SH3GL1

protein-coding

SH3 domain containing GRB2 like 1, endophilin A2, the group of N-BAR domain containing

Gene summary

This gene encodes a member of the endophilin family of Src homology 3 domain-containing proteins. The encoded protein is involved in endocytosis and may also play a role in the cell cycle. Overexpression of this gene may play a role in leukemogenesis, and the encoded protein has been implicated in acute myeloid leukemia as a fusion partner of the myeloid-lymphoid leukemia protein. Pseudogenes of this gene are located on the long arm of chromosomes 11 and 17. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jan 2011]

MANE transcript

NM_003025.4

Inheritance

ClinVar variants

P:1U:60B:5

Top phenotype

IMMUNODEFICIENCY, COMMON VARIABLE, 16

gnomAD constraint

pLI —, LoF o/e 0.34

Max pathogenic AF

—

Genomic locus

chr19:4,360,370-4,400,547

External References & Databases

Ensembl (ENSG00000141985)

Transcript & Mutation Effects

hg38 • Region Span ~40.2 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

immunodeficiency diseaseLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0021094

Submitter: Ambry Genetics

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SH3GL1 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 50

not providedTotal: 4

IMMUNODEFICIENCY, COMMON VARIABLE, 16Total: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_003025.4. 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			5 clinvar	2 clinvar	2 clinvar	9
missense			48 clinvar	1 clinvar		49
nonsense			1 clinvar			1
start loss						0
frameshift	1 clinvar					1
splice donor/acceptor (+/-2bp)			6 clinvar			6
Total	1	0	60	3	2	66

Highest pathogenic variant AF is 0.0000065748814

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 25 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_003025.4	RefSeq	NP_003016.1	10	MANE Select
ENST00000269886.7	Ensembl	ENSP00000269886.2	10	MANE Select
NM_001199943.2	RefSeq	NP_001186872.1	9	Standard
NM_001199944.2	RefSeq	NP_001186873.1	10	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Endocytosis - Homo sapiens (human)
Disease
Signal Transduction
Vesicle-mediated transport
Membrane Trafficking

Biological Process

signal transduction
central nervous system development
synaptic vesicle uncoating
modulation of excitatory postsynaptic potential
positive regulation of synaptic vesicle endocytosis

Molecular Function

protein binding
protein C-terminus binding
lipid binding
SH3 domain binding
phosphatase binding

Cellular Component

podosome
cytoplasm
cytosol
cell junction
early endosome membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000269886
Coding exons: 10
Length: 40178
Individuals with no LoFs: 125712
Homozygous LoFs: 0
Heterozygous LoFs: 17
Defined: 125729
p: 0.0000676

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.918	195	235	0.831	0.0000170	2391
Missense (PolyPhen)		37	63.344	0.58411		681
Synonymous	-3.26	155	111	1.39	0.00000895	701
Loss of Function	2.77	7	20.6	0.340	0.00000111	231

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	0.00029	0.00028	rare
European (Non-Finnish)	0.000063	0.000062	rare
South Asian	0.000067	0.000065	rare
Other	0.00017	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Implicated in endocytosis. May recruit other proteins to membranes with high curvature (By similarity). {ECO:0000250}.;
Disease: DISEASE: Note=In some cases of acute leukemia, a translocation results in the formation of a KMT2A/MLL1-EEN fusion gene. {ECO:0000269|PubMed:9122235}.;

Intolerance Scores

LoFtool: 0.292
RVIS EVS: -1.02
RVIS percentile EVS: 8

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.907

Gene Damage Prediction

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