TSPYL2

protein-coding

TSPY like 2

Gene summary

This gene encodes a member of the testis-specific protein Y-encoded, TSPY-like/SET/nucleosome assembly protein-1 superfamily. The encoded protein is localized to the nucleolus where it functions in chromatin remodeling and as an inhibitor of cell-cycle progression. This protein may play a role in the suppression of tumor growth. [provided by RefSeq, Sep 2009]

MANE transcript

NM_022117.4

Inheritance

—

ClinVar variants

U:117B:10

Top phenotype

TSPYL2-related condition

gnomAD constraint

pLI —, LoF o/e 0.13

Max pathogenic AF

—

Genomic locus

chrX:53,082,367-53,088,540

External References & Databases

Ensembl (ENSG00000184205)

Transcript & Mutation Effects

hg38 • Region Span ~6.2 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TSPYL2 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 93

not providedTotal: 15

TSPYL2-related conditionTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_022117.4. 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			6 clinvar	3 clinvar		9
missense			97 clinvar	6 clinvar	1 clinvar	104
nonsense			3 clinvar			3
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			10 clinvar			10
Total	0	0	117	9	1	127

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 48 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_022117.4	RefSeq	NP_071400.1	7	MANE Select
ENST00000375442.8	Ensembl	ENSP00000364591.4	7	MANE Select
ENST00000578306.5	Ensembl	ENSP00000462635.1	2	Standard
ENST00000579390.1	Ensembl	ENSP00000462287.1	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

XBP1(S) activates chaperone genes

Biological Process

nucleosome assembly
cell cycle
negative regulation of DNA replication
regulation of signal transduction
negative regulation of cell growth

Molecular Function

rDNA binding
protein binding

Cellular Component

nucleus
nucleoplasm
nucleolus
cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000375442
Coding exons: 7
Length: 6174
Individuals with no LoFs: 125729
Homozygous LoFs: 6
Heterozygous LoFs: 5
Defined: 125740
p: 0.0000437

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.330	262	277	0.944	0.0000213	4664
Missense (PolyPhen)		54	88.548	0.60984		1572
Synonymous	-3.27	157	113	1.39	0.00000943	1245
Loss of Function	3.18	2	15.5	0.129	0.00000109	270

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00015	0.00011	rare
Finnish	0.000066	0.000046	rare
European (Non-Finnish)	0.000079	0.000053	rare
South Asian	0.00011	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Part of the CASK/TBR1/TSPYL2 transcriptional complex which modulates gene expression in response to neuronal synaptic activity, probably by facilitating nucleosome assembly. May inhibit cell proliferation by inducing p53-dependent CDKN1A expression. {ECO:0000269|PubMed:11395479, ECO:0000269|PubMed:17317670}.;

Recessive Scores

pRec: 0.277

Intolerance Scores

LoFtool: 0.452
RVIS EVS: -0.71
RVIS percentile EVS: 14.5

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.731

Gene Damage Prediction

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