PUS7

protein-coding

pseudouridine synthase 7, the group of Pseudouridine synthases

Gene summary

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. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_019042.5

Inheritance

AD, AR

ClinVar variants

P:38U:103B:19

Top phenotype

Intellectual developmental disorder with abnormal behavior, microcephaly, and short stature

gnomAD constraint

pLI —, LoF o/e 0.57

Max pathogenic AF

—

Genomic locus

chr7:105,439,661-105,522,271

External References & Databases

Ensembl (ENSG00000091127)

Transcript & Mutation Effects

hg38 • Region Span ~82.6 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

syndromic intellectual disabilitySUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0000508

Submitter: Orphanet

intellectual developmental disorder with abnormal behavior, microcephaly, and short statureSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0032687

Submitter: PanelApp Australia

intellectual developmental disorder with abnormal behavior, microcephaly, and short statureMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0032687

Submitter: Ambry Genetics

intellectual developmental disorder with abnormal behavior, microcephaly, and short statureSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0032687

Submitter: Labcorp Genetics (formerly Invitae)

intellectual developmental disorder with abnormal behavior, microcephaly, and short statureSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0032687

Submitter: G2P

Clinical Genomic Database (CGD)

Intellectual developmental disorder with abnormal behavior, microcephaly, and short statureAR

Manifestation: Audiologic/Otolaryngologic; Craniofacial; Musculoskeletal; Neurologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 30526862; 30778726

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PUS7 variants in ClinVar

7 Conditions Cataloged

Inborn genetic diseasesTotal: 84

Intellectual developmental disorder with abnormal behavior, microcephaly, and short statureTotal: 46

not providedTotal: 28

PUS7-related disorderTotal: 10

not specifiedTotal: 6

Pervasive developmental disorderTotal: 1

See casesTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_019042.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			3 clinvar	12 clinvar	2 clinvar	17
missense		6 clinvar	94 clinvar	4 clinvar	1 clinvar	105
nonsense	6 clinvar	3 clinvar				9
start loss						0
frameshift	12 clinvar	5 clinvar				17
splice donor/acceptor (+/-2bp)		6 clinvar	6 clinvar			12
Total	18	20	103	16	3	160

Highest pathogenic variant AF is 0.00001505344

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 67 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_019042.5	RefSeq	NP_061915.2	15	MANE Select
ENST00000469408.6	Ensembl	ENSP00000417402.1	15	MANE Select
NM_001318163.1	RefSeq	NP_001305092.1	16	Standard
NM_001318164.2	RefSeq	NP_001305093.1	15	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

tRNA modification in the nucleus and cytosol
tRNA processing
Metabolism of RNA

Biological Process

negative regulation of translation
tRNA pseudouridine synthesis
regulation of hematopoietic stem cell differentiation
mRNA pseudouridine synthesis
regulation of mesoderm development

Molecular Function

RNA binding
pseudouridine synthase activity
enzyme binding

Cellular Component

nucleus

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000356362
Coding exons: 15
Length: 82607
Individuals with no LoFs: 125703
Homozygous LoFs: 0
Heterozygous LoFs: 45
Defined: 125748
p: 0.000179

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.43	281	357	0.787	0.0000181	4371
Missense (PolyPhen)		77	108.39	0.71042		1342
Synonymous	-0.451	134	128	1.05	0.00000698	1206
Loss of Function	2.37	20	35.2	0.569	0.00000185	444

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00037	0.00037	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00017	0.00016	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00021	0.00021	rare
South Asian	0.00037	0.00029	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Pseudouridylate synthase that catalyzes pseudouridylation of RNAs (PubMed:28073919, PubMed:29628141). 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 (PubMed:29628141). Also catalyzes pseudouridylation of mRNAs: mediates pseudouridylation of mRNAs with the consensus sequence 5'-UGUAG-3' (PubMed:28073919). 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 (PubMed:29628141). {ECO:0000269|PubMed:28073919, ECO:0000269|PubMed:29628141}.;

Recessive Scores

pRec: 0.109

Intolerance Scores

LoFtool: 0.754
RVIS EVS: -0.58
RVIS percentile EVS: 18.72

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.337

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium