STAM2

protein-coding

signal transducing adaptor molecule 2, the group of ESCRT-0

Gene summary

The protein encoded by this gene is closely related to STAM, an adaptor protein involved in the downstream signaling of cytokine receptors, both of which contain a SH3 domain and the immunoreceptor tyrosine-based activation motif (ITAM). Similar to STAM, this protein acts downstream of JAK kinases, and is phosphorylated in response to cytokine stimulation. This protein and STAM thus are thought to exhibit compensatory effects on the signaling pathway downstream of JAK kinases upon cytokine stimulation. [provided by RefSeq, Jul 2008]

MANE transcript

NM_005843.6

Inheritance

—

ClinVar variants

U:71B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.46

Max pathogenic AF

—

Genomic locus

chr2:152,116,801-152,175,763

External References & Databases

Ensembl (ENSG00000115145)

Transcript & Mutation Effects

hg38 • Region Span ~59.0 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 STAM2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 67

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005843.6. 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	1 clinvar		3
missense			67 clinvar	1 clinvar		68
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	71	2	0	73

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 12 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_005843.6	RefSeq	NP_005834.4	14	MANE Select
ENST00000263904.5	Ensembl	ENSP00000263904.4	14	MANE Select
ENST00000865052.1	Ensembl	ENSP00000535111.1	15	Standard
ENST00000865052.2	Ensembl	ENSP00000535111.1	15	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Jak-STAT signaling pathway - Homo sapiens (human)
Endocytosis - Homo sapiens (human)
EGF-EGFR Signaling Pathway
Disease
Signal Transduction

Biological Process

intracellular protein transport
endosomal transport
macroautophagy
multivesicular body assembly
negative regulation of epidermal growth factor receptor signaling pathway

Molecular Function

protein binding

Cellular Component

nucleoplasm
cytoplasm
cytosol
early endosome membrane
ESCRT-0 complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000263904
Coding exons: 14
Length: 59192
Individuals with no LoFs: 125676
Homozygous LoFs: 0
Heterozygous LoFs: 72
Defined: 125748
p: 0.000286

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.348	253	269	0.940	0.0000127	3444
Missense (PolyPhen)		70	86.922	0.80532		1138
Synonymous	0.738	84	93.1	0.903	0.00000448	975
Loss of Function	2.65	13	28.2	0.461	0.00000119	376

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00056	0.00055	rare
Latino/Admixed American	0.00021	0.00020	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.00011	0.00011	rare
Finnish	0.00067	0.00065	rare
European (Non-Finnish)	0.00028	0.00028	rare
South Asian	0.00024	0.00023	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Involved in intracellular signal transduction mediated by cytokines and growth factors. Upon IL-2 and GM-CSL stimulation, it plays a role in signaling leading to DNA synthesis and MYC induction. May also play a role in T-cell development. Involved in down-regulation of receptor tyrosine kinase via multivesicular body (MVBs) when complexed with HGS (ESCRT-0 complex). The ESCRT-0 complex binds ubiquitin and acts as sorting machinery that recognizes ubiquitinated receptors and transfers them to further sequential lysosomal sorting/trafficking processes (By similarity). {ECO:0000250}.;

Recessive Scores

pRec: 0.234

Intolerance Scores

LoFtool: 0.763
RVIS EVS: -0.38
RVIS percentile EVS: 27.69

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.810

Gene Damage Prediction

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