SH2D1A SH2 domain containing 1A [Homo sapiens (human)] - Gene

Summary

Official Symbol: SH2D1Aprovided by HGNC
Official Full Name: SH2 domain containing 1Aprovided by HGNC
Primary source: HGNC:HGNC:10820
See related: Ensembl:ENSG00000183918 MIM:300490; AllianceGenome:HGNC:10820
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: LYP; SAP; XLP; DSHP; EBVS; IMD5; XLPD; MTCP1; XLPD1; SAP/SH2D1A
Summary: This gene encodes a protein that plays a major role in the bidirectional stimulation of T and B cells. This protein contains an SH2 domain and a short tail. It associates with the signaling lymphocyte-activation molecule, thereby acting as an inhibitor of this transmembrane protein by blocking the recruitment of the SH2-domain-containing signal-transduction molecule SHP-2 to its docking site. This protein can also bind to other related surface molecules that are expressed on activated T, B and NK cells, thereby modifying signal transduction pathways in these cells. Mutations in this gene cause lymphoproliferative syndrome X-linked type 1 or Duncan disease, a rare immunodeficiency characterized by extreme susceptibility to infection with Epstein-Barr virus, with symptoms including severe mononucleosis and malignant lymphoma. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
Expression: Biased expression in lymph node (RPKM 17.0), spleen (RPKM 6.1) and 7 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: Xq25

Exon count:: 4

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	X	NC_000023.11 (124346563..124373160)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	X	NC_060947.1 (122657134..122683529)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	X	NC_000023.10 (123480413..123507010)

Chromosome X - NC_000023.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

SAP-expressing T peripheral helper cells identify systemic lupus erythematosus patients with lupus nephritis.
Title: SAP-expressing T peripheral helper cells identify systemic lupus erythematosus patients with lupus nephritis.
Overexpression of SH2D1A promotes cancer progression and is associated with immune cell infiltration in hepatocellular carcinoma via bioinformatics and in vitro study.
Title: Overexpression of SH2D1A promotes cancer progression and is associated with immune cell infiltration in hepatocellular carcinoma via bioinformatics and in vitro study.
Case Report: Meningoencephalitis With Thrombotic Occlusive Vasculopathy in a Young EBV-Naive Boy Is Associated With a Novel SH2D1A Mutation.
Title: Case Report: Meningoencephalitis With Thrombotic Occlusive Vasculopathy in a Young EBV-Naïve Boy Is Associated With a Novel SH2D1A Mutation.
Epstein-Barr Virus-Negative Granulomatous Disease Due to SAP Deficiency.
Title: Epstein-Barr Virus-Negative Granulomatous Disease Due to SAP Deficiency.
SLAM/SAP Decreased Follicular Regulatory T Cells in Patients with Graves' Disease.
Title: SLAM/SAP Decreased Follicular Regulatory T Cells in Patients with Graves' Disease.
SAP interacts with CD28 to inhibit PD-1 signaling in T lymphocytes.
Title: SAP interacts with CD28 to inhibit PD-1 signaling in T lymphocytes.
Diagnostic challenges for a novel SH2D1A mutation associated with X-linked lymphoproliferative disease.
Title: Diagnostic challenges for a novel SH2D1A mutation associated with X-linked lymphoproliferative disease.
A Novel Missense Mutation Affecting the N-terminal Domain of SAP Protein in X-linked Lymphoproliferative Disease.
Title: A Novel Missense Mutation Affecting the N-terminal Domain of SAP Protein in X-linked Lymphoproliferative Disease.
hese data indicate NK cell-mediated cytotoxicity is not equally affected in Acute lymphoblastic leukemia (ALL) patients, nevertheless a positive correlation between low SAP expression and decreased NK cell-mediated cytotoxicity was observed in ALL patients with a leukocyte count >/=50,000xmm3
Title: Functional characterization of NK cells in Mexican pediatric patients with acute lymphoblastic leukemia: Report from the Mexican Interinstitutional Group for the Identification of the Causes of Childhood Leukemia.
A new SH2D1A mutation in a female adult XLP disease with hemophagocytic lymphohistiocytosis and NK-cell leukemia.
Title: A new SH2D1A mutation in a female adult XLP disease with hemophagocytic lymphohistiocytosis and NK-cell leukemia.

Submit: New GeneRIF Correction See all GeneRIFs (89)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
X-linked lymphoproliferative disease due to SH2D1A deficiency MedGen: C5399825 OMIM: 308240 GeneReviews: X-Linked Lymphoproliferative Disease	not available

Copy number response

Description
Copy number response Triplosensitivity No evidence available (Last evaluated 2021-01-27) ClinGen Genome Curation Page Haploinsufficency Sufficient evidence for dosage pathogenicity (Last evaluated 2021-01-27) ClinGen Genome Curation PagePubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein-macromolecule adaptor activity	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in adaptive immune response	IEA Inferred from Electronic Annotation more info
involved_in cell-cell signaling	IEA Inferred from Electronic Annotation more info
involved_in cellular defense response	IEA Inferred from Electronic Annotation more info
involved_in humoral immune response	IEA Inferred from Electronic Annotation more info
involved_in natural killer cell activation	IDA Inferred from Direct Assay more info	PubMed
involved_in natural killer cell mediated cytotoxicity	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of T cell receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of natural killer cell mediated cytotoxicity	IEA Inferred from Electronic Annotation more info
involved_in regulation of immune response	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
is_active_in cytoplasm	TAS Traceable Author Statement more info	PubMed
located_in cytosol	TAS Traceable Author Statement more info

General protein information

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Preferred Names: SH2 domain-containing protein 1A

Names: Duncan disease SH2-protein; SLAM associated protein/SH2 domain protein 1A; SLAM-associated protein; T cell signal transduction molecule SAP; signaling lymphocyte activation molecule-associated protein; signaling lymphocytic activation molecule-associated protein

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_007464.1 RefSeqGene

Range

4983..31861

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_106

mRNA and Protein(s)

NM_001114937.3 → NP_001108409.1 SH2 domain-containing protein 1A isoform 2

See identical proteins and their annotated locations for NP_001108409.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) uses an alternate in-frame splice site in the 3' coding region, compared to variant 1, resulting in a shorter protein (isoform 2), compared to isoform 1.

Source sequence(s)

AA190204, AF100541, AL023657, DA007747

Consensus CDS

CCDS48162.1

UniProtKB/Swiss-Prot

O60880

Related

ENSP00000353126.4, ENST00000360027.5

Conserved Domains (1) summary

cd10400
Location:2 → 104

SH2_SAP1a; Src homology 2 (SH2) domain found in SLAM-associated protein (SAP) 1a
NM_002351.5 → NP_002342.1 SH2 domain-containing protein 1A isoform 1

See identical proteins and their annotated locations for NP_002342.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).

Source sequence(s)

AA190204, AL023657

Consensus CDS

CCDS14608.1

UniProtKB/Swiss-Prot

A8MSW0, O60880, O95383, O95384, O95385, O95386, Q6FGS6, Q9UNR0

Related

ENSP00000360181.5, ENST00000371139.9

Conserved Domains (1) summary

cd10400
Location:2 → 104

SH2_SAP1a; Src homology 2 (SH2) domain found in SLAM-associated protein (SAP) 1a