BUD13

Summary

BUD13 (BUD13 spliceosome associated protein, HGNC:28199) is a protein-coding gene on chromosome 11q23.3, encoding BUD13 homolog (Q9BRD0). Involved in pre-mRNA splicing as component of the activated spliceosome. It is a selective cancer dependency (DepMap: 74.3% of cell lines).

Enables RNA binding activity. Involved in mRNA splicing, via spliceosome. Located in nucleoplasm. Part of U2-type precatalytic spliceosome.

Source: NCBI Gene 84811 — RefSeq curated summary.

At a glance

• Gene–disease (curated): achalasia-progeroid syndrome (Moderate, GenCC) — +1 more curated relationship
• GWAS associations: 112
• Clinical variants (ClinVar): 135 total — 1 pathogenic
• Phenotypes (HPO): 29
• Cancer dependency (DepMap): dependent in 74.3% of screened cell lines
• MANE Select transcript: NM_032725

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28199
Approved symbol	BUD13
Name	BUD13 spliceosome associated protein
Location	11q23.3
Locus type	gene with protein product
Status	Approved
Aliases	MGC13125, fSAP71, Cwc26
Ensembl gene	ENSG00000137656
Ensembl biotype	protein_coding
OMIM	620691
Entrez	84811

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 4 protein_coding, 1 nonsense_mediated_decay

ENST00000260210, ENST00000375445, ENST00000419189, ENST00000911264, ENST00000952479

RefSeq mRNA: 2 — MANE Select: NM_032725 NM_001159736, NM_032725

CCDS: CCDS53712, CCDS8374

Canonical transcript exons

ENST00000260210 — 10 exons

Exon	Start	End
ENSE00000930675	116770129	116770222
ENSE00000930676	116765362	116765446
ENSE00000930677	116762553	116763266
ENSE00000930678	116760735	116760952
ENSE00000930679	116759074	116759179
ENSE00000930680	116758269	116758407
ENSE00000930681	116757766	116757950
ENSE00001944245	116772822	116772987
ENSE00003467669	116757146	116757227
ENSE00003848521	116748173	116748575

Expression profiles

Bgee: expression breadth ubiquitous, 246 present calls, max score 95.08.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 16.6140 / max 163.9584, expressed in 1804 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
122419	16.6140	1804

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	95.08	gold quality
oocyte	CL:0000023	93.80	gold quality
tendon of biceps brachii	UBERON:0008188	90.06	gold quality
upper arm skin	UBERON:0004263	87.85	silver quality
embryo	UBERON:0000922	87.62	gold quality
ganglionic eminence	UBERON:0004023	87.62	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.51	gold quality
ventricular zone	UBERON:0003053	87.40	gold quality
mucosa of transverse colon	UBERON:0004991	86.83	gold quality
granulocyte	CL:0000094	86.21	gold quality
tendon	UBERON:0000043	86.05	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.92	gold quality
left testis	UBERON:0004533	85.67	gold quality
right testis	UBERON:0004534	85.47	gold quality
testis	UBERON:0000473	85.22	gold quality
thymus	UBERON:0002370	84.93	gold quality
lymph node	UBERON:0000029	84.17	gold quality
cartilage tissue	UBERON:0002418	84.00	gold quality
smooth muscle tissue	UBERON:0001135	83.99	gold quality
body of uterus	UBERON:0009853	83.92	gold quality
left ovary	UBERON:0002119	83.77	gold quality
muscle layer of sigmoid colon	UBERON:0035805	83.72	gold quality
lower esophagus mucosa	UBERON:0035834	83.70	gold quality
rectum	UBERON:0001052	83.65	gold quality
calcaneal tendon	UBERON:0003701	83.65	gold quality
medial globus pallidus	UBERON:0002477	83.59	gold quality
spleen	UBERON:0002106	83.51	gold quality
esophagus squamous epithelium	UBERON:0006920	83.38	gold quality
right lung	UBERON:0002167	83.34	gold quality
islet of Langerhans	UBERON:0000006	83.33	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.88

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

13 targeting BUD13, 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-3162-3P	100.00	65.37	363
HSA-MIR-6753-3P	99.93	66.57	637
HSA-MIR-7107-3P	99.93	66.73	627
HSA-MIR-7159-5P	99.53	72.12	2472
HSA-MIR-516A-3P	99.46	67.96	1378
HSA-MIR-516B-3P	99.46	67.96	1378
HSA-MIR-7162-5P	99.46	68.08	1368
HSA-MIR-4666A-5P	99.41	69.72	1887
HSA-MIR-6780A-3P	98.42	67.49	1518
HSA-MIR-6732-3P	98.17	67.52	802
HSA-MIR-4799-3P	97.78	65.97	893
HSA-MIR-4720-5P	97.46	65.67	893
HSA-MIR-5588-5P	97.46	65.70	913

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 74.3% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 11)

• Single nucleotide polymorphism bud13 gene is associated with hyperlipidaemia. (PMID:24780069)
• Significant linkage disequilibria were noted among ZNF259, BUD13 and MLXIPL SNPs and serum lipid levels. (PMID:24989072)
• Common SNPs within the BUD13-APOA5 gene region can effect triglyceride and LDL cholesterol response to statin therapy. (PMID:25900265)
• Single nucleotide polymorphisms (Rs17119975) of BUD13 protein did not increase the risk of CHD in the Chinese population. (PMID:26397108)
• When the inter-dependence between alleles was examined using conditional models, five loci on BUD13, ZNF259, and ApoA5 showed possible independent associations. (PMID:26634697)
• by an integrated analysis of the genotypes and the serum levels of APOA5, BUD13 and triglyceride, we observed that BUD13 was another potential mediator, besides APOA5, of the association between rs651821 and serum triglyceride. rs671 (ALDH2), an east Asian-specific common variant, was found to be associated with MetS (Pcombined = 9.7 x 10(-22) ) in Han Chinese (PMID:28371326)
• Data concluded that novel mutations in BUD13 did not confer risk for MetS in our study population, but these mutations changed the level of metabolic complements. (PMID:28659142)
• Our results indicate that both gender and age have great impacts on the association of the rs964184 polymorphism with coronary heart disease among Chinese. (PMID:29339699)
• Long non-coding RNA DBH-AS1 promotes cancer progression in diffuse large B-cell lymphoma by targeting FN1 via RNA-binding protein BUD13. (PMID:32091157)
• Kernel machine SNP set analysis finds the association of BUD13, ZPR1, and APOA5 variants with metabolic syndrome in Tehran Cardio-metabolic Genetics Study. (PMID:33986338)
• Alternative splicing of BUD13 determines the severity of a developmental disorder with lipodystrophy and progeroid features. (PMID:35670808)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	bud13	ENSDARG00000006666
mus_musculus	Bud13	ENSMUSG00000032077
rattus_norvegicus	Bud13	ENSRNOG00000018665
drosophila_melanogaster	CG13625	FBGN0039210
caenorhabditis_elegans		WBGENE00011142

Protein

Protein identifiers

BUD13 homolog — Q9BRD0 (reviewed: Q9BRD0)

All UniProt accessions (2): Q9BRD0, H7C462

UniProt curated annotations — full annotation on UniProt →

Function. Involved in pre-mRNA splicing as component of the activated spliceosome. As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs.

Subunit / interactions. Part of the activated spliceosome B/catalytic step 1 spliceosome, one of the forms of the spliceosome which has a well-formed active site but still cannot catalyze the branching reaction and is composed of at least 52 proteins, the U2, U5 and U6 snRNAs and the pre-mRNA. Component of the minor spliceosome, which splices U12-type introns.

Subcellular location. Nucleus.

Disease relevance. Achalasia-progeroid syndrome (ACHPS) [MIM:621123] An autosomal recessive syndrome characterized by lipodystrophy with onset in childhood, progeroid appearance, corneal clouding, achalasia, progressive hearing loss, and variable severity. Some affected individuals manifest stunted growth and intellectual disability, and death within the first decade of life has been reported. The disease is caused by variants affecting the gene represented in this entry. A nonsense substitution NM_032725.4:c.688C>T, predicted to result in variant p.Arg230Ter, was found in 5 patients. This variant protein as such could not be detected in patients cells, possibly due to nonsense-mediated mRNA decay. However, this variant also affects BUD13 splicing and results in the production of a stable, disease-associated isoform p.Arg230_Arg284del. Expression of p.Arg230_Arg284del inversely correlates with disease severity and life expectancy. Patients with high p.Arg230_Arg284del levels have a milder disease course and survive into adulthood.

Similarity. Belongs to the CWC26 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9BRD0-1	1	yes
Q9BRD0-2	2

RefSeq proteins (2): NP_001153208, NP_116114* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR018609	Bud13	Family
IPR051112	CWC26_splicing_factor	Family

Pfam: PF09736

UniProt features (56 total): modified residue 32, compositionally biased region 6, sequence variant 5, helix 5, region of interest 3, chain 1, coiled-coil region 1, cross-link 1, splice variant 1, strand 1

Structure

Experimental structures (PDB)

11 structures.

PDB	Method	Resolution (Å)
7DVQ	ELECTRON MICROSCOPY	2.89
8I0R	ELECTRON MICROSCOPY	3
7QTT	ELECTRON MICROSCOPY	3.1
6FF4	ELECTRON MICROSCOPY	3.4
8I0P	ELECTRON MICROSCOPY	3.4
6FF7	ELECTRON MICROSCOPY	4.5
5Z58	ELECTRON MICROSCOPY	4.9
5Z56	ELECTRON MICROSCOPY	5.1
8CH6	ELECTRON MICROSCOPY	5.9
5Z57	ELECTRON MICROSCOPY	6.5
7ABI	ELECTRON MICROSCOPY	8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BRD0-F1	60.52	0.13

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 (33): 28, 123, 127, 135, 139, 147, 151, 159, 163, 172, 175, 197, 201, 214, 222, 226, 235, 236, 240, 248 …

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-72163	mRNA Splicing - Major Pathway
R-HSA-72172	mRNA Splicing
R-HSA-72203	Processing of Capped Intron-Containing Pre-mRNA
R-HSA-8953854	Metabolism of RNA

MSigDB gene sets: 148 (showing top): REACTOME_PROCESSING_OF_CAPPED_INTRON_CONTAINING_PRE_MRNA, GOBP_PROTEIN_RNA_COMPLEX_ORGANIZATION, GOBP_RNA_SPLICING, REACTOME_MRNA_SPLICING, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN, GOBP_RIBONUCLEOPROTEIN_COMPLEX_BIOGENESIS, REACTOME_METABOLISM_OF_RNA, OSMAN_BLADDER_CANCER_DN, GOCC_U2_TYPE_SPLICEOSOMAL_COMPLEX, GOCC_PRECATALYTIC_SPLICEOSOME, GOCC_U2_SNRNP, GOCC_CATALYTIC_STEP_2_SPLICEOSOME, GOCC_SPLICEOSOMAL_COMPLEX, GOCC_RIBONUCLEOPROTEIN_COMPLEX, GOCC_U12_TYPE_SPLICEOSOMAL_COMPLEX

GO Biological Process (4): mRNA splicing, via spliceosome (GO:0000398), U2-type prespliceosome assembly (GO:1903241), mRNA processing (GO:0006397), RNA splicing (GO:0008380)

GO Molecular Function (2): RNA binding (GO:0003723), protein binding (GO:0005515)

GO Cellular Component (7): nucleus (GO:0005634), nucleoplasm (GO:0005654), spliceosomal complex (GO:0005681), U2-type spliceosomal complex (GO:0005684), U2 snRNP (GO:0005686), RES complex (GO:0070274), U2-type precatalytic spliceosome (GO:0071005)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
mRNA Splicing	1
Processing of Capped Intron-Containing Pre-mRNA	1
Metabolism of RNA	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA processing	2
nuclear protein-containing complex	2
RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	1
mRNA processing	1
spliceosomal complex assembly	1
mRNA metabolic process	1
nucleic acid binding	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cellular anatomical structure	1
ribonucleoprotein complex	1
spliceosomal complex	1
spliceosomal snRNP complex	1
U2-type spliceosomal complex	1
U1 snRNP	1
U2 snRNP	1
U4/U6 x U5 tri-snRNP complex	1
precatalytic spliceosome	1

Protein interactions and networks

STRING

1789 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BUD13	RBMX2	Q9Y388	993
BUD13	SNIP1	Q8TAD8	986
BUD13	APOA5	Q6Q788	828
BUD13	ZPR1	O75312	827
BUD13	RNF113A	O15541	774
BUD13	SF3B4	Q15427	747
BUD13	CWC27	Q6UX04	745
BUD13	CETP	P11597	715
BUD13	CDC5L	Q99459	687
BUD13	SF3A3	Q12874	680
BUD13	SF3B1	O75533	666
BUD13	CWC22	Q9HCG8	647
BUD13	DHX16	O60231	645
BUD13	EFTUD2	Q15029	644
BUD13	PHF5A	Q7RTV0	628

IntAct

161 interactions, top by confidence:

A	B	Type	Score
BUD13	GPKOW	psi-mi:“MI:0915”(physical association)	0.940
GPKOW	BUD13	psi-mi:“MI:0915”(physical association)	0.940
ESR1	ESR1	psi-mi:“MI:0914”(association)	0.870
GPKOW	DHX16	psi-mi:“MI:0914”(association)	0.820
RBMX2	BUD13	psi-mi:“MI:0915”(physical association)	0.770
BUD13	RBMX2	psi-mi:“MI:0915”(physical association)	0.770
RPL14	RRP8	psi-mi:“MI:0914”(association)	0.640
NOL12	RRP8	psi-mi:“MI:0914”(association)	0.640
LIN28A	IGF2BP3	psi-mi:“MI:0914”(association)	0.640
DHX38	DHX16	psi-mi:“MI:0914”(association)	0.630
NPM1	MPHOSPH10	psi-mi:“MI:0914”(association)	0.610
USP54	DYRK1A	psi-mi:“MI:0914”(association)	0.550
H1-6	ZNF724	psi-mi:“MI:0914”(association)	0.530
ZNF512	ZNF724	psi-mi:“MI:0914”(association)	0.530
RPL37A	MPHOSPH10	psi-mi:“MI:0914”(association)	0.530
ZNF2	MPHOSPH10	psi-mi:“MI:0914”(association)	0.530
RPL18	NOP56	psi-mi:“MI:0914”(association)	0.530
PDGFB	DKC1	psi-mi:“MI:0914”(association)	0.530
MAGEB2	POLRMT	psi-mi:“MI:0914”(association)	0.530

BioGRID (157): BUD13 (Two-hybrid), BUD13 (Affinity Capture-MS), BUD13 (Affinity Capture-MS), BUD13 (Affinity Capture-MS), BUD13 (Biochemical Activity), BUD13 (Affinity Capture-MS), BUD13 (Affinity Capture-MS), BUD13 (Affinity Capture-MS), BUD13 (Affinity Capture-MS), BUD13 (Affinity Capture-MS), BUD13 (Affinity Capture-MS), BUD13 (Affinity Capture-MS), BUD13 (Affinity Capture-MS), BUD13 (Affinity Capture-MS), BUD13 (Affinity Capture-MS)

ESM2 similar proteins: A2AJT4, A7MD48, B0S733, D3ZTQ1, P0CB65, Q12872, Q14241, Q149C2, Q1MSJ5, Q2KIC0, Q2KJH5, Q2T9Y0, Q3ED78, Q3USH5, Q4FZU3, Q4QQU1, Q4R8G4, Q568R1, Q5HZB6, Q5NCR9, Q5PPJ2, Q5RFN3, Q5SFM8, Q5U2T8, Q5XIN3, Q5ZI03, Q86X95, Q8BKA3, Q8BZX4, Q8C761, Q8CFC7, Q8K019, Q8NA72, Q8R149, Q8TDR0, Q8TF01, Q8VZ67, Q8WVS4, Q8WXA9, Q91WE2

Diamond homologs: O94417, P0CN00, P0CN01, P30640, P46947, Q4PI72, Q4QQU1, Q4W9Z9, Q52F10, Q5AWZ6, Q5ZIJ0, Q6BU18, Q6CAX1, Q6FL63, Q75AG5, Q7RWR8, Q8R149, Q9BRD0, Q5AL13, Q6CJ08

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
BUD13	“form complex”	“U2 snRNP complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 167 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
Peptide chain elongation	18	19.9×	5e-17
Viral mRNA Translation	18	19.9×	5e-17
Transport of Mature Transcript to Cytoplasm	6	19.9×	7e-06
PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA	18	19.6×	5e-17
mRNA 3’-end processing	11	18.8×	2e-10
Selenocysteine synthesis	18	18.8×	8e-17
Eukaryotic Translation Termination	18	18.8×	8e-17
Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)	18	18.4×	1e-16

GO biological processes:

GO term	Partners	Fold	FDR
negative regulation of mRNA splicing, via spliceosome	8	40.9×	1e-09
cytoplasmic translation	20	24.7×	7e-20
RNA splicing, via transesterification reactions	5	20.8×	2e-04
regulation of alternative mRNA splicing, via spliceosome	12	19.5×	2e-10
ribosomal large subunit biogenesis	6	17.7×	7e-05
translation	21	14.4×	4e-16
rRNA processing	13	12.3×	5e-09
ribosomal small subunit biogenesis	8	12.2×	2e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	107
Likely benign	12
Benign	1

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
3767879	NM_032725.4(BUD13):c.688C>T (p.Arg230Ter)	Pathogenic

SpliceAI

1291 predictions. Top by Δscore:

Variant	Effect	Δscore
11:116757141:CTTA:C	donor_loss	1.0000
11:116757142:TTACC:T	donor_loss	1.0000
11:116757224:CTCA:C	acceptor_gain	1.0000
11:116757225:TCA:T	acceptor_gain	1.0000
11:116757226:CA:C	acceptor_gain	1.0000
11:116757226:CAC:C	acceptor_gain	1.0000
11:116757228:C:CC	acceptor_gain	1.0000
11:116757231:A:AC	acceptor_gain	1.0000
11:116757231:A:C	acceptor_gain	1.0000
11:116757946:CAAGC:C	acceptor_gain	1.0000
11:116757949:GC:G	acceptor_gain	1.0000
11:116757949:GCCTG:G	acceptor_loss	1.0000
11:116757950:CC:C	acceptor_gain	1.0000
11:116757951:C:CC	acceptor_gain	1.0000
11:116757951:C:CG	acceptor_loss	1.0000
11:116757952:T:G	acceptor_loss	1.0000
11:116758267:AC:A	donor_gain	1.0000
11:116758268:CC:C	donor_gain	1.0000
11:116758289:CAG:C	donor_gain	1.0000
11:116758296:T:C	donor_gain	1.0000
11:116758321:T:A	donor_gain	1.0000
11:116758403:TTCAG:T	acceptor_gain	1.0000
11:116758404:TCAG:T	acceptor_gain	1.0000
11:116758405:CAG:C	acceptor_gain	1.0000
11:116758405:CAGC:C	acceptor_gain	1.0000
11:116758408:C:CC	acceptor_gain	1.0000
11:116759177:AGCCT:A	acceptor_loss	1.0000
11:116759179:CC:C	acceptor_loss	1.0000
11:116759179:CCTA:C	acceptor_gain	1.0000
11:116759180:CTATG:C	acceptor_loss	1.0000

AlphaMissense

4065 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:116757160:C:A	W584C	1.000
11:116757160:C:G	W584C	1.000
11:116757162:A:G	W584R	1.000
11:116757162:A:T	W584R	1.000
11:116757184:A:C	F576L	0.999
11:116757184:A:T	F576L	0.999
11:116757186:A:G	F576L	0.999
11:116758277:C:A	W497C	0.999
11:116758277:C:G	W497C	0.999
11:116758279:A:G	W497R	0.999
11:116758279:A:T	W497R	0.999
11:116748502:A:G	W614R	0.998
11:116748502:A:T	W614R	0.998
11:116748575:T:A	R589S	0.998
11:116748575:T:G	R589S	0.998
11:116757146:C:G	R589T	0.998
11:116757158:T:A	D585V	0.998
11:116757159:C:G	D585H	0.998
11:116757161:C:G	W584S	0.998
11:116757187:T:A	R575S	0.998
11:116757187:T:G	R575S	0.998
11:116757188:C:G	R575T	0.998
11:116757190:G:C	N574K	0.998
11:116757190:G:T	N574K	0.998
11:116757846:A:G	L535P	0.998
11:116757858:A:G	L531P	0.998
11:116772927:A:G	L13P	0.998
11:116748500:C:A	W614C	0.997
11:116748500:C:G	W614C	0.997
11:116748563:A:C	F593L	0.997

dbSNP variants (sampled 300 via entrez): RS1000182040 (11:116753955 G>A), RS1000197221 (11:116758055 C>A,T), RS1000306542 (11:116764189 G>A,C,T), RS1000527960 (11:116748083 T>C), RS1000726014 (11:116758841 C>T), RS1000792308 (11:116760256 T>C), RS1000936708 (11:116756708 T>C), RS1000947519 (11:116774475 T>A), RS1000998195 (11:116774249 T>G), RS1001196208 (11:116768730 G>A), RS1001353385 (11:116770405 T>C), RS1001540789 (11:116752059 T>G), RS1001574327 (11:116774608 A>G), RS1001577311 (11:116748491 C>T), RS1001691927 (11:116758242 T>C,G)

Disease associations

OMIM: gene MIM:620691 | disease phenotypes: MIM:621123

GenCC curated gene-disease

Disease	Classification	Inheritance
achalasia-progeroid syndrome	Moderate	Autosomal recessive
progeroid syndrome	Limited	Autosomal recessive

Mondo (2): achalasia-progeroid syndrome (MONDO:0700300), progeroid syndrome (MONDO:0015333)

Orphanet (0):

HPO phenotypes

29 total (29 of 29 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000252	Microcephaly
HP:0000325	Triangular face
HP:0000337	Broad forehead
HP:0000407	Sensorineural hearing impairment
HP:0000490	Deeply set eye
HP:0000518	Cataract
HP:0000556	Retinal dystrophy
HP:0000958	Dry skin
HP:0001249	Intellectual disability
HP:0001252	Hypotonia
HP:0001508	Failure to thrive
HP:0001653	Mitral regurgitation
HP:0001659	Aortic regurgitation
HP:0002571	Achalasia
HP:0003119	Abnormal circulating lipid concentration
HP:0003124	Hypercholesterolemia
HP:0003593	Infantile onset
HP:0004322	Short stature
HP:0007392	Excessive wrinkled skin
HP:0007957	Corneal opacity
HP:0009064	Generalized lipodystrophy
HP:0009803	Short phalanx of finger
HP:0011402	Demyelinating sensory neuropathy
HP:0011463	Childhood onset
HP:0011800	Midface retrusion
HP:0011968	Feeding difficulties
HP:0031568	Thickened aortic valve cusp
HP:0034392	Joint contracture

GWAS associations

112 associations (top):

Study	Trait	p-value
GCST000137_4	Triglycerides	2.000000e-26
GCST000138_5	Triglycerides	2.000000e-17
GCST000266_5	Multiple sclerosis (severity)	6.000000e-06
GCST000789_1	Cardiovascular risk factors (age interaction)	8.000000e-06
GCST000807_7	LDL cholesterol	2.000000e-06
GCST000809_11	Triglycerides	4.000000e-21
GCST000918_4	HIV-1 susceptibility	8.000000e-06
GCST001003_1	Metabolic syndrome	5.000000e-09
GCST001004_5	Triglycerides-Blood Pressure (TG-BP)	3.000000e-09
GCST001005_4	HDL Cholesterol - Triglycerides (HDLC-TG)	3.000000e-15
GCST001006_5	Waist Circumference - Triglycerides (WC-TG)	7.000000e-16
GCST001007_7	Metabolic syndrome (bivariate traits)	6.000000e-09
GCST001142_1	Vitamin E levels	8.000000e-12
GCST001230_3	Triglycerides	2.000000e-86
GCST001450_3	Response to Vitamin E supplementation	3.000000e-12
GCST001450_5	Response to Vitamin E supplementation	4.000000e-07
GCST001905_3	Hypertriglyceridemia	5.000000e-35
GCST002173_5	Lipid traits	3.000000e-07
GCST002468_1	Triglycerides	6.000000e-33
GCST002616_18	Mitochondrial DNA levels	6.000000e-06
GCST002932_36	Manganese levels	4.000000e-06
GCST003123_26	Severe influenza A (H1N1) infection	1.000000e-10
GCST003264_989	Post bronchodilator FEV1/FVC ratio	2.000000e-06
GCST003264_992	Post bronchodilator FEV1/FVC ratio	2.000000e-06
GCST003364_2	Triglyceride levels	1.000000e-30
GCST003655_9	Cutaneous squamous cell carcinoma	9.000000e-09
GCST003771_5	Loneliness	5.000000e-06
GCST003772_16	Loneliness (linear analysis)	8.000000e-06
GCST004241_2	Triglyceride levels	2.000000e-44
GCST004603_66	Platelet count	1.000000e-16

EFO canonical traits (47, from GWAS)

EFO ID	Trait name
EFO:0004530	triglyceride measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0008007	age at assessment
EFO:0000180	HIV-1 infection
EFO:0000195	metabolic syndrome
EFO:0006312	mitochondrial DNA measurement
EFO:1001488	influenza A (H1N1)
EFO:0004713	FEV/FVC ratio
EFO:1001927	cutaneous squamous cell carcinoma
EFO:0007865	loneliness measurement
EFO:0004309	platelet count
EFO:0004842	eosinophil count
EFO:0005090	basophil count
EFO:0008336	disease progression measurement
EFO:0007785	femoral neck bone mineral density
EFO:0005763	pulse pressure measurement
EFO:0009188	Red cell distribution width
EFO:0008579	risk-taking behaviour
EFO:0004329	alcohol drinking
EFO:0010354	diacylglycerol 36:1 measurement
EFO:0010419	triacylglycerol 54:1 measurement
EFO:0010420	triacylglycerol 54:2 measurement
EFO:0010421	triacylglycerol 54:3 measurement
EFO:0010422	triacylglycerol 54:4 measurement
EFO:0010355	diacylglycerol 36:2 measurement
EFO:0010423	triacylglycerol 54:5 measurement
EFO:0010416	triacylglycerol 52:4 measurement
EFO:0010417	triacylglycerol 52:5 measurement
EFO:0010414	triacylglycerol 52:2 measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D011371	Progeria	C16.320.488.875; C16.320.565.753; C18.452.648.753

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression	3
Smoke	decreases expression, increases abundance	2
aristolochic acid I	decreases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
FR900359	affects phosphorylation	1
bisphenol A	decreases expression	1
sodium arsenite	affects cotreatment, decreases expression, increases abundance	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
coumarin	affects phosphorylation	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
abrine	increases expression	1
Resveratrol	increases expression, affects cotreatment	1
Temozolomide	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Caffeine	affects phosphorylation	1
Cisplatin	increases expression	1
Coal	increases abundance, decreases expression	1
Doxorubicin	decreases expression	1
Formaldehyde	decreases expression	1
Manganese	increases abundance, affects cotreatment, decreases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Tetrachlorodibenzodioxin	affects expression	1
Dronabinol	decreases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1
Cyclosporine	increases expression	1
Copper Sulfate	decreases expression	1
Acrylamide	decreases expression	1
Vitamin K 3	affects expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00425607	PHASE2	COMPLETED	Phase II Trial of Lonafarnib (a Farnesyltransferase Inhibitor) for Progeria
NCT00879034	PHASE2	COMPLETED	A Study of Zoledronic Acid, Pravastatin, and Lonafarnib for Patients With Progeria
NCT00916747	PHASE2	UNKNOWN	Study of Zoledronic Acid, Pravastatin, and Lonafarnib for Patients With Progeria
NCT02579044	PHASE1/PHASE2	ENROLLING_BY_INVITATION	Phase I/II Trial of Everolimus in Combination With Lonafarnib in Progeria
NCT00094393	Not specified	COMPLETED	Clinical Studies of Progeria
NCT03895528	Not specified	APPROVED_FOR_MARKETING	Lonafarnib for Patients With Hutchinson-Gilford Progeria Syndrome or Progeroid Laminopathy