SIT1

protein-coding

signaling threshold regulating transmembrane adaptor 1

Gene summary

Enables kinase binding activity. Involved in regulation of T cell activation. Located in plasma membrane. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_014450.3

Inheritance

—

ClinVar variants

P:1U:25B:3

Top phenotype

IMMUNODEFICIENCY 135

gnomAD constraint

pLI —, LoF o/e 0.6

Max pathogenic AF

—

Genomic locus

chr9:35,649,295-35,650,931

External References & Databases

Ensembl (ENSG00000137078)

Transcript & Mutation Effects

hg38 • Region Span ~1.6 kb

Loading mutation effect viewer...

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 SIT1 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 25

not providedTotal: 1

IMMUNODEFICIENCY 135Total: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_014450.3. 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				1 clinvar		1
missense			25 clinvar	2 clinvar		27
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)	1 clinvar					1
Total	1	0	25	3	0	29

Highest pathogenic variant AF is 0.0001425386

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 8 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_014450.3	RefSeq	NP_055265.1	5	MANE Select
ENST00000259608.8	Ensembl	ENSP00000259608.3	5	MANE Select
ENST00000922878.1	Ensembl	ENSP00000592937.1	5	Standard
ENST00000922878.2	Ensembl	ENSP00000592937.1	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Biological Process

adaptive immune response
signal transduction
T cell homeostasis
regulation of T cell activation

Molecular Function

protein binding
kinase binding
SH2 domain binding

Cellular Component

plasma membrane
integral component of plasma membrane
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000259608
Coding exons: 5
Length: 1646
Individuals with no LoFs: 125647
Homozygous LoFs: 0
Heterozygous LoFs: 94
Defined: 125741
p: 0.000374

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.17	79	114	0.692	0.00000678	1202
Missense (PolyPhen)		15	31.491	0.47633		357
Synonymous	0.153	48	49.4	0.972	0.00000294	416
Loss of Function	1.16	6	9.96	0.603	4.24e-7	111

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.0040	0.0040	notable
European (Non-Finnish)	0.000035	0.000035	rare
South Asian	0.000033	0.000033	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Negatively regulates TCR (T-cell antigen receptor)- mediated signaling in T-cells. Involved in positive selection of T-cells. {ECO:0000269|PubMed:10209036}.;

Recessive Scores

pRec: 0.0998

Intolerance Scores

LoFtool: 0.230
RVIS EVS: 0.31
RVIS percentile EVS: 72.23

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.925

Gene Damage Prediction

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