SLA

protein-coding

Src like adaptor, the group of SH2 domain containing|MicroRNA protein coding host genes

Gene summary

Predicted to enable epidermal growth factor receptor binding activity and phosphotyrosine residue binding activity. Predicted to be involved in regulation of MAPK cascade and signal transduction. Predicted to be located in cytosol. Predicted to be part of COP9 signalosome. Predicted to be active in cytoplasm; nucleoplasm; and plasma membrane. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_001045556.3

Inheritance

—

ClinVar variants

U:39B:4

Top phenotype

Inborn genetic diseases

gnomAD constraint

pLI —, LoF o/e 0.23

Max pathogenic AF

—

Genomic locus

chr8:133,036,728-133,102,912

External References & Databases

Ensembl (ENSG00000155926)

Transcript & Mutation Effects

hg38 • Region Span ~66.2 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 SLA variants in ClinVar

7 Conditions Cataloged

not providedTotal: 67

not specifiedTotal: 54

Inborn genetic diseasesTotal: 23

Iodotyrosyl coupling defectTotal: 12

TG-related disorderTotal: 2

Autoimmune thyroid disease, susceptibility to, 3Total: 2

Congenital hypothyroidismTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001045556.3. 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	2 clinvar		3
missense			35 clinvar	2 clinvar		37
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	39	4	0	43

Highest pathogenic variant AF is 0.00007124537

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 36 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001045556.3	RefSeq	NP_001039021.1	7	MANE Select
ENST00000338087.10	Ensembl	ENSP00000337548.5	7	MANE Select
NM_001045557.3	RefSeq	NP_001039022.2	8	Standard
NM_001282964.2	RefSeq	NP_001269893.1	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

TCR
PDGFR-beta signaling pathway

Biological Process

positive regulation of signal transduction
cell differentiation
peptidyl-tyrosine autophosphorylation
regulation of cell population proliferation

Molecular Function

non-membrane spanning protein tyrosine kinase activity
SH3/SH2 adaptor activity
protein binding

Cellular Component

endosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000427060
Coding exons: 7
Length: 66326
Individuals with no LoFs: 125735
Homozygous LoFs: 0
Heterozygous LoFs: 8
Defined: 125743
p: 0.0000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.876	150	183	0.818	0.0000103	2026
Missense (PolyPhen)		59	90.77	0.64999		994
Synonymous	0.158	76	77.8	0.977	0.00000477	646
Loss of Function	2.98	4	17.5	0.229	0.00000103	175

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000060	0.000058	rare
Ashkenazi Jewish	0.00020	0.00020	rare
East Asian	0.00011	0.00011	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0	0.0	absent
South Asian	0.000065	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Adapter protein, which negatively regulates T-cell receptor (TCR) signaling. Inhibits T-cell antigen-receptor induced activation of nuclear factor of activated T-cells. Involved in the negative regulation of positive selection and mitosis of T-cells. May act by linking signaling proteins such as ZAP70 with CBL, leading to a CBL dependent degradation of signaling proteins. {ECO:0000269|PubMed:10449770, ECO:0000269|PubMed:11696592}.;

Recessive Scores

pRec: 0.329

Intolerance Scores

LoFtool: 0.168
RVIS EVS: -0.09
RVIS percentile EVS: 46.74

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.866

Gene Damage Prediction

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