PUS7

Summary

PUS7 (pseudouridine synthase 7, HGNC:26033) is a protein-coding gene on chromosome 7q22.3, encoding Pseudouridylate synthase 7 homolog (Q96PZ0). Pseudouridylate synthase that catalyzes pseudouridylation of RNAs.

Enables enzyme binding activity and tRNA pseudouridine(13) synthase activity. Involved in several processes, including pseudouridine synthesis; regulation of hematopoietic stem cell differentiation; and regulation of mesoderm development. Is active in nucleus. Implicated in intellectual developmental disorder with abnormal behavior, microcephaly, and short stature.

Source: NCBI Gene 54517 — RefSeq curated summary.

At a glance

• Gene–disease (curated): intellectual developmental disorder with abnormal behavior, microcephaly, and short stature (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 4
• Clinical variants (ClinVar): 194 total — 19 pathogenic, 14 likely-pathogenic
• Phenotypes (HPO): 50
• MANE Select transcript: NM_019042

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26033
Approved symbol	PUS7
Name	pseudouridine synthase 7
Location	7q22.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ20485
Ensembl gene	ENSG00000091127
Ensembl biotype	protein_coding
OMIM	616261
Entrez	54517

Gene structure

Transcript identifiers

Ensembl transcripts: 24 — 21 protein_coding, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000356362, ENST00000469408, ENST00000478208, ENST00000481939, ENST00000482157, ENST00000487277, ENST00000873980, ENST00000873981, ENST00000873982, ENST00000929035, ENST00000929036, ENST00000929037, ENST00000929038, ENST00000929039, ENST00000929040, ENST00000929041, ENST00000929042, ENST00000929043, ENST00000929044, ENST00000929045, ENST00000947300, ENST00000947301, ENST00000947302, ENST00000947303

RefSeq mRNA: 3 — MANE Select: NM_019042 NM_001318163, NM_001318164, NM_019042

CCDS: CCDS34725

Canonical transcript exons

ENST00000469408 — 16 exons

Exon	Start	End
ENSE00001131558	105472132	105472193
ENSE00001131570	105482312	105482440
ENSE00001131583	105495142	105495253
ENSE00001131648	105481052	105481177
ENSE00001131661	105491540	105491617
ENSE00001131682	105506189	105506273
ENSE00001210362	105505955	105506056
ENSE00001386207	105470688	105470848
ENSE00001388464	105502420	105502564
ENSE00001436586	105508115	105508544
ENSE00001883407	105456503	105457926
ENSE00003590056	105468337	105468463
ENSE00003606037	105462621	105462750
ENSE00003613900	105465313	105465414
ENSE00003640932	105459168	105459259
ENSE00003847884	105522052	105522271

Expression profiles

Bgee: expression breadth ubiquitous, 254 present calls, max score 97.92.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 17.0523 / max 166.7885, expressed in 1773 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
85437	12.7480	1746
85438	4.3043	1441

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	97.92	gold quality
secondary oocyte	CL:0000655	93.65	gold quality
oocyte	CL:0000023	93.06	gold quality
endothelial cell	CL:0000115	92.19	gold quality
hair follicle	UBERON:0002073	88.70	gold quality
calcaneal tendon	UBERON:0003701	87.24	gold quality
skin of hip	UBERON:0001554	85.37	gold quality
sural nerve	UBERON:0015488	84.66	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	84.32	gold quality
cervix squamous epithelium	UBERON:0006922	83.97	silver quality
gingival epithelium	UBERON:0001949	83.92	gold quality
squamous epithelium	UBERON:0006914	83.76	gold quality
oviduct epithelium	UBERON:0004804	83.62	gold quality
cartilage tissue	UBERON:0002418	83.55	gold quality
gastrocnemius	UBERON:0001388	83.17	gold quality
cortical plate	UBERON:0005343	83.14	gold quality
ventricular zone	UBERON:0003053	82.90	gold quality
esophagus squamous epithelium	UBERON:0006920	82.78	gold quality
gingiva	UBERON:0001828	82.77	gold quality
muscle of leg	UBERON:0001383	82.75	gold quality
tibialis anterior	UBERON:0001385	82.43	gold quality
mucosa of sigmoid colon	UBERON:0004993	82.29	gold quality
lower esophagus mucosa	UBERON:0035834	82.25	gold quality
ganglionic eminence	UBERON:0004023	82.08	gold quality
embryo	UBERON:0000922	81.88	gold quality
tibia	UBERON:0000979	81.15	gold quality
islet of Langerhans	UBERON:0000006	80.98	gold quality
esophagus mucosa	UBERON:0002469	80.90	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.76	gold quality
oral cavity	UBERON:0000167	80.54	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

84 targeting PUS7, 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-4795-3P	100.00	74.62	4024
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-3912-5P	99.95	66.11	925
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-498-3P	99.91	71.27	1114
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-8067	99.86	69.59	2260
HSA-MIR-548BB-3P	99.86	70.58	4354

Literature-anchored findings (GeneRIF, showing 10)

• Our results confirm that PUS7 is a bona fide Mendelian disease gene and expand the list of human diseases caused by impaired pseudouridylation. (PMID:30778726)
• Pseudouridine synthase 7 is a nuclear protein involved in stem cell development and intellectual disabilities, and is a novel interactor of SIRT1. The binding regions are predicted and analyzed based on molecular docking studies. The direct interaction occurs between SIRT1 and PUS7, as evidenced by pull-down studies and surface plasmon resonance (SPR) assay. (PMID:31451225)
• Pseudouridylate Synthase 7 Promotes Cell Proliferation and Invasion in Colon Cancer Through Activating PI3K/AKT/mTOR Signaling Pathway. (PMID:33811565)
• HSP90-dependent PUS7 overexpression facilitates the metastasis of colorectal cancer cells by regulating LASP1 abundance. (PMID:33990203)
• The human pseudouridine synthase PUS7 recognizes RNA with an extended multi-domain binding surface. (PMID:34718722)
• Pseudouridine synthases modify human pre-mRNA co-transcriptionally and affect pre-mRNA processing. (PMID:35051350)
• PUS7 deficiency in human patients causes profound neurodevelopmental phenotype by dysregulating protein translation. (PMID:35144859)
• PUS7 promotes the proliferation of colorectal cancer cells by directly stabilizing SIRT1 to activate the Wnt/beta-catenin pathway. (PMID:36222184)
• Comprehensive analysis to identify PUS7 as a prognostic biomarker from pan-cancer analysis to osteosarcoma validation. (PMID:38819212)
• PUS7-dependent pseudouridylation of ALKBH3 mRNA inhibits gastric cancer progression. (PMID:39175405)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	pus7	ENSDARG00000031774
mus_musculus	Pus7	ENSMUSG00000057541
rattus_norvegicus	Pus7	ENSRNOG00000010572
drosophila_melanogaster	Pus7	FBGN0035901

Paralogs (1): PUS7L (ENSG00000129317)

Protein

Protein identifiers

Pseudouridylate synthase 7 homolog — Q96PZ0 (reviewed: Q96PZ0)

All UniProt accessions (3): Q96PZ0, E7EUH7, H0Y863

UniProt curated annotations — full annotation on UniProt →

Function. Pseudouridylate synthase that catalyzes pseudouridylation of RNAs. Acts as a regulator of protein synthesis in embryonic stem cells by mediating pseudouridylation of RNA fragments derived from tRNAs (tRFs): pseudouridylated tRFs inhibit translation by targeting the translation initiation complex. Also catalyzes pseudouridylation of mRNAs: mediates pseudouridylation of mRNAs with the consensus sequence 5’-UGUAG-3’. Acts as a regulator of pre-mRNA splicing by mediating pseudouridylation of pre-mRNAs at locations associated with alternatively spliced regions. Pseudouridylation of pre-mRNAs near splice sites directly regulates mRNA splicing and mRNA 3’-end processing. In addition to mRNAs and tRNAs, binds other types of RNAs, such as snRNAs, Y RNAs and vault RNAs, suggesting that it can catalyze pseudouridylation of many RNA types.

Subunit / interactions. Interacts with SIRT1.

Subcellular location. Nucleus.

Disease relevance. Intellectual developmental disorder with abnormal behavior, microcephaly, and short stature (IDDABS) [MIM:618342] An autosomal recessive disorder characterized by intellectual disability, developmental delay with poor or absent speech, short stature, progressive microcephaly, hyperactivity and aggressive behavior. Some patients manifest sensorineural hearing loss. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the pseudouridine synthase TruD family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q96PZ0-1	1	yes
Q96PZ0-2	2

RefSeq proteins (3): NP_001305092, NP_001305093, NP_061915* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001656	PsdUridine_synth_TruD	Family
IPR011760	PsdUridine_synth_TruD_insert	Domain
IPR020103	PsdUridine_synth_cat_dom_sf	Homologous_superfamily
IPR020119	PsdUridine_synth_TruD_CS	Conserved_site
IPR042214	TruD_catalytic	Homologous_superfamily

Pfam: PF01142

Enzyme classification (BRENDA):

• EC 5.4.99.27 — tRNA pseudouridine13 synthase (BRENDA: 5 organisms, 10 substrates, 0 inhibitors, 1 Km, 1 kcat entries)

Substrate kinetics (BRENDA)

1 substrates with measured Km, best-characterized 1. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
TRNA URIDINE13	0.0004	1

Catalyzed reactions (Rhea), 3 shown:

• uridine(13) in tRNA = pseudouridine(13) in tRNA (RHEA:42540)
• a uridine in tRNA = a pseudouridine in tRNA (RHEA:54572)
• a uridine in mRNA = a pseudouridine in mRNA (RHEA:56644)

UniProt features (58 total): helix 23, strand 19, sequence variant 4, modified residue 4, compositionally biased region 2, chain 1, domain 1, splice variant 1, mutagenesis site 1, region of interest 1, active site 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
5KKP	X-RAY DIFFRACTION	2.26

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96PZ0-F1	80.67	0.58

Functional residue map

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

Catalytic / active sites (1): 294 (nucleophile)

Post-translational modifications (4): 1, 10, 127, 610

Mutagenesis-validated functional residues (1):

Position	Phenotype
294	loss of pseudouridylate synthase activity.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-6782315	tRNA modification in the nucleus and cytosol

MSigDB gene sets: 275 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_DN, GOBP_HEMATOPOIETIC_PROGENITOR_CELL_DIFFERENTIATION, GOBP_TRNA_METABOLIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_TRANSLATION, GOBP_MRNA_MODIFICATION, GOBP_HEMATOPOIETIC_STEM_CELL_DIFFERENTIATION, GOBP_PSEUDOURIDINE_SYNTHESIS, GOBP_TRANSLATION, WEI_MYCN_TARGETS_WITH_E_BOX, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, ONKEN_UVEAL_MELANOMA_UP, GOBP_RNA_MODIFICATION, GOBP_REGULATION_OF_MESODERM_DEVELOPMENT, GOBP_RNA_SPLICING, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_METABOLIC_PROCESS

GO Biological Process (10): pseudouridine synthesis (GO:0001522), mRNA processing (GO:0006397), RNA splicing (GO:0008380), negative regulation of translation (GO:0017148), tRNA pseudouridine synthesis (GO:0031119), regulation of hematopoietic stem cell differentiation (GO:1902036), mRNA pseudouridine synthesis (GO:1990481), regulation of mesoderm development (GO:2000380), tRNA processing (GO:0008033), RNA modification (GO:0009451)

GO Molecular Function (6): RNA binding (GO:0003723), pseudouridine synthase activity (GO:0009982), enzyme binding (GO:0019899), tRNA pseudouridine(13) synthase activity (GO:0160150), isomerase activity (GO:0016853), tRNA pseudouridine synthase activity (GO:0106029)

GO Cellular Component (1): nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
tRNA processing	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA processing	3
pseudouridine synthesis	2
RNA modification	1
mRNA metabolic process	1
translation	1
regulation of translation	1
negative regulation of gene expression	1
negative regulation of protein metabolic process	1
tRNA modification	1
hematopoietic stem cell differentiation	1
regulation of hematopoietic progenitor cell differentiation	1
regulation of stem cell differentiation	1
mRNA modification	1
mesoderm development	1
regulation of developmental process	1
tRNA metabolic process	1
RNA metabolic process	1
macromolecule modification	1
nucleic acid binding	1
intramolecular transferase activity	1
protein binding	1
tRNA pseudouridine synthase activity	1
catalytic activity	1
pseudouridine synthase activity	1
catalytic activity, acting on a tRNA	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

2091 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PUS7	PUS1	Q9Y606	879
PUS7	TRUB1	Q8WWH5	873
PUS7	RPUSD2	Q8IZ73	811
PUS7	PUS3	Q9BZE2	809
PUS7	PUS10	Q3MIT2	807
PUS7	NSUN2	Q08J23	745
PUS7	TRUB2	O95900	737
PUS7	DKC1	O60832	736
PUS7	RPUSD4	Q96CM3	722
PUS7	RPUSD3	Q6P087	721
PUS7	FTSJ1	Q9UET6	667
PUS7	RPUSD1	Q9UJJ7	663
PUS7	NHP2	Q9NX24	648
PUS7	NOP10	Q9NPE3	643
PUS7	TRDMT1	O14717	620

IntAct

86 interactions, top by confidence:

A	B	Type	Score
CCM2	KRIT1	psi-mi:“MI:0914”(association)	0.960
MED17	MED19	psi-mi:“MI:0914”(association)	0.840
GATAD2A	CDK2AP1	psi-mi:“MI:0914”(association)	0.730
RHOD	PLXNB2	psi-mi:“MI:0914”(association)	0.640
THUMPD1	YBX1	psi-mi:“MI:0914”(association)	0.530
LUC7L2	ZNF593	psi-mi:“MI:0914”(association)	0.530
ATP6V0A1	ATP6AP2	psi-mi:“MI:0914”(association)	0.530
H3C1	SMCHD1	psi-mi:“MI:2364”(proximity)	0.410
CXXC4	TIA1	psi-mi:“MI:0914”(association)	0.350
ORF37	RPP40	psi-mi:“MI:0914”(association)	0.350
FGB	NME2	psi-mi:“MI:0914”(association)	0.350
SSB	RPS3A	psi-mi:“MI:0914”(association)	0.350
PIPSL	C1orf226	psi-mi:“MI:0914”(association)	0.350
S100B	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
S100P	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
FTL	SH3PXD2B	psi-mi:“MI:0914”(association)	0.350
S100A6	VWA8	psi-mi:“MI:0914”(association)	0.350
APOBEC3C	GTPBP10	psi-mi:“MI:0914”(association)	0.350
	SUPT5H	psi-mi:“MI:0914”(association)	0.350
	GTPBP10	psi-mi:“MI:0914”(association)	0.350
	GTPBP1	psi-mi:“MI:0914”(association)	0.350
BBS1	SHTN1	psi-mi:“MI:0914”(association)	0.350
DOK4	SHTN1	psi-mi:“MI:0914”(association)	0.350
AHR	SHTN1	psi-mi:“MI:0914”(association)	0.350
ANKRD49	SHTN1	psi-mi:“MI:0914”(association)	0.350
ZBTB2	SHTN1	psi-mi:“MI:0914”(association)	0.350

BioGRID (138): PUS7 (Affinity Capture-MS), ACOT13 (Co-fractionation), ACTN4 (Co-fractionation), BYSL (Co-fractionation), DDX3X (Co-fractionation), DHX15 (Co-fractionation), DHX16 (Co-fractionation), DOHH (Co-fractionation), EIF4G1 (Co-fractionation), EIF4G3 (Co-fractionation), ENOPH1 (Co-fractionation), MCM3 (Co-fractionation), MCM5 (Co-fractionation), NHP2L1 (Co-fractionation), NOC3L (Co-fractionation)

ESM2 similar proteins: A2VE39, A7YT82, D2HRF1, F6VSS6, O14730, O60551, O70310, P30419, P31717, P49916, P97386, Q08DI8, Q1L8I0, Q1RMT7, Q28E61, Q2T9V5, Q2VPA6, Q32P41, Q3MIT2, Q4KLT3, Q4V7N2, Q5R981, Q5RAF3, Q5U2Z5, Q5ZLV4, Q6GQ76, Q6ING2, Q6NS23, Q7SXA9, Q803R5, Q8BYH3, Q8CE46, Q8CE96, Q8K1Q0, Q8K4M9, Q8N1G2, Q91VU7, Q91XL9, Q96PZ0, Q9BXW6

Diamond homologs: A1TZ52, A1W165, A4FYL2, A4VJV1, A5ICB9, A5UE25, A5W822, A6Q2U7, A6UV17, A7H5G6, A7HGV2, A8FNC4, B0KSC6, B0RU01, B0URU7, B1JB31, B2UU74, B3PJA9, B5Z7T0, B6JME7, B6YTE4, B7V8C2, B8J7C8, B9M644, C1DSR9, C3K704, C6A1K9, O27572, O28596, O74343, P44039, P55985, P59892, P59893, Q08647, Q08DI8, Q0I5H8, Q12WH6, Q17426, Q17WX3

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	19
Likely pathogenic	14
Uncertain significance	95
Likely benign	16
Benign	11

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1098305	GRCh37/hg19 7q22.3(chr7:104696686-105407628)	Pathogenic
1098369	NM_019042.5(PUS7):c.1774del (p.Asp592fs)	Pathogenic
1676078	NM_019042.5(PUS7):c.965_966dup (p.Phe323fs)	Pathogenic
1802167	NM_019042.5(PUS7):c.1097_1098del (p.Leu366fs)	Pathogenic
2227934	NM_019042.5(PUS7):c.393_397del (p.Glu132fs)	Pathogenic
3258111	NM_019042.5(PUS7):c.532C>T (p.Arg178Ter)	Pathogenic
4056373	NM_019042.5(PUS7):c.155_161delinsAAC (p.Leu52fs)	Pathogenic
4056400	NM_019042.5(PUS7):c.920+4_920+7del	Pathogenic
4280298	NM_019042.5(PUS7):c.1507del (p.Asp503fs)	Pathogenic
4280300	NM_019042.5(PUS7):c.424del (p.Glu141_Ile142insTer)	Pathogenic
4280301	NM_019042.5(PUS7):c.1270G>T (p.Glu424Ter)	Pathogenic
4280302	NM_019042.5:c.(1757+1_1758-1)_(1848+1_1849-1)del	Pathogenic
4280303	NM_019042.5(PUS7):c.156_159del (p.Ile54fs)	Pathogenic
4280304	NM_019042.5(PUS7):c.1918C>T (p.Arg640Ter)	Pathogenic
4280306	NM_019042.5(PUS7):c.998del (p.Asn333fs)	Pathogenic
619230	NM_019042.5(PUS7):c.89_90del (p.Thr30fs)	Pathogenic
619231	NM_019042.5(PUS7):c.1348C>T (p.Arg450Ter)	Pathogenic
619232	NM_019042.4(PUS7):c.(1757+1_1758-1)_(1848+1_1849-1)del	Pathogenic
619234	NM_019042.5(PUS7):c.329_332del (p.Thr110fs)	Pathogenic
1184593	NM_019042.5(PUS7):c.1385_1386del (p.Ser462fs)	Likely pathogenic
2431797	NM_019042.5(PUS7):c.1196G>A (p.Trp399Ter)	Likely pathogenic
2431821	NM_019042.5(PUS7):c.303del (p.Phe101fs)	Likely pathogenic
2501667	NM_019042.5(PUS7):c.843-1G>A	Likely pathogenic
3258110	NM_019042.5(PUS7):c.1121A>C (p.Tyr374Ser)	Likely pathogenic
3367106	NM_019042.5(PUS7):c.702C>A (p.Tyr234Ter)	Likely pathogenic
4280297	NM_019042.5(PUS7):c.1169T>C (p.Val390Ala)	Likely pathogenic
4280299	NM_019042.5(PUS7):c.1238-1G>A	Likely pathogenic
4280305	NM_019042.5(PUS7):c.586G>T (p.Val196Phe)	Likely pathogenic
4280307	NM_019042.5(PUS7):c.1228C>T (p.Arg410Cys)	Likely pathogenic
4814170	NM_019042.5(PUS7):c.399-2A>T	Likely pathogenic

SpliceAI

2726 predictions. Top by Δscore:

Variant	Effect	Δscore
7:105457922:GCCTT:G	acceptor_gain	1.0000
7:105457923:CCTTC:C	acceptor_gain	1.0000
7:105457924:CTT:C	acceptor_gain	1.0000
7:105457925:TT:T	acceptor_gain	1.0000
7:105457927:C:A	acceptor_loss	1.0000
7:105457927:C:CC	acceptor_gain	1.0000
7:105459164:TTA:T	donor_loss	1.0000
7:105459166:A:AC	donor_gain	1.0000
7:105459166:A:AT	donor_loss	1.0000
7:105459166:AC:A	donor_gain	1.0000
7:105459167:C:CG	donor_gain	1.0000
7:105459167:CC:C	donor_gain	1.0000
7:105459167:CCAG:C	donor_gain	1.0000
7:105459167:CCAGA:C	donor_gain	1.0000
7:105459255:CTTCC:C	acceptor_gain	1.0000
7:105459257:TCC:T	acceptor_gain	1.0000
7:105459258:CC:C	acceptor_gain	1.0000
7:105459258:CCC:C	acceptor_gain	1.0000
7:105459259:CC:C	acceptor_gain	1.0000
7:105459260:C:CA	acceptor_loss	1.0000
7:105459260:C:CC	acceptor_gain	1.0000
7:105459261:T:G	acceptor_loss	1.0000
7:105459263:C:CT	acceptor_gain	1.0000
7:105459264:A:T	acceptor_gain	1.0000
7:105459268:C:CT	acceptor_loss	1.0000
7:105459268:CATA:C	acceptor_gain	1.0000
7:105459269:A:AC	acceptor_gain	1.0000
7:105459269:A:C	acceptor_gain	1.0000
7:105459271:A:AC	acceptor_gain	1.0000
7:105459271:A:C	acceptor_gain	1.0000

AlphaMissense

4386 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:105457857:C:G	R640P	1.000
7:105457863:G:T	A638D	1.000
7:105457866:A:C	M637R	1.000
7:105457866:A:T	M637K	1.000
7:105457872:G:T	A635D	1.000
7:105457876:A:G	Y634H	1.000
7:105457890:A:G	L629P	1.000
7:105457890:A:T	L629Q	1.000
7:105457908:A:G	L623P	1.000
7:105462654:C:A	R575L	1.000
7:105462654:C:G	R575P	1.000
7:105462655:G:C	R575G	1.000
7:105462663:C:A	G572V	1.000
7:105462663:C:T	G572E	1.000
7:105462664:C:A	G572W	1.000
7:105462664:C:G	G572R	1.000
7:105462664:C:T	G572R	1.000
7:105465342:C:A	G533V	1.000
7:105465342:C:T	G533D	1.000
7:105465343:C:G	G533R	1.000
7:105465351:G:C	P530R	1.000
7:105465351:G:T	P530H	1.000
7:105468351:A:G	L504P	1.000
7:105468407:A:C	N485K	1.000
7:105468407:A:T	N485K	1.000
7:105468412:A:G	W484R	1.000
7:105468412:A:T	W484R	1.000
7:105468419:G:C	S481R	1.000
7:105468419:G:T	S481R	1.000
7:105468421:T:G	S481R	1.000

dbSNP variants (sampled 300 via entrez): RS1000066699 (7:105469613 C>T), RS1000127028 (7:105483635 G>C), RS1000142579 (7:105476833 C>T), RS1000274072 (7:105502274 C>T), RS1000329436 (7:105463160 A>G), RS1000386635 (7:105512005 C>G), RS1000402954 (7:105463461 T>C), RS1000410193 (7:105490163 T>C,G), RS1000496147 (7:105467045 T>C,G), RS1000499132 (7:105483914 T>C), RS1000548721 (7:105466824 C>T), RS1000588519 (7:105457674 A>C,G), RS1000617569 (7:105500459 G>A,T), RS1000686591 (7:105500250 G>A), RS1000739580 (7:105462075 AAGAT>A)

Disease associations

OMIM: gene MIM:616261 | disease phenotypes: MIM:618342, MIM:618512

GenCC curated gene-disease

Disease	Classification	Inheritance
intellectual developmental disorder with abnormal behavior, microcephaly, and short stature	Strong	Autosomal recessive
syndromic intellectual disability	Supportive	Autosomal dominant

Mondo (4): intellectual developmental disorder with abnormal behavior, microcephaly, and short stature (MONDO:0032687), O’Donnell-Luria-Rodan syndrome (MONDO:0032793), pervasive developmental disorder (MONDO:0000594), syndromic intellectual disability (MONDO:0000508)

Orphanet (1): Rare pervasive developmental disorder (Orphanet:168778)

HPO phenotypes

50 total (30 of 50 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000179	Thick lower lip vermilion
HP:0000194	Open mouth
HP:0000218	High palate
HP:0000232	Everted lower lip vermilion
HP:0000252	Microcephaly
HP:0000278	Retrognathia
HP:0000286	Epicanthus
HP:0000307	Pointed chin
HP:0000319	Smooth philtrum
HP:0000322	Short philtrum
HP:0000325	Triangular face
HP:0000347	Micrognathia
HP:0000369	Low-set ears
HP:0000407	Sensorineural hearing impairment
HP:0000411	Protruding ear
HP:0000431	Wide nasal bridge
HP:0000463	Anteverted nares
HP:0000490	Deeply set eye
HP:0000494	Downslanted palpebral fissures
HP:0000668	Hypodontia
HP:0000678	Dental crowding
HP:0000718	Aggressive behavior
HP:0000733	Motor stereotypy
HP:0000736	Short attention span
HP:0000750	Delayed speech and language development
HP:0000752	Hyperactivity
HP:0001249	Intellectual disability
HP:0001263	Global developmental delay
HP:0001270	Motor delay

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST002539_67	Schizophrenia	1.000000e-09
GCST006618_2	Uterine fibroid size (maximum dimension)	4.000000e-07
GCST008103_9	Bipolar disorder	1.000000e-09
GCST90000047_141	Age at first sexual intercourse	5.000000e-11

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0009410	uterine fibroid measurement
EFO:0009749	age at first sexual intercourse measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D002659	Child Development Disorders, Pervasive	F03.625.164

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, increases expression, affects cotreatment	3
Estradiol	increases expression	3
Tretinoin	decreases expression	3
Valproic Acid	affects expression, increases expression, increases methylation	3
Cadmium Chloride	increases abundance, increases expression, decreases expression	3
Air Pollutants	increases abundance, decreases expression	2
Cyclosporine	decreases expression, increases expression	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
bisphenol F	affects cotreatment, decreases expression	1
TAK-243	increases sumoylation	1
alpha phellandrene	decreases expression	1
triphenyl phosphate	affects expression	1
trichostatin A	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
2-amino-9H-pyrido(2,3-b)indole	increases expression	1
sodium arsenite	decreases expression	1
cobaltous chloride	decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
coumarin	increases phosphorylation	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
azoxystrobin	decreases expression	1
perfluoro-n-nonanoic acid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	decreases expression	1
pyrachlostrobin	decreases expression	1
LDN 193189	affects cotreatment, decreases expression	1
picoxystrobin	decreases expression	1
Temozolomide	increases expression	1
Sunitinib	increases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2CW	Abcam HeLa PUS7 KO	Cancer cell line	Female
CVCL_E0MD	Ubigene HeLa PUS7 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00205699	PHASE4	COMPLETED	Metabolic Effects of Antipsychotics in Children
NCT01238575	PHASE4	COMPLETED	Guanfacine for the Treatment of Hyperactivity in Pervasive Developmental Disorder
NCT02199925	PHASE4	UNKNOWN	An Open-Label Study to Evaluate the Efficacy of High-Dose Gammaplex in Children on the Autism Spectrum
NCT00399698	PHASE3	COMPLETED	Study to Determine Whether There Are Any Cognitive or Motor Effects From Taking the Medicine Risperidone.
NCT00870727	PHASE3	COMPLETED	Study of Aripiprazole in the Treatment of Pervasive Developmental Disorders
NCT02985749	PHASE3	COMPLETED	A Study of Oxytocin for the Treatment of Social Impairment in Individuals With High Functioning Autism Spectrum Disorder
NCT00198055	PHASE2	COMPLETED	A Study of Aripiprazole in Children and Adolescents With Aspergers and Pervasive Developmental Disorder.
NCT00308074	PHASE2	COMPLETED	An Open-Label Trial of Aripiprazole in Autism Spectrum Disorders
NCT01602016	PHASE2	TERMINATED	A Folinic Acid Intervention for Autism Spectrum Disorders
NCT05664841	PHASE2	RECRUITING	The Impact of a Virtual Magic Trick Training Program
NCT00325572	PHASE1	TERMINATED	Evaluation and Treatment of Copper/Zinc Imbalance in Children With Autism
NCT00773812	PHASE1	COMPLETED	Placebo-Controlled Pilot Trial of Mecamylamine for Treatment of Autism Spectrum Disorders
NCT01243905	PHASE2/PHASE3	UNKNOWN	Group Psychoeducational Program for Mothers of Children With High Functional Pervasive Developmental Disorders
NCT00318162	PHASE1/PHASE2	UNKNOWN	Trial of Low-Dose Naltrexone for Children With Pervasive Developmental Disorder (PDD)
NCT00004458	Not specified	TERMINATED	Longitudinal and Biological Study of Childhood Disintegrative Disorder
NCT00025779	Not specified	COMPLETED	Methylphenidate in Children and Adolescents With Pervasive Developmental Disorders
NCT00464477	Not specified	COMPLETED	Advanced Grandparental Age as a Risk Factor for Autism
NCT00531830	Not specified	UNKNOWN	Assessment of Factors Which Predict Improvement in Children With PDD After a Year of Integrative Therapy
NCT00579267	Not specified	COMPLETED	Reliability and Validity of the MINI International Neuropsychiatric Interview for Children and Adolescents (MINI-KID)
NCT00902798	Not specified	COMPLETED	Cognitive Enhancement Therapy for Adult Autism Spectrum Disorder
NCT01160783	Not specified	ACTIVE_NOT_RECRUITING	Genetic Contributions to Autism Spectrum Disorders
NCT01553240	Not specified	TERMINATED	Neurocircuitry of Autism- fMRI and Transcranial Magnetic Stimulation Studies
NCT01631851	Not specified	COMPLETED	Cognitive-Behavioral Therapy for Irritability in Adolescents With High Functioning Autism Spectrum Disorder
NCT01808066	Not specified	COMPLETED	GroundsKeeper: A Qualitative Study of Applied Game-based Interactives in Special Education Programs
NCT01921244	Not specified	COMPLETED	Shared Decision Making to Improve Care and Outcomes for Children With Autism
NCT03170453	Not specified	COMPLETED	Confirmatory Efficacy Trial of Cognitive Enhancement Therapy for Adult Autism Spectrum Disorder
NCT03177590	Not specified	COMPLETED	Recording Facial and Vocal Emotional Productions in Children With Autism as Part of the JEMImE Project
NCT03560453	Not specified	COMPLETED	Facilitating Employment for Youth With Autism
NCT03602378	Not specified	UNKNOWN	QoL and Stress in Parents of Children With Developmental Disabilities and Chronic Disease
NCT04654260	Not specified	ACTIVE_NOT_RECRUITING	Behavior Therapy for Irritability in Autism
NCT04788537	Not specified	COMPLETED	Services to Enhance Social Functioning in Adults With Autism Spectrum Disorders