BUD23

Summary

BUD23 (BUD23 rRNA methyltransferase and ribosome maturation factor, HGNC:16405) is a protein-coding gene on chromosome 7q11.23, encoding 18S rRNA (guanine-N(7))-methyltransferase (O43709). S-adenosyl-L-methionine-dependent methyltransferase that specifically methylates the N(7) position of a guanine in 18S rRNA. It is a common-essential gene (DepMap: required in 99.9% of cancer cell lines).

This gene encodes a protein containing a nuclear localization signal and an S-adenosyl-L-methionine binding motif typical of methyltransferases, suggesting that the encoded protein may act on DNA methylation. This gene is deleted in Williams syndrome, a multisystem developmental disorder caused by the deletion of contiguous genes at 7q11.23. Alternatively spliced transcript variants have been found.

Source: NCBI Gene 114049 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 91 total — 1 pathogenic
• Phenotypes (HPO): 186
• Cancer dependency (DepMap): dependent in 99.9% of screened cell lines (common-essential)
• MANE Select transcript: NM_017528

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16405
Approved symbol	BUD23
Name	BUD23 rRNA methyltransferase and ribosome maturation factor
Location	7q11.23
Locus type	gene with protein product
Status	Approved
Aliases	MGC19709, MGC2022, MGC5140, PP3381, WBMT, MERM1
Ensembl gene	ENSG00000071462
Ensembl biotype	protein_coding
OMIM	615733
Entrez	114049

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 12 protein_coding

ENST00000265758, ENST00000855996, ENST00000855997, ENST00000855998, ENST00000855999, ENST00000917796, ENST00000917797, ENST00000917798, ENST00000917799, ENST00000917800, ENST00000917801, ENST00000917802

RefSeq mRNA: 2 — MANE Select: NM_017528 NM_001202560, NM_017528

CCDS: CCDS5557, CCDS56490

Canonical transcript exons

ENST00000265758 — 12 exons

Exon	Start	End
ENSE00001601031	73697832	73698212
ENSE00002293483	73683597	73683673
ENSE00003484109	73693992	73694050
ENSE00003504374	73693329	73693414
ENSE00003527587	73697605	73697694
ENSE00003531862	73686818	73686900
ENSE00003591178	73690916	73691012
ENSE00003640086	73693624	73693669
ENSE00003653794	73683767	73683804
ENSE00003754797	73686636	73686731
ENSE00003788140	73692596	73692646
ENSE00003790136	73686999	73687095

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 98.92.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 58.6286 / max 414.1190, expressed in 1823 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
79013	58.5789	1823
79015	0.0497	21

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right testis	UBERON:0004534	98.92	gold quality
left testis	UBERON:0004533	98.75	gold quality
testis	UBERON:0000473	97.74	gold quality
islet of Langerhans	UBERON:0000006	97.65	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	97.14	gold quality
gastrocnemius	UBERON:0001388	97.06	gold quality
apex of heart	UBERON:0002098	96.79	gold quality
muscle of leg	UBERON:0001383	96.72	gold quality
oocyte	CL:0000023	96.66	gold quality
right uterine tube	UBERON:0001302	96.22	gold quality
heart left ventricle	UBERON:0002084	95.92	gold quality
hindlimb stylopod muscle	UBERON:0004252	95.91	gold quality
right atrium auricular region	UBERON:0006631	95.90	gold quality
body of tongue	UBERON:0011876	95.84	gold quality
cardiac ventricle	UBERON:0002082	95.82	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	95.78	gold quality
adenohypophysis	UBERON:0002196	95.69	gold quality
stromal cell of endometrium	CL:0002255	95.60	gold quality
trachea	UBERON:0003126	95.54	gold quality
endocervix	UBERON:0000458	95.44	gold quality
pituitary gland	UBERON:0000007	95.40	gold quality
metanephros cortex	UBERON:0010533	95.38	gold quality
superior surface of tongue	UBERON:0007371	95.35	gold quality
left lobe of thyroid gland	UBERON:0001120	95.29	gold quality
right ovary	UBERON:0002118	95.28	gold quality
pancreas	UBERON:0001264	95.26	gold quality
nipple	UBERON:0002030	95.26	gold quality
rectum	UBERON:0001052	95.25	gold quality
left adrenal gland	UBERON:0001234	95.25	gold quality
left ovary	UBERON:0002119	95.24	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-GEOD-134144	yes	28.96
E-CURD-112	yes	13.11
E-CURD-53	no	854.31
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

21 targeting BUD23, 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-6778-3P	99.96	67.29	2693
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-153-5P	99.89	73.86	6317
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-526B-3P	99.88	74.06	2587
HSA-MIR-93-5P	99.88	73.98	2606
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-3158-5P	99.65	67.51	1763
HSA-MIR-6749-3P	99.00	65.73	1443
HSA-MIR-2467-3P	98.65	67.18	1969
HSA-MIR-4308	97.56	67.13	1385
HSA-MIR-509-3-5P	97.21	67.74	1517
HSA-MIR-509-5P	97.21	67.90	1512
HSA-MIR-4418	97.04	67.16	1372

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.9% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 12)

• Characterization of two novel genes, WBSCR20 and WBSCR22, deleted in Williams-Beuren syndrome (PMID:11978965)
• WBSCR22 protein level is decreased in lymphoblastoid cell lines. (PMID:24086612)
• Merm1 is a novel regulator of chromatin structure affecting GR recruitment and function (PMID:24488492)
• Knockdown of Merm1/Wbscr22 attenuates sensitivity of H460 non-small cell lung cancer cells to SN-38 and 5-FU without alteration to p53 expression levels. (PMID:25352209)
• The key role of WBSCR22 in 40S subunit biogenesis is independent of its function as an RNA methyltransferase. (PMID:25525153)
• DIMT1L and WBSCR22-TRMT112 are required for distinct pre-rRNA processing reactions leading to synthesis of 18S rRNA. Ribosome biogenesis requires the presence of the modification enzyme rather than its RNA-modifying catalytic activity. (PMID:25851604)
• The localization of the TRMT112 protein is determined by WBSCR22, and the WBSCR22-TRMT112 complex is localized in the cell nucleus. (PMID:26214185)
• Study results demonstrated that WBSCR22 is involved in colorectal cancer (CRC) resistance to oxaliplatin, suggesting WBSCR22 may represent a novel oxaliplatin resistance biomarker as well as a potential target for CRC therapeutics. (PMID:29133897)
• Merm1 is capable of maintaining hypomethylated rRNA gene bodies and co-localizes with RNA polymerase I in the nucleolus. Merm1 interacts with Dnmt3a and represses its methyltransferase activity with the requirement of the binding motif for S-adenosyl-L-methionine. (PMID:30535232)
• Cardiac mitochondrial function depends on BUD23 mediated ribosome programming. (PMID:31939735)
• WBSCR22 confers cell survival and predicts poor prognosis in glioma. (PMID:32380188)
• WBSCR22 and TRMT112 synergistically suppress cell proliferation, invasion and tumorigenesis in pancreatic cancer via transcriptional regulation of ISG15. (PMID:35088887)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	bud23	ENSDARG00000063596
mus_musculus	Bud23	ENSMUSG00000005378
rattus_norvegicus	Bud23	ENSRNOG00000033700
drosophila_melanogaster	CG10903	FBGN0037543
caenorhabditis_elegans		WBGENE00016166

Protein

Protein identifiers

18S rRNA (guanine-N(7))-methyltransferase — O43709 (reviewed: O43709)

Alternative names: Bud site selection protein 23 homolog, Metastasis-related methyltransferase 1, Williams-Beuren syndrome chromosomal region 22 protein, rRNA methyltransferase and ribosome maturation factor

All UniProt accessions (1): O43709

UniProt curated annotations — full annotation on UniProt →

Function. S-adenosyl-L-methionine-dependent methyltransferase that specifically methylates the N(7) position of a guanine in 18S rRNA. Requires the methyltransferase adapter protein TRM112 for full rRNA methyltransferase activity. Involved in the pre-rRNA processing steps leading to small-subunit rRNA production independently of its RNA-modifying catalytic activity. Important for biogenesis end export of the 40S ribosomal subunit independent on its methyltransferase activity. Locus-specific steroid receptor coactivator. Potentiates transactivation by glucocorticoid (NR3C1), mineralocorticoid (NR3C2), androgen (AR) and progesterone (PGR) receptors. Required for the maintenance of open chromatin at the TSC22D3/GILZ locus to facilitate NR3C1 loading on the response elements. Required for maintenance of dimethylation on histone H3 ‘Lys-79’ (H3K79me2), although direct histone methyltransferase activity is not observed in vitro.

Subunit / interactions. Heterodimer with TRMT112; this heterodimerization is necessary for the metabolic stability and activity of the catalytic subunit BUD23. Interacts with GRIP1.

Subcellular location. Nucleus. Nucleoplasm. Cytoplasm. Perinuclear region.

Tissue specificity. Widely expressed, with high levels in heart, skeletal muscle and kidney. Detected at high levels in bronchial brushings and in normal lung (at protein level). In fetal lung tissue, expressed in the developing bronchial lumen lining cells (at protein level). Tends to be down-regulated in lungs affected by inflammatory diseases or neoplasia (at protein level). Expressed in immune cells, including B and T lymphocytes and macrophages.

Post-translational modifications. May be ubiquitinated and targeted to degradation in response to pro-inflammatory cytokine signaling.

Disease relevance. BUD23 is located in the Williams-Beuren syndrome (WBS) critical region. WBS results from a hemizygous deletion of several genes on chromosome 7q11.23, thought to arise as a consequence of unequal crossing over between highly homologous low-copy repeat sequences flanking the deleted region. Haploinsufficiency of BUD23 may be the cause of certain cardiovascular and musculo-skeletal abnormalities observed in the disease.

Induction. Up-regulated in CD8+ T lymphocytes by treatment with anti-CD3 and in B lymphocytes by treatment with CD40 ligand and anti-B cell receptor antibody. In macrophages, no induction following LPS treatment. Down-regulated by a combined treatment with TNF and IFNG (at protein level).

Similarity. Belongs to the class I-like SAM-binding methyltransferase superfamily. BUD23/WBSCR22 family.

Isoforms (3)

UniProt ID	Names	Canonical?
O43709-1	1	yes
O43709-2	2
O43709-3	3

RefSeq proteins (2): NP_001189489, NP_059998* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013216	Methyltransf_11	Domain
IPR022238	Bud23_C	Domain
IPR029063	SAM-dependent_MTases_sf	Homologous_superfamily
IPR039769	Bud23-like	Family

Pfam: PF08241, PF12589

Enzyme classification (BRENDA):

• EC 2.1.1.309 — 18S rRNA (guanine1575-N7)-methyltransferase (BRENDA: 3 organisms, 10 substrates, 0 inhibitors, 0 Km, 0 kcat entries)

Catalyzed reactions (Rhea), 1 shown:

• a guanosine in 18S rRNA + S-adenosyl-L-methionine = an N(7)-methylguanosine in 18S rRNA + S-adenosyl-L-homocysteine (RHEA:54584)

UniProt features (29 total): helix 10, strand 9, turn 3, splice variant 2, mutagenesis site 2, chain 1, region of interest 1, modified residue 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
7WTU	ELECTRON MICROSCOPY	3
7WTT	ELECTRON MICROSCOPY	3.1
7WTS	ELECTRON MICROSCOPY	3.2
7WTW	ELECTRON MICROSCOPY	3.2
7WTV	ELECTRON MICROSCOPY	3.5
6G4W	ELECTRON MICROSCOPY	4.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O43709-F1	87.37	0.63

Functional residue map

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

Post-translational modifications (1): 240

Mutagenesis-validated functional residues (2):

Position	Phenotype
180	resistant to down-regulation in response to tnf and ifng combined treatment and effective coactivator for nr3c1, even in
196	resistant to down-regulation in response to tnf and ifng combined treatment and effective coactivator for nr3c1, even in

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-6790901	rRNA modification in the nucleus and cytosol
R-HSA-6791226	Major pathway of rRNA processing in the nucleolus and cytosol
R-HSA-72312	rRNA processing
R-HSA-8868773	rRNA processing in the nucleus and cytosol
R-HSA-8953854	Metabolism of RNA

MSigDB gene sets: 547 (showing top): GOBP_RIBOSOME_BIOGENESIS, SHEPARD_CRASH_AND_BURN_MUTANT_UP, DACOSTA_UV_RESPONSE_VIA_ERCC3_UP, GOBP_RNA_METHYLATION, KEGG_HISTIDINE_METABOLISM, GOBP_RNA_MODIFICATION, HEN1_01, CAR_MYST2, CAR_MLANA, MODULE_98, chr7q11, GOBP_RRNA_MODIFICATION, DACOSTA_UV_RESPONSE_VIA_ERCC3_TTD_UP, GOBP_METHYLATION, GOBP_RIBONUCLEOPROTEIN_COMPLEX_BIOGENESIS

GO Biological Process (6): chromatin organization (GO:0006325), rRNA (guanine-N7)-methylation (GO:0070476), positive regulation of rRNA processing (GO:2000234), rRNA processing (GO:0006364), methylation (GO:0032259), ribosome biogenesis (GO:0042254)

GO Molecular Function (7): RNA binding (GO:0003723), methyltransferase activity (GO:0008168), rRNA (guanine) methyltransferase activity (GO:0016435), protein heterodimerization activity (GO:0046982), protein binding (GO:0005515), S-adenosylmethionine-dependent methyltransferase activity (GO:0008757), transferase activity (GO:0016740)

GO Cellular Component (5): nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), perinuclear region of cytoplasm (GO:0048471), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
rRNA processing in the nucleus and cytosol	2
Metabolism of RNA	1
rRNA processing	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
nuclear lumen	2
cellular component organization	1
RNA (guanine-N7)-methylation	1
rRNA base methylation	1
rRNA processing	1
positive regulation of RNA metabolic process	1
regulation of rRNA processing	1
RNA processing	1
rRNA metabolic process	1
ribosome biogenesis	1
metabolic process	1
ribonucleoprotein complex biogenesis	1
nucleic acid binding	1
transferase activity, transferring one-carbon groups	1
rRNA methyltransferase activity	1
protein dimerization activity	1
binding	1
methyltransferase activity	1
catalytic activity	1
intracellular membrane-bounded organelle	1
intracellular membraneless organelle	1
cytoplasm	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

2192 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BUD23	TRMT112	Q9UI30	970
BUD23	TRMT11	Q7Z4G4	794
BUD23	HEMK2	Q9Y5N5	777
BUD23	ALKBH8	Q96BT7	737
BUD23	EMG1	Q92979	731
BUD23	TYW2	Q53H54	730
BUD23	WDR4	P57081	718
BUD23	METTL1	Q9UBP6	713
BUD23	NSUN5	Q96P11	708
BUD23	NOP2	P46087	637
BUD23	RRP8	O43159	627
BUD23	TRMT61A	Q96FX7	625
BUD23	METTL5	Q9NRN9	624
BUD23	DHX37	Q8IY37	613
BUD23	UTP14A	Q9BVJ6	609

IntAct

44 interactions, top by confidence:

A	B	Type	Score
TRMT112	BUD23	psi-mi:“MI:0915”(physical association)	0.910
BUD23	TRMT112	psi-mi:“MI:0915”(physical association)	0.910
TRMT112	BUD23	psi-mi:“MI:0914”(association)	0.910
BUD23	TRMT112	psi-mi:“MI:0403”(colocalization)	0.910
BUD23	UBE2O	psi-mi:“MI:0914”(association)	0.730
N	RBM47	psi-mi:“MI:0914”(association)	0.530
BUD23	OAS1	psi-mi:“MI:0915”(physical association)	0.370
BUD23	PKN1	psi-mi:“MI:0915”(physical association)	0.370
VCP	BUD23	psi-mi:“MI:0915”(physical association)	0.370
Rpl35	RPS6	psi-mi:“MI:0914”(association)	0.350
NPM1	RPSA	psi-mi:“MI:0914”(association)	0.350
ORF57	GTPBP1	psi-mi:“MI:0914”(association)	0.350
CUL3	PXDNL	psi-mi:“MI:0914”(association)	0.350
BUD23	H2AC21	psi-mi:“MI:0914”(association)	0.350
P/V/C	PLRG1	psi-mi:“MI:0914”(association)	0.350
N	RBM47	psi-mi:“MI:0914”(association)	0.350
KLF16		psi-mi:“MI:0914”(association)	0.350
KLF8		psi-mi:“MI:0914”(association)	0.350
BUD23	NOP14	psi-mi:“MI:0914”(association)	0.350

BioGRID (82): TRMT112 (Affinity Capture-MS), UBE2O (Affinity Capture-MS), HIST2H2AB (Affinity Capture-MS), WBSCR22 (Affinity Capture-MS), FEN1 (Co-fractionation), KIF2A (Co-fractionation), NMD3 (Co-fractionation), WBSCR22 (Affinity Capture-MS), WBSCR22 (Affinity Capture-MS), WBSCR22 (Affinity Capture-MS), TRMT112 (Affinity Capture-MS), TRMT112 (Affinity Capture-MS), UBE2O (Affinity Capture-MS), HIST2H2AB (Affinity Capture-MS), WBSCR22 (Affinity Capture-MS)

ESM2 similar proteins: A0A5F8AH41, A1A4L5, A2AV36, A5WVX1, A8E7D2, B3DLB3, C0IN03, D4ABH7, D9IVE5, O43709, P0C5J1, P0DPD7, P0DPE0, P0DPE1, P10937, P10938, P11086, P40935, Q06AU9, Q07G10, Q29S19, Q32PY6, Q3T0H0, Q3UY23, Q3UZW7, Q501S4, Q5M8E6, Q5RFI3, Q6NTR1, Q6P4Z6, Q6PCI6, Q7T0L7, Q7Z5W3, Q7ZVS8, Q80Y20, Q80Y81, Q8BMK1, Q8BWQ4, Q8CAE2, Q8CGS5

Diamond homologs: A0A075D5I4, A0A075D654, A0A075D657, A0A075D6M1, A0A0E0SMA3, A0A1C9U5X5, A0A1C9U5X7, A0A1D6NER6, A0A8X8M4T9, A0A8X8M4W6, A0A8X8M501, A0A8X8M505, A0L0G4, A1RGE6, A1S382, A3D0Y0, A4Y9Y4, A5U866, A6WS34, A8H8Q9, A9L1I5, B0RS27, B0TUZ2, B1W525, B2SHS9, B8E5Q5, B8H209, C3SBS8, C3SBW0, C8YTM5, G0FUS0, H2E7T5, H2E7T6, L7IP31, O13871, O43709, P0A9H7, P0A9H8, P0CT10, P31049

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
BUD23	“form complex”	“BUD23-TRM112 methyltransferase complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 35 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Major pathway of rRNA processing in the nucleolus and cytosol	6	16.8×	2e-04
Metabolism of RNA	5	9.5×	2e-03
Viral Infection Pathways	5	7.0×	5e-03
Infectious disease	5	5.6×	9e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	48
Likely benign	3
Benign	1

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1703587	GRCh37/hg19 7q11.23(chr7:72589195-74225562)	Pathogenic

SpliceAI

1733 predictions. Top by Δscore:

Variant	Effect	Δscore
7:73683669:AGCTG:A	donor_gain	1.0000
7:73683670:GCTG:G	donor_gain	1.0000
7:73683670:GCTGG:G	donor_gain	1.0000
7:73683671:CTGG:C	donor_loss	1.0000
7:73683672:TGGTA:T	donor_loss	1.0000
7:73683673:GGT:G	donor_loss	1.0000
7:73683674:G:GG	donor_gain	1.0000
7:73683675:TAAGT:T	donor_loss	1.0000
7:73686571:T:TA	acceptor_gain	1.0000
7:73686625:T:A	acceptor_gain	1.0000
7:73686634:A:AG	acceptor_gain	1.0000
7:73686635:G:GA	acceptor_gain	1.0000
7:73686730:GG:G	donor_gain	1.0000
7:73686731:GG:G	donor_gain	1.0000
7:73686816:A:AG	acceptor_gain	1.0000
7:73686817:G:GG	acceptor_gain	1.0000
7:73686817:GCT:G	acceptor_gain	1.0000
7:73686817:GCTGT:G	acceptor_gain	1.0000
7:73691013:G:GG	donor_gain	1.0000
7:73692590:TTTCA:T	acceptor_loss	1.0000
7:73692591:TTCAG:T	acceptor_loss	1.0000
7:73692592:TCAG:T	acceptor_loss	1.0000
7:73692593:CAGG:C	acceptor_loss	1.0000
7:73692594:A:AG	acceptor_gain	1.0000
7:73692594:AGGT:A	acceptor_loss	1.0000
7:73692595:G:GG	acceptor_gain	1.0000
7:73692595:GGTCC:G	acceptor_gain	1.0000
7:73692644:CAGGT:C	donor_loss	1.0000
7:73692646:GGTG:G	donor_loss	1.0000
7:73692648:T:A	donor_loss	1.0000

AlphaMissense

1821 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:73693366:T:C	F183S	0.999
7:73687094:A:C	S121R	0.998
7:73690916:C:A	S121R	0.998
7:73690916:C:G	S121R	0.998
7:73690932:T:A	W127R	0.998
7:73690932:T:C	W127R	0.998
7:73693350:G:C	A178P	0.998
7:73693351:C:A	A178D	0.998
7:73690934:G:C	W127C	0.997
7:73690934:G:T	W127C	0.997
7:73693365:T:C	F183L	0.997
7:73693367:C:A	F183L	0.997
7:73693367:C:G	F183L	0.997
7:73686885:A:C	S84R	0.996
7:73686887:C:A	S84R	0.996
7:73686887:C:G	S84R	0.996
7:73687090:C:G	C119W	0.996
7:73686834:A:C	S67R	0.995
7:73686836:T:A	S67R	0.995
7:73686836:T:G	S67R	0.995
7:73687088:T:C	C119R	0.995
7:73690924:C:A	A124D	0.994
7:73692612:C:A	A159D	0.994
7:73686686:T:C	L46P	0.993
7:73687086:G:A	G118D	0.993
7:73690920:T:C	S123P	0.993
7:73690936:T:C	L128P	0.993
7:73692615:T:A	V160D	0.993
7:73693359:G:C	A181P	0.993
7:73686823:G:T	G63V	0.992

dbSNP variants (sampled 300 via entrez): RS1000360227 (7:73695715 T>A), RS1000844855 (7:73690667 G>A,C), RS1001091525 (7:73696896 C>T), RS1001172826 (7:73692131 C>T), RS1001220 (7:73696273 C>T), RS1001364949 (7:73697324 G>A), RS1001446592 (7:73684536 C>A,G), RS1001737875 (7:73685874 C>T), RS1002363690 (7:73697869 C>T), RS1002819584 (7:73698083 G>C), RS1002896981 (7:73693972 G>A), RS1003180306 (7:73695102 C>T), RS1003232588 (7:73695397 G>A), RS1003389245 (7:73689096 C>A), RS1003464839 (7:73687751 C>G,T)

Disease associations

OMIM: gene MIM:615733 | disease phenotypes: MIM:194050

GenCC curated gene-disease

Mondo (1): Williams syndrome (MONDO:0008678)

Orphanet (1): Williams syndrome (Orphanet:904)

HPO phenotypes

186 total (30 of 186 shown, HPO-id order):

HPO	Term
HP:0000010	Recurrent urinary tract infections
HP:0000014	Abnormality of the bladder
HP:0000015	Bladder diverticulum
HP:0000023	Inguinal hernia
HP:0000025	Functional abnormality of male internal genitalia
HP:0000028	Cryptorchidism
HP:0000044	Hypogonadotropic hypogonadism
HP:0000075	Renal duplication
HP:0000076	Vesicoureteral reflux
HP:0000083	Renal insufficiency
HP:0000089	Renal hypoplasia
HP:0000093	Proteinuria
HP:0000121	Nephrocalcinosis
HP:0000125	Pelvic kidney
HP:0000147	Polycystic ovaries
HP:0000154	Wide mouth
HP:0000158	Macroglossia
HP:0000179	Thick lower lip vermilion
HP:0000212	Gingival overgrowth
HP:0000232	Everted lower lip vermilion
HP:0000252	Microcephaly
HP:0000275	Narrow face
HP:0000280	Coarse facial features
HP:0000286	Epicanthus
HP:0000307	Pointed chin
HP:0000337	Broad forehead
HP:0000343	Long philtrum
HP:0000347	Micrognathia
HP:0000348	High forehead
HP:0000358	Posteriorly rotated ears

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST010725_13	Malaria	8.000000e-06
GCST010725_74	Malaria	6.000000e-06
GCST010725_91	Malaria	7.000000e-06
GCST90020026_592	Hip index	1.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0008039	BMI-adjusted hip circumference

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D018980	Williams Syndrome	C10.597.606.360.970; C14.280.484.048.750.535.960; C16.131.260.970; C16.320.180.970

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases abundance, increases expression, affects binding, increases reaction, decreases expression (+1 more)	3
Hydrogen Peroxide	affects expression	2
Cyclosporine	increases expression	2
Aflatoxin B1	increases methylation	2
aristolochic acid I	increases expression	1
bisphenol A	decreases expression	1
beta-lapachone	increases expression	1
arsenite	affects binding, increases reaction	1
cobaltous chloride	decreases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
benzo(e)pyrene	increases methylation	1
corosolic acid	decreases expression	1
Decitabine	decreases expression, decreases reaction	1
Acetaminophen	increases expression	1
Ethanol	affects cotreatment, increases abundance, increases expression	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Atrazine	decreases expression	1
Diazinon	increases methylation	1
Diethylstilbestrol	decreases expression	1
Gasoline	affects cotreatment, increases abundance, increases expression	1
Manganese	affects cotreatment, increases abundance, increases expression	1
Methapyrilene	increases methylation	1
Polycyclic Aromatic Hydrocarbons	increases expression, affects cotreatment, increases abundance	1
Ribonucleotides	affects binding	1
Smoke	decreases expression	1
T-2 Toxin	increases expression	1
Thiram	increases expression	1
Valproic Acid	increases expression	1
Antirheumatic Agents	decreases expression	1
Okadaic Acid	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00768820	PHASE4	RECRUITING	The Psychiatric and Cognitive Phenotypes in Velocardiofacial Syndrome
NCT04807517	PHASE4	COMPLETED	Buspirone Treatment of Anxiety in Williams Syndrome
NCT00876200	PHASE2	COMPLETED	Efficacy of Minoxidil in Children With Williams-Beuren Syndrome
NCT06087757	PHASE2	ACTIVE_NOT_RECRUITING	Clemastine Treatment in Individuals With Williams Syndrome
NCT06315699	PHASE2	COMPLETED	Clemastine Fumarate in the Treatment of Neurodevelopmental Delays in Williams Syndrome
NCT00004351	Not specified	COMPLETED	Study of Phenotype and Genotype Correlations in Patients With Contiguous Gene Deletion Syndromes
NCT00013962	Not specified	COMPLETED	Vitamin D Metabolism and the Williams Syndrome
NCT01132885	Not specified	RECRUITING	Defining the Brain Phenotype of Children With Williams Syndrome
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
NCT01864304	Not specified	COMPLETED	Fat Distribution and Glucose Metabolism in Williams Syndrome
NCT02212314	Not specified	COMPLETED	Response Inhibition Training for Children With Williams Syndrome
NCT02692846	Not specified	COMPLETED	WS-SAVE Study (Williams Syndrome Skin and Vessel Elasticity Study)
NCT02706639	Not specified	COMPLETED	Williams Syndrome (WS) and Supravalvar Aortic Stenosis (SVAS) DNA and Tissue Bank
NCT02840448	Not specified	COMPLETED	Impact of Elastin Mediated Vascular Stiffness on End Organs
NCT03758651	Not specified	COMPLETED	Williams Syndrome Strength, Hormones, Activity & Adiposity, DNA Programming, Eating Study
NCT03827525	Not specified	UNKNOWN	Cognitive and Behavioral Therapy of Anxiety in Williams Syndrome
NCT03836300	Not specified	ENROLLING_BY_INVITATION	Parent and Infant Inter(X)Action Intervention (PIXI)
NCT04051086	Not specified	UNKNOWN	Quantification of Elastin Markers Synthesis in Williams-Beuren Syndrome and 7q11.23 Micro-duplication Syndrome
NCT04095585	Not specified	COMPLETED	Molecular Characterization of Patients Affected by Williams Syndrome and Autism.
NCT04463316	Not specified	RECRUITING	GROWing Up With Rare GENEtic Syndromes
NCT04610424	Not specified	UNKNOWN	Cooperative Parent Mediated Therapy in Children With Fragile X Syndrome and Williams Syndrome
NCT05430763	Not specified	WITHDRAWN	Motor Deficits and Signal Conduction in Individuals With Williams Syndrome
NCT06740162	Not specified	RECRUITING	Physical Activity and Community EmPOWERment Project
NCT06930417	Not specified	RECRUITING	Characterization and Natural History of Williams Syndrome and Other Chromosome 7q11.23 Variants
NCT07285720	Not specified	RECRUITING	Phonological Constraints on Language Development in Individuals With Williams Syndrome
NCT07493096	Not specified	RECRUITING	Intensive Multimodal Neurorehabilitation Targeting Neuroplasticity in Pediatric Neurodevelopmental and Chromosomal Disorders
NCT07509879	Not specified	NOT_YET_RECRUITING	Research on the Molecular Mechanism of Cognitive Differences Between Williams Syndrome and Autism Spectrum Disorder
NCT07537374	Not specified	NOT_YET_RECRUITING	A Case-Control Observational Study of Peripheral Blood-Derived iPSC Models to Investigate Oligodendrocyte Lineage Development in Children With Williams Syndrome and Healthy Controls