conclude that CHSTs involved in the synthesis of CS-A and CS-E might influence ovarian cancer progression, and we suggest CHST11 as independent unfavorable prognostic factor in this entity. (PMID:26084610)
• These results have demonstrated that CHST11 and CHST13 negatively modulate metastasis and drug resistance of HCC cells probably via oncogenic MAPK signal pathway. (PMID:26993826)
• data demonstrate that the hip osteoarthritis susceptibility is mediated by differential protein binding to the alleles of rs835487 and rs835488, which are located within an enhancer whose target may be CHST11 during chondrogenesis or an alternative gene. (PMID:27391021)
• A C4ST-1 construct was designed and expressed in both Escherichia coli and Pichia pastoris in its non-glycosylated and glycosylated forms. Both constructs showed similar activity albeit different kinetic parameters when acting on a microbially prepared unsulfated chondroitin substrate. Moreover, the glycosylated form of C4ST-1 showed lower stability than the non-glycosylated form. (PMID:28761999)
• Our findings confirm the crucial role of CHST11 in skeletal morphogenesis and show that CHST11 defects have variable manifestations that include a variety of limb malformations and skeletal defects (PMID:29514872)
• An epigenome-wide association study of posttraumatic stress disorder in US veterans implicates several new DNA methylation loci. (PMID:32171335)
• Carbohydrate (Chondroitin 4) Sulfotransferase-11-Mediated Induction of Epithelial-Mesenchymal Transition and Generation of Cancer Stem Cells. (PMID:32344408)
• Chondroitin-4-sulfate transferase-1 depletion inhibits formation of a proteoglycan-rich layer and alters immunotolerance of bone marrow mesenchymal stem cells on titanium oxide surfaces. (PMID:32707405)
• The CHST11 gene is linked to lung cancer and pulmonary fibrosis. (PMID:36181245)
• High Expression of CHST11 Correlates with Poor Prognosis and Tumor Immune Infiltration of Pancreatic Cancer. (PMID:36546737)
• KIAA1429-mediated m6A modification of CHST11 promotes progression of diffuse large B-cell lymphoma by regulating Hippo-YAP pathway. (PMID:37076815)
• Effect of CHST11, a novel biomarker, on the biological functionalities of clear cell renal cell carcinoma. (PMID:38565604)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	chst11	ENSDARG00000034375
mus_musculus	Chst11	ENSMUSG00000034612
rattus_norvegicus	Chst11	ENSRNOG00000008885

Paralogs (6): CHST10 (ENSG00000115526), CHST8 (ENSG00000124302), CHST12 (ENSG00000136213), CHST9 (ENSG00000154080), CHST14 (ENSG00000169105), CHST13 (ENSG00000180767)

Protein

Protein identifiers

Carbohydrate sulfotransferase 11 — Q9NPF2 (reviewed: Q9NPF2)

Alternative names: Chondroitin 4-O-sulfotransferase 1, Chondroitin 4-sulfotransferase 1

All UniProt accessions (4): F8VRG6, F8VXK3, F8VXK7, Q9NPF2

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the transfer of sulfate to position 4 of the N-acetylgalactosamine (GalNAc) residue of chondroitin. Chondroitin sulfate constitutes the predominant proteoglycan present in cartilage and is distributed on the surfaces of many cells and extracellular matrices. Can also sulfate Gal residues in desulfated dermatan sulfate. Preferentially sulfates in GlcA->GalNAc unit than in IdoA->GalNAc unit. Does not form 4, 6-di-O-sulfated GalNAc when chondroitin sulfate C is used as an acceptor.

Subcellular location. Golgi apparatus membrane.

Tissue specificity. Widely expressed. Highly expressed in spleen, thymus, bone marrow, peripheral blood leukocytes, lymph node, heart, brain, lung and placenta.

Post-translational modifications. N-glycosylated; required for activity and stability.

Disease relevance. A chromosomal aberration involving CHST11 is found in B-cell chronic lymphocytic leukemias. Translocation t(12;14)(q23;q32) with IgH. Osteochondrodysplasia, brachydactyly, and overlapping malformed digits (OCBMD) [MIM:618167] An autosomal recessive disorder characterized by bilateral symmetric skeletal defects that primarily affect the limbs. Affected individuals have mild short stature due to shortening of the lower leg bones, as well as hand and foot malformations, predominantly brachydactyly and overlapping digits. Other skeletal defects include scoliosis, dislocated patellae and fibulae, and pectus excavatum. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the sulfotransferase 2 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9NPF2-1	1	yes
Q9NPF2-2	2, C4S-1A

RefSeq proteins (2): NP_001167453, NP_060883* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005331	Sulfotransferase	Family
IPR018011	Carb_sulfotrans_8-10	Family

Pfam: PF03567

Enzyme classification (BRENDA):

• EC 2.8.2.5 — chondroitin 4-sulfotransferase (BRENDA: 8 organisms, 31 substrates, 8 inhibitors, 14 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

3 substrates with measured Km, best-characterized 3. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
3’-PHOSPHOADENYLYLSULFATE	0.0003–1.4	6
CHONDROITIN	0.0038–2.7	4
3’-PHOSPHOADENYLYL SULFATE	0.0013–0.036	2

Catalyzed reactions (Rhea), 1 shown:

• chondroitin beta-D-glucuronate + n 3’-phosphoadenylyl sulfate = chondroitin 4’-sulfate + n adenosine 3’,5’-bisphosphate + n H(+) (RHEA:16101)

UniProt features (18 total): mutagenesis site 5, glycosylation site 4, topological domain 2, binding site 2, chain 1, splice variant 1, sequence variant 1, sequence conflict 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NPF2-F1	89.39	0.74

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): 124–130; 186–194

Glycosylation sites (4): 205, 223, 321, 342

Mutagenesis-validated functional residues (5):

Position	Phenotype
125	abolishes enzyme activity but does not affect stability of the protein.
205	induces a weak decrease in enzyme activity but has no effect on stability of the protein. unstable protein; when associa
223	induces a weak decrease in enzyme activity but has no effect on stability of the protein. unstable protein; when associa
321	induces a strong decrease in enzyme activity but has no effect on stability of the protein. unstable protein; when assoc
342	induces a strong decrease in enzyme activity has no effect on stability of the protein.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-2022870	CS-GAG biosynthesis

MSigDB gene sets: 415 (showing top): GSE45365_NK_CELL_VS_CD11B_DC_DN, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_RESPIRATORY_GASEOUS_EXCHANGE_BY_RESPIRATORY_SYSTEM, GOBP_CARTILAGE_DEVELOPMENT, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_EMBRYONIC_DIGIT_MORPHOGENESIS, GOBP_EMBRYONIC_SKELETAL_SYSTEM_DEVELOPMENT, SP3_Q3, GOBP_EMBRYONIC_SKELETAL_SYSTEM_MORPHOGENESIS, GOBP_GROWTH, JOHANSSON_GLIOMAGENESIS_BY_PDGFB_UP, DARWICHE_SKIN_TUMOR_PROMOTER_DN, DARWICHE_PAPILLOMA_RISK_LOW_UP, DARWICHE_PAPILLOMA_RISK_HIGH_DN

GO Biological Process (21): in utero embryonic development (GO:0001701), chondrocyte development (GO:0002063), apoptotic process (GO:0006915), transforming growth factor beta receptor signaling pathway (GO:0007179), respiratory gaseous exchange by respiratory system (GO:0007585), post-embryonic development (GO:0009791), carbohydrate biosynthetic process (GO:0016051), proteoglycan biosynthetic process (GO:0030166), negative regulation of transforming growth factor beta receptor signaling pathway (GO:0030512), polysaccharide localization (GO:0033037), post-anal tail morphogenesis (GO:0036342), regulation of cell population proliferation (GO:0042127), embryonic digit morphogenesis (GO:0042733), negative regulation of apoptotic process (GO:0043066), developmental growth (GO:0048589), embryonic viscerocranium morphogenesis (GO:0048703), chondroitin sulfate proteoglycan biosynthetic process (GO:0050650), embryonic limb morphogenesis (GO:0030326), embryonic skeletal system morphogenesis (GO:0048704), chondroitin sulfate proteoglycan metabolic process (GO:0050654), cartilage development (GO:0051216)

GO Molecular Function (5): dermatan 4-sulfotransferase activity (GO:0001537), sulfotransferase activity (GO:0008146), chondroitin 4-sulfotransferase activity (GO:0047756), N-acetylgalactosamine 4-sulfate 6-O-sulfotransferase activity (GO:0050659), transferase activity (GO:0016740)

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

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
multicellular organismal process	2
proteoglycan metabolic process	2
embryonic morphogenesis	2
chordate embryonic development	1
chondrocyte differentiation	1
cell development	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
cellular response to transforming growth factor beta stimulus	1
transforming growth factor beta receptor superfamily signaling pathway	1
multicellular organism development	1
carbohydrate metabolic process	1
biosynthetic process	1
glycoprotein biosynthetic process	1
transforming growth factor beta receptor signaling pathway	1
regulation of transforming growth factor beta receptor signaling pathway	1
negative regulation of transmembrane receptor protein serine/threonine kinase signaling pathway	1
macromolecule localization	1
anatomical structure morphogenesis	1
cell population proliferation	1
regulation of cellular process	1
embryonic limb morphogenesis	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
developmental process	1
growth	1
embryonic cranial skeleton morphogenesis	1
proteoglycan biosynthetic process	1
chondroitin sulfate proteoglycan metabolic process	1
protein O-linked glycosylation via xylose	1
limb morphogenesis	1
embryonic appendage morphogenesis	1
embryonic organ morphogenesis	1
skeletal system morphogenesis	1
embryonic skeletal system development	1
dermatan sulfotransferase activity	1
transferase activity, transferring sulphur-containing groups	1
chondroitin sulfotransferase activity	1

Protein interactions and networks

STRING

892 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CHST11	CHST3	Q7LGC8	739
CHST11	CHST15	Q7LFX5	729
CHST11	CHST7	Q9NS84	666
CHST11	CHSY1	Q86X52	661
CHST11	CSGALNACT1	Q8TDX6	661
CHST11	CSGALNACT2	Q8N6G5	635
CHST11	XYLT1	Q86Y38	633
CHST11	HS2ST1	Q7LGA3	597
CHST11	CHST6	Q9GZX3	565
CHST11	CHPF	Q8IZ52	537
CHST11	SOX6	P35712	527
CHST11	DSE	Q9UL01	514
CHST11	SOX5	P35711	513
CHST11	XYLT2	Q9H1B5	507
CHST11	IGHV4-38-2	P0DP08	489

IntAct

15 interactions, top by confidence:

A	B	Type	Score
NIPAL1	ESYT2	psi-mi:“MI:0914”(association)	0.640
SDF4	GTPBP6	psi-mi:“MI:0914”(association)	0.530
CHST11	ANXA6	psi-mi:“MI:0915”(physical association)	0.400
CHRNB2	TMEM131L	psi-mi:“MI:0914”(association)	0.350
SCN4A	C2CD4B	psi-mi:“MI:0914”(association)	0.350
NRSN1	FAM171A2	psi-mi:“MI:0914”(association)	0.350
TMEM59	GPR89A	psi-mi:“MI:0914”(association)	0.350
TMEM59	GOLIM4	psi-mi:“MI:0914”(association)	0.350
NIPA1	UNC119B	psi-mi:“MI:0914”(association)	0.350
SLC17A9	PIPSL	psi-mi:“MI:0914”(association)	0.350
SLC30A5	NBAS	psi-mi:“MI:0914”(association)	0.350
SLC30A7	ESYT2	psi-mi:“MI:0914”(association)	0.350
SLC39A7	ESYT2	psi-mi:“MI:0914”(association)	0.350
SLC7A5	KLRG2	psi-mi:“MI:0914”(association)	0.350

BioGRID (25): CHST11 (Affinity Capture-MS), CHST11 (Affinity Capture-MS), CHST11 (Reconstituted Complex), CHST11 (Affinity Capture-MS), CHST11 (Affinity Capture-MS), CHST11 (Affinity Capture-MS), CHST11 (Affinity Capture-RNA), CHST11 (Affinity Capture-RNA), CHST11 (Affinity Capture-RNA), CHST11 (Proximity Label-MS), CHST11 (Affinity Capture-RNA), CHST11 (Affinity Capture-MS), CHST11 (Affinity Capture-MS), CHST11 (Affinity Capture-MS), CHST11 (Affinity Capture-MS)

ESM2 similar proteins: A0A8C2LVE3, A2BGL3, F4HXW9, O08889, O17645, O43909, O43916, O93336, O93403, O95461, P25722, P69478, P79948, Q0IIY2, Q2TBF2, Q5NDE4, Q5NDE5, Q5NDE6, Q5NDE7, Q5NDE8, Q5NVB3, Q5R621, Q5RJQ0, Q5XHM7, Q66PG1, Q66PG2, Q66PG3, Q6DBY9, Q6NVP8, Q6P9A2, Q6PA90, Q76EC5, Q76KB1, Q7LFX5, Q7LGA3, Q7LGC8, Q7T3S3, Q800H9, Q8BUB6, Q8CHI9

Diamond homologs: O43529, O54702, P69478, Q5RBZ6, Q5XHM7, Q5ZIE4, Q6AXM1, Q6GNS1, Q6PGK7, Q76EC5, Q7L1S5, Q7T3S3, Q805E5, Q8BQ86, Q8NET6, Q99LL3, Q9H2A9, Q9JME2, Q9NPF2, Q9NRB3, Q80V53, Q8NCH0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	40
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2144 predictions. Top by Δscore:

Variant	Effect	Δscore
12:104457515:G:GG	donor_gain	1.0000
12:104601904:A:AG	acceptor_gain	1.0000
12:104601905:G:GT	acceptor_gain	1.0000
12:104601905:GT:G	acceptor_gain	1.0000
12:104601905:GTC:G	acceptor_gain	1.0000
12:104601905:GTCA:G	acceptor_gain	1.0000
12:104601905:GTCAT:G	acceptor_gain	1.0000
12:104601991:GGTA:G	donor_loss	1.0000
12:104601992:G:GA	donor_loss	1.0000
12:104601993:T:G	donor_loss	1.0000
12:104756944:TGCA:T	acceptor_loss	1.0000
12:104756945:GCA:G	acceptor_loss	1.0000
12:104756946:CA:C	acceptor_loss	1.0000
12:104756947:A:AG	acceptor_gain	1.0000
12:104756947:AGCT:A	acceptor_gain	1.0000
12:104756947:AGCTG:A	acceptor_gain	1.0000
12:104756948:G:GG	acceptor_gain	1.0000
12:104756948:G:GT	acceptor_loss	1.0000
12:104756948:GC:G	acceptor_gain	1.0000
12:104756948:GCT:G	acceptor_gain	1.0000
12:104756948:GCTG:G	acceptor_gain	1.0000
12:104756948:GCTGG:G	acceptor_gain	1.0000
12:104757731:GCT:G	donor_gain	1.0000
12:104554880:A:AG	donor_gain	0.9900
12:104601992:G:GG	donor_gain	0.9900
12:104687877:G:T	donor_gain	0.9900
12:104689761:C:T	donor_gain	0.9900
12:104756944:T:TA	acceptor_gain	0.9900
12:104457498:C:A	donor_gain	0.9800
12:104508862:T:G	acceptor_gain	0.9800

AlphaMissense

2330 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:104757105:T:C	C121R	1.000
12:104757106:G:A	C121Y	1.000
12:104757106:G:T	C121F	1.000
12:104757107:C:G	C121W	1.000
12:104757119:G:C	K125N	1.000
12:104757119:G:T	K125N	1.000
12:104757126:T:C	C128R	1.000
12:104757127:G:A	C128Y	1.000
12:104757130:C:T	T129I	1.000
12:104757135:T:A	W131R	1.000
12:104757135:T:C	W131R	1.000
12:104757140:G:C	K132N	1.000
12:104757140:G:T	K132N	1.000
12:104757142:G:C	R133P	1.000
12:104757330:T:G	Y196D	1.000
12:104757334:G:C	R197P	1.000
12:104757339:A:C	K199Q	1.000
12:104757339:A:G	K199E	1.000
12:104757340:A:T	K199M	1.000
12:104757341:G:C	K199N	1.000
12:104757341:G:T	K199N	1.000
12:104757343:T:C	F200S	1.000
12:104757366:T:C	F208L	1.000
12:104757368:C:A	F208L	1.000
12:104757368:C:G	F208L	1.000
12:104757382:G:A	G213D	1.000
12:104757516:C:G	H258D	1.000
12:104757517:A:G	H258R	1.000
12:104757518:C:A	H258Q	1.000
12:104757518:C:G	H258Q	1.000

dbSNP variants (sampled 300 via entrez): RS1000001426 (12:104551587 G>C), RS1000011431 (12:104697436 CT>C), RS1000012085 (12:104465062 G>A), RS1000016456 (12:104458339 A>G), RS1000030020 (12:104631078 A>T), RS1000033198 (12:104497492 C>T), RS1000044964 (12:104736802 C>A), RS1000045724 (12:104722546 G>A), RS1000056933 (12:104634151 G>A,T), RS1000071233 (12:104579039 A>G), RS1000085212 (12:104658795 A>G), RS1000087994 (12:104755321 ACT>A), RS1000095642 (12:104670549 A>G), RS1000109334 (12:104550906 C>G), RS1000111076 (12:104599512 G>A)

Disease associations

OMIM: gene MIM:610128 | disease phenotypes: MIM:618167, MIM:186000

GenCC curated gene-disease

Disease	Classification	Inheritance
osteochondrodysplasia, brachydactyly, and overlapping malformed digits	Strong	Autosomal recessive

Mondo (5): primary ovarian failure (MONDO:0005387), osteochondrodysplasia, brachydactyly, and overlapping malformed digits (MONDO:0032574), synpolydactyly type 1 (MONDO:0008513), brachydactyly (MONDO:0021004), chondrodysplasia (MONDO:0022723)

Orphanet (2): Synpolydactyly type 1 (Orphanet:295195), NON RARE IN EUROPE: Primary ovarian failure (Orphanet:619)

HPO phenotypes

22 total (22 of 22 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000767	Pectus excavatum
HP:0001049	Absent dorsal skin creases over affected joints
HP:0001156	Brachydactyly
HP:0001181	Adducted thumb
HP:0001387	Joint stiffness
HP:0001845	Overlapping toe
HP:0001852	Sandal gap
HP:0002650	Scoliosis
HP:0002829	Arthralgia
HP:0002938	Lumbar hyperlordosis
HP:0002999	Patellar dislocation
HP:0003388	Easy fatigability
HP:0003502	Mild short stature
HP:0008080	Hallux varus
HP:0009774	Triangular shaped phalanges of the hand
HP:0009778	Short thumb
HP:0009882	Short distal phalanx of finger
HP:0010055	Broad hallux
HP:0010109	Short hallux
HP:0010557	Overlapping fingers
HP:0100259	Postaxial polydactyly

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST000861_3	Cannabis dependence	8.000000e-06
GCST001762_19	Obesity-related traits	3.000000e-06
GCST002408_11	Response to methotrexate in juvenile idiopathic arthritis	4.000000e-06
GCST006585_978	Blood protein levels	3.000000e-19
GCST007006_12	Logical memory (delayed recall) in normal cognition	7.000000e-07
GCST008161_41	Waist circumference adjusted for body mass index	3.000000e-06
GCST008839_342	Height	1.000000e-08
GCST012319_11	LDL levels x SSRI levels (escitalopram or citalopram) interaction in schizophrenia or bipolar disorder	6.000000e-06
GCST012420_4	tricyclic pyrone compound response (IC50)	4.000000e-06

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004627	IGF-1 measurement
EFO:0004874	memory performance
EFO:0007789	BMI-adjusted waist circumference
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0600033	response to mitochondrial complex I inhibitor

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D059327	Brachydactyly	C05.660.585.262; C16.131.621.585.262
D016649	Primary Ovarian Insufficiency	C12.050.351.500.056.630.750; C12.100.250.056.630.750; C19.391.630.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	5
sodium arsenite	affects methylation, decreases expression, increases expression	3
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	3
potassium chromate(VI)	affects cotreatment, decreases expression	2
Estradiol	affects cotreatment, increases expression	2
Nickel	increases expression	2
Tretinoin	decreases expression, increases expression	2
FR900359	decreases reaction, increases expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1
bisphenol A	affects cotreatment, decreases methylation	1
lead acetate	increases expression	1
arsenite	affects binding, increases reaction	1
mono-(2-ethylhexyl)phthalate	increases expression	1
butyraldehyde	increases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
nickel sulfate	decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
chromium hexavalent ion	decreases expression	1
CGP 52608	affects binding, increases reaction	1
perfluoro-n-nonanoic acid	increases expression	1
2-palmitoylglycerol	increases expression	1
Bortezomib	decreases expression	1
Sunitinib	increases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Acetaminophen	increases expression	1
Calcitriol	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00417066	PHASE4	COMPLETED	Flexible GnRH Antagonist vs Flare up GnRH Agonist Protocol in Poor Responders
NCT00732693	PHASE4	COMPLETED	Evaluation of Physiologic and Standard Sex Steroid Replacement Regimens in Women With Premature Ovarian Failure
NCT00837616	PHASE4	COMPLETED	Estrogen Dosing in Turner Syndrome: Pharmacology and Metabolism
NCT01853501	PHASE4	UNKNOWN	Effects of ADSC Therapy in Women With POF
NCT02783937	PHASE4	COMPLETED	Filgrastim for Premature Ovarian Insufficiency
NCT03535480	PHASE4	UNKNOWN	Autologous Bone Marrow Stem Cell Ovarian Transplantation to Restore Ovarian Function in Premature Ovarian Failure
NCT00140998	PHASE3	COMPLETED	Estrogen Treatment (Oral vs. Patches) in Turner Syndrome
NCT00001951	PHASE2	COMPLETED	Hormone Replacement in Young Women With Premature Ovarian Failure
NCT00370019	PHASE2	WITHDRAWN	Effects of an Estrogen Replacement Therapy Skin Patch on Ovulation in Women With Premature Ovarian Failure
NCT00429494	PHASE2	COMPLETED	GnRH Analogue for Ovarian Function Preservation in Hematopoietic Stem Cell Transplantation Patients
NCT03816852	PHASE2	SUSPENDED	The Safety and Efficiency Study of Mesenchymal Stem Cell (19#iSCLife®-POI) in Premature Ovarian Insufficiency
NCT04536467	PHASE2	UNKNOWN	Prevention of Chemotherapy-Induced Ovarian Failure With Goserelin in Premenopausal Lymphoma Patients
NCT06117982	PHASE2	COMPLETED	The Impact of Granulocyte Colony Stimulating Factor on Premature Ovarian Insufficiency
NCT02912104	PHASE1	COMPLETED	A Therapeutic Trial of Human Amniotic Epithelial Cells Transplantation for Primary Ovarian Failure
NCT03178695	PHASE1	COMPLETED	Inovium Ovarian Rejuvenation Trials
NCT04815213	PHASE1	ACTIVE_NOT_RECRUITING	The Use of Expandeded Mesenchymal Stromal Cells (MSC) in Premature Ovarian Failure (POF) in Adult Humans
NCT05138367	PHASE1	COMPLETED	Effects of UCA-PSCs in Women With POF
NCT06132542	PHASE1	UNKNOWN	Autologous ADMSC Transplantation in Patients With POI
NCT00948857	PHASE2/PHASE3	TERMINATED	Dehydroepiandrosterone (DHEA) Treatment and Premature Ovarian Failure (POF)
NCT04031456	PHASE2/PHASE3	RECRUITING	Autologous PRP Infusion May Restore Ovarian Function and May Promote Folliculogenesis in POI Patients
NCT02043743	PHASE1/PHASE2	UNKNOWN	Autologous Stem Cells Transplantation in Patients With Idiopathic and Drug Induced Premature Ovarian Failure
NCT02062931	PHASE1/PHASE2	UNKNOWN	Autologous Mesenchymal Stem Cells Transplantation In Women With Premature Ovarian Failure
NCT02151890	PHASE1/PHASE2	COMPLETED	Pregnancy After Stem Cell Transplantation in Premature Ovarian Failure
NCT02372474	PHASE1/PHASE2	COMPLETED	It is a Real The First Baby Of Autologous Stem Cell Therapy in Premature Ovarian Failure
NCT02603744	PHASE1/PHASE2	UNKNOWN	Autologous Adipose Derived Mesenchymal Stromal Cells Transplantation in Women With Premature Ovarian Failure (POF)
NCT02644447	PHASE1/PHASE2	COMPLETED	Transplantation of HUC-MSCs With Injectable Collagen Scaffold for POF
NCT03069209	PHASE1/PHASE2	UNKNOWN	Autologous Bone Marrow-Derived Stem Cell Transplantation in Patients With Premature Ovarian Failure (POF)
NCT03985462	PHASE1/PHASE2	WITHDRAWN	Very Small Embryonic-like Stem Cells for Ovary
NCT04009473	PHASE1/PHASE2	UNKNOWN	Stem Cell Therapy and Growth Factor Ovarian in Vitro Activation
NCT04071574	PHASE1/PHASE2	COMPLETED	Comparative Study on the Efficacy of Ovarian Stimulation Protocols on the Success Rate of ICSI in Female Infertility
NCT04922398	PHASE1/PHASE2	UNKNOWN	Ovarian Injection of PRP (Platelet -Rich Plasma) Vs Normal Saline in Premature Ovarian Insufficiency
NCT05462379	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Autologous Heterotopic Fresh Ovarian Graft in Woman With LACC Eligible for Pelvic Radiotherapy Treatment.
NCT06202547	PHASE1/PHASE2	UNKNOWN	Intra-ovarian Injection of MSC-EVs in Idiopathic Premature Ovarian Failure
NCT01129947	EARLY_PHASE1	WITHDRAWN	The Use of DHEA in Women With Premature Ovarian Failure
NCT05522634	EARLY_PHASE1	UNKNOWN	A Clinical Study of Chinese Herbal Compound TJAOA101 in the Treatment of Premature Ovarian Insufficiency
NCT07308327	EARLY_PHASE1	ACTIVE_NOT_RECRUITING	The Influence of Gut Microbiota on Ovarian Function: A Single-center, Randomized,Double Blind, Parallel-controlled, Exploratory Clinical Trial
NCT00001275	Not specified	COMPLETED	Ovarian Follicle Function in Patients With Primary Ovarian Failure
NCT00001306	Not specified	COMPLETED	Steroid Therapy in Autoimmune Premature Ovarian Failure
NCT00006156	Not specified	COMPLETED	Feasibility Study for Development of an Early Test for Ovarian Failure
NCT00119925	Not specified	UNKNOWN	‘SPRING’-Study: Subfertility Guidelines: Patient Related Implementation in the Netherlands Among Gynaecologists