TESPA1

protein-coding

thymocyte expressed, positive selection associated 1

Gene summary

Predicted to enable phospholipase binding activity and signaling receptor binding activity. Predicted to be involved in COP9 signalosome assembly; positive regulation of T cell differentiation in thymus; and positive regulation of T cell receptor signaling pathway. Predicted to act upstream of or within TCR signalosome assembly. Located in cytosol. Part of COP9 signalosome. [provided by Alliance of Genome Resources, Jul 2025]

Previous symbols:

KIAA0748

MANE transcript

NM_001136030.3

Inheritance

—

ClinVar variants

U:58B:3

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.5

Max pathogenic AF

—

Genomic locus

chr12:54,948,015-54,984,762

External References & Databases

Ensembl (ENSG00000135426)

Transcript & Mutation Effects

hg38 • Region Span ~36.7 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 TESPA1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 53

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001136030.3. 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			2 clinvar	2 clinvar		4
missense			54 clinvar	1 clinvar		55
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	58	3	0	61

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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_001136030.3	RefSeq	NP_001129502.1	9	MANE Select
ENST00000449076.6	Ensembl	ENSP00000400892.1	9	MANE Select
NM_001098815.3	RefSeq	NP_001092285.1	9	Standard
NM_001261844.1	RefSeq	NP_001248773.1	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

COP9 signalosome assembly
positive regulation of T cell differentiation in thymus
positive regulation of T cell receptor signaling pathway

Molecular Function

signaling receptor binding

Cellular Component

cytoplasm
endoplasmic reticulum membrane
COP9 signalosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000449076
Coding exons: 9
Length: 36729
Individuals with no LoFs: 124958
Homozygous LoFs: 0
Heterozygous LoFs: 70
Defined: 125028
p: 0.000280

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.729	245	279	0.877	0.0000146	3436
Missense (PolyPhen)		67	95.027	0.70506		1185
Synonymous	1.01	88	101	0.872	0.00000497	964
Loss of Function	2.37	13	26.1	0.498	0.00000139	283

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00077	0.00077	rare
Latino/Admixed American	0.00026	0.00026	rare
Ashkenazi Jewish	0.00020	0.00020	rare
East Asian	0.00011	0.00011	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00020	0.00020	rare
South Asian	0.00052	0.00052	rare
Other	0.00083	0.00082	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Required for the development and maturation of T-cells, its function being essential for the late stages of thymocyte development (By similarity). Plays a role in T-cell antigen receptor (TCR)-mediated activation of the ERK and NFAT signaling pathways, possibly by serving as a scaffolding protein that promotes the assembly of the LAT signalosome in thymocytes. May play a role in the regulation of inositol 1,4,5-trisphosphate receptor-mediated Ca(2+) release and mitochondrial Ca(2+) uptake via the mitochondria-associated endoplasmic reticulum membrane (MAM) compartment. {ECO:0000250, ECO:0000269|PubMed:22561606}.;

Intolerance Scores

RVIS EVS: 1.49
RVIS percentile EVS: 95.35

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.114

Gene Damage Prediction

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