SH3BP5L

Summary

SH3BP5L (SH3 binding domain protein 5 like, HGNC:29360) is a protein-coding gene on chromosome 1q44, encoding SH3 domain-binding protein 5-like (Q7L8J4). Functions as a guanine nucleotide exchange factor (GEF) for RAB11A.

Enables guanyl-nucleotide exchange factor activity. Predicted to be involved in intracellular signal transduction. Predicted to be active in cytoplasm.

Source: NCBI Gene 80851 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 57 total
• MANE Select transcript: NM_030645

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29360
Approved symbol	SH3BP5L
Name	SH3 binding domain protein 5 like
Location	1q44
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1720
Ensembl gene	ENSG00000175137
Ensembl biotype	protein_coding
OMIM	620652
Entrez	80851

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 12 protein_coding, 3 protein_coding_CDS_not_defined

ENST00000366472, ENST00000475978, ENST00000484202, ENST00000494837, ENST00000870257, ENST00000870258, ENST00000870259, ENST00000870260, ENST00000870261, ENST00000931893, ENST00000931894, ENST00000931895, ENST00000931896, ENST00000931897, ENST00000966015

RefSeq mRNA: 4 — MANE Select: NM_030645 NM_001322462, NM_001322463, NM_001322464, NM_030645

CCDS: CCDS31126

Canonical transcript exons

ENST00000366472 — 7 exons

Exon	Start	End
ENSE00001276497	248825835	248825915
ENSE00001441809	248824753	248825366
ENSE00001833074	248810446	248812370
ENSE00003576778	248812989	248813162
ENSE00003621119	248814449	248814610
ENSE00003662494	248816534	248816662
ENSE00003681884	248816822	248816884

Expression profiles

Bgee: expression breadth ubiquitous, 225 present calls, max score 93.28.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.7116 / max 47.7928, expressed in 1739 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
18526	3.8789	1597
18527	2.7888	1306
18525	0.0440	18

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	93.28	gold quality
right hemisphere of cerebellum	UBERON:0014890	90.80	gold quality
cerebellar hemisphere	UBERON:0002245	90.51	gold quality
cerebellar cortex	UBERON:0002129	90.37	gold quality
granulocyte	CL:0000094	90.12	gold quality
apex of heart	UBERON:0002098	89.86	gold quality
stromal cell of endometrium	CL:0002255	89.47	gold quality
right frontal lobe	UBERON:0002810	89.38	gold quality
cerebellum	UBERON:0002037	89.24	gold quality
gastrocnemius	UBERON:0001388	88.91	gold quality
prefrontal cortex	UBERON:0000451	88.80	gold quality
muscle of leg	UBERON:0001383	88.56	gold quality
cortical plate	UBERON:0005343	88.36	gold quality
mucosa of transverse colon	UBERON:0004991	88.34	gold quality
lower esophagus	UBERON:0013473	88.18	gold quality
lower esophagus muscularis layer	UBERON:0035833	88.16	gold quality
blood	UBERON:0000178	88.08	gold quality
right uterine tube	UBERON:0001302	87.97	gold quality
Brodmann (1909) area 9	UBERON:0013540	87.70	gold quality
esophagus mucosa	UBERON:0002469	87.67	gold quality
esophagus	UBERON:0001043	87.65	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	87.33	gold quality
anterior cingulate cortex	UBERON:0009835	87.32	gold quality
small intestine Peyer’s patch	UBERON:0003454	87.01	gold quality
muscle layer of sigmoid colon	UBERON:0035805	86.88	gold quality
right adrenal gland	UBERON:0001233	86.82	gold quality
metanephros cortex	UBERON:0010533	86.67	gold quality
right adrenal gland cortex	UBERON:0035827	86.66	gold quality
right lobe of liver	UBERON:0001114	86.50	gold quality
hindlimb stylopod muscle	UBERON:0004252	86.48	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	3.05

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

77 targeting SH3BP5L, 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-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548Y	99.94	71.28	3514
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488
HSA-MIR-548D-5P	99.94	71.23	3502
HSA-MIR-548H-5P	99.94	71.24	3488
HSA-MIR-548I	99.94	71.25	3481

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	sh3bp5lb	ENSDARG00000007136
danio_rerio	sh3bp5la	ENSDARG00000019160
mus_musculus	Sh3bp5l	ENSMUSG00000013646
rattus_norvegicus	Sh3bp5l	ENSRNOG00000054400
drosophila_melanogaster	pcs	FBGN0033988
caenorhabditis_elegans		WBGENE00007270
caenorhabditis_elegans		WBGENE00019365

Paralogs (1): SH3BP5 (ENSG00000131370)

Protein

Protein identifiers

SH3 domain-binding protein 5-like — Q7L8J4 (reviewed: Q7L8J4)

All UniProt accessions (1): Q7L8J4

UniProt curated annotations — full annotation on UniProt →

Function. Functions as a guanine nucleotide exchange factor (GEF) for RAB11A.

Similarity. Belongs to the SH3BP5 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q7L8J4-1	1	yes
Q7L8J4-2	2

RefSeq proteins (4): NP_001309391, NP_001309392, NP_001309393, NP_085148* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007940	SH3BP5	Family

Pfam: PF05276

UniProt features (19 total): modified residue 8, compositionally biased region 4, region of interest 3, coiled-coil region 2, chain 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7L8J4-F1	74.38	0.52

Functional residue map

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

Post-translational modifications (8): 13, 30, 49, 343, 350, 358, 362, 378

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 104 (showing top): TGGTGCT_MIR29A_MIR29B_MIR29C, SP3_Q3, AP2_Q3, RYTTCCTG_ETS2_B, WHN_B, AML1_01, TGCCTTA_MIR124A, chr1q44, GINESTIER_BREAST_CANCER_ZNF217_AMPLIFIED_DN, GOMF_GUANYL_NUCLEOTIDE_EXCHANGE_FACTOR_ACTIVITY, GOMF_NUCLEOSIDE_TRIPHOSPHATASE_REGULATOR_ACTIVITY, GOMF_ENZYME_INHIBITOR_ACTIVITY, GOMF_ENZYME_REGULATOR_ACTIVITY, BRUINS_UVC_RESPONSE_LATE, STAT6_01

GO Biological Process (1): intracellular signal transduction (GO:0035556)

GO Molecular Function (3): protein kinase inhibitor activity (GO:0004860), guanyl-nucleotide exchange factor activity (GO:0005085), protein binding (GO:0005515)

GO Cellular Component (1): cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular anatomical structure	2
signal transduction	1
protein kinase activity	1
kinase inhibitor activity	1
protein kinase regulator activity	1
GTP binding	1
GDP binding	1
GTPase regulator activity	1
binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1142 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SH3BP5L	CLSTN3	Q9BQT9	460
SH3BP5L	CDH18	Q13634	454
SH3BP5L	TELO2	Q9Y4R8	447
SH3BP5L	RAB11FIP3	O75154	444
SH3BP5L	ZNF672	Q499Z4	433
SH3BP5L	SPATA45	Q537H7	419
SH3BP5L	OR6K3	Q8NGY3	419
SH3BP5L	SNCAIP	Q9Y6H5	415
SH3BP5L	CCDC122	Q5T0U0	414
SH3BP5L	ZNF670	Q9BS34	398
SH3BP5L	NEDD9	Q14511	390
SH3BP5L	RNF146	Q9NTX7	381
SH3BP5L	PLA2G6	O60733	375
SH3BP5L	CCDC137	Q6PK04	373
SH3BP5L	CYSRT1	A8MQ03	369

IntAct

58 interactions, top by confidence:

A	B	Type	Score
YWHAG	SH3BP5L	psi-mi:“MI:0915”(physical association)	0.810
RAB11B	SH3BP5L	psi-mi:“MI:0915”(physical association)	0.740
YWHAZ	SH3BP5L	psi-mi:“MI:0915”(physical association)	0.670
RAB11B	SH3BP5	psi-mi:“MI:0914”(association)	0.640
YWHAG	BLTP3B	psi-mi:“MI:0914”(association)	0.640
YWHAH	PLEKHG3	psi-mi:“MI:0914”(association)	0.610
EMC2	SH3BP5L	psi-mi:“MI:0915”(physical association)	0.560
SH3BP5L	CEP57	psi-mi:“MI:0915”(physical association)	0.560
SH3BP5L	FAM161B	psi-mi:“MI:0915”(physical association)	0.560
RAB14	SH3BP5L	psi-mi:“MI:0915”(physical association)	0.560
SUOX	SH3BP5L	psi-mi:“MI:0915”(physical association)	0.560
RAB25	SH3BP5L	psi-mi:“MI:0915”(physical association)	0.560
CCK	SH3BP5L	psi-mi:“MI:0915”(physical association)	0.560
SH3GLB1	SH3BP5L	psi-mi:“MI:0915”(physical association)	0.560
PRPF40A	SH3BP5L	psi-mi:“MI:0915”(physical association)	0.560
RAB11A	SH3BP5	psi-mi:“MI:0914”(association)	0.530
YWHAQ	IGLC7	psi-mi:“MI:0914”(association)	0.530
YWHAB	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
YWHAQ	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
NINL	SH3BP5L	psi-mi:“MI:0915”(physical association)	0.370
SH3BP5L	PPP1R12A	psi-mi:“MI:0914”(association)	0.350

BioGRID (59): SH3BP5L (Affinity Capture-MS), SH3BP5L (Two-hybrid), BICD1 (Affinity Capture-MS), THG1L (Affinity Capture-MS), TNKS (Affinity Capture-MS), TNKS2 (Affinity Capture-MS), BTRC (Affinity Capture-MS), SH3BP5L (Affinity Capture-MS), SH3BP5L (Affinity Capture-MS), PPP1R12A (Affinity Capture-MS), HEXIM1 (Affinity Capture-MS), MIPOL1 (Affinity Capture-MS), FBXW11 (Affinity Capture-MS), CARM1 (Affinity Capture-MS), WTAP (Affinity Capture-MS)

ESM2 similar proteins: A0PJT0, A1YB07, A2A6T1, A4IH82, B1A193, D3ZD05, O14526, O60239, O75145, O75335, O94876, P60469, P84903, Q0V8K7, Q13136, Q1LU99, Q1LZH7, Q2QL82, Q2QLG9, Q3TBD2, Q495M9, Q58CP9, Q5R9X9, Q5RB40, Q5U4W1, Q5U584, Q63ZY3, Q69ZZ6, Q6AYB8, Q6DIS8, Q6NZT2, Q6P402, Q7L8J4, Q80T11, Q86YS3, Q8BIJ7, Q8BQP8, Q8BX02, Q8CJ96, Q91Y80

Diamond homologs: A4IH82, O60239, Q0V8K7, Q21194, Q5R9X9, Q5U584, Q7L8J4, Q91Y80, Q99LH9, Q9V785, Q9Z131, P42171

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 29 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
Activation of BAD and translocation to mitochondria	5	190.3×	8e-10
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	5	167.9×	1e-09
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	5	167.9×	1e-09
Activation of BH3-only proteins	5	124.1×	5e-09
RHO GTPases activate PKNs	6	95.2×	8e-10
Intrinsic Pathway for Apoptosis	5	73.2×	8e-08
Translocation of SLC2A4 (GLUT4) to the plasma membrane	7	54.0×	8e-10
SARS-CoV-1-host interactions	5	43.9×	1e-06

GO biological processes:

GO term	Partners	Fold	FDR
intracellular protein localization	5	20.1×	4e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	47
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1267 predictions. Top by Δscore:

Variant	Effect	Δscore
1:248812990:T:TA	donor_gain	1.0000
1:248814444:CTCA:C	donor_loss	1.0000
1:248814446:CACCT:C	donor_loss	1.0000
1:248814447:A:AC	donor_gain	1.0000
1:248814448:C:CC	donor_gain	1.0000
1:248814448:C:CT	donor_loss	1.0000
1:248814448:CCTTG:C	donor_gain	1.0000
1:248814606:TGAGC:T	acceptor_gain	1.0000
1:248814608:AGC:A	acceptor_gain	1.0000
1:248814609:GC:G	acceptor_gain	1.0000
1:248814610:CC:C	acceptor_gain	1.0000
1:248814611:C:CC	acceptor_gain	1.0000
1:248816530:ATACC:A	donor_loss	1.0000
1:248816531:TACC:T	donor_loss	1.0000
1:248816532:ACC:A	donor_loss	1.0000
1:248816532:ACCT:A	donor_gain	1.0000
1:248816533:CCTC:C	donor_gain	1.0000
1:248816535:T:TA	donor_gain	1.0000
1:248816658:GCCTC:G	acceptor_gain	1.0000
1:248816659:CCTCC:C	acceptor_gain	1.0000
1:248816660:CTC:C	acceptor_gain	1.0000
1:248816661:TC:T	acceptor_gain	1.0000
1:248816662:CC:C	acceptor_gain	1.0000
1:248816663:C:CC	acceptor_gain	1.0000
1:248816663:CTGG:C	acceptor_loss	1.0000
1:248816664:T:A	acceptor_loss	1.0000
1:248816674:C:CT	acceptor_gain	1.0000
1:248816675:A:T	acceptor_gain	1.0000
1:248816817:CTCA:C	donor_loss	1.0000
1:248816818:TCA:T	donor_loss	1.0000

AlphaMissense

2527 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:248812268:G:C	H272D	1.000
1:248812268:G:T	H272N	1.000
1:248812270:A:G	I271T	1.000
1:248812278:G:C	S268R	1.000
1:248812278:G:T	S268R	1.000
1:248812280:T:G	S268R	1.000
1:248812282:A:C	I267S	1.000
1:248812282:A:G	I267T	1.000
1:248812291:A:G	L264P	1.000
1:248812291:A:T	L264Q	1.000
1:248812300:A:G	L261P	1.000
1:248812300:A:T	L261H	1.000
1:248812320:C:A	K254N	1.000
1:248812320:C:G	K254N	1.000
1:248812322:T:C	K254E	1.000
1:248812993:A:G	L236P	1.000
1:248813017:A:G	L228P	1.000
1:248813022:A:C	F226L	1.000
1:248813022:A:T	F226L	1.000
1:248813023:A:C	F226C	1.000
1:248813023:A:G	F226S	1.000
1:248813024:A:G	F226L	1.000
1:248813024:A:T	F226I	1.000
1:248813027:A:C	Y225D	1.000
1:248813044:A:T	I219N	1.000
1:248813090:C:G	A204P	1.000
1:248813153:C:G	A183P	1.000
1:248814449:C:A	K179N	1.000
1:248814449:C:G	K179N	1.000
1:248814459:G:T	A176D	1.000

dbSNP variants (sampled 300 via entrez): RS1000285507 (1:248814140 T>TA), RS1000603834 (1:248811366 G>A,C), RS1000808697 (1:248811125 G>A), RS1000903703 (1:248818098 A>T), RS1000977060 (1:248827552 C>T), RS1001265737 (1:248813912 G>C,T), RS1001895463 (1:248817862 A>T), RS1001925212 (1:248824327 G>A), RS1002079055 (1:248812395 G>A,C), RS1002121217 (1:248813282 C>A), RS1002150793 (1:248813562 A>G), RS1002298778 (1:248825595 C>T), RS1002413396 (1:248825323 GGC>G), RS1002593441 (1:248819097 C>A,G,T), RS1002661525 (1:248827037 G>A)

Disease associations

OMIM: gene MIM:620652 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST002935_1	Lead levels	2.000000e-07

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

21 total (human), top 21 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression	2
aristolochic acid I	increases expression	1
FR900359	affects phosphorylation	1
triphenyl phosphate	affects expression	1
beta-lapachone	increases expression	1
ferrous chloride	decreases expression	1
aflatoxin B2	decreases methylation	1
coumarin	decreases phosphorylation	1
beta-methylcholine	affects expression	1
CGP 52608	affects binding, increases reaction	1
corosolic acid	increases expression	1
2-palmitoylglycerol	increases expression	1
Leflunomide	decreases expression	1
Air Pollutants	affects expression, increases abundance	1
Estradiol	affects expression	1
Ozone	affects expression, increases abundance	1
Smoke	decreases expression	1
Tretinoin	increases expression	1
Urethane	increases expression	1
Cadmium Chloride	increases expression	1
Copper Sulfate	increases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_TK95	HAP1 SH3BP5L (-) 1	Cancer cell line	Male
CVCL_XS76	HAP1 SH3BP5L (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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