SH3TC1

Summary

SH3TC1 (SH3 domain and tetratricopeptide repeats 1, HGNC:26009) is a protein-coding gene on chromosome 4p16.1, encoding SH3 domain and tetratricopeptide repeat-containing protein 1 (Q8TE82).

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 395 total
• MANE Select transcript: NM_018986

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26009
Approved symbol	SH3TC1
Name	SH3 domain and tetratricopeptide repeats 1
Location	4p16.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ20356
Ensembl gene	ENSG00000125089
Ensembl biotype	protein_coding
Entrez	54436

Gene structure

Transcript identifiers

Ensembl transcripts: 29 — 10 retained_intron, 8 protein_coding, 6 nonsense_mediated_decay, 5 protein_coding_CDS_not_defined

ENST00000245105, ENST00000382521, ENST00000457650, ENST00000502350, ENST00000502559, ENST00000502669, ENST00000503284, ENST00000504223, ENST00000504822, ENST00000506360, ENST00000507123, ENST00000507801, ENST00000507891, ENST00000508183, ENST00000508438, ENST00000508641, ENST00000509553, ENST00000510763, ENST00000511002, ENST00000512100, ENST00000512966, ENST00000513495, ENST00000514274, ENST00000515682, ENST00000682056, ENST00000682862, ENST00000684537, ENST00000684698, ENST00000874439

RefSeq mRNA: 3 — MANE Select: NM_018986 NM_001318480, NM_001410712, NM_018986

CCDS: CCDS3399, CCDS93475, CCDS93476

Canonical transcript exons

ENST00000245105 — 18 exons

Exon	Start	End
ENSE00001348659	8240698	8241103
ENSE00001810207	8199290	8199405
ENSE00003459475	8212701	8212828
ENSE00003512977	8216111	8216257
ENSE00003522214	8216957	8217167
ENSE00003582177	8222840	8222970
ENSE00003592613	8231976	8232156
ENSE00003595903	8225175	8225216
ENSE00003603573	8205167	8205366
ENSE00003604948	8236278	8236428
ENSE00003620054	8233363	8233513
ENSE00003628565	8209748	8209822
ENSE00003638021	8235433	8235555
ENSE00003639041	8226980	8228644
ENSE00003667426	8214475	8214580
ENSE00003668727	8218271	8218347
ENSE00003682417	8219335	8219530
ENSE00003691383	8237474	8237670

Expression profiles

Bgee: expression breadth ubiquitous, 196 present calls, max score 97.27.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 9.0939 / max 183.5226, expressed in 1160 samples.

FANTOM5 promoters (16 alternative TSS)

Promoter ID	TPM avg	Samples expressed
46852	8.3830	1143
46853	0.2998	159
46850	0.0718	19
46860	0.0564	15
46856	0.0492	20
46849	0.0411	17
46858	0.0377	15
46859	0.0375	15
46855	0.0373	11
46851	0.0266	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
thymus	UBERON:0002370	97.27	gold quality
granulocyte	CL:0000094	92.86	gold quality
monocyte	CL:0000576	92.58	gold quality
mononuclear cell	CL:0000842	92.44	gold quality
leukocyte	CL:0000738	92.09	gold quality
metanephros cortex	UBERON:0010533	91.77	gold quality
right lung	UBERON:0002167	90.57	gold quality
spleen	UBERON:0002106	90.10	gold quality
adult mammalian kidney	UBERON:0000082	89.23	gold quality
gall bladder	UBERON:0002110	88.39	gold quality
upper lobe of left lung	UBERON:0008952	88.08	gold quality
upper lobe of lung	UBERON:0008948	87.18	gold quality
esophagus mucosa	UBERON:0002469	85.80	gold quality
lymph node	UBERON:0000029	85.59	gold quality
right lobe of liver	UBERON:0001114	85.46	gold quality
sural nerve	UBERON:0015488	85.39	gold quality
colonic epithelium	UBERON:0000397	85.19	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	84.47	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	84.46	gold quality
omental fat pad	UBERON:0010414	84.29	gold quality
vermiform appendix	UBERON:0001154	84.23	gold quality
peritoneum	UBERON:0002358	84.18	gold quality
blood	UBERON:0000178	83.23	gold quality
body of stomach	UBERON:0001161	83.23	gold quality
adipose tissue of abdominal region	UBERON:0007808	83.21	gold quality
subcutaneous adipose tissue	UBERON:0002190	83.05	gold quality
body of pancreas	UBERON:0001150	82.84	gold quality
tibial nerve	UBERON:0001323	82.81	gold quality
tonsil	UBERON:0002372	82.70	gold quality
kidney	UBERON:0002113	82.32	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-CURD-79	yes	803.20
E-MTAB-9067	yes	13.31
E-ANND-3	yes	12.09
E-CURD-122	yes	4.91

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

8 targeting SH3TC1, 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-548AW	99.99	72.57	3559
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-548AS-3P	99.12	69.12	2294
HSA-MIR-5006-5P	98.79	66.92	1246
HSA-MIR-4733-3P	98.35	65.20	994
HSA-MIR-660-5P	98.16	68.27	680
HSA-MIR-1202	97.19	66.43	827
HSA-MIR-3972	97.19	66.46	808

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	SH3TC1	ENSDARG00000077330
mus_musculus	Sh3tc1	ENSMUSG00000036553
rattus_norvegicus	Sh3tc1	ENSRNOG00000007993

Paralogs (1): SH3TC2 (ENSG00000169247)

Protein

Protein identifiers

SH3 domain and tetratricopeptide repeat-containing protein 1 — Q8TE82 (reviewed: Q8TE82)

All UniProt accessions (13): Q8TE82, A0A804HI81, A0A804HJ39, A0A804HJH0, A0A804HK80, D6REB6, D6RI07, E7EQR1, H0Y9A4, H0YA34, H0YAJ7, Q6NVH2, U3KQ04

RefSeq proteins (3): NP_001305409, NP_001397641, NP_061859* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001452	SH3_domain	Domain
IPR011990	TPR-like_helical_dom_sf	Homologous_superfamily
IPR019734	TPR_rpt	Repeat
IPR036028	SH3-like_dom_sf	Homologous_superfamily
IPR042772	SH3TC1/SH3TC2	Family

Pfam: PF00018

UniProt features (25 total): repeat 9, sequence variant 5, compositionally biased region 4, region of interest 2, modified residue 2, chain 1, domain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TE82-F1	77.76	0.35

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 (2): 1, 1248

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 130 (showing top): MODULE_97, MODULE_182, ACEVEDO_LIVER_TUMOR_VS_NORMAL_ADJACENT_TISSUE_DN, chr4p16, GARY_CD5_TARGETS_DN, TGGNNNNNNKCCAR_UNKNOWN, RYTTCCTG_ETS2_B, HOEBEKE_LYMPHOID_STEM_CELL_UP, VALK_AML_CLUSTER_15, RGAGGAARY_PU1_Q6, MODULE_48, IZADPANAH_STEM_CELL_ADIPOSE_VS_BONE_UP, MODULE_95, RIGGI_EWING_SARCOMA_PROGENITOR_UP, NERF_Q2

GO Biological Process (1): biological_process (GO:0008150)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (1): cellular_component (GO:0005575)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	1

Protein interactions and networks

STRING

452 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SH3TC1	AFAP1	Q8N556	538
SH3TC1	GLT8D1	Q68CQ7	499
SH3TC1	ABLIM2	Q6H8Q1	492
SH3TC1	SORCS2	Q96PQ0	458
SH3TC1	EMSY	Q7Z589	429
SH3TC1	HCFC1R1	Q9NWW0	429
SH3TC1	UNKL	Q9H9P5	405
SH3TC1	ZBED1	O96006	380
SH3TC1	OR7D2	Q96RA2	373
SH3TC1	MS4A13	Q5J8X5	370
SH3TC1	CCDC167	Q9P0B6	370
SH3TC1	AADACL2	Q6P093	368
SH3TC1	METTL26	Q96S19	357
SH3TC1	CD58	P19256	351
SH3TC1	RGPD4	Q7Z3J3	349

IntAct

5 interactions, top by confidence:

A	B	Type	Score
ATF6	APOD	psi-mi:“MI:0914”(association)	0.350
P		psi-mi:“MI:0914”(association)	0.350
AFG2B	MMP24OS	psi-mi:“MI:0914”(association)	0.350

BioGRID (8): SH3TC1 (Affinity Capture-MS), SH3TC1 (Affinity Capture-RNA), SH3TC1 (Affinity Capture-MS), SH3TC1 (Affinity Capture-RNA), SH3TC1 (Affinity Capture-MS), SH3TC1 (Affinity Capture-RNA), SH3TC1 (Cross-Linking-MS (XL-MS)), SH3TC1 (Affinity Capture-RNA)

ESM2 similar proteins: A0JNQ6, A6NC42, A6NGQ2, A6NGR9, A6QP75, A7E3N7, A9X185, E1BDF2, E9PGG2, F6SZT2, P0C7A0, P85965, Q06VW1, Q0ZFW8, Q14DK4, Q3UK37, Q3UV16, Q3ZBN4, Q400G9, Q4VXA5, Q587J8, Q5JSQ8, Q60953, Q60I26, Q60I27, Q6NUI2, Q6ZUX3, Q810I0, Q8BH06, Q8C0R7, Q8IWB1, Q8IWY9, Q8IYX4, Q8K4C2, Q8N6L0, Q8N7F7, Q8NCV1, Q8TE82, Q91WA6, Q95JV3

Diamond homologs: Q80VA5, Q8TE82, Q8TF17

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	323
Likely benign	26
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

4103 predictions. Top by Δscore:

Variant	Effect	Δscore
4:8212696:TCCA:T	acceptor_loss	1.0000
4:8212698:CAG:C	acceptor_loss	1.0000
4:8212699:A:AG	acceptor_gain	1.0000
4:8212699:A:AT	acceptor_loss	1.0000
4:8212700:G:GT	acceptor_gain	1.0000
4:8212700:GA:G	acceptor_gain	1.0000
4:8212700:GAC:G	acceptor_gain	1.0000
4:8212700:GACC:G	acceptor_gain	1.0000
4:8212700:GACCT:G	acceptor_gain	1.0000
4:8212824:TTGGG:T	donor_gain	1.0000
4:8212825:TGGG:T	donor_gain	1.0000
4:8212826:GGG:G	donor_gain	1.0000
4:8212826:GGGG:G	donor_gain	1.0000
4:8212827:GG:G	donor_gain	1.0000
4:8212827:GGG:G	donor_gain	1.0000
4:8212828:GG:G	donor_gain	1.0000
4:8212828:GGTG:G	donor_loss	1.0000
4:8212829:G:GG	donor_gain	1.0000
4:8212829:GT:G	donor_loss	1.0000
4:8212830:T:A	donor_loss	1.0000
4:8214555:G:GT	donor_gain	1.0000
4:8216254:GAAG:G	donor_gain	1.0000
4:8216257:GGTG:G	donor_loss	1.0000
4:8216259:T:G	donor_loss	1.0000
4:8217168:G:GG	donor_gain	1.0000
4:8219234:A:G	donor_gain	1.0000
4:8219334:GCT:G	acceptor_gain	1.0000
4:8219334:GCTGT:G	acceptor_gain	1.0000
4:8222836:CCA:C	acceptor_loss	1.0000
4:8222837:CAGGT:C	acceptor_loss	1.0000

AlphaMissense

8598 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:8233393:A:C	K1054N	0.991
4:8233393:A:T	K1054N	0.991
4:8214532:T:C	F145L	0.989
4:8214534:T:A	F145L	0.989
4:8214534:T:G	F145L	0.989
4:8233448:T:A	W1073R	0.988
4:8233448:T:C	W1073R	0.988
4:8214559:T:C	F154L	0.986
4:8214561:T:A	F154L	0.986
4:8214561:T:G	F154L	0.986
4:8217160:T:C	F278L	0.986
4:8217162:T:A	F278L	0.986
4:8217162:T:G	F278L	0.986
4:8219488:T:C	F357S	0.983
4:8233392:A:T	K1054I	0.983
4:8240743:G:C	A1267P	0.983
4:8236416:A:C	S1182R	0.981
4:8236418:C:A	S1182R	0.981
4:8236418:C:G	S1182R	0.981
4:8232125:A:C	S1034R	0.980
4:8232127:C:A	S1034R	0.980
4:8232127:C:G	S1034R	0.980
4:8237645:G:A	G1243D	0.978
4:8240710:G:C	A1256P	0.977
4:8214560:T:C	F154S	0.975
4:8219487:T:C	F357L	0.975
4:8219489:T:A	F357L	0.975
4:8219489:T:G	F357L	0.975
4:8240732:C:A	A1263E	0.975
4:8240741:C:A	A1266D	0.975

dbSNP variants (sampled 300 via entrez): RS1000004494 (4:8229404 C>A,T), RS1000009772 (4:8185816 C>A), RS1000099630 (4:8220203 G>A,C), RS1000189471 (4:8197843 G>A), RS1000194685 (4:8199454 G>T), RS1000199705 (4:8233989 TCATC>T), RS10002039 (4:8189726 T>G), RS1000254482 (4:8188132 A>G), RS1000283447 (4:8225017 C>T), RS1000337200 (4:8241151 G>A,T), RS10003718 (4:8200357 G>T), RS1000378263 (4:8183447 G>A), RS1000393999 (4:8195226 A>G), RS1000426295 (4:8212997 C>A,T), RS1000444777 (4:8185510 C>G)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST003791_3	Response to metformin (IC50)	3.000000e-06
GCST008361_3	Response to cognitive-behavioural therapy in major depressive disorder	2.000000e-06
GCST010172_15	Idiopathic downbeat nystagmus	7.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0006952	cytotoxicity measurement
EFO:0007820	cognitive behavioural therapy

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Cyclosporine	decreases expression, increases expression	5
bisphenol A	affects expression, decreases methylation	2
sodium arsenite	increases expression	2
(+)-JQ1 compound	decreases expression	2
Benzo(a)pyrene	affects methylation, decreases methylation	2
Calcitriol	affects cotreatment, increases expression	2
Nickel	increases expression	2
Tobacco Smoke Pollution	decreases expression, increases expression	2
Valproic Acid	increases expression, increases methylation	2
Particulate Matter	increases abundance, increases expression, affects cotreatment	2
bufotalin	increases expression	1
chloroacetaldehyde	decreases expression	1
propionaldehyde	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
benzo(e)pyrene	increases methylation	1
cupric chloride	increases expression	1
hydroquinone	increases expression	1
S-(1,2-dichlorovinyl)cysteine	decreases expression, affects response to substance, increases expression, affects cotreatment	1
adefovir dipivoxil	decreases expression	1
clothianidin	increases expression	1
prothioconazole	increases expression	1
PCI 5002	increases expression, affects cotreatment	1
Rosiglitazone	increases expression	1
Sunitinib	decreases expression	1
Leflunomide	increases expression	1
Cidofovir	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Vehicle Emissions	increases methylation	1
Cisplatin	increases expression	1
Formaldehyde	increases expression	1

Clinical trials (associated diseases)

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