SH3GL1

Summary

SH3GL1 (SH3 domain containing GRB2 like 1, endophilin A2, HGNC:10830) is a protein-coding gene on chromosome 19p13.3, encoding Endophilin-A2 (Q99961). Implicated in endocytosis.

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.

Source: NCBI Gene 6455 — RefSeq curated summary.

At a glance

• Gene–disease (curated): immunodeficiency disease (Limited, GenCC)
• GWAS associations: 3
• Clinical variants (ClinVar): 77 total
• Phenotypes (HPO): 3
• MANE Select transcript: NM_003025

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10830
Approved symbol	SH3GL1
Name	SH3 domain containing GRB2 like 1, endophilin A2
Location	19p13.3
Locus type	gene with protein product
Status	Approved
Aliases	SH3P8, SH3D2B, CNSA1, EEN, MGC111371
Ensembl gene	ENSG00000141985
Ensembl biotype	protein_coding
OMIM	601768
Entrez	6455

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 10 protein_coding

ENST00000269886, ENST00000417295, ENST00000593591, ENST00000598219, ENST00000598230, ENST00000598564, ENST00000908568, ENST00000908569, ENST00000936273, ENST00000945946

RefSeq mRNA: 3 — MANE Select: NM_003025 NM_001199943, NM_001199944, NM_003025

CCDS: CCDS32874, CCDS56076, CCDS59335

Canonical transcript exons

ENST00000269886 — 10 exons

Exon	Start	End
ENSE00000951624	4365482	4365625
ENSE00000951625	4364088	4364221
ENSE00000951626	4363720	4363878
ENSE00000951627	4363370	4363473
ENSE00000951628	4362612	4362736
ENSE00000951629	4362329	4362385
ENSE00001355358	4400324	4400547
ENSE00001617278	4366501	4366573
ENSE00002981321	4360370	4361796
ENSE00003606076	4366926	4366994

Expression profiles

Bgee: expression breadth ubiquitous, 290 present calls, max score 99.08.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 34.9033 / max 788.3649, expressed in 1822 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
178430	34.9033	1822

Top tissues by expression

296 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	99.08	gold quality
esophagus mucosa	UBERON:0002469	97.29	gold quality
skin of leg	UBERON:0001511	97.15	gold quality
skin of abdomen	UBERON:0001416	96.79	gold quality
esophagus	UBERON:0001043	95.62	gold quality
pharyngeal mucosa	UBERON:0000355	95.57	gold quality
zone of skin	UBERON:0000014	95.48	gold quality
ectocervix	UBERON:0012249	95.47	gold quality
stromal cell of endometrium	CL:0002255	95.40	gold quality
olfactory bulb	UBERON:0002264	94.91	silver quality
left adrenal gland cortex	UBERON:0035825	94.47	gold quality
right adrenal gland cortex	UBERON:0035827	94.43	gold quality
left adrenal gland	UBERON:0001234	94.42	gold quality
right adrenal gland	UBERON:0001233	94.36	gold quality
mucosa of stomach	UBERON:0001199	94.33	gold quality
vagina	UBERON:0000996	94.11	gold quality
adrenal cortex	UBERON:0001235	94.02	gold quality
left uterine tube	UBERON:0001303	93.85	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	93.78	gold quality
lower esophagus	UBERON:0013473	93.70	gold quality
lower esophagus muscularis layer	UBERON:0035833	93.67	gold quality
right ovary	UBERON:0002118	93.63	gold quality
type B pancreatic cell	CL:0000169	93.57	silver quality
adrenal gland	UBERON:0002369	93.56	gold quality
endocervix	UBERON:0000458	93.54	gold quality
peripheral nervous system	UBERON:0000010	93.50	gold quality
nerve	UBERON:0001021	93.50	gold quality
tibial nerve	UBERON:0001323	93.50	gold quality
upper arm skin	UBERON:0004263	93.41	gold quality
uterine cervix	UBERON:0000002	93.37	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.34

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): RUNX1, SP1

miRNA regulators (miRDB)

66 targeting SH3GL1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-6798-5P	100.00	65.77	699
HSA-MIR-520G-5P	99.99	66.76	658
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-3682-5P	99.93	67.97	1163
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-3663-3P	99.84	70.39	798
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-636	99.80	69.58	1500
HSA-MIR-320A-3P	99.77	69.73	2107
HSA-MIR-320B	99.77	69.73	2107
HSA-MIR-320C	99.77	69.73	2107
HSA-MIR-320D	99.77	69.73	2107
HSA-MIR-4429	99.77	69.62	2111
HSA-MIR-8084	99.73	69.57	1760
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-4255	99.72	67.70	1541
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-6132	99.60	65.83	1554
HSA-MIR-6836-5P	99.60	65.62	1538
HSA-MIR-122B-5P	99.46	70.81	1457

Literature-anchored findings (GeneRIF, showing 22)

• new mechanism for MLL-EEN-mediated leukemogenesis in which MLL-EEN interferes with the Ras-suppressing activities of EBP through direct interaction. (PMID:14551139)
• EEN part plays an essential role in leukemogenesis caused by MLL-EEN. (PMID:15077184)
• Our results suggest that distinct subcellular localization of the endophilin A family members probably underpins their diverse cellular functions and indicates a role for EEN/EA2 in the cell cycle. (PMID:15214844)
• findings reveal a concomitant activation of endocytosis and ERK signaling by BPGAP1 via the coupling of its proline-rich region, which targets EEN and its functional GAP domain (PMID:15944398)
• SH3GL1 is possibly one of the disease associated genes of adolescent idiopathic scoliosis. (PMID:20627007)
• Idiopathic scoliosis is a multifactorial genetic disease and SH3GL1 may be one of the pathogenic genes for this disease. (PMID:22183150)
• A protein encoded by this locus was found to be differentially expressed in postmortem brains from patients with atypical frontotemporal lobar degeneration. (PMID:22360420)
• Two endophilin A2 mutants, E264A and E264R, have different effects on how endophilin interacts with other proteins, such as dynamin or beta1-adrenergic receptors. (PMID:22750032)
• SH3GL1 may be involved in the oncogenic process of gliomas and effectively elicit an autologous antibody response in low-grade gliomas. (PMID:23050879)
• MIR218 functions as a tumor suppressor by regulating SH3GL1 expression in medulloblastoma cancer cells. (PMID:23970061)
• these data suggest that EEN may play a pivotal role in excessive cell proliferation and insufficient cell apoptosis of bone marrow plasma cells in multiple myeloma. (PMID:24704450)
• results establish a novel function of endoA2 in clathrin-independent endocytosis (PMID:25517096)
• Endo II expression was highest in triple-negative breast cancers tumors compared with other subtypes, and at the level of gene expression, high Endo II was associated with reduced relapse-free survival in patients with basal-like breast cancers. (PMID:25784716)
• inhibition of SH3GL1 reverses multidrug resistance through declining P-glycoprotein expression via the EGFR/ERK/AP-1 pathway. (PMID:27220321)
• Endophilin-A2 was identified as a novel molecule regulating macrophage-derived foam cell formation by mechanisms attributable to clathrin-mediated endocytosis and beyond clathrin-mediated endocytosis (PMID:27741419)
• Expression level of SH3GL1 was widely upregulated in human OS tissues, and their overexpression was significantly correlated with more aggressive clinicopathological features. (PMID:28702842)
• Our study provides novel evidence of Endo II function in HER2+ cancer cell motility and trafficking of HER2 that relates to effective treatments with trastuzumab or T-DM1. Thus, differential expression of Endo II may relate to sensitivity or resistance to trastuzumab-based therapies for HER2+ cancers (PMID:28974266)
• Study observed elevated EA2 gene expression in the subcutaneous compared to that in the visceral human adipose tissue. EA2 gene expression negatively correlated with adiponectin and chemerin in visceral adipose tissue, and positively correlated with TNF-alpha in subcutaneous adipose tissue. EA2 gene expression was significantly downregulated during differentiation of preadipocytes in vitro. (PMID:29113429)
• FBP17 and CIP4 prime the membrane of resting cells for fast endophilin-mediated endocytosis by recruiting the 5’-lipid phosphatase SHIP2 and lamellipodin to mediate the local production of phosphatidylinositol-3,4-bisphosphate and endophilin pre-enrichment. (PMID:30061681)
• EV71 enters Caco-2 cells mainly via an endophilin-A2-mediated endocytic pathway. (PMID:31132962)
• Endophilin A2 regulates B-cell endocytosis and is required for germinal center and humoral responses. (PMID:34323351)
• The SH3 binding site in front of the WH1 domain contributes to the membrane binding of the BAR domain protein endophilin A2. (PMID:37812440)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	sh3gl1b	ENSDARG00000002642
danio_rerio	sh3gl1a	ENSDARG00000067958
mus_musculus	Sh3gl1	ENSMUSG00000003200
rattus_norvegicus	Sh3gl1	ENSRNOG00000049683
drosophila_melanogaster	Dlish	FBGN0034264
caenorhabditis_elegans		WBGENE00015128

Paralogs (12): SORBS1 (ENSG00000095637), SH3GLB1 (ENSG00000097033), NCF4 (ENSG00000100365), SH3GL2 (ENSG00000107295), SH3D19 (ENSG00000109686), SORBS3 (ENSG00000120896), SH3GL3 (ENSG00000140600), SH3GLB2 (ENSG00000148341), SH3RF1 (ENSG00000154447), SORBS2 (ENSG00000154556), SH3RF2 (ENSG00000156463), SH3RF3 (ENSG00000172985)

Protein

Protein identifiers

Endophilin-A2 — Q99961 (reviewed: Q99961)

Alternative names: EEN fusion partner of MLL, Endophilin-2, Extra eleven-nineteen leukemia fusion gene protein, SH3 domain protein 2B, SH3 domain-containing GRB2-like protein 1

All UniProt accessions (5): Q99961, M0QYE0, M0R0I3, M0R2K6, Q6FGM0

UniProt curated annotations — full annotation on UniProt →

Function. Implicated in endocytosis. May recruit other proteins to membranes with high curvature.

Subunit / interactions. Interacts with ARC. Interacts with SYNJ1 and DNM1. Interacts with PDCD6IP. Interacts with BIN2.

Subcellular location. Cytoplasm. Early endosome membrane. Cell projection. Podosome.

Tissue specificity. Ubiquitous. Higher expression in pancreas, placenta, prostate, testis and uterus.

Disease relevance. In some cases of acute leukemia, a translocation results in the formation of a KMT2A/MLL1-EEN fusion gene.

Domain organisation. An N-terminal amphipathic helix, the BAR domain and a second amphipathic helix inserted into helix 1 of the BAR domain (N-BAR domain) induce membrane curvature and bind curved membranes.

Similarity. Belongs to the endophilin family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q99961-1	1	yes
Q99961-2	2
Q99961-3	3

RefSeq proteins (3): NP_001186872, NP_001186873, NP_003016* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001452	SH3_domain	Domain
IPR004148	BAR_dom	Domain
IPR027267	AH/BAR_dom_sf	Homologous_superfamily
IPR035824	Endophilin_A_SH3	Domain
IPR036028	SH3-like_dom_sf	Homologous_superfamily
IPR050384	Endophilin_SH3RF	Family

Pfam: PF00018, PF03114

UniProt features (17 total): modified residue 4, region of interest 4, domain 2, splice variant 2, chain 1, sequence conflict 1, coiled-coil region 1, compositionally biased region 1, site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q99961-F1	84.43	0.62

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 15–16 (breakpoint for translocation to form kmt2a/mll1-een oncogene)

Post-translational modifications (4): 288, 292, 298, 315

Function

Pathways and Gene Ontology

Reactome pathways

15 pathways

ID	Pathway
R-HSA-182971	EGFR downregulation
R-HSA-6807004	Negative regulation of MET activity
R-HSA-8856825	Cargo recognition for clathrin-mediated endocytosis
R-HSA-8856828	Clathrin-mediated endocytosis
R-HSA-8875360	InlB-mediated entry of Listeria monocytogenes into host cell
R-HSA-162582	Signal Transduction
R-HSA-1643685	Disease
R-HSA-177929	Signaling by EGFR
R-HSA-199991	Membrane Trafficking
R-HSA-5653656	Vesicle-mediated transport
R-HSA-5663205	Infectious disease
R-HSA-6806834	Signaling by MET
R-HSA-8876384	Listeria monocytogenes entry into host cells
R-HSA-9006934	Signaling by Receptor Tyrosine Kinases
R-HSA-9824439	Bacterial Infection Pathways

MSigDB gene sets: 187 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_UP, MULLIGHAN_NPM1_SIGNATURE_3_UP, ENK_UV_RESPONSE_KERATINOCYTE_UP, GOBP_VESICLE_MEDIATED_TRANSPORT, REACTOME_MEMBRANE_TRAFFICKING, WANG_ESOPHAGUS_CANCER_VS_NORMAL_DN, MODULE_120, RICKMAN_METASTASIS_DN, GOBP_MEMBRANE_ORGANIZATION, KEGG_ENDOCYTOSIS, ACEVEDO_LIVER_CANCER_UP, GOBP_IMPORT_INTO_CELL, GOBP_ENDOCYTOSIS, REACTOME_EGFR_DOWNREGULATION, GRADE_COLON_AND_RECTAL_CANCER_UP

GO Biological Process (3): endocytosis (GO:0006897), signal transduction (GO:0007165), central nervous system development (GO:0007417)

GO Molecular Function (4): lipid binding (GO:0008289), identical protein binding (GO:0042802), cadherin binding (GO:0045296), protein binding (GO:0005515)

GO Cellular Component (10): podosome (GO:0002102), cytoplasm (GO:0005737), cytosol (GO:0005829), early endosome membrane (GO:0031901), presynapse (GO:0098793), glutamatergic synapse (GO:0098978), endosome (GO:0005768), membrane (GO:0016020), cell projection (GO:0042995), anchoring junction (GO:0070161)

Reactome top-level categories

Rollup of top-11 pathways:

Category	Pathways
Signaling by Receptor Tyrosine Kinases	2
Signaling by EGFR	1
Signaling by MET	1
Clathrin-mediated endocytosis	1
Membrane Trafficking	1
Listeria monocytogenes entry into host cells	1
Vesicle-mediated transport	1
Disease	1
Bacterial Infection Pathways	1
Signal Transduction	1
Infectious disease	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
binding	2
synapse	2
vesicle budding from membrane	1
membrane invagination	1
vesicle-mediated transport	1
import into cell	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
nervous system development	1
system development	1
protein binding	1
cell adhesion molecule binding	1
actin-based cell projection	1
intracellular anatomical structure	1
cytoplasm	1
early endosome	1
endosome membrane	1
endomembrane system	1
cytoplasmic vesicle	1
cell junction	1

Protein interactions and networks

STRING

1364 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SH3GL1	SYNJ1	O43426	950
SH3GL1	SYNJ2	O15056	886
SH3GL1	ARC	Q7LC44	767
SH3GL1	LRRK2	Q5S007	740
SH3GL1	PDCD6IP	Q8WUM4	738
SH3GL1	MAP4K3	Q8IVH8	724
SH3GL1	ATG3	Q9NT62	639
SH3GL1	AMPH	P49418	633
SH3GL1	PTK2	Q05397	604
SH3GL1	TET1	Q8NFU7	601
SH3GL1	FNBP1	Q96RU3	594
SH3GL1	RAB5B	P35239	590
SH3GL1	DNM2	P50570	589
SH3GL1	EPN2	O95208	576
SH3GL1	EPS15	P42566	575

IntAct

212 interactions, top by confidence:

A	B	Type	Score
DPPA4	SH3GL1	psi-mi:“MI:0915”(physical association)	0.900
SH3GL1	DPPA4	psi-mi:“MI:0915”(physical association)	0.900
SGF29	NDC80	psi-mi:“MI:0914”(association)	0.840
SH3GL3	SH3GL1	psi-mi:“MI:0915”(physical association)	0.830
SH3GL1	SH3GL3	psi-mi:“MI:0915”(physical association)	0.830
RB1CC1	ATG13	psi-mi:“MI:0914”(association)	0.820
SH3GL2	SH3GL1	psi-mi:“MI:0914”(association)	0.800
SH3GL1	SH3GL1	psi-mi:“MI:0915”(physical association)	0.800
SH3GL1	SH3GL2	psi-mi:“MI:0915”(physical association)	0.800
SH2D4A	SH3GL1	psi-mi:“MI:0915”(physical association)	0.760
SH3GL1	SH2D4A	psi-mi:“MI:0915”(physical association)	0.760
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
SH3GL1	PRR5-ARHGAP8	psi-mi:“MI:0915”(physical association)	0.670
GPKOW	SH3GL1	psi-mi:“MI:0915”(physical association)	0.670
PRR5-ARHGAP8	SH3GL1	psi-mi:“MI:0915”(physical association)	0.670

BioGRID (236): SH3GL1 (Two-hybrid), SH3GL1 (Two-hybrid), SH3GL2 (Two-hybrid), MTA1 (Two-hybrid), GPKOW (Two-hybrid), VPS37C (Two-hybrid), DPPA4 (Two-hybrid), SH2D4A (Two-hybrid), MAL2 (Two-hybrid), FAM102A (Two-hybrid), SH3GL1 (Affinity Capture-MS), SH3GL1 (Affinity Capture-MS), SH3GL1 (Affinity Capture-MS), SH3GL1 (Affinity Capture-MS), SH3GL1 (Affinity Capture-MS)

ESM2 similar proteins: A0A1B7YDZ4, B1H267, B3STP6, O14243, O43150, O97902, P34445, P40531, P47057, P91124, Q09746, Q10253, Q1AAU6, Q2KJA1, Q2KJB5, Q2T9M1, Q3ZBM5, Q4R7Q5, Q54XE8, Q5PPZ5, Q5R613, Q5REH1, Q62083, Q62419, Q68FW8, Q6CTQ0, Q6FPT9, Q6NRL2, Q6P8X1, Q75C43, Q7SIG6, Q7XPJ0, Q80ZJ7, Q86XE0, Q8IVI9, Q99961, Q9C6C3, Q9D8U8, Q9EP80, Q9FG38

Diamond homologs: A0JNJ1, A1CEK6, A1DFN5, A2QW93, A4RF61, A6QLK6, A7A261, F1LRS8, O35179, O35964, O43307, O74749, O75791, O75886, O88811, O89100, O93436, P02549, P07751, P09215, P09216, P10830, P13395, P16054, P16086, P16546, P23298, P24723, P28867, P29355, P32793, P34885, P38753, P43603, P53281, P62993, P62994, P70297, P87379, P97306

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
PTK2	unknown	SH3GL1	phosphorylation
SRC	down-regulates	SH3GL1	phosphorylation
SRC	unknown	SH3GL1	phosphorylation
LRRK2	down-regulates	SH3GL1	phosphorylation
SH3GL1	up-regulates	Endocytosis

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 133 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Signaling by FGFR1 in disease	5	17.6×	2e-03
Signaling by SCF-KIT	5	15.0×	3e-03
Recycling pathway of L1	5	13.5×	3e-03
Programmed Cell Death	6	10.6×	3e-03
Clathrin-mediated endocytosis	10	10.3×	3e-05
Apoptosis	5	10.1×	6e-03

GO biological processes:

GO term	Partners	Fold	FDR
endocytosis	12	9.7×	4e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

77 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	48
Likely benign	3
Benign	10

Top pathogenic / likely-pathogenic (0)

SpliceAI

1564 predictions. Top by Δscore:

Variant	Effect	Δscore
19:4361795:CG:C	acceptor_gain	1.0000
19:4361797:C:CC	acceptor_gain	1.0000
19:4362327:A:AC	donor_gain	1.0000
19:4362328:C:CC	donor_gain	1.0000
19:4362328:CG:C	donor_gain	1.0000
19:4362606:CATTA:C	donor_loss	1.0000
19:4362609:TA:T	donor_loss	1.0000
19:4362732:GCATC:G	acceptor_gain	1.0000
19:4362733:CATC:C	acceptor_gain	1.0000
19:4362733:CATCC:C	acceptor_gain	1.0000
19:4362734:ATC:A	acceptor_gain	1.0000
19:4362734:ATCC:A	acceptor_loss	1.0000
19:4362735:TC:T	acceptor_gain	1.0000
19:4362735:TCC:T	acceptor_loss	1.0000
19:4362736:CCTG:C	acceptor_gain	1.0000
19:4362737:C:CC	acceptor_gain	1.0000
19:4362737:CTGT:C	acceptor_loss	1.0000
19:4363364:GCTCA:G	donor_loss	1.0000
19:4363365:CTCA:C	donor_loss	1.0000
19:4363366:TCACC:T	donor_loss	1.0000
19:4363367:CACC:C	donor_loss	1.0000
19:4363368:A:AC	donor_gain	1.0000
19:4363369:C:CC	donor_gain	1.0000
19:4363369:C:T	donor_loss	1.0000
19:4363369:CCTG:C	donor_gain	1.0000
19:4363470:CGAT:C	acceptor_gain	1.0000
19:4363472:AT:A	acceptor_gain	1.0000
19:4363473:TCTG:T	acceptor_loss	1.0000
19:4363474:C:CA	acceptor_loss	1.0000
19:4363474:C:CC	acceptor_gain	1.0000

AlphaMissense

2415 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:4361671:C:G	G346R	1.000
19:4361680:A:G	W343R	1.000
19:4361680:A:T	W343R	1.000
19:4361727:A:G	F327S	1.000
19:4361756:G:C	F317L	1.000
19:4361756:G:T	F317L	1.000
19:4361758:A:G	F317L	1.000
19:4363847:A:G	L166P	1.000
19:4363850:C:G	R165P	1.000
19:4364161:A:G	L131P	1.000
19:4364200:C:T	G118D	1.000
19:4361640:G:T	P356Q	0.999
19:4361641:G:A	P356S	0.999
19:4361641:G:T	P356T	0.999
19:4361643:A:G	F355S	0.999
19:4361649:C:T	G353D	0.999
19:4361670:C:T	G346D	0.999
19:4361678:C:A	W343C	0.999
19:4361678:C:G	W343C	0.999
19:4361709:A:C	I333S	0.999
19:4361709:A:T	I333N	0.999
19:4361733:A:G	L325P	0.999
19:4361733:A:T	L325Q	0.999
19:4361757:A:C	F317C	0.999
19:4361757:A:G	F317S	0.999
19:4361769:G:T	A313E	0.999
19:4361774:G:C	C311W	0.999
19:4363379:A:G	L240P	0.999
19:4363400:A:G	L233P	0.999
19:4363413:C:G	A229P	0.999

dbSNP variants (sampled 300 via entrez): RS1000005923 (19:4375656 A>C), RS1000055207 (19:4399857 A>G), RS1000064713 (19:4375993 G>A), RS1000106244 (19:4402378 G>A), RS1000165276 (19:4362444 T>C), RS1000235422 (19:4380157 T>A,C,G), RS1000315471 (19:4400545 A>G), RS1000432925 (19:4365815 G>A), RS1000502006 (19:4363076 G>A), RS1000525373 (19:4391458 G>A,C), RS1000609882 (19:4371369 C>T), RS1000674311 (19:4366588 A>C,G), RS1000709887 (19:4400945 C>A,G), RS1000730199 (19:4367829 C>T), RS1000997731 (19:4363972 C>G,T)

Disease associations

OMIM: gene MIM:601768 | disease phenotypes: MIM:601626

GenCC curated gene-disease

Disease	Classification	Inheritance
immunodeficiency disease	Limited	Autosomal recessive

Mondo (2): acute myeloid leukemia (MONDO:0018874), immunodeficiency disease (MONDO:0021094)

Orphanet (1): Acute myeloid leukemia (Orphanet:519)

HPO phenotypes

3 total (3 of 3 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0001442	Typified by somatic mosaicism
HP:0004808	Acute myeloid leukemia

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST90000025_668	Appendicular lean mass	6.000000e-16
GCST90002383_96	Hematocrit	8.000000e-17
GCST90002404_552	Red cell distribution width	2.000000e-10

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004980	appendicular lean mass
EFO:0004348	hematocrit
EFO:0009188	Red cell distribution width

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D015470	Leukemia, Myeloid, Acute	C04.557.337.539.275; C15.378.508.539.275

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

44 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression	3
methacrylaldehyde	increases abundance, affects cotreatment, increases oxidation	2
Acrolein	affects cotreatment, increases oxidation, increases abundance	2
Ozone	increases abundance, affects cotreatment, increases oxidation	2
Tobacco Smoke Pollution	affects expression, increases expression	2
bisphenol F	increases expression	1
biochanin A	increases expression	1
2,4,6-tribromophenol	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
baicalein	decreases expression, increases reaction	1
bisphenol A	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, decreases expression	1
decabromobiphenyl ether	decreases expression	1
beta-lapachone	decreases expression	1
tetrabromobisphenol A	decreases expression	1
aflatoxin B2	decreases methylation	1
cupric chloride	increases expression	1
nickel sulfate	increases expression	1
nutlin 3	affects cotreatment, increases secretion	1
ICG 001	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
bisphenol S	decreases methylation	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Arsenic Trioxide	affects cotreatment, decreases expression	1
Acetaminophen	increases expression	1
Air Pollutants	increases abundance, increases oxidation, affects cotreatment	1
Atrazine	decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B3GZ	Abcam HEK293T SH3GL1 KO	Transformed cell line	Female

Clinical trials (associated diseases)

547 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00001542	PHASE4	COMPLETED	Fluconazole Prophylaxis of Thrush in AIDS
NCT00144157	PHASE4	COMPLETED	Open Label Study of NVP+CBV Treatment in Women Who Have Received sdNVP for the pMTCT of HIV
NCT00162643	PHASE4	UNKNOWN	PI Vs. NNRTI Based Therapy for HIV Advanced Disease
NCT00273988	PHASE4	COMPLETED	Pharmacokinetic Study of Interaction Between Nevirapine and Methadone in HIV-1 Infected, Opioid-dependent Adults
NCT00981318	PHASE4	TERMINATED	Pilot Assessment of Lopinavir/Ritonavir and Maraviroc
NCT01086878	PHASE4	COMPLETED	Safety of Cotrimoxazole in HIV- and HAART-exposed Infants
NCT01090102	PHASE4	COMPLETED	Mesalamine to Reduce T Cell Activation in HIV Infection
NCT01147042	PHASE4	TERMINATED	Biochemical Response to Interferon-Gamma in Subjects With Specific Gene Mutation in Chronic Granulomatous Disease
NCT01230580	PHASE4	UNKNOWN	Protease Inhibitor Monotherapy Versus Ongoing Triple-therapy in the Long Term Management of HIV Infection (PIVOT)
NCT01465958	PHASE4	COMPLETED	Pharmacokinetics, Safety, and Tolerability of Subcutaneous GAMUNEX-C in Pediatric Subjects With Primary Immunodeficiency
NCT02274662	PHASE4	COMPLETED	Expanded Access Protocol Thymus Transplantation
NCT02348177	PHASE4	COMPLETED	Pharmacokinetics of Lopinavir/Ritonavir Superboosting in Infants and Young Children Co-infected With HIV and TB
NCT02396979	PHASE4	COMPLETED	Intervention of HIV, Drug Use and the Criminal Justice System in Malaysia
NCT02490956	PHASE4	UNKNOWN	Diagnostic Immunization With Rabies Vaccine in Patients With PID
NCT02503293	PHASE4	COMPLETED	A Study to Compare Quality of Life and Satisfaction in Primary Immunodeficient Patients Treated With Subcutaneous Injections of Gammanorm® 165 mg/mL Administered With Two Different Delivery Devices: Injections Using Pump or Rapid Push
NCT02881437	PHASE4	COMPLETED	IgG Level in Primary Immunodeficiency Switching From Standard SCIG to Every Other Week HyQvia
NCT03033745	PHASE4	COMPLETED	Safety and Tolerability of Higher Infusion Parameters of IgPro20 (Hizentra) in Subjects With Primary Immunodeficiency (PID)
NCT03677557	PHASE4	UNKNOWN	Safety, Tolerability, Patient Satisfaction and Cost of 16.5% Subcutaneous Immunoglobulin (Cutaquig®) Treatment
NCT04192487	PHASE4	COMPLETED	Effects of Crofelemer on the Gut Microbiome in Healthy Volunteers and in HIV+ Patients With Non-Infectious Diarrhea
NCT04566692	PHASE4	COMPLETED	A Study to Evaluate IGSC 20% Biweekly Dosing in Treatment-Experienced Participants and Loading/Maintenance Dosing in Treatment-Naïve Participants With Primary Immunodeficiency
NCT05493969	PHASE4	NOT_YET_RECRUITING	Efficacy and Tolerability of DTG Plus 3TC in HIV Infected Adults With Virologically Suppression and TDF Toxicity
NCT06576024	PHASE4	COMPLETED	Immunogenicity and Safety of Inactivated Hepatitis A Vaccine in HIV-infected People
NCT06634641	PHASE4	RECRUITING	Clozapine-related Immunodeficiency in Parkinsons Disease
NCT07076446	PHASE4	ACTIVE_NOT_RECRUITING	An Open-label, Multicenter Study to Assess the Pharmacokinetics (PK), Safety, and Tolerability of Subcutaneous IgPro20 in Immunoglobulin (IG) Treatment-naïve Participants With Primary Immunodeficiency (PID)
NCT00199147	PHASE4	UNKNOWN	Efficacy of G-CSF-Priming in Elderly AML Patients
NCT00304447	PHASE4	COMPLETED	Study Evaluating the Effect of Corticosteroids on Mylotarg® Infusion-Related Adverse Events in Patients With Leukemia
NCT00464217	PHASE4	COMPLETED	Treatment of the Acute Myeloblastic Leukaemia in Patients Over 65 Years
NCT00487448	PHASE4	COMPLETED	SMD_FLAG-IDA_98: FLAG-IDA in Induction Treatment of High Risk Myelodysplastic Syndromes or Secondary Acute Myeloblastic Leukemia
NCT00488709	PHASE4	COMPLETED	Fludarabine, Cytarabine, Topotecan in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia
NCT00686543	PHASE4	COMPLETED	Oral Posaconazole in High Risk Patients With Gastrointestinal Dysfunction (Study P05115)
NCT01041040	PHASE4	COMPLETED	LAM07: Study to Analyze the Efficacy of a Risk Adapted Treatment Strategy, Including Gemtuzumab Ozogamicin (GO) During Consolidation, for Patients With Acute Myeloid Leukemia (AML)
NCT01198054	PHASE4	TERMINATED	LENA-LMA-5:Lenalidomide in Acute Myeloid Leukemia (AML)
NCT01200355	PHASE4	COMPLETED	Posaconazole Versus Micafungin for Prophylaxis Against Invasive Fungal Infections During Neutropenia in Patients Undergoing Chemotherapy for Acute Myelogenous Leukemia, Acute Lymphocytic Leukemia or Myelodysplastic Syndrome
NCT01347996	PHASE4	COMPLETED	Maintenance Therapy With Ceplene® (Histamine) and IL-2 on Immune Response and MRD in Acute Myeloid Leukemia
NCT01587430	PHASE4	UNKNOWN	3 Anthracyclines, 2 Types of Consolidation With Different ARA-C Doses and Maintenance in Adult Acute Myeloid Leukemia
NCT01819792	PHASE4	COMPLETED	Respiratory Viral Infections During Acute Myeloid Leukemia (AML)Chemotherapy Related Aplasia
NCT02024308	PHASE4	UNKNOWN	AML1-ETO Acute Myeloid Leukemia With Fludarabine and Cytarabine Chemotherapy
NCT02027064	PHASE4	UNKNOWN	Interferon for the Intervention of Molecular Relapse in t (8; 21) AML After Allo-HSCT
NCT02277847	PHASE4	UNKNOWN	Idarubicin at Different Dosages as Induction Therapy for Newly Diagnosed Acute Myeloid Leukaemia
NCT02386800	PHASE4	ACTIVE_NOT_RECRUITING	CINC424A2X01B Rollover Protocol